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Primer for family, friends and care providers

2019-04-24T17:07:58Z

MEandCFS:/* Learn more */ fixing citation error

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
'''Primer for family, friends and care providers''' is for those who know or care for someone with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS), a complicated and life-altering systemic, biological, [[neuro-immune disease]].<ref name=":0">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|website=Open Medicine Foundation|language=en-US|access-date=2019-01-24}}</ref> Patient care and severity of the disease is poorly understood due to decades of research neglect and a lack of clinical care worldwide.<ref>{{Cite web|url=http://healthaffairs.org/blog/2016/02/04/reexamining-chronic-fatigue-syndrome-research-and-treatment-policy/|title=Reexamining Chronic Fatigue Syndrome Research And Treatment Policy|last=Tuller|first=David|date=Feb 4, 2016|website=healthaffairs.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite news|url=http://www.meaction.net/2017/01/22/funding-for-me-research-centers-announced-falls-way-short/|title=Funding for U.S. research centers falls way short - #MEAction|date=2017-01-22|work=#MEAction|access-date=2018-09-07|language=en-US}}</ref>

Diagnosing [[ME/CFS]] is difficult as there is no clinically accepted [[biomarker]] and there are numerous [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|definitions and criteria]] that have been developed and utilized over the decades.
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref name=":5">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":8">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":7">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":6">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda1994">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":023">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref> There have been media reports of athletes diagnosed with [[myalgic encephalomyelitis]] (ME) or [[chronic fatigue syndrome]] (CFS) who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":9">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":10">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":11">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref>{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref> CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":02">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

== Recommended reading for care providers ==
* [https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref name=":14">{{Cite web|url=https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view?usp=embed_facebook|title=Caregivers Guide to ME.pdf|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=Google Docs|publisher=MEAction|archive-url=|archive-date=|dead-url=|access-date=2019-03-31}}</ref> by #[[MEAction]]
<blockquote>Myalgic Encephalomyelitis (also known as Chronic Fatigue Syndrome or ME/CFS) is a complex, challenging disease for everyone involved - not least the caregiver. Caring for someone with ME will require adaptability, steadfast patience and commitment over many years, if not a lifetime.<ref name=":14" /></blockquote>

:Table of Contents:
::1) Educate Yourself
::2) Take Care of Yourself
::3) Family Dynamic
::4) Relationship with the Patient
::5) Resources
::6) Advocate
::7) Power of Attorney
::8) Get Organized
::9) Join the Community
::10) Read more<ref name=":14" />

[[Greg Crowhurst]] has cared for his wife [[Linda Crowhurst|Linda]] for decades as she is [[Severe and very severe ME|very severely ill with ME]]. Greg has written several books on caring for someone with ME.

*[[Severe ME - Featuring: "Justice for Karina Hansen"]]
*[[Severe ME: Notes for Carers]]
*[[Caring for ME]]

'''Other books/guides'''
*[[A Beginner's Guide to ME/CFS]]
*[[Caring For The M.E. Patient]]
*[[Chronic Fatigue Syndrome/ME: Support for Family and Friends]]
*[[Understanding M.E. - A Guide For Friends, Family & Carers]]
*[[What Is M.E.? A Guide For Children]]

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":043">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />

=== Not a mental health disorder ===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

=== ME/CFS is not contagious ===
There is no evidence that ME/CFS patients are contagious.<ref name=":032">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":7" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and many rely on SSDI/SSI.<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
*:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
*:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>

*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":22">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-28}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":7" /><ref name="Carruthers, 20032" /><ref name=":6" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":12">{{Cite journal|last=Cairns|first=R.|last2=Hotopf|first2=M.|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":12" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

== Symptoms ==
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":0" /><ref name=":03">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":2">[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref><ref name=":4">{{Cite web|url=https://www.webmd.com/chronic-fatigue-syndrome/symptoms-chronic-fatigue|title=What Are the Symptoms of Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=WebMD|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-01-24}}</ref> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months..<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":0" /><ref name=":03" /><ref name=":2" /><ref name=":4" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]
*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]] <ref name=":8" /><ref name=":7" />

=== Other possible symptoms ===
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ) <ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness - Report Guide for Clinicians|last=|first=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> from the [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]<ref>{{Cite web|url=http://linkis.com/org/tUheh|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Toward Optimized Practice (TOP) - CPGs|website=linkis.com|access-date=2018-09-07}}</ref>

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Drugs, treatments, and therapies==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [https://me-pedia.org/wiki/Category:Potential_treatments potential treatments], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.

=== Drugs ===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]

Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in early 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>{{Cite news|url=https://www.healthrising.org/blog/2016/02/04/low-dose-naltrexone-combo-chronic-fatigue/|title=Low Dose Naltrexone Drug Combination Proposed for Chronic Fatigue Syndrome (ME/CFS)|last=Johnson|first=Cort|date=2016-02-04|work=Health Rising|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=https://cas.uab.edu/younger/2017/02/ldn-chronic-fatigue-syndrome-clinical-trial/|title=LDN Chronic Fatigue Syndrome Clinical Trial - Neuroinflammation, Pain and Fatigue Laboratory|date=2017-02-23|work=Neuroinflammation, Pain and Fatigue Laboratory|access-date=2018-09-07|language=en-US}}</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Controversy===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Psychiatry has taken an inappropriate lead and treatment path for an organic biological disease. In the UK, [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are employed by ME Clinics. Exercise exacerbates symptoms and can further injure patients.<ref>{{Cite web|url=http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html|title=Slightly Alive: Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS|last=Schweitzer|first=Mary|date=2016-03-17|website=Slightly Alive|access-date=2018-09-07}}</ref><ref>{{Cite news|url=https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients|title=GET and CBT are dangerous treatments for ME patients|last=Evison|first=Michael|date=|work=Campaigns by You|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-GB}}</ref> Depression and anxiety drugs are utilized usually with poor and even damaging results.<ref>{{Cite web|url=http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title=CFS or depression - what are the differences - DoctorMyhill|last=Myhill|first=Sarah|date=|website=drmyhill.co.uk|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>

Treating a biological disease as a mental illness is cost effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance having clauses excluding a mental health illness/disease kick in stopping any payment or shortening the payout time-frame.<ref>{{Cite web|url=http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/|title=Trial by Error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really?|last=Tuller|first=David|date=Nov 17, 2015|website=www.virology.ws|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders|title=Physical Illnesses May Soon Be Labeled “Mental Disorders”|last=Bernhard|first=Toni|date=Dec 27, 2012|website=Psychology Today|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite web|url=http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=People with mental illness face widespread discrimination|last=Batty|first=David|date=2004-04-28|website=the Guardian|language=en|access-date=2018-09-07}}</ref><ref>{{Cite news|url=http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/|title=Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits|date=2016-03-21|work=Thoughts About M.E.|access-date=2018-09-07|language=en-US}}</ref>

==== Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
GET and CBT are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

===Claims of curative treatments===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":9" /><ref name=":10" /><ref name=":11" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

=== Working with government to move forward ===

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[NIH]], the [[CDC]] reinstating and increasing funding and education based on [[IOM]] recommendations and the [[HHS]] funding to develop Centers of Excellence.<ref>{{Cite news|url=http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/|title=#MEAction meets with Senate staffers - #MEAction|date=2016-03-16|work=#MEAction|access-date=2018-09-07|language=en-US}}</ref> #[[MEAction]] reports on this ongoing process.

====CDC Website updates====
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>{{Cite web|url=http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/|title=Trial By Error: The CDC Drops CBT/GET|last=Tuller|first=David|date=Jul 10, 2017|website=www.virology.ws|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/treatment/index.html|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html|title=Information for Healthcare Providers {{!}} ME/CFS {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html|title=New ME/CFS Web Content for Healthcare Providers {{!}} CDC Online Newsroom {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME]<ref>{{Cite news|url=https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/|title=CDC Revises Its Information on ME - #MEAction|last=Seltzer|first=Jaime|date=2018-07-29|work=#MEAction|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref> #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

== Recommended viewing ==

==== Documentary ====
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

==== Short film ====
*[[The Last Great Medical Cover Up|''The Last Great Medical Cover Up'']] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)

==== News media ====

*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)

==== Talks and interviews ====
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Unrest]] at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20 - Youtube] (2016)

== Recommended reading ==
====Government health organizations====

:'''US'''

:[[Centers for Disease Control]] (CDC)
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html Factsheets - Pediatric]<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html|title=ME/CFS in Children Fact Sheets {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-07-14|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref> Fact sheets for Healthcare Professionals, Parents/Guardians, and Education Professionals. (2017)

:[[National Institutes of Health]] (NIH)
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]

:[[Institute of Medicine]] (IOM)
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - Key Facts|last=|first=|date=Feb 2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> From the [[Institute of Medicine report]]. (2015)

:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=Feb 2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Report Brief on the Institute of Medicine report. (2015)

==== ME/CFS research foundations ====

:'''UK'''

:[[Invest in ME]]
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]<ref>{{Cite web|url=http://www.investinme.org/faqs.shtml|title=Invest in ME Research - UK Charity for Myalgic Encephalomyelitis FAQs|last=Research|first=Invest in ME|website=www.investinme.org|access-date=2018-09-07}}</ref>

:'''US'''

:[[Open Medicine Foundation]] (OMF)
:*[https://www.omf.ngo/what-is-mecfs/ What is ME/CFS?]<ref name=":0" />

==== ME/CFS organizations ====

:'''Australia'''

:[[Emerge Australia]]
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]<ref>{{Cite news|url=https://emerge.org.au/mecfs/|title=What is ME/CFS? - Emerge Australia|work=Emerge Australia|access-date=2018-09-07|language=en-US}}</ref>

:'''UK'''

:[[ME Association]]
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]<ref>{{Cite web|url=https://www.meassociation.org.uk/about/what-is-mecfs/|title=What is ME/CFS?|website=www.meassociation.org.uk|language=en-US|access-date=2018-09-07}}</ref>

:[[Tymes Trust]] (Pediatric)
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs]<ref>{{Cite web|url=https://www.tymestrust.org/pdfs/mecfsseid.pdf|title=Paediatric ME, CFS, SEID for Families and their GPs|last=|first=|date=|website=tymestrust.org|publisher=The Young ME Sufferers Trust|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2016)

:'''US'''
:[[Massachusetts CFIDS/ME & FM Association]]
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]<ref>{{Cite web|url=https://www.massmecfs.org/cfids-me-cfs|title=ME/CFS|website=www.massmecfs.org|access-date=2019-01-24}}</ref>

:[[Solve ME/CFS]]
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?]<ref>{{Cite web|url=https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view|title=What, Exactly, Is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?|last=|first=|date=|website=drive.google.com|publisher=Solve ME/CFS Initiative|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=}}</ref>

:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS]<ref>{{Cite news|url=https://solvecfs.org/what-is-mecfs/|title=Get the Facts about ME/CFS - Solve ME/CFS Initiative|work=Solve ME/CFS Initiative|access-date=2018-09-07|language=en-US}}</ref> (2016)

:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?]<ref>{{Cite web|url=http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf|title=What is ME/CFS?|last=|first=|date=2013|website=solvecfs.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2013)

:'''International'''
:[[MEAction]]
:*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref name=":14" /> (2018) Guide for Caretakers

:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)]<ref>{{Cite web|url=http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf|title=Facts about Myalgic Encephalomyelitis (ME) - (Also called chronic fatigue syndrome or CFS)|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2015)

:*[http://www.meaction.net/reports-and-fact-sheets/?utm_content=bufferc2125&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Reports and Fact Sheets]<ref>{{Cite web|url=https://www.meaction.net/resources/reports-and-fact-sheets/|title=Learn about ME. Find educational tools for your advocacy.|last=|first=|date=|website=meaction.net|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2015)

==== Other organizations ====

:[https://rarediseases.org/ National Organization for Rare Disorders] (NORD)
:*[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]<ref>{{Cite news|url=https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/|title=Myalgic Encephalomyelitis - NORD (National Organization for Rare Disorders)|work=NORD (National Organization for Rare Disorders)|access-date=2018-09-07|language=en-US}}</ref>

==== Other reading====

:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?]<ref>{{Cite news|url=https://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/|title=What Do You Do When a Loved One Becomes Chronically Ill?|last=Jackson|first=Suzan|date=2016-10-28|work=thirdAGE|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== Research avenues ==

*Dr. [[Anthony Komaroff]] Webinar [https://www.youtube.com/watch?v=ENrdrGj0p-c Hot Areas in ME/CFS Research] (2016)
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]] CDC Video (2016)

==History==
*[[Osler's Web|''Osler's Web'']] is a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>{{Cite news|url=https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/|title=Not, sadly, the first|last=Senior|first=Richard|date=Jul 26, 2006|work=New Scientist|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref> See Editor's Note<ref>{{Cite news|url=https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/|title=First official UK death from chronic fatigue syndrome|last=Hooper|first=Rowan|date=Jun 16, 2006|work=New Scientist|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== Notable studies ==
* 2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref name=":16">{{Cite web|url=https://pubs.rsna.org/doi/10.1148/radiol.14141079|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30|title=Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome|date=Oct 29, 2014|last=|first=|authorlink=Michael Zeineh|last2=|first2=|authorlink2=James Kang|archive-url=|archive-date=|dead-url=|last3=|authorlink3=Scott Atlas|last4=|authorlink4=Mira Raman|authorlink5=Allan Reiss|authorlink6=Jane Norris|authorlink7=Ian Valencia|authorlink8=Jose Montoya|publisher=Radiology}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.<ref name=":16" /></blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*[https://me-pedia.org/wiki/List_of_enterovirus_infection_studies List of enterovirus infection studies]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|dead-url=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref>
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

== See also ==
* [[Biopsychosocial model]] (BPS) An unproven psychiatric paradigm model applied to ME/CFS in the [[United Kingdom|UK]].
== Learn more ==
'''Potential treatments and research'''
*[[Ampligen]] Used in [[Argentina]] for the treatment of [[Severe and very severe ME|severe ME/CFS]].
*[[Brain imaging]]
*[[Natural killer cell]]
*[[Vagus nerve infection hypothesis]]

'''Guides and reports'''
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref name=":14" /> (2018) Guide for Caretakers
*"[[In the Expectation of Recovery]]" by [[Centre for Welfare Reform]] UK

'''[[Patient mental health]]'''

:Patients that had been deemed as suffering from mental health and not a biological illness.
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.
*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>{{Cite news|url=http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm|title=Depression in Fibromyalgia and Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Aug 2, 2018|work=Verywell Health|access-date=2018-09-07|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite web|url=http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title=CFS or depression - what are the differences - DoctorMyhill|website=drmyhill.co.uk|language=en|access-date=2018-09-07}}</ref>

'''Outbreaks'''
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]

*[[List of outbreaks]]

== References ==

[[Category:Primers]]
<references />

Brain fog

2019-04-21T14:00:40Z

MEandCFS:Removed working memory image as brain fog does not necessarily impact working memory

{{stub}}
'''Brain fog''' manifests as [[Memory problems|impaired working memory]] and concentration accompanied by difficulty processing complex information.<ref name=":0">{{Cite news|url=https://solvecfs.org/research/solve-me-cfs-initiative-science-discovery-program-for-researchers/brain-fog-in-cfs-whats-going-on/|title=Brain Fog in ME/CFS: What’s Going On? - Solve ME/CFS Initiative|work=Solve ME/CFS Initiative|access-date=2018-08-10|language=en-US}}</ref>

It is a type of [[cognitive impairment]] experienced by [[ME/CFS]] patients. [[Fibromyalgia]] patients often refer to it as "fibro-fog".<ref>{{Cite news|url=https://www.verywellhealth.com/brain-fibro-fog-causes-symptoms-possible-treatment-716014|title=What Is Fibro Fog and ME/CFS Brain Fog?|last=Dellwo|first=Adrienne|date=Feb 28, 2018|work=Verywell Health|access-date=2018-08-10|archive-url=|archive-date=|dead-url=}}</ref>
==Presentation==

==Prevalence==
*Katrina Berne reports a prevalence of 75-100% for confusion and inability to think clearly.<ref>{{citation |last= Berne |first= Katrina |date= 1 Dec 1995 |title= Running on Empty: The Complete Guide to Chronic Fatigue Syndrome (CFIDS), 2nd ed. |url= https://www.amazon.co.uk/Running-Empty-Complete-Chronic-Syndrome/dp/0897931912/ |publisher= Hunter House |page= 59 |isbn= 978-0897931915}}</ref>

==Symptom recognition==

==Notable studies==
*2013, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896080/ What is brain fog? An evaluation of the symptom in postural tachycardia syndrome]<ref name="Ross, 2013" />
*2016, [https://www.sciforschenonline.org/journals/clinical-research/CLROA-2-110.php qEEG / LORETA in Assessment of Neurocognitive Impairment in a Patient with Chronic Fatigue Syndrome: A Case Report]<ref name=":1">{{Cite web|url=https://www.sciforschenonline.org/journals/clinical-research/CLROA-2-110.php|title=qEEG / LORETA in Assessment of Neurocognitive Impairment in a Patient with Chronic Fatigue Syndrome: A Case Report|last=dr.marcie.zinn@gmail.com|first=Zinn ML, DePaul University, Center for Community Research, Chicago, IL, Tel/ Fax: (773) 325-4923; E-mail:|date=2016|website=www.sciforschenonline.org|archive-url=|archive-date=|dead-url=|access-date=2018-08-28|last2=Zinn|first2=Mark A.|last3=Jason|first4=|first3=Leonard|issn=2469-6714|publisher=SciForschen|doi=10.16966/2469-6714.110}}</ref>
<blockquote>Our case study confirmed the pattern of dysregulation in the cortex reviewed in the introduction. Furthermore, since both periods of phase shift/lock durations were found to be significantly shorter, that might contribute to an increased rate of phase reset, also seen in our data. Phase reset deregulation--phase locking periods being too brief and phase reset happening too often—appear to be consistent with the associated lower rate of information processing and reaction times found in the ME and CFS literature. These deregulated states represent the [[brain]] during nonoptimal functioning, rendering it inefficient for most types of information processing functioning, whether it is executive functioning, [[Memory problems|memory]], perceptual reasoning or information processing speed. When phase lock is significantly less than normal, as in this data set, the ability of the brain to sustain commitment of resources to mediate different functions is severely compromised. Phase shift duration in this data is also hypoactive, meaning that significantly less neurons are being recruited to perform a function than normal. The results here indicate slowed verbal comprehension, executive functions, perceptual reasoning, processing speed and memory, the sum total of which is known as [[cognitive impairment]].<ref name=":1" /></blockquote>

[[File:CLROA-2-110-F1.gif|850px|thumb|center|
Figure 1: Results of LORETA current source density in a case with CFS showing widespread decreased current density for delta at 2 Hz and beta (12- 15 Hz) demonstrating a global reduction in brain functioning (blue). The higher frequencies (beta) have been shown to be a function of delta frequencies. In other words, local oscillations are under constant influence of global brain dynamics (Buzsaki, 2006).<ref name=":1" />]]

*2018, [https://insights.ovid.com/pubmed?pmid=29528888 Cognitive Impairment in Fibromyalgia: A Meta-Analysis of Case–Control Studies]<ref>{{Cite web|title=Cognitive Impairment in Fibromyalgia: A Meta-Analysis of Case–Control Studies|url=https://insights.ovid.com/pubmed?pmid=29528888|website=insights.ovid.com|access-date=2018-08-28|language=en|date=Jun 1, 2018|last=Wu|first=Yu-Lin|archive-url=|archive-date=|dead-url=|last2=Huang|first2=Chun-Jen|last3=Fang|first3=Su-Chen|last4=Ko|first4=Ling-Hsin|last5=Tsai|first5=Pei-Shan}}</ref>

==Possible causes==

==Potential treatments==

==Learn more==
*Aug 20, 2013, [https://solvecfs.org/research/solve-me-cfs-initiative-science-discovery-program-for-researchers/brain-fog-in-cfs-whats-going-on/ Brain Fog in ME/CFS: What’s Going On?]<ref name=":0" />
*Feb 7, 2016, [https://www.meaction.net/2016/02/07/case-study-brain-fog-in-cfs-can-be-seen-in-qeegloreta-analysis/ Case Study: “Brain Fog” in CFS can be seen in qEEG/Loreta]<ref>{{Cite news|url=https://www.meaction.net/2016/02/07/case-study-brain-fog-in-cfs-can-be-seen-in-qeegloreta-analysis/|title=Case Study: "Brain Fog" in CFS can be seen in qEEG/Loreta - #MEAction|last=M|first=Beth|date=2016-02-07|work=#MEAction|access-date=2018-08-28|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

*Mar 21, 2018, [https://fibromyalgianewstoday.com/2018/03/21/fibromyalgia-cognitive-dysfunction-study-identifies-main-types/ Study Identifies the Types of Cognitive Dysfunction That Are Most Prevalent in Fibromyalgia]<ref>{{Cite news|url=https://fibromyalgianewstoday.com/2018/03/21/fibromyalgia-cognitive-dysfunction-study-identifies-main-types/|title=Fibromyalgia Study Identifies Main Types of Patients' Cognitive Dysfunction|last=Pena|first=Amy|date=2018-03-21|work=Fibromyalgia News Today|access-date=2018-08-28|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

*[https://mpkb.org/home/symptoms/neurological/cognitive Cognitive dysfunction (brain fog)]<ref name=":02">{{Cite web|title=Cognitive dysfunction (brain fog) (MPKB)|url=https://mpkb.org/home/symptoms/neurological/cognitive|website=mpkb.org|access-date=2018-08-28|language=en}}</ref>
<blockquote>According to the Marshall Pathogenesis, [[cognitive dysfunction]] is caused by [[microbe]]<nowiki/>s. More severe forms of cognitive dysfunction are seen in diseases such as [[Alzheimer's]], diseases for which there is strong evidence of a [[bacteria]]<nowiki/>l etiology. Often associated with [[chronic fatigue syndrome]],1) cognitive dysfunction is also seen in patients with [[multiple sclerosis]],2) [[depression]],3) [[fibromyalgia]],4) and dozens of others diseases.<ref name=":02" /></blockquote>

==See also==
*[[Aphasia]]
*[[Cognitive dysfunction]]
*[[Dyscalculia]]
*[[Dysphasia]]
*[[Fibromyalgia]]
*[[ME/CFS]]
*[[Memory problems]]
*[[Word-finding problems]]

== References ==
<references>
<ref name="Ross, 2013">{{Citation
| last1 = Ross | first1 = A. J. | authorlink1 =
| last2 = Medow | first2 = M. S. | authorlink2 = Marvin Medow
| last3 = Rowe | first3 = P. C. | authorlink3 = Peter Rowe
| last4 = Stewart | first4 = J. M. | authorlink4 = Julian Stewart
| title = What is brain fog? An evaluation of the symptom in postural tachycardia syndrome.
| journal = Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society | volume = 23 | issue = 6 | page = 305–311
| date = 2013
| doi = 10.1007/s10286-013-0212-z
}}
</ref>
</references>

[[Category:Signs and symptoms]]
[[Category:Cognitive signs and symptoms]]

Cognitive dysfunction

2019-04-21T13:59:43Z

MEandCFS:removed working memory image as working memory does not capture cognitive dysfunction

'''Cognitive dysfunction''' is a constant struggle for most [[ME/CFS]] patients and they often describe it as "[[brain fog]]".<ref>{{Cite news|url=https://www.verywellhealth.com/living-with-brain-fogfibro-fog-715710|title=Living with a Foggy Brain from Fibromyalgia or ME/CFS|last=Dellwo|first=Adrienne|date=Jun 29, 2018|work=Verywell Health|access-date=2018-08-10|archive-url=|archive-date=|dead-url=}}</ref> It is also a symptom of [[fibromyalgia]] and patients refer to it as "[[Brain fog|fibro fog]]".<ref>{{Cite news|url=https://www.verywellhealth.com/brain-fibro-fog-causes-symptoms-possible-treatment-716014|title=What Is Fibro Fog and ME/CFS Brain Fog?|last=Dellwo|first=Adrienne|date=Feb 28, 2018|work=Verywell Health|access-date=2018-08-10|archive-url=|archive-date=|dead-url=}}</ref>

Cognitive dysfunction in [[ME/CFS]] can take many different forms. Cognitive issues commonly observed in [[ME/CFS]] include [[attention deficit]], [[auditory sequencing problems]], [[brain fog]], [[concentration problems]], [[difficulty comprehending social cues]], [[dyscalculia]], [[dyslexia]], [[executive function problems]], [[linguistics reversals]], [[memory loss]], [[multi-tasking problems]], [[planning problems]], [[receptive language problems]], [[slowed thought]], [[spatial disorientation]], [[word-finding problems]],{{Citation needed}} cognitive overload, slow processing of information and poor working memory.<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

=== Exercise and Cognitive Dysfunction ===
A healthy person becomes more alert after exercise, but people with ME/CFS find their cognitive difficulties increase, they become much slower at mental activities, and cognitive tasks seem to take extra effort.<ref name=":1" />

==Prevalence==

==Symptom recognition==
'''Mandatory'''

Cognitive dysfunction is a mandatory symptom to diagnose ME/CFS with the [[Canadian Consensus Criteria]] (CCC).<ref>{{Cite web|url=http://me-pedia.org/wiki/Canadian_Consensus_Criteria#Definition|title=Canadian Consensus Criteria - MEpedia|website=me-pedia.org|language=en|access-date=2018-08-10}}</ref>.

'''Optional'''

Cognitive dysfunction is an optional symptom in [[Systemic Exertion Intolerance Disease]] (SEID) criteria<ref>{{Cite web|url=http://me-pedia.org/wiki/Systemic_Exertion_Intolerance_Disease#Diagnostic_Criteria|title=Systemic Exertion Intolerance Disease - MEpedia|website=me-pedia.org|language=en|access-date=2018-08-10}}</ref> and the [[International Consensus Criteria]] (ICC) which diagnoses [[myalgic encephalomyelitis]] (ME).<ref>{{Cite web|url=http://me-pedia.org/wiki/International_Consensus_Criteria#1._Neurocognitive_impairments|title=International Consensus Criteria - MEpedia|website=me-pedia.org|language=en|access-date=2018-08-10}}</ref>

== Diagnosis ==
* [https://www.mayoclinic.org/diseases-conditions/mild-cognitive-impairment/diagnosis-treatment/drc-20354583 Mild cognitive impairment (MCI)]<ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/mild-cognitive-impairment/diagnosis-treatment/drc-20354583|title=Mild cognitive impairment - Diagnosis and treatment - Mayo Clinic|website=www.mayoclinic.org|language=en|access-date=2018-08-28}}</ref>
* [https://cft.foodforthebrain.org/ Food For The Brain - Cognitive Function Test]<ref>{{Cite web|url=https://cft.foodforthebrain.org/|title=Cognitive Function Test|website=cft.foodforthebrain.org|access-date=2018-08-28}}</ref>
* [http://www.dysautonomiainternational.org/blog/wordpress/cognitive-dysfunction-and-brain-fog-in-pots/ Cognitive Dysfunction and “Brain Fog” in POTS]<ref>{{Cite web|url=http://www.dysautonomiainternational.org/blog/wordpress/cognitive-dysfunction-and-brain-fog-in-pots/|title=Cognitive Dysfunction and “Brain Fog” in POTS {{!}} The Dysautonomia Dispatch|last=Arnold|first=Amy|date=Feb 3, 2016|website=www.dysautonomiainternational.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-28}}</ref>
==Notable studies==
*2001, Neuropsychological functioning in chronic fatigue syndrome: a review. ([[pubmed:11167310|Abstract]])<ref>{{Cite journal|last=Michiels|first=V.|last2=Cluydts|first2=R.|date=2001|title=Neuropsychological functioning in chronic fatigue syndrome: a review|url=https://www.ncbi.nlm.nih.gov/pubmed/11167310|journal=Acta Psychiatrica Scandinavica|volume=103|issue=2|pages=84–93|issn=0001-690X|pmid=11167310|via=}}</ref>
*2006, Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome<ref name="Capuron, 2006" /> [https://www.nature.com/articles/1301005 (Full text)]
*2015, Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome<ref>{{Cite journal|last=Mizuno|first=Kei|last2=Tanaka|first2=Masaaki|last3=Tanabe|first3=Hiroki C.|last4=Joudoi|first4=Takako|last5=Kawatani|first5=Junko|last6=Shigihara|first6=Yoshihito|last7=Tomoda|first7=Akemi|last8=Miike|first8=Teruhisa|last9=Imai-Matsumura|first9=Kyoko|date=2015-09-10|title=Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589845/|journal=NeuroImage : Clinical|volume=9|pages=355–368|doi=10.1016/j.nicl.2015.09.001|issn=2213-1582|pmid=26594619|via=}}</ref> ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589845/ Full Text])
*2016, Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence<ref>Cvejic E;Birch RC;Vollmer-Conna U, 2016, 'Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence', Current Rheumatology Reports, vol. 18, http://dx.doi.org/10.1007/s11926-016-0577-9</ref> [https://www.ncbi.nlm.nih.gov/pubmed/27032787 (Abstract)]
*2016, qEEG / LORETA in Assessment of Neurocognitive Impairment in a Patient with Chronic Fatigue Syndrome: A Case Report<ref name=":12">{{Cite web|url=https://www.sciforschenonline.org/journals/clinical-research/CLROA-2-110.php|title=qEEG / LORETA in Assessment of Neurocognitive Impairment in a Patient with Chronic Fatigue Syndrome: A Case Report|last=dr.marcie.zinn@gmail.com|first=Zinn ML, DePaul University, Center for Community Research, Chicago, IL, Tel/ Fax: (773) 325-4923; E-mail:|date=2016|website=www.sciforschenonline.org|archive-url=|archive-date=|dead-url=|access-date=2018-08-28|last2=Zinn|first2=Mark A.|last3=Jason|first4=|first3=Leonard|issn=2469-6714|publisher=SciForschen|doi=10.16966/2469-6714.110}}</ref> ([https://sciforschenonline.org/journals/clinical-research/CLROA-2-110.php Full Text])

<blockquote>Our case study confirmed the pattern of dysregulation in the cortex reviewed in the introduction. Furthermore, since both periods of phase shift/lock durations were found to be significantly shorter, that might contribute to an increased rate of phase reset, also seen in our data. Phase reset deregulation--phase locking periods being too brief and phase reset happening too often—appear to be consistent with the associated lower rate of information processing and reaction times found in the ME and CFS literature. These deregulated states represent the brain during nonoptimal functioning, rendering it inefficient for most types of information processing functioning, whether it is executive functioning, [[Memory problems|memory]], perceptual reasoning or information processing speed. When phase lock is significantly less than normal, as in this data set, the ability of the brain to sustain commitment of resources to mediate different functions is severely compromised. Phase shift duration in this data is also hypoactive, meaning that significantly less neurons are being recruited to perform a function than normal. The results here indicate slowed verbal comprehension, executive functions, perceptual reasoning, processing speed and memory, the sum total of which is known as [[cognitive impairment]].<ref name=":12" /></blockquote>

[[File:CLROA-2-110-F1.gif|850px|thumb|center|
Figure 1: Results of LORETA current source density in a case with CFS showing widespread decreased current density for delta at 2 Hz and beta (12- 15 Hz) demonstrating a global reduction in brain functioning (blue). The higher frequencies (beta) have been shown to be a function of delta frequencies. In other words, local oscillations are under constant influence of global brain dynamics (Buzsaki, 2006).<ref name=":12" />]]

==Possible causes==
[[Mady Hornig]] has found evidence in the [[cerebrospinal fluid]] (CSF) of ME/CFS patients that may explain their cognitive dysfunction.<ref>{{Cite news|url=https://www.sciencedaily.com/releases/2015/03/150331074341.htm|title=Scientists find clues into cognitive dysfunction in chronic fatigue syndrome|last=|first=|date=Mar 31, 2015|work=ScienceDaily|access-date=2018-08-10|archive-url=|archive-date=|dead-url=|language=en}}</ref>

==Potential treatments==

==Learn more==
*2015, [https://www.masscfids.org/resource-library/15-conference-reports/395-dr-gudrun-lange-reviews-neuropsychological-testing-for-cfs-and-fm Dr. Gudrun Lange Reviews Neuropsychological Testing for CFS and FM]<ref>{{Cite web|url=https://www.massmecfs.org/resource-library/15-conference-reports/395-dr-gudrun-lange-reviews-neuropsychological-testing-for-cfs-and-fm|title=Dr. Gudrun Lange Reviews Neuropsychological Testing for CFS and FM|last=|first=|date=Nov 20, 2015|website=www.massmecfs.org|language=en-GB|archive-url=|archive-date=|dead-url=|access-date=2018-08-10}}</ref>
*2016, [http://www.meaction.net/2016/02/07/case-study-brain-fog-in-cfs-can-be-seen-in-qeegloreta-analysis/ Case Study: "Brain Fog" in CFS can be seen in qEEG/Loreta]<ref>{{Cite news|url=http://www.meaction.net/2016/02/07/case-study-brain-fog-in-cfs-can-be-seen-in-qeegloreta-analysis/|title=Case Study: "Brain Fog" in CFS can be seen in qEEG/Loreta - #MEAction|last=M|first=Beth|date=2016-02-07|work=#MEAction|access-date=2018-08-28|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*2018, [https://fibromyalgianewstoday.com/2018/03/21/fibromyalgia-cognitive-dysfunction-study-identifies-main-types/ Study Identifies the Types of Cognitive Dysfunction That Are Most Prevalent in Fibromyalgia]<ref>{{Cite news|url=https://fibromyalgianewstoday.com/2018/03/21/fibromyalgia-cognitive-dysfunction-study-identifies-main-types/|title=Fibromyalgia Study Identifies Main Types of Patients' Cognitive Dysfunction|last=Pena|first=Amy|date=2018-03-21|work=Fibromyalgia News Today|access-date=2018-08-28|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*[https://mpkb.org/home/symptoms/neurological/cognitive Cognitive dysfunction (brain fog)]<ref name=":0">{{Cite web|url=https://mpkb.org/home/symptoms/neurological/cognitive|title=Cognitive dysfunction (brain fog) (MPKB)|website=mpkb.org|language=en|access-date=2018-08-28}}</ref>
<blockquote>According to the Marshall Pathogenesis, cognitive dysfunction is caused by [[microbe]]<nowiki/>s. More severe forms of cognitive dysfunction are seen in diseases such as [[Alzheimer's]], diseases for which there is strong evidence of a [[bacteria]]<nowiki/>l etiology. Often associated with [[chronic fatigue syndrome]],1) cognitive dysfunction is also seen in patients with [[multiple sclerosis]],2) [[depression]],3) [[fibromyalgia]],4) and dozens of others diseases.<ref name=":0" /></blockquote>
* Jun 4, 2018, [https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/ Victory For ME Disability Claim – U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability]<ref name=":03">{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-02}}</ref>
:[[Brian Vastag]] was able to prove with [[qEEG]] and cognitive tests he had "significant problems with [[Visual dysfunction|visual perception]] and analysis, scanning speed, attention, visual motor coordination, motor and mental speed, [[Memory problems|memory]], and [[Word-finding problems|verbal fluency]]" winning his long term disability (LTD) claim.<ref name=":03" />

==See also==
*[[Aphasia]]
*[[Dyscalculia]]
*[[Dysphasia]]
*[[Memory problems]]
*[[Word-finding problems]]

==References==
<references>
<ref name="Capuron, 2006">{{Citation
| last1 = Capuron | first1 = Lucile | authorlink1 =
| last2 = Welberg | first2 = Leonie | authorlink2 =
| last3 = Heim | first3 = Christine | authorlink3 =
| last4 = Wagner | first4 = Dieter | authorlink4 =
| last5 = Solomon | first5 = Laura | authorlink5 =
| last6 = Papanicolaou | first6 = Dimitris A | authorlink6 =
| last7 = Craddock | first7 = R Cameron | authorlink7 =
| last8 = Miller | first8 = Andrew H | authorlink8 =
| last9 = Reeves | first9 = William C | authorlink9 = William Reeves
| title = Cognitive Dysfunction Relates to Subjective Report of Mental Fatigue in Patients with Chronic Fatigue Syndrome
| journal = Neuropsychopharmacology | volume = 31 | issue = | page = 1777–1784
| date = 2006
| doi = 10.1038/sj.npp.1301005
}}
</ref>
</references>
[[Category:Signs and symptoms]]
[[Category:Cognitive signs and symptoms]]

Fibromyalgia

2019-04-21T13:48:54Z

MEandCFS:il

[[Fibromyalgia]] '''(FM/FMS)''' is a chronic disorder characterized by widespread [[Musculoskeletal system|musculoskeletal]] pain, [[fatigue]], and tenderness in localized areas. [[Myalgia|Muscle pain]] is widespread, on both sides of the body, and above and below the waist.

Sufferers are fatigued and tired even when sleeping for long periods of time, and sleep is often disrupted by pain. Many FM sufferers have [[Sleep dysfunction|sleep disorders]] like [[sleep apnea]] and [[restless legs syndrome]] (RLS).<ref name=":26" /><ref name=":27" /><ref name=":35" /> [[Cognitive impairment]], when one cannot focus or pay attention and the patient has difficulty concentrating on mental tasks, is known by FM sufferers as "[[fibro fog]]".<ref name=":17">{{Cite news|url=https://www.verywellhealth.com/brain-fibro-fog-causes-symptoms-possible-treatment-716014|title=What Is Fibro Fog and ME/CFS Brain Fog?|last=Dellwo|first=Adrienne|date=|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref><ref name=":26" /><ref name=":27" /><ref name=":35" /> Some experience [[depression]], [[headache]]s, and lower [[abdominal pain]] or [[wikipedia:Cramp|cramping]]. Other symptoms include [[Paresthesia|tingling]] or [[numbness]] in hands and feet, pain in jaw and disorders of the jaw such as [[temporomandibular joint disorder|temporomandibular joint disorder]] (TMJ/TMD), [[Menstrual cycle#Health effects in other conditions|menstrual cycle]] cramps, and [[digestive problems]] like i[[Irritable bowel syndrome|rritable bowel syndrome]] (IBS).<ref name=":26">{{Cite news|url=https://www.webmd.com/fibromyalgia/guide/fibromyalgia-symptoms#1|title=Fibromyalgia Symptoms|work=WebMD|access-date=2018-08-09|language=en-US}}</ref><ref name=":27">{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/fibromyalgia/symptoms-causes/syc-20354780|title=Fibromyalgia - Symptoms and causes|work=Mayo Clinic|access-date=2018-08-09|language=en}}</ref><ref name=":35" />

The [[United Kingdom|United Kingdom]] (UK) [[National Health Service]] (NHS) lists FM as one of 20 most painful conditions.<ref>{{Cite web|url=https://www.newsweek.com/20-most-painful-conditions-nhs-1191081|title=Here are 20 of the most painful health conditions you can get|last=EDT|first=Hannah Osborne On 10/29/18 at 7:14 AM|date=2018-10-29|website=Newsweek|language=en|access-date=2019-03-26}}</ref><ref name=":39">{{Cite web|url=https://www.cambridge-news.co.uk/news/uk-world-news/nhs-gout-ulcer-endometriosis-arthritis-15339123|title=The NHS says these are the 20 most painful health conditions you can suffer from|last=Campbell|first=James|last2=Pengelly|first2=Ella|date=2019-03-26|website=cambridgenews|access-date=2019-03-26}}</ref> The NHS describes the pain as diffuse aching or burning, head to toe, and can be worse at some times than at others. The pain can change location. "The fatigue ranges from feeling tired, to the exhaustion of a [[flu-like illness]]."<ref name=":39" /> The [[United States|United States]] (US) [[Centers for Disease Control and Prevention]] (CDC) states FM "can cause pain, [[Fibromyalgia disability process|disability, and lower quality of life]]."<ref>{{Cite web|url=https://www.cdc.gov/arthritis/basics/fibromyalgia.htm|title=Fibromyalgia {{!}} Arthritis {{!}} CDC|date=2018-10-04|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

The [[wikipedia:American_College_of_Rheumatology|American College of Rheumatology]] (ACR) created and updates the diagnostic criteria for FM.<ref name=":12" /><ref name=":13" /> ''See:'' [[Fibromyalgia#Diagnosis|Fibromyalgia (''Diagnosis'' section)]].

[[File:Fibro_Tender_Points.png|400px|thumb|right|1990 ACR Diagnostic Criteria: 18 Tender Points]]
[[File:Fibro_Widespread_Pain.png|400px|thumb|right|2010 ACR Preliminatry Diagnostic Criteria: '''Wisedpread Pain Index (WPI'''), 19 Tender Point Areas]]

==Prevalence==
FM is the second most common [https://en.wikipedia.org/wiki/Rheumatism rheumatic disorder] behind [[wikipedia:Osteoarthritis|osteoarthritis]] and is "now considered to be a lifelong [[central nervous system]] disorder."<ref>{{Cite news|url=https://naidw.org/blog/members-myblogs/fibromyalgia-now-considered-as-a-lifelong-central-nervous-system-disorder|title=Fibromyalgia now considered as a lifelong central nervous system disorder|work=NAIDW.org®|access-date=2018-08-09|language=en-gb}}</ref> An estimated 10 million people in the US and 3-6% of the world population have FM. It is seen in women, men, children, and all ethnic groups. It is often seen in families and diagnosed between the ages of 20 to 50 years; incidence increases with age.<ref>{{Cite news|url=http://www.fmaware.org/about-fibromyalgia/prevalence/|title=Prevalence - National Fibromyalgia Association (NFA)|work=National Fibromyalgia Association (NFA)|access-date=2018-08-09|language=en-US}}</ref>

FM has a female:male 7:1 ratio under the ''American College of Rheumatology (ACR) 1990 Diagnostic Criteria'' and 2:1 when the ''ACR 2010 Preliminary Diagnostic Criteria'' is used.<ref>{{Cite journal|last=Boomershine|first=Chad|date=Nov 4, 2017|title=Fibromyalgia: Practice Essentials, Background, Pathophysiology|url=http://emedicine.medscape.com/article/329838-overview#a5|journal=Medscape|volume=|pages=|via=|publisher=|editor-last=Diamond|editor-first=Herbert|at=Sex-related differences in incidence}}</ref> ''See'': [[Fibromyalgia#American College of Rheumatology (ACR) Criteria|Fibromyalgia (''American College of Rheumatology (ACR) Criteria'' section)]]. A September 2018, Wolfe et al study ''Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias''<ref name=":28" /> found fewer women and more men are diagnosed under the 2010/11 criteria (this criterion further updated in 2016<ref>{{Cite journal|date=2016-12-01|title=2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria|url=https://www.sciencedirect.com/science/article/pii/S0049017216302086|journal=Seminars in Arthritis and Rheumatism|language=en|volume=46|issue=3|pages=319–329|doi=10.1016/j.semarthrit.2016.08.012|issn=0049-0172}}</ref>). They found the ratio is F/M 1.5:1.<ref name=":28">{{Cite journal|last=Wolfe|first=Frederick|last2=Walitt|first2=Brian|last3=Perrot|first3=Serge|last4=Rasker|first4=Johannes J.|last5=Häuser|first5=Winfried|date=2018-09-13|title=Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203755|journal=PLOS ONE|language=en|volume=13|issue=9|pages=e0203755|doi=10.1371/journal.pone.0203755|issn=1932-6203|pmc=|pmid=30212526|via=}}</ref><blockquote>What we did not find in our unbiased CritFM samples was 9:1 female to male fibromyalgia ratios that are widely described by expert sources [11–13]. We believe that such findings only occur in the presence of selection bias or biased ascertainment.<ref name=":28" /></blockquote><blockquote>As unbiased epidemiological studies show only a small increase in the female to male sex ratio (~1.5:1) as opposed to the observed ratio in clinical studies of 9:1, we believe that the over-identification of fibromyalgia in women and the consequent under-identification of men is the result of bias.<ref name=":28" /></blockquote>
==Fibromyalgia in ME/CFS==
"The most common overlapping condition with [[ME/CFS]] is fibromyalgia."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and FM are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref name=":36">{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Dr. [[Jarred Younger]] has said that many patients that meet the criteria for FM also meet criteria for [[chronic fatigue syndrome]] (CFS) but the reverse is not necessarily true as a lot of people with [[CFS]] do not have [[chronic pain]].<ref>{{Cite web|url=https://www.youtube.com/watch?v=wJB95m4FLa0#t=57m27s|title=Webinar with Jarred Younger, Ph.D.|last=Younger|first=Jared|date=May 20, 2016|website=YouTube|at=57:27|via=|archive-url=|archive-date=|dead-url=|access-date=|publisher=SolveCFS|type=Video}}</ref> However, the [[Canadian Consensus Criteria]] (CCC) requires the symptom of pain to diagnose ME/CFS.<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> It is the pattern (on both sides of the body, and above and below the waist) of chronic widespread [[Musculoskeletal system|musculoskeletal]] pain (involving muscle, cartilage, ligaments, and connective tissue) in FM that sets it apart from other diseases that have pain; it also causes [[cognitive symptoms]] and [[unrefreshing sleep]].<ref name=":17" /><ref name=":26" /><ref name=":27" />

==Health complications==
FM is not a [https://en.wikipedia.org/wiki/Progressive_disease progressive disease] but according to Dr. [[Daniel Clauw|Dan Clauw]] the "slow gradual worsening of chronic pain patients over time is due to downstream consequences of poorly controlled pain and other symptoms, wherein individuals then progressively get less active, sleep worse, are under more stress and unknowingly develop bad habits which worsen pain and other symptoms."<ref>{{Cite news|url=http://nationalpainreport.com/ask-the-dctors-is-fibromyalgia-progressive-8831105.html|title=Ask the Doctors: Is Fibromyalgia Progressive?|date=2016-08-09|work=National Pain Report|access-date=2018-08-09|language=en-US}}</ref>

*[https://www.sharecare.com/health/fibromyalgia-effects Fibromyalgia Complications]<ref name=":19" />

:<blockquote>People who have fibromyalgia frequently complain of a variety of symptoms that affect other parts of the body. Many people complain of [[gastrointestinal]] issues and restless legs syndrome (RLS). Additionally, the [[chronic pain]] and discomfort of fibromyalgia may lead to [[depression]].<ref name=":19">{{Cite news|url=https://www.sharecare.com/health/fibromyalgia-effects|title=Fibromyalgia Complications - Fibromyalgia - Joint Health|work=Sharecare|access-date=2018-08-09|language=en}}</ref></blockquote>

*[https://www.sharecare.com/health/fibromyalgia-effects/can-fibromyalgia-cause-medical-conditions Can fibromyalgia cause other medical conditions?]<ref name=":20" />

:<blockquote>Fibromyalgia is not known to cause other medical conditions. However, people who have fibromyalgia seem to be at high risk for developing other painful conditions, including [https://en.wikipedia.org/wiki/Osteoarthritis osteoarthritis] (the common type of arthritis caused by wear and tear on the joints) as well as other related conditions, such as [[rheumatoid arthritis]], [[lupus]], and [https://en.wikipedia.org/wiki/Ankylosing_spondylitis ankylosing spondylitis]. Also, people with fibromyalgia are frequently diagnosed with chronic fatigue syndrome, irritable bowel syndrome (IBS), and temporomandibular joint (TMJ) disorder.<ref name=":20">{{Cite web|url=https://www.sharecare.com/health/fibromyalgia-effects/can-fibromyalgia-cause-medical-conditions|title=Can fibromyalgia cause other medical conditions? {{!}} Fibromyalgia Complications|last=Honor Society of Nursing|first=|date=|website=Sharecare|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref></blockquote>
==Risk factors==
[[Lupus]] and [[rheumatoid arthritis]] (RA) are risk factors in developing FM. Car accidents, [[post-traumatic stress disorder]] (PTSD), [https://en.wikipedia.org/wiki/Repetitive_strain_injury repetitive injuries], illness such as a [https://en.wikipedia.org/wiki/Viral_disease viral infection], [https://en.wikipedia.org/wiki/Family_history_(medicine) family history], and [https://en.wikipedia.org/wiki/Obesity obesity] have all been linked to FM.<ref name=":35">{{Cite web|url=https://www.cdc.gov/arthritis/basics/fibromyalgia.htm|title=Fibromyalgia {{!}} Arthritis {{!}} CDC|date=2018-04-03|website=www.cdc.gov|language=en-us|access-date=2018-08-09}}</ref><ref>{{Cite news|url=https://www.niams.nih.gov/health_info/Fibromyalgia/|title=Fibromyalgia What Causes it?|last=Director|first=Nancy Garrick, Deputy|date=2017-04-05|work=National Institute of Arthritis and Musculoskeletal and Skin Diseases|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref><ref>{{Cite news|url=http://www.prohealth.com/library/showarticle.cfm?libid=22315|title=When Fibromyalgia Is More than Pain - Prohealth|date=2016-01-08|work=Prohealth|access-date=2018-08-09|language=en-US}}</ref>

==Diagnosis==
[https://www.verywellhealth.com/what-are-fibromyalgia-tender-points-189768 Tender points], not [https://en.wikipedia.org/wiki/Myofascial_trigger_point trigger points], are used to diagnose FM.<ref>{{Cite web|url=http://www.healthcentral.com/chronic-pain/c/662034/176031/fibromyalgia-trigger/|title=The Difference Between Fibromyalgia Tender Points and Myofascial Trigger Points - Chronic Pain {{!}} HealthCentral|last=Cooper|first=Celeste|date=May 8, 2015|website=www.healthcentral.com|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref> Tender points will be above and below the waist and on both sides of the body. (See: Illustrations of the 1990 and 2010 American College of Rheumatology (ACR) Criteria depicting tender points near the top of this page.) It is important to check for other conditions that could be causing pain such as [[hypothyroidism]], RA or lupus, osteoarthritis, ankylosing spondylitis, and [[wikipedia:Polymyalgia_rheumatica|polymyalgia rheumatica]].<ref>{{Cite news|url=https://www.webmd.com/fibromyalgia/guide/fibromyalgia-diagnosis-and-misdiagnosis#1|title=How Is Fibromyalgia Diagnosed?|work=WebMD|access-date=2018-08-12|language=en-US}}</ref>

===United States===
===== Blood test =====
EpicGenetics has a [[blood test]] that is identifying the presence of specific [[Leucocyte|white blood cell]] abnormalities of patients diagnosed with FM and has partnered with two universities to offer [[whole exome sequencing]] free of charge to those who test positive with their [http://fmtest.com/ FM/a® test].<ref>{{Cite news|url=http://www.businesswire.com/news/home/20170419005324/en/EpicGenetics-Assistance-Leading-Medical-Centers-Expands-Clinical|title=EpicGenetics, with the Assistance of Leading Medical Centers, Expands Clinical Study of FM/a® Test to Diagnose Fibromyalgia, Identify Genetic Markers Unique to the Disorder and Explore Direct Treatment Approaches|last=|first=|date=Apr 19, 2017|work=|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref><ref name=":38">{{Cite web|url=http://fmtest.com/|title=Home|last=perceptivadmin|website=EpicGenetics' FM/a® Test is FDA-compliant and has successfully diagnosed patients with fibromyalgia since 2012.|language=en-US|access-date=2019-03-25}}</ref> Most insurance companies will cover the test.<ref>{{Cite web|url=https://www.painnewsnetwork.org/stories/2015/5/27/fibromyalgia-blood-test-gets-insurance-coverage|title=Fibromyalgia Blood Test Gets Insurance Coverage|last=Anson|first=Pat|authorlink=|last2=|first2=|authorlink2=|date=May 27, 2015|website=Pain News Network|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-03-25}}</ref><ref>{{Cite web|url=http://nationalpainreport.com/more-insurance-companies-now-paying-for-fibromyalgia-blood-test-8829994.html|title=More Insurance Companies Now Paying for Fibromyalgia Blood Test|last=Gregory-Burch|first=Donna|authorlink=|last2=|first2=|authorlink2=|date=2016-04-04|website=National Pain Report|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-03-25}}</ref> EpicGenetics offers help to determine if your insurance will [http://fmtest.com/ cover their test].<ref name=":38" />

==== American College of Rheumatology (ACR) Criteria ====

=====1990 ACR criteria=====

*1990, [http://www.rheumatology.org/Portals/0/Files/1990_Criteria_for_Classification_Fibro.pdf The American College Of Rheumatology 1990 Criteria For The Classification Of Fibromyalgia]<ref name=":12">{{Cite web|url=https://www.rheumatology.org/Portals/0/Files/1990_Criteria_for_Classification_Fibro.pdf|title=The American College of Rheumatology Criteria for the Classification of Fibromyalgia|last=Wolfe|first=Frederick|last2=Smythe|first2=Hugh|date=1990|website=rheumatology.org|publisher=|others=Abeles, Micha; Clark, Patricia; Fam, Adel; Farber, Stephen; Fiechtner, Justus; Franklin, Michael; Gatter, Robert; Hamaty, Daniel; Lessard, James; Lightbroun, Alan; Masi, Alfonse; McCain, Glenn; Reynolds, W. John; Romano, Thomas; Russell, Jon; Sheon, Robert|archive-url=|archive-date=|dead-url=|access-date=|last3=Yunus|first3=Muhammad|last4=Bennett|first4=Robert|last5=Bombardier|first5=Claire|last6=Goldenberg|first6=Don|last7=Tugwell|first7=Peter|last8=Campbell|first8=Stephen}}</ref> "American College of Rheumatology guidelines suggest that people with fibromyalgia have pain in at least 11 of these tender points when a doctor applies a certain amount of pressure."<ref>{{Cite news|url=http://www.health.com/health/gallery/0,,20345635,00.html|title=18 Points Used to Diagnose Fibromyalgia|last=|first=|date=Feb 4, 2011|work=Health.com|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref><ref>{{Cite web|url=https://www.masscfids.org/8-resource-library/diagnosis/266-tender-points-might-no-longer-be-used-for-diagnosis-of-fibromyalgia|title=Tender Points might no longer be used for diagnosis of Fibromyalgia|last=Proskauer|first=Charmian|date=Feb 2011|website=www.masscfids.org|language=en-GB|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref>

=====2010 ACR criteria=====

*2010, The [https://www.fibroknowledge.com/site/acr-2010 2010 American College of Rheumatology (ACR) Preliminary Diagnostic Criteria for Fibromyalgia: Overview]<ref name=":13">{{Cite web|url=https://www.fibroknowledge.com/sites/default/files/downloads/file/2010_ACR_CRITERIA.pdf|title=American College of Rheumatology (ACR) Preliminary Diagnostic Criteria for Fibromyalgia|last=|first=|date=2010|website=fibroknowledge.com|type=PDF|archive-url=|archive-date=|dead-url=|access-date=}}</ref> was proposed and modified in 2011<ref>{{Cite news|url=http://www.rheumatologynetwork.com/fibromyalgia/new-and-modified-fibromyalgia-diagnostic-criteria|title=New and Modified Fibromyalgia Diagnostic Criteria|last=Garg|first=Neha|date=Feb 9, 2012|work=Rheumatology Network|access-date=Aug 9, 2017|archive-url=|archive-date=|dead-url=|last2=Deodhar|first2=Atul}}</ref> with the modification being validated in 2013 and published in 2014.<ref>{{Cite journal|last=Bennett|first=Robert M.|last2=Friend|first2=Ronald|last3=Marcus|first3=Dawn|last4=Bernstein|first4=Cheryl|last5=Han|first5=Bobby Kwanghoon|last6=Yachoui|first6=Ralph|last7=Deodhar|first7=Atul|last8=Kaell|first8=Alan|last9=Bonafede|first9=Peter|date=2014|title=Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary American College of Rheumatology criteria and the development of alternative criteria|url=https://www.ncbi.nlm.nih.gov/pubmed/24497443|journal=Arthritis Care & Research|volume=66|issue=9|pages=1364–1373|doi=10.1002/acr.22301|issn=2151-4658|pmid=24497443|via=}}</ref> September of 2016, another revision has been made.<ref name=":14">{{Cite news|url=http://acrabstracts.org/abstract/2016-revisions-to-the-20102011-fibromyalgia-diagnostic-criteria/|title=2016 Revisions to the 2010/2011 Fibromyalgia Diagnostic Criteria - ACR Meeting Abstracts|last=|first=|date=Sep 28, 2016|work=ACR Meeting Abstracts|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

:Men do not seem to form the tender points needed for diagnosis under the 1990 criteria,<ref>{{Cite news|url=http://www.webmd.com/fibromyalgia/features/how-fibromyalgia-affects-men#2|title=How Fibromyalgia Affects Men: Symptoms and Diagnosis|work=WebMD|access-date=2018-08-09|language=en-US}}</ref> the 2010 proposed criteria diagnoses more men with a F/M ratio of 2:1.<ref>{{Cite journal|last=Boomershine|first=Chad|date=Nov 4, 2017|title=Fibromyalgia: Practice Essentials, Background, Pathophysiology|url=http://emedicine.medscape.com/article/329838-overview#a5|journal=Medscape|volume=|pages=|via=}}</ref>
:Tender points were used to diagnose with the 1990 criteria, however "considerable skill is needed to correctly check for a patient’s tender points (i.e., digital palpation that is done with certain amount of applied pressure), yet this technique is not typically taught at most medical schools."<ref name=":0">{{Cite web|url=https://www.masscfids.org/8-resource-library/diagnosis/266-tender-points-might-no-longer-be-used-for-diagnosis-of-fibromyalgia#2|title=Tender Points might no longer be used for diagnosis of Fibromyalgia|last=Proskauer|first=Charmian|date=Feb 5, 2011|website=www.masscfids.org|language=en-GB|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref>
:The new standards were designed to:
:*eliminate the use of a tender point examination
:*include a severity scale by which to identify and measure characteristic FM symptoms
:*utilize an index by which to rate pain<ref name=":0" />

There are 19 tender point areas in the widespread pain index '''''(WPI)''''', whereas the 1990 criteria had 18 tender points.<ref name=":0" /><ref>{{Cite news|url=https://www.verywellhealth.com/what-are-fibromyalgia-tender-points-189768|title=Why Tender Points Are No Longer Used to Diagnose Fibromyalgia|last=Eustice|first=Carol|date=Oct 3, 2018|work=Verywell Health|access-date=2018-10-04|archive-url=|archive-date=|dead-url=}}</ref>

====== Widespread pain index and Symptom severity ======

The '''''Widespread Pain Index (WPI)''''' and '''''Symptom Severity''' '''(SS)''''' is explained in the study ''Fibromyalgia Syndrome: An Overview of Pathophysiology, Diagnosis and Management''.<ref name=":21" />
[[File:Widespread Pain Index Areas with numbers.svg|200px|thumb|right|'''''WPI''''' 19 areas of pain. Count 1 point for each area of pain<ref name=":21" />]]
<blockquote>In place of the tender point count, patients (or their physician) may endorse 19 body regions in which pain has been experienced during the past week. One point is given for each area, so the score is between 0-19. This number is referred to as the '''''Widespread Pain Index (WPI)''''' and it is one of the two required scores needed for a doctor to make a diagnosis of fibromyalgia.</blockquote><blockquote>The second part of the score required to assess the diagnosis of fibromyalgia involves the evaluation of a person's symptoms. The patient ranks specific symptoms on a scale of 0-3. These symptoms include: [[Fatigue]], [[Unrefreshing sleep|Waking unrefreshed]], [[Cognitive dysfunction|Cognitive symptoms]], Somatic (physical) symptoms in general (such as [[headache]], [[wikipedia:Weakness|weakness]], [[Gastrointestinal system|bowel problems]], [[nausea]], [[dizziness]], [[numbness]] / [[Paresthesia|tingling]], [[hair loss]]). The numbers assigned to each are added up, for a total of 0-12.</blockquote><blockquote>The diagnosis is based on both the '''''WPI''''' score and the '''''SS''''' score either:</blockquote>
:::<blockquote>'''''WPI''''' of at least 7 and '''''SS''''' scale score of at least 5, '''OR'''</blockquote>
:::<blockquote>'''''WPI''''' of 4-6<ref name=":14" /> and '''''SS''''' scale score of at least 9.<ref name=":21" /></blockquote>

[[File:WPI SS Fibro.JPG|600px|thumb|center|Table 2: '''''SS''''' scale score. Add a 4th column for Somatic (physical) symptoms in general (such as headache, weakness, bowel problems, nausea, dizziness, numbness/tingling, hair loss). The patient ranks specific symptoms on a scale of 0-3. The numbers assigned to each are added up, for a total of 0-12.<ref name=":21" /> ]]

The [[Social Security Administration]] (SSA) accepts a diagnosis of FM with the 1990 or 2010 ACR criteria.<ref>{{Cite web|url=https://www.ssa.gov/OP_Home/rulings/di/01/SSR2012-02-di-01.html|title=Social Security Ruling: SSR 12-2p|last=ORDP,OPPS|first=|date=Jul 25, 2012|website=www.ssa.gov|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref> See the [[Fibromyalgia disability process]] page.

=== Sleep study ===
[[Sleep dysfunction]] is often involved in FM. Treating a sleep disorder can help with FM symptoms. A diagnosed sleep disorder is also helpful if one needs to [[Fibromyalgia disability process|file for disability]].

*[https://www.verywellhealth.com/sleep-study-fibromyalgia-cfs-716054 Getting a Sleep Study with Fibromyalgia or Chronic Fatigue Syndrome]<ref>{{Cite news|url=https://www.verywellhealth.com/sleep-study-fibromyalgia-cfs-716054|title=Getting a Sleep Study with Fibromyalgia or Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Feb 15, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>

*[http://www.sciencedaily.com/releases/2008/09/080903134311.htm What A Sleep Study Can Reveal About Fibromyalgia]<ref>{{Cite news|url=https://www.sciencedaily.com/releases/2008/09/080903134311.htm|title=What A Sleep Study Can Reveal About Fibromyalgia|work=ScienceDaily|access-date=2018-08-09|language=en}}</ref>

*[http://linkis.com/nationalpainreport.com/lzYea Fibromyalgia Sufferers Have Difficulty Maintaining Continuous Sleep, Study Says]<ref>{{Cite news|url=http://linkis.com/nationalpainreport.com/lzYea|title=Fibromyalgia Sufferers Have Difficulty Maintaining Continuous Sleep, Study Says|last=|first=|date=Mar 25, 2016|work=National Pain Report|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

=== ICD Diagnostic code===
'''ICD-10'''

The [[World Health Organization]] (WHO) International Classification of Diseases (ICD) lists FM as a "disease of the [[musculoskeletal system]] and connective tissue", under the code M79.7 (WHO ICD-10 Version: 2016).<ref name=":24">{{Cite web|url=http://apps.who.int/classifications/icd10/browse/2016/en#/M79.7|title=ICD-10 Version:2016|last=World Health Organization|first=|date=2016|website=apps.who.int|at=M79.7 Fibromyalgia|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-15|authorlink=World Health Organization|last2=|first2=|authorlink2=}}</ref> The WHO's ICD-10 does not refer to FM as a syndrome and it is not classified in the category for [[Medically unexplained physical symptoms|medically unexplained symptoms]].<ref name=":37" /><ref name=":24" />

*'''M79.7 Fibromyalgia'''
::Fibromyositis
::Fibrositis
::Myofibrositis<ref name=":24" />

In 2015, the [[United States|US]] finally adopted ICD-10 and FM as a diagnosis.<ref name=":37">{{Cite web|url=http://www.icd10data.com/ICD10CM/Codes/M00-M99/M70-M79/M79-/M79.7|title=2018 ICD-10-CM Diagnosis Code M79.7: Fibromyalgia|website=www.icd10data.com|language=en|access-date=2018-08-09|date=2018|last=World Health Organization|first=|archive-url=|archive-date=|dead-url=|authorlink=World Health Organization|last2=|first2=|authorlink2=}}</ref> <ref>{{Cite news|url=http://nationalpainreport.com/the-health-care-industry-finally-recognizes-fibromyalgia-8827637.html|title=The Health Care Industry Finally Recognizes Fibromyalgia|last=Liptan|first=Ginevra|date=2015-09-30|work=National Pain Report|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

'''ICD-11 (2019)'''

[https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/849253504 ICD-11] (2019) has diagnostic code ''MG30.1 Chronic widespread pain,'' and changed the category from a [[:Category:Musculoskeletal disorders|Musculoskeletal disease]], to the ''General signs and symptoms category'', sometimes referred to as [[Medically unexplained physical symptoms]].<ref name=":18">{{Cite web|url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/849253504|title=ICD-11 - Mortality and Morbidity Statistics|website=icd.who.int|language=en|access-date=2018-08-09}}</ref>

*'''MG30.01 Chronic widespread pain'''

'''Parent'''
::MG30.0 Chronic primary pain

'''Description'''
<blockquote>Chronic widespread pain (CWP) is diffuse pain in at least 4 of 5 body regions and is associated with significant emotional distress (anxiety, anger/frustration or depressed mood) or functional disability (interference in daily life activities and reduced participation in social roles) [1]. CWP is multifactorial: biological, psychological and social factors contribute to the pain syndrome. The diagnosis is appropriate when the pain is not directly attributable to a nociceptive process in these regions and there are features consistent with nociplastic pain [2] and identified psychological and social contributors.<ref name=":18" /></blockquote>

'''Inclusions'''
:*Fibromyalgia
'''Exclusions'''
:*Acute pain (MG31)<ref name=":18" />

==Pathophysiology==
"Fibromyalgia (FM) is a [[chronic pain]] disorder with unknown etiology and unclear pathophysiology. There is no evidence that a single event “causes” FM. Rather, many physical and/or emotional [[Stress|stressors]] may trigger or aggravate symptoms. These have included certain [[Infection|infections]], such as a [[Viral infection|viral illness]] or [[Lyme disease]], as well as emotional or physical [[trauma]]."<ref>{{Cite web|url=https://www.uptodate.com/contents/pathogenesis-of-fibromyalgia#!|title=Pathogenesis of fibromyalgia|last=Goldenberg|first=Don L|date=|website=www.uptodate.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-09|authorlink=|last2=Schur|first2=Paul H|authorlink2=|last3=Romain|first3=Paul L}}</ref> The widespread pain is severe, debilitating, and abnormal in processing its pain. There is also [[Sleep dysfunction|sleep disturbance]] and fatigue. Cause or causes are unproven.<ref>{{Cite news|url=https://www.omf.ngo/what-is-mecfs-old/fibromyalgia/|title=What is Fibromyalgia? {{!}} Open Medicine Foundation|work=Open Medicine Foundation|access-date=2018-08-09|language=en-US}}</ref>

*May 2012, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394355/ Fibromyalgia Syndrome: An Overview of Pathophysiology, Diagnosis and Management]<ref name=":21">{{Cite journal|last=Jahan|first=Firdous|last2=Nanji|first2=Kashmira|last3=Qidwai|first3=Waris|last4=Qasim|first4=Rizwan|date=2012|title=Fibromyalgia Syndrome: An Overview of Pathophysiology, Diagnosis and Management|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394355/|journal=Oman Medical Journal|volume=27|issue=3|pages=192–195|doi=10.5001/omj.2012.44|issn=1999-768X|pmc=|pmid=22811766|via=}}</ref> ''See'' Table 1: "Conditions associated with fibromyalgia." Musculoskeletal, [[genitourianry]], [[Gastrointestinal system|gastro intestinal]], and miscellaneous conditions often exist among fibromyalgia patients.

<blockquote>Pathophysiology: Although the etiology remains unclear, characteristic alterations in the [[Sleep dysfunction|pattern of sleep]] and changes in neuroendocrine transmitters such as [[serotonin]], substance P, growth hormone and [[cortisol]] suggest that regulation of the [[Autonomic nervous system|autonomic]] and neuro-endocrine system appears to be the basis of the syndrome. Fibromyalgia is not a life-threatening, deforming, or [https://en.wikipedia.org/wiki/Progressive_disease progressive disease]. [[Anxiety]] and [[depression]] are the most common association. Aberrant pain processing, which can result in [[chronic pain]], may be the result of several interplaying mechanisms. [[Central sensitization]], blunting of inhibitory pain pathways and alterations in [[neurotransmitters]] lead to aberrant neuro-chemical processing of sensory signals in the CNS, thus lowering the threshold of pain and amplification of normal sensory signals causing constant pain.<ref name=":21" /></blockquote>

<blockquote>The frequent co-morbidity of fibromyalgia with [[Mood swings|mood disorders]] suggests a major role for the stress response and for [[neuroendocrine]] abnormalities. The [[hypothalamic pituitary axis]] (HPA) is a critical component of the stress-adaptation response. In FMS, stress adaptation response is disturbed leading to stress induce symptoms. Psychiatric co-morbidity has been associated with FMS and needs to be identified during the consultation process, as this requires special consideration during treatment.<ref name=":21" /></blockquote>

*May 2018, [https://www.chiropractic.ca/wp-content/uploads/2018/05/107243-2_Chiro_62_1d_Bourgaize.pdf A comparison of the clinical manifestation and pathophysiology of myofascial pain syndrome and fibromyalgia: implications for differential diagnosis and management]<ref>{{Cite journal|last=Bourgaize|first=Sheryl|last2=Newton|first2=Genevieve|last3=Kumbhare|first3=Dinesh|last4=Srbely|first4=John|date=2018|title=A comparison of the clinical manifestation and pathophysiology of myofascial pain syndrome and fibromyalgia: implications for differential diagnosis and management (Table 1).|url=https://www.chiropractic.ca/wp-content/uploads/2018/05/107243-2_Chiro_62_1d_Bourgaize.pdf|format=PDF|journal=Journal of the Canadian Chiropractic Assoc.|volume=|pages=26-41|at=|via=|page=}}</ref> ''See'' Table 1 "Summary of the pathophysiology of fibromyalgia and myofascial pain syndrome." pg. 29 (pg. 4 of PDF)

*Jun 2018, [https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625 SNPs in inflammatory genes ''CCL11'', ''CCL4'' and ''MEFV'' in a fibromyalgia family study]<ref>{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=Placa|first5=Deirdre La|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=Amand|first9=R. Paul St|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref><ref>{{Cite news|url=https://fibromyalgianewstoday.com/2018/07/03/immune-system-may-play-role-fibromyalgia-study/|title=Fibromyalgia May Be Linked to Immune System, Study Suggests|last=Inacio|first=Patricia|date=2018-07-03|work=Fibromyalgia News Today|access-date=2018-08-22|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

<blockquote>SNPs with significant TDTs were found in 36% of the cohort for CCL11 and 12% for MEFV, along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM.</blockquote>

*Jul 2018, [https://fibromyalgianewstoday.com/2018/07/31/primary-secondary-fibromyalgia-share-similar-symptom-burden-study/ Primary and Secondary Fibromyalgia Share Same Symptom Burden, Study Suggests]<ref name=":22">{{Cite news|url=https://fibromyalgianewstoday.com/2018/07/31/primary-secondary-fibromyalgia-share-similar-symptom-burden-study/|title=Primary, Secondary Fibromyalgia Share Same Symptom Burden, Study Says|last=Carvalho|first=John|date=2018-07-31|work=Fibromyalgia News Today|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

<blockquote>Fibromyalgia can be considered either primary, or dominant, also known as idiopathic fibromyalgia, or secondary. In the primary form, the causes of the disorder are unknown, but in secondary fibromyalgia, the disorder usually occurs alongside other debilitating medical conditions, such as rheumatoid arthritis (RA), lupus, and multiple sclerosis.<ref name=":22" /></blockquote>

===Immune system research===

Dr. [[Jarred Younger]] believes an overactive [[immune system]] is the cause and will be conducting a study to test this hypothesis.<ref>{{Cite news|url=http://nationalpainreport.com/new-uab-study-could-radically-change-fibromyalgia-treatment-as-we-know-it-8833437.html|title=New UAB Study Could Radically Change Fibromyalgia Treatment As We Know It|last=Gregory Burch|first=Donna|date=2017-04-24|work=National Pain Report|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite web|url=https://www.youtube.com/watch?v=8e5xKX036bE|title=Testing the fibromyalgia immune system with lipopolysaccharide (LPS)|last=Younger|first=Jarred|date=May 24, 2017|website=YouTube|archive-url=|archive-date=|dead-url=|access-date=|via=Younger Lab}}</ref> An overactive immune system can cause [[inflammation]] and [[chronic pain]].<ref>{{Cite news|url=https://www.epainassist.com/autoimmune/what-is-overactive-immune-system|title=What is Overactive Immune System{{!}}Causes{{!}}Symptoms{{!}}Treatment|last=Kerkar|first=Pramod|date=2016-09-29|work=ePainAssist|access-date=2018-10-04|archive-url=|archive-date=|dead-url=|language=en-gb}}</ref><ref>{{Cite news|url=https://www.webmd.com/a-to-z-guides/autoimmune-diseases|title=Autoimmune Diseases|work=WebMD|access-date=2018-10-04|language=en-US}}</ref>

Dr. William Pridgen's research of [[HSV-1]] (cold sore virus) as being involved in FM has conducted a successful Phase III clinical trial, which had been fast-tracked by the [[Food and Drug Administration]] (FDA), of a combination drug that suppresses this virus and also helps with pain. ''See'': [https://www.me-pedia.org/wiki/Fibromyalgia_drugs#Drug_trials Fibromyalgia drugs (''Drug trials: IMC-1'')].<ref>{{Cite web|url=https://www.me-pedia.org/wiki/Fibromyalgia_drugs#Drug_trials|title=Fibromyalgia drugs - MEpedia|last=|first=|date=|website=www.me-pedia.org|at=Drug trials: IMC-1|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-01}}</ref>

On September 5th, 2018, EpicGenetics announced that [http://www.massgeneral.org/ Massachusetts General Hospital] received approval from the FDA to test the [[wikipedia:BCG_vaccine|Bacille Calmette-Guerin (BCG) vaccine]] (an old Tuberculosis vaccine) on patients that tested positive with its FM/a® test.<ref>{{Cite news|url=http://nationalpainreport.com/can-an-existing-vaccine-help-treat-fibromyalgia-8837139.html|title=Can an Existing Vaccine Help Treat Fibromyalgia?|last=Coghlan|first=Ed|date=2018-09-05|work=National Pain Report|access-date=2018-09-10|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite web|url=https://www.celestecooper.com/2018/07/the-fma-blood-test-and-participation-in.html#.Wz4nxdJKjIU|title=The FM/a® Blood Test and Participation in Fibromyalgia Vaccine Study|last=Cooper|first=Celeste|date=Jul 5, 2018|website=www.celestecooper.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref> <ref>{{Cite news|url=http://www.prohealth.com/library/showArticle.cfm?libid=30644|title=Century-old Vaccine Gives New Hope to Fibromyalgia Community - Prohealth|last=Gregory Burch|first=Donna|date=2017-08-14|work=Prohealth|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=https://www.prohealth.com/library/century-old-vaccine-gives-new-hope-to-fibromyalgia-community-42689#comment-2286|title=Century-old Vaccine Gives New Hope to Fibromyalgia Community - Prohealth|last=Gregory Burch|first=Donna|date=2017-08-14|work=Prohealth|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|at=See Comments Section: CDW12 says: June 26, 2018 at 2:05 pm|language=en-US}}</ref><ref>{{Cite news|url=http://www.prohealth.com/library/showArticle.cfm?libid=30644|title=Century-old Vaccine Gives New Hope to Fibromyalgia Community - Prohealth|last=Gregory Burch|first=Donna|date=2017-08-14|work=Prohealth|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

Recognizing FM may involve activation of the [[immune system]] researchers performed [[Whole exome sequencing|exome sequencing]] on [[chemokine]] genes in a region of [[chromosome]] 17 identified in a genome-wide family association study. Their conclusion: "SNPs with significant TDTs were found in 36% of the cohort for ''CCL11'' and 12% for ''MEFV'', along with a protein variant in CCL4 (41%) that affects CCR5 down-regulation, supporting an immune involvement for FM."<ref name=":42">{{Cite journal|last=Zhang|first=Zhifang|last2=Feng|first2=Jinong|last3=Mao|first3=Allen|last4=Le|first4=Keith|last5=Placa|first5=Deirdre La|last6=Wu|first6=Xiwei|last7=Longmate|first7=Jeffrey|last8=Marek|first8=Claudia|last9=Amand|first9=R. Paul St|date=2018-06-21|title=SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study|url=http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198625|journal=PLOS ONE|language=en|volume=13|issue=6|pages=e0198625|doi=10.1371/journal.pone.0198625|issn=1932-6203|pmid=29927949|via=}}</ref>

=== Brain and spinal cord research ===
A 2004 study by Heffez et al. studied 270 patients with FM and found that 46% had [[cervical spinal stenosis]] and 20% [[chiari malformation]].<ref>{{Cite journal|last=Heffez|first=Dan S.|last2=Ross|first2=Ruth E.|last3=Shade-Zeldow|first3=Yvonne|last4=Kostas|first4=Konstantinos|last5=Shah|first5=Sagar|last6=Gottschalk|first6=Robert|last7=Elias|first7=Dean A.|last8=Shepard|first8=Alan|last9=Leurgans|first9=Sue E.|date=2004-04-09|title=Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia|url=https://link.springer.com/article/10.1007/s00586-004-0672-x|journal=European Spine Journal|language=en|volume=13|issue=6|pages=516–523|doi=10.1007/s00586-004-0672-x|issn=0940-6719|pmc=3476600|pmid=15083352|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=|via=}}</ref> In 2007, Heffez et al. saw significant improvement in physical and mental well-being was found in patients with cervical stenosis who received surgery.<ref>{{Cite journal|last=Heffez|first=Dan S.|last2=Ross|first2=Ruth E.|last3=Shade-Zeldow|first3=Yvonne|last4=Kostas|first4=Konstantinos|last5=Morrissey|first5=Mary|last6=Elias|first6=Dean A.|last7=Shepard|first7=Alan|date=2007|title=Treatment of cervical myelopathy in patients with the fibromyalgia syndrome: outcomes and implications|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2200733/|journal=European Spine Journal|volume=16|issue=9|pages=1423–1433|doi=10.1007/s00586-007-0366-2|issn=0940-6719|pmc=2200733|pmid=17426987|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=|via=}}</ref> A second study in 2007 by Andrew Holman found that 71% had cervical [[spinal cord]] compression.<ref>{{Cite journal|date=2008-07-01|title=Positional Cervical Spinal Cord Compression and Fibromyalgia: A Novel Comorbidity With Important Diagnostic and Treatment Implications|url=https://www.sciencedirect.com/science/article/pii/S1526590008004379|journal=The Journal of Pain|language=en|volume=9|issue=7|pages=613–622|doi=10.1016/j.jpain.2008.01.339|issn=1526-5900|last=|first=|quote=|author-link=Andrew Holman|author-link2=|author-link3=|author-link4=|author-link5=|via=}}</ref> It is important to note that in the past many patients were misdiagnosed with FM when further testing would have revealed the true source of their pain; the 2010 (updated in 2016) ACR criteria has helped curb misdiagnoses.<ref>{{Cite news|title=Fibromyalgia Expert Says Misdiagnosis is Rampant|url=http://nationalpainreport.com/fibromyalgia-expert-says-misdiagnosis-is-rampant-8832803.html|work=National Pain Report|date=2017-02-02|access-date=2018-11-26|language=en-US}}</ref><ref>{{Cite news|title=Common Misdiagnoses of Fibromyalgia|url=https://www.webmd.com/fibromyalgia/guide/common-misdiagnoses-of-fibromyalgia#|work=WebMD|access-date=2018-11-26|language=en-US|last=|first=|date=|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite web|title=Fibromyalgia Misdiagnosis: What Else Could it Be?|url=https://www.integrativepractitioner.com/topics/news/fibromyalgia-misdiagnosis-what-else-could-it-be|website=www.integrativepractitioner.com|access-date=2018-11-26|language=en|date=Jun 6, 2016|last=|first=|archive-url=|archive-date=|dead-url=}}</ref><ref name=":28" />

Various types of [[brain imaging]] are being used to research FM. (''See'': [[Fibromyalgia notable studies]] for images.)

In 2002, an [[Functional magnetic resonance imaging|fMRI]] study conducted by Richard Gracely and Daniel Claw found people with FM "have measurable pain signals in their brains, from a gentle finger squeeze that barely feels unpleasant to people without the disease."<ref>{{Cite web|url=https://www.sciencedaily.com/releases/2002/06/020607073056.htm|title=Fibromyalgia Pain Isn't All In Patient's Heads, New Brain Study Finds|last=|first=|date=Jun 7, 2002|website=sciencedaily.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref> A 2007 study by Borsook et al., ''Neuroimaging revolutionizes therapeutic approaches to chronic pain'' found decreased [[gray matter]] density relative to controls in [[cingulate cortex]] (CC), medial [[prefrontal cortex]] (Med. PFC), [[parahippocampal gyrus]] (PHG) and [[insula]].<ref name=":03">{{Cite journal|last=Borsook|first=David|last2=Moulton|first2=Eric A|last3=Schmidt|first3=Karl F|last4=Becerra|first4=Lino R|date=2007-09-11|title=Neuroimaging Revolutionizes Therapeutic Approaches to Chronic Pain|url=https://link.springer.com/article/10.1186/1744-8069-3-25|journal=Molecular Pain|language=en|volume=3|issue=1|pages=1744–8069-3-25|doi=10.1186/1744-8069-3-25|issn=1744-8069|pmid=17848191|via=}}</ref> In 2015, Loggia et al. imaged [[neuroinflammation]] due to [[Glial cell|glial]] activation using [https://www.itnonline.com/article/mrpet-ultimate-imaging-hybrid MR/PET imaging]<ref>{{Cite news|url=https://www.itnonline.com/article/mrpet-ultimate-imaging-hybrid|title=MR/PET: The Ultimate Imaging Hybrid|last=Ros|first=Pablo R.|date=2012-05-29|work=Imaging Technology News|access-date=2018-10-30|archive-url=|archive-date=|dead-url=|language=en}}</ref>.<ref>{{Cite journal|last=Loggia|first=Marco L.|last2=Chonde|first2=Daniel B.|last3=Akeju|first3=Oluwaseun|last4=Arabasz|first4=Grae|last5=Catana|first5=Ciprian|last6=Edwards|first6=Robert R.|last7=Hill|first7=Elena|last8=Hsu|first8=Shirley|last9=Izquierdo-Garcia|first9=David|date=2015-01-08|title=Evidence for brain glial activation in chronic pain patients|url=https://academic.oup.com/brain/article/138/3/604/333527?searchresult=1|journal=Brain|language=en|volume=138|issue=3|pages=604–615|doi=10.1093/brain/awu377|issn=1460-2156}}</ref> In 2017, López-Solà et al. identified three [[brain]] patterns based on [[Functional magnetic resonance imaging|fMRI]] responses to pressure pain and non-painful multisensory stimulation. "These patterns, taken together, discriminate FM from matched healthy controls with 92% sensitivity and 94% specificity."<ref name=":34">{{Cite journal|last=López-Solà|first=Marina|last2=Woo|first2=Choong-Wan|last3=Pujol|first3=Jesus|last4=Deus|first4=Joan|last5=Harrison|first5=Ben J.|last6=Monfort|first6=Jordi|last7=Wager|first7=Tor D.|date=2017|title=Towards a neurophysiological signature for fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pubmed/27583567|journal=Pain|volume=158|issue=1|pages=34–47|doi=10.1097/j.pain.0000000000000707|issn=1872-6623|pmid=27583567|via=}}</ref> In 2018, Albrecht et al used [[Positron emission tomography|PET]] scans to document [[Glial cell|glial]] activation.<ref name=":52">{{Cite journal|last=Albrecht|first=Daniel S.|last2=Forsberg|first2=Anton|last3=Sandstrom|first3=Angelica|last4=Bergan|first4=Courtney|last5=Kadetoff|first5=Diana|last6=Protsenko|first6=Ekaterina|last7=Lampa|first7=Jon|last8=Lee|first8=Yvonne C.|last9=Höglundi|first9=Caroline Olgart|date=2018-09-14|others=Catana, Ciprian; Cervenka, Simon; Akeju, Oluwaseun; Lekander, Mats; Cohen, George; Halldin, Christer; Taylor, Norman; Kim, Minhae; Hooker, Jacob M.; Loggia, Marco L.|title=Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation|url=https://www.sciencedirect.com/science/article/pii/S0889159118302423|journal=Brain, Behavior, and Immunity|language=en|volume=|pages=|doi=10.1016/j.bbi.2018.09.018|issn=0889-1591|via=}}</ref> Also in 2018, Martucci et al. found unbalanced activity between the ventral and dorsal cervical spinal cord. Ventral neural processes were increased and dorsal neural processes were decreased which may reflect the presence of [[central sensitization]] contributing to [[fatigue]] and other bodily symptoms in FM.<ref>{{Cite journal|last=Martucci|first=Katherine T|last2=Weber|first2=Kenneth A|last3=Mackey|first3=Sean C|date=2018-10-03|title=Altered Cervical Spinal Cord Resting State Activity in Fibromyalgia|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40746|journal=Arthritis & Rheumatology|language=en|doi=10.1002/art.40746|issn=2326-5191}}</ref>

=== Fibromyalgia is not depression ===
* Oct 24, 2003, [https://www.webmd.com/depression/news/20031024/fibromyalgia-isnt-depression#1 Fibromyalgia Isn't Depression]<ref name=":40">{{Cite web|url=https://www.webmd.com/depression/news/20031024/fibromyalgia-isnt-depression|title=Fibromyalgia Isn't Depression|last=DeNoon|first=Daniel J.|authorlink=|last2=|first2=|authorlink2=|date=Oct 24, 2003|website=WebMD|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-04-13}}</ref>
<blockquote>[[Depression]] doesn't cause the pain of fibromyalgia, a new study shows.<ref name=":40" /></blockquote>

<blockquote>"People still doubt fibromyalgia is a disease," Giesecke tells WebMD. "Previously, we found that fibromyalgia patients really do have increased central pain processing. Now we can show this is not affected by depression. Something is wrong here, and it is not at all connected with depression."<ref name=":40" /></blockquote>

<blockquote>"Giesecke's group looked at [[brain]] responses to painful stimuli, and then checked to see if there was any difference between depressed and nondepressed fibromyalgia patients. They showed the activation of areas of the brain related to pain were not different in patients with and without depression." But there is a difference between people with and without fibromyalgia, he says.<ref name=":40" /> </blockquote><blockquote>The researchers use an imaging device called [[functional magnetic resonance imaging]], or fMRI, to look at how the brain responds to pain. Study participants get a mildly painful pressure on their thumb, which makes the brain's pain centers "light up" on the image. Thumb pressure -- at a level healthy people hardly feel -- sets off a firestorm in the pain centers of fibromyalgia patients' brains.<ref>{{Cite web|url=https://www.webmd.com/depression/news/20031024/fibromyalgia-isnt-depression|title=Fibromyalgia Isn't Depression|last=DeNoon|first=Daniel J.|authorlink=|last2=|first2=|authorlink2=|date=Oct 24, 2003|website=WebMD|page=2|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-04-13}}</ref></blockquote>
* Jun 30, 2013, [https://www.healthcentral.com/article/psychiatrists-admit-fibromyalgia-is-neuropathic-not-a-form-of-depression Psychiatrists Admit Fibromyalgia is Neuropathic - Not a Form of Depression]<ref name=":41">{{Cite web|url=https://www.healthcentral.com/article/psychiatrists-admit-fibromyalgia-is-neuropathic-not-a-form-of-depression|title=Psychiatrists Admit Fibromyalgia is Neuropathic – Not a Form of Depression - Causes - Chronic Pain {{!}} HealthCentral|last=Lee Richards|first=Karen|authorlink=|last2=|first2=|authorlink2=|date=Jun 30, 2013|website=www.healthcentral.com|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-04-13}}</ref>
<blockquote>The study the APA referred to was published in the June issue of [http://brain.oxfordjournals.org/content/136/6/1857.abstract ''Brain''], a journal of neurology. The researchers investigated the function and structure of small nerve fibers in 25 FM patients, 10 patients with monopolar depression without pain and with healthy control subjects. Using three different methods of testing, the researchers found that compared with control subjects, patients with fibromyalgia, but not patients with depression, had impaired small fiber function.<ref name=":41" /></blockquote><blockquote>The ''Psychiatric News'' alert quoted the study authors saying, "This strengthens the notion that fibromyalgia syndrome is not a variant of depression, but rather represents an independent entity that may be associated with depressive symptoms," the researchers said. Furthermore, the findings point "towards a neuropathic nature of pain in fibromyalgia syndrome."<ref name=":41" /></blockquote>
* Jan 10, 2019, [https://themighty.com/2019/01/do-i-have-fibromyalgia-or-depression/ 17 Signs You Have Fibromyalgia, Not 'Just' Depression]<ref name=":43">{{Cite web|url=https://themighty.com/2019/01/do-i-have-fibromyalgia-or-depression/|title=17 Signs You Have Fibromyalgia, Not 'Just' Depression|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 10, 2019|website=The Mighty|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-04-13}}</ref>
<blockquote>Fibromyalgia is [https://themighty.com/2018/05/what-fibromyalgia-gets-misdiagnosed-as/ often misdiagnosed as a number of other illnesses]. Though fibro has its own unique set of diagnostic criteria, many of its symptoms can mimic symptoms of other conditions – both physical and mental, acute and chronic.<ref name=":43" /></blockquote><blockquote>One of the most common conditions fibromyalgia gets mistaken for is depression. While each condition causes a unique set of symptoms, many of them may overlap. Like fibro, depression can cause physical symptoms such as pain, fatigue and brain fog. And living with a chronic physical symptoms can have significant effects on your mood, sometimes causing feelings of hopelessness, anxiety or general discontent – which are also symptoms of depression.<ref name=":43" /></blockquote>

== Comorbidities, overlapping conditions, and common symptoms ==
[[File:Fibromyalgia and comorbid conditions.JPG|700px|thumb|center|Comorbid conditions of fibromyalgia (FM) are [[ME/CFS]] which is the most common;<ref name=":30" /><ref name=":31" /> [[Autoimmune disease|autoimmune disease<nowiki/>s]]; [[Migraine|migraine<nowiki/>s]]; [[Multiple chemical sensitivity|multiple chemical sensitivities]] (MCS); and [[orthostatic intolerance]] (OI) / [[postural orthostatic tachycardia syndrome]] (POTS).<ref name=":30" /><ref name=":33">{{Cite news|url=https://www.verywellhealth.com/fibromyalgia-comorbid-overlapping-conditions-716184|title=Illness That Come Along with Fibromyalgia & Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Feb 26, 2018|work=Verywell Health|access-date=2018-08-19|archive-url=|archive-date=|dead-url=}}</ref><ref name=":21" /><ref name=":44" /> Overlapping conditions are [[depression]] and [[anxiety]]; [[Digestive problems|digestive conditions]], [[Menstrual|menstrual problems]]; [[Gulf War Illness]] (GWI); [[nervous system]] disorders; [[Hypotension|low blood pressure]] (Low BP); other pain conditions; and [[sleep dysfunction]]/disturbance<ref name=":30" /> <ref name=":33" /><ref name=":21" />]]

*[[Allodynia]]
** [http://chronicfatigue.about.com/od/glossary/g/allodynia.htm Allodynia: A Rare & Distinct Type of Pain in Fibromyalgia & ME/CFS]<ref name=":1">{{Cite news|url=https://www.verywellhealth.com/allodynia-definition-and-types-fibromyalgia-715929|title=Allodynia: A Rare & Distinct Type of Pain in Fibromyalgia & ME/CFS|last=Dellwo|first=Adrienne|date=Feb 23, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref> Types of Allodynia: Tactile; Mechanical; and Thermal. "Type of pain, generally on the skin, that's caused by something that wouldn't normally cause pain."<ref name=":1" />
*[[Autoimmune disease]]<nowiki/>s "Research suggests that RA and other inflammatory diseases may somehow increase the risk for fibromyalgia."<ref>{{Cite news|url=https://www.health.com/health/gallery/0,,20520705,00.html#restless-legs-0|title=7 Conditions Linked to Fibromyalgia|work=Health.com|access-date=2018-08-19|language=en}}</ref>

*[[Body temperature]] (''See:'' [[small fiber peripheral neuropathy]] for temperature sensitivity; burning, tingling, and prickling due to [[paresthesia]]; [[numbness]]; [[Dry eye syndrome|dry eyes]] and [[dry mouth]]; and more.)<ref>{{Cite news|url=https://www.verywellhealth.com/small-fiber-neuropathy-may-cause-fibromyalgia-pain-3972935|title=Does Fibromyalgia Come From Small Nerves in Your Skin?|last=Dellwo|first=Adrienne|date=Feb 23, 2018|work=Verywell Health|access-date=2018-10-04|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite news|url=https://www.verywellhealth.com/neuropathy-in-fibromyalgia-cfs-3973033|title=Does Your Pain Come From Damage to Small Nerves?|last=Dellwo|first=Adrienne|date=Feb 1, 2018|work=Verywell Health|access-date=2018-10-04|archive-url=|archive-date=|dead-url=}}</ref><ref name=":02">{{Cite news|url=https://www.healthline.com/health/small-fiber-neuropathy#symptoms|title=Small Fiber Neuropathy: Symptoms, Treatment, Causes, and More|last=Vandergriendt|first=Carly|date=Jan 4, 2018|work=Healthline|access-date=2018-10-04|archive-url=|archive-date=|dead-url=|last2=Weatherspoon|first2=Deborah|language=en}}</ref><ref>{{Cite news|url=https://www.webmd.com/brain/understanding-peripheral-neuropathy-basics#3|title=Peripheral Neuropathy -- Symptoms, Types, and Causes of Peripheral Neuropathy|last=|first=|date=|work=WebMD|access-date=2018-10-04|archive-url=|archive-date=|dead-url=|page=3|language=en-US}}</ref>
**[https://www.verywell.com/temperature-sensitivity-in-fibromyalgia-and-mecfs-716025 Temperature Sensitivity in Fibromyalgia & Chronic Fatigue Syndrome]<ref name=":2">{{Cite news|url=https://www.verywellhealth.com/temperature-sensitivity-in-fibromyalgia-and-mecfs-716025|title=Temperature Sensitivity in Fibromyalgia & ME/CFS|last=Dellwo|first=Adrienne|date=Mar 15, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>

<blockquote>When you're exposed to heat, does it feel like you're burning up? Does it seem impossible for you to cool off? Or maybe it's cold that bothers you, chilling you to the bone, leaving you unable to warm up? Or are you one of those people with fibromyalgia (FMS) and chronic fatigue syndrome (ME/CFS) who is cold all the time, or hot all the time, or alternately hot or cold while out of sync with the environment?<ref name=":2" /></blockquote>

[[File:Costal cartilages.JPG|200px|thumb|left|Costochondritis is inflammation of the costal cartilages (shown in red) causing chest and ribcage pain]]

:* [https://www.verywell.com/costochondritis-in-fibromyalgia-716178 Costochondritis in Fibromyalgia]<ref name=":10">{{Cite news|url=https://www.verywellhealth.com/costochondritis-in-fibromyalgia-716178|title=Costochondritis Chest Pain in Fibromyalgia|last=Dellow|first=Adrienne|date=Feb 14, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite journal|date=2018-05-25|title=Costochondritis|url=https://en.wikipedia.org/w/index.php?title=Costochondritis&oldid=842926736|journal=Wikipedia|language=en}}</ref>
<blockquote>Costochondritis is inflammation of the cartilage that connects your ribs to your breastbone. Depending on how much inflammation there is, it can range from mildly annoying to intensely painful. People sometimes describe the pain as stabbing, aching, or burning.</blockquote>

<blockquote>Costochondritis can make you think you're having heart problems, which is a scary thing. Even though costochondritis is common, you should get medical attention if you have unexplained chest pain. You don't want to assume that it's FMS-related and end up with permanent heart damage or worse.</blockquote>

<blockquote>The pain can radiate to your shoulder and arms as well (another way the condition mimics a heart attack). Sometimes the pain is accompanied by redness and/or swelling in the most painful areas. When that's the case, it's called Tietze's Syndrome.<ref name=":10" /></blockquote>

* [[Depression]] and [[Anxiety]]

Fibromyalgia sufferers are "up to three times more likely to have depression at the time of their diagnosis than someone without fibromyalgia."<ref>{{Cite news|url=https://www.webmd.com/fibromyalgia/fibromyalgia-and-depression#1|title=Fibromyalgia and Depression|work=WebMD|access-date=2018-08-19|language=en-US}}</ref> Up to 20 percent of FM patients will have either depression or anxiety.<ref>{{Cite web|url=https://adaa.org/understanding-anxiety/related-illnesses/other-related-conditions/fibromyalgia|title=Fibromyalgia {{!}} Anxiety and Depression Association of America, ADAA|website=adaa.org|language=en|access-date=2018-08-19}}</ref>
* [[Dry eye syndrome]]
** [https://www.news-medical.net/health/Fibromyalgia-and-Dry-Eyes-and-Mouth.aspx Fibromyalgia and Dry Eyes and Mouth]<ref name=":110">{{Cite news|url=https://www.news-medical.net/health/Fibromyalgia-and-Dry-Eyes-and-Mouth.aspx|title=Fibromyalgia and Dry Eyes and Mouth|last=Mandal|first=Ananya|date=2013-06-30|work=News-Medical.net|access-date=2018-10-04|archive-url=|archive-date=|dead-url=|last2=Cashin-Garbutt|first2=April|language=en}}</ref>

* [[Fatigue]]
** [https://www.docsopinion.com/2017/11/08/causes-fatigue-tiredness-chronic-fatigue/ 19 Important Causes of Fatigue – Tiredness and Chronic Fatigue Explained]<ref name=":29">{{Cite web|url=https://www.docsopinion.com/2017/11/08/causes-fatigue-tiredness-chronic-fatigue/|title=19 Important Causes of Fatigue - Tiredness and Chronic Fatigue Explained|website=www.docsopinion.com|access-date=2019-01-30}}</ref> ''See'': 3. Fibromyalgia <blockquote>Fatigue is a universal symptom of fibromyalgia. It is often most marked when arising from sleep in the morning. A typical quote is “''No matter how much sleep I get, it feels like a truck ran me over in the morning'' (20).” Minor activities often seem to aggravate the fatigue.<ref name=":29" /></blockquote>

*[[Fibro fog]] and [[Cognitive dysfunction]]

:*[http://www.news-medical.net/health/What-is-Fibro-Fog-Fibromyalgia-and-Cognitive-Dysfunction.aspx What is Fibro Fog? - Fibromyalgia and Cognitive Dysfunction]<ref name=":3">{{Cite news|url=https://www.news-medical.net/health/What-is-Fibro-Fog-Fibromyalgia-and-Cognitive-Dysfunction.aspx|title=What is Fibro Fog? - Fibromyalgia and Cognitive Dysfunction|last=Mandal|first=Ananya|date=2013-06-03|work=News-Medical.net|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref> 'Mental confusion along with difficulty in concentration and loss of memory is often termed “[[fibro fog]]"'.<ref name=":3" />

:* [https://www.verywellhealth.com/brain-fibro-fog-causes-symptoms-possible-treatment-716014 What Is Fibro Fog and ME/CFS Brain Fog?]<ref name=":17" />
:* [https://fibromyalgianewstoday.com/2018/03/21/fibromyalgia-cognitive-dysfunction-study-identifies-main-types/ Study Identifies the Types of Cognitive Dysfunction That Are Most Prevalent in Fibromyalgia]<ref>{{Cite news|url=https://fibromyalgianewstoday.com/2018/03/21/fibromyalgia-cognitive-dysfunction-study-identifies-main-types/|title=Fibromyalgia Study Identifies Main Types of Patients' Cognitive Dysfunction|last=Pena|first=Ana|date=2018-03-21|work=Fibromyalgia News Today|access-date=2018-08-28|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

*[[Gastrointestinal system]]
**[[Irritable bowel syndrome]]: [http://chronicfatigue.about.com/od/whyfmscfsarelinked/a/IBS.htm Irritable Bowel Syndrome in Fibromyalgia & Chronic Fatigue Syndrome - Why Do They Go Together?]<ref name=":4">{{Cite news|url=https://www.verywellhealth.com/irritable-bowel-syndrome-in-fibromyalgia-cfs-716167|title=Irritable Bowel Syndrome in Fibromyalgia & ME/CFS|last=Dellwo|first=Adrienne|date=Jan 28, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>

:<blockquote>Fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome (IBS) frequently go together. No one really knows why, but we do know that all three conditions can include imbalances of serotonin -- although in fibromyalgia (FMS) and Chronic Fatigue Syndrome (CFS or ME/CFS) it's an imbalance in the brain, while with IBS it's in the gut.<ref name=":4" /></blockquote>
* [[Gulf War Illness]]
**[https://www.publichealth.va.gov/exposures/gulfwar/fibromyalgia.asp Fibromyalgia in Gulf War Veterans]<ref>{{Cite web|url=https://www.publichealth.va.gov/exposures/gulfwar/fibromyalgia.asp|title=Fibromyalgia in Gulf War Veterans - Public Health|last=Administration|first=US Department of Veterans Affairs, Veterans Health|website=www.publichealth.va.gov|language=en|access-date=2018-08-19}}</ref> GWI increases risk of developing fibromyalgia.

*[https://en.wikipedia.org/wiki/Interstitial_cystitis Interstitial Cystitis]<ref>{{Cite journal|date=2018-07-11|title=Interstitial cystitis|url=https://en.wikipedia.org/w/index.php?title=Interstitial_cystitis&oldid=849828657|journal=Wikipedia|language=en}}</ref> (Painful bladder)
**[https://www.verywellhealth.com/chronic-fatigue-syndrome-interstitial-cystitis-716168 Fibromyalgia, Chronic Fatigue Syndrome & Interstitial Cystitis]<ref name=":5">{{Cite news|url=https://www.verywellhealth.com/chronic-fatigue-syndrome-interstitial-cystitis-716168|title=Fibromyalgia, Chronic Fatigue Syndrome & Interstitial Cystitis|last=Dellwo|first=Adrienne|date=Feb 16, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref> "Fibromyalgia, chronic fatigue syndrome and interstitial cystitis (IC) -- a painful bladder condition -- frequently occur together. Women may be up to 10 times more likely than men to develop it."<ref name=":5" />
**[[pubmed:20719340|Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome.]]<ref>{{Cite journal|last=Nickel|first=J. Curtis|last2=Tripp|first2=Dean A.|last3=Pontari|first3=Michel|last4=Moldwin|first4=Robert|last5=Mayer|first5=Robert|last6=Carr|first6=Lesley K.|last7=Doggweiler|first7=Ragi|last8=Yang|first8=Claire C.|last9=Mishra|first9=Nagendra|date=2010|title=Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20719340|journal=The Journal of Urology|volume=184|issue=4|pages=1358–1363|doi=10.1016/j.juro.2010.06.005|issn=1527-3792|pmid=20719340|via=}}</ref>

*Language Impairment
**[[Word-finding problems]]
:*[https://www.verywellhealth.com/language-impairment-in-fibromyalgia-cfs-716024 Language Impairment in Fibromyalgia and Chronic Fatigue Syndrome Impaired Language in Fibromyalgia & Chronic Fatigue Syndrome]<ref name=":6" /> "Searching their brains for simple words that they just can't remember. On other occasions, individuals with these diagnoses may find it hard to write or even understand language."<ref name=":6">{{Cite news|url=https://www.verywellhealth.com/language-impairment-in-fibromyalgia-cfs-716024|title=Language Impairment in Fibromyalgia and Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Feb 12, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>

:*"The diagnosis of [[Aphasia]] is a condition that robs you of the ability to communicate. It can affect your ability to speak, write and understand language, both verbal and written"<ref>{{Cite news|url=http://www.mayoclinic.org/diseases-conditions/aphasia/basics/definition/con-20027061|title=Aphasia - Symptoms and causes|work=Mayo Clinic|access-date=2018-08-09|language=en}}</ref> but with [[dysphasia]] you will have those symptoms and trouble listening and doing numeral calculations.<ref>{{Cite web|url=http://www.ayushveda.com/healthcare/dysphasia.htm|title=Dysphasia - Causes, Symptoms & Treatment|website=www.ayushveda.com|access-date=2018-08-09}}</ref> ''See also'': [[Dyscalculia]].
* [[ME/CFS]]
:*[https://www.verywellhealth.com/fibromyalgia-comorbid-overlapping-conditions-716184 Comorbid Conditions in Fibromyalgia & Chronic Fatigue Syndrome]<ref>{{Cite news|url=https://www.verywellhealth.com/fibromyalgia-comorbid-overlapping-conditions-716184|title=Illness That Come Along with Fibromyalgia & Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Feb 26, 2018|work=Verywell Health|access-date=2018-08-19|archive-url=|archive-date=|dead-url=}}</ref><ref name=":30" /><ref name=":36" />
* [[Migraine]]
:*[https://migrainecenters.com/blog/migraines-and-fibromyalgia/ Migraines and Fibromyalgia]<ref name=":32" />
<blockquote>Both fibromyalgia and migraine may reflect problems in the brain’s pain processing center. It is believed that both conditions are caused by excitation of the nervous system or an over-response to stimuli. Stress is usually cited as a trigger for both migraine and fibromyalgia attacks.<ref name=":32">{{Cite news|url=https://migrainecenters.com/blog/migraines-and-fibromyalgia/|title=Migraines and Fibromyalgia - Migraine Centers|date=2016-05-06|work=Migraine Centers|access-date=2018-08-19|language=en-US}}</ref></blockquote>
* [[Multiple chemical sensitivity|Multiple Chemical Sensitivity]] (MCS) It is thought that both Fibromyalgia and MCS are [[Central sensitization|central sensitivity]] syndromes.<ref>{{Cite news|url=https://www.verywellhealth.com/chemical-sensitivity-in-fibromyalgia-716170|title=Multiple Chemical Sensitivity in Fibromyalgia & ME/CFS|last=Dellwo|first=Adrienne|date=Jul 23, 2018|work=Verywell Health|access-date=2018-08-19|archive-url=|archive-date=|dead-url=}}</ref>

*OBGYN
**[https://www.verywellhealth.com/menstrual-periods-and-fibromyalgia-715596 Menstrual Periods with Fibromyalgia: Personal Stories]<ref>{{Cite news|url=https://www.verywellhealth.com/menstrual-periods-and-fibromyalgia-715596|title=Menstrual Periods with Fibromyalgia: Personal Stories|last=Dellwo|first=Adrienne|date=May 18, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>
**[https://www.verywellhealth.com/fibromyalgia-tied-to-hysterectomy-gynecologic-disease-715626 Fibromyalgia Tied to Hysterectomy, Gynecologic Disease].<ref name=":7" />
:<blockquote>You may have heard about a possible link between gynecologic surgery (such as a hysterectomy) and the development of fibromyalgia, and doctors have long suspected that fibromyalgia has strong hormonal ties and triggers. This does not seem surprising as we've long suspected a link between endocrine disorders, gynecological conditions, and autoimmune conditions.<ref name=":7">{{Cite news|url=https://www.verywellhealth.com/fibromyalgia-tied-to-hysterectomy-gynecologic-disease-715626|title=Fibromyalgia Tied to Hysterectomy, Gynecologic Disease|last=Dellwo|first=Adrienne|date=Feb 16, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref></blockquote>

*[[Orthostatic intolerance]] (OI) and [[Postural orthostatic tachycardia syndrome]] (POTS)<ref name=":44">{{Cite journal|last=Yun|first=Dong Joo|last2=Choi|first2=Han Na|last3=Oh|first3=Gun-Sei|date=2013|title=A Case of Postural Orthostatic Tachycardia Syndrome Associated with Migraine and Fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710947/|journal=The Korean Journal of Pain|volume=26|issue=3|pages=303–306|doi=10.3344/kjp.2013.26.3.303|issn=2005-9159|pmid=23862007|via=}}</ref>

:*[http://drlapp.com/wp-content/uploads/TTT_symptoms.pdf Symptoms Predict the Outcome of Tilt Table Testing in CFS/ME/FM]<ref>{{Cite web|url=http://drlapp.com/wp-content/uploads/TTT_symptoms.pdf|title=Symptoms Predict the Outcome of Tilt Table Testing in CFS/ME/FM|last=Lapp|first=Charles W.|last2=Black|first2=Laura|date=|website=drlapp.com|archive-url=|archive-date=|dead-url=|access-date=|last3=Smith|first3=Rebekah S.}}</ref> (PDF) Symptoms can include low blood pressure and/or sudden high blood pressure, dizziness, fainting.

:*[https://www.healthrising.org/blog/2017/09/21/fibromyalgia-problems-standing-orthostatic-intolerance/ An Overlooked Issue in Fibromyalgia? Study Highlights Problems Standing (Orthostatic Intolerance)]<ref>{{Cite news|url=https://www.healthrising.org/blog/2017/09/21/fibromyalgia-problems-standing-orthostatic-intolerance/|title=An Overlooked Issue in Fibromyalgia? Study Highlights Orthostatic Intolerance - Problems Standing - Health Rising|last=Johnson|first=Cort|date=2017-09-21|work=Health Rising|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
* [[Raynaud's Syndrome]]
** [https://www.verywellhealth.com/raynauds-syndrome-chronic-fatigue-716185 Raynaud's Syndrome in Fibromyalgia & Chronic Fatigue Syndrome]<ref name=":04">{{Cite news|url=https://www.verywellhealth.com/raynauds-syndrome-chronic-fatigue-716185|title=Cold Hands & Feet? Raynaud's Syndrome in Fibromyalgia & ME/CFS|last=Dellwo|first=Adrienne|date=Jan 28, 2018|work=Verywell Health|access-date=2018-10-11|archive-url=|archive-date=|dead-url=}}</ref> <blockquote>In Raynaud's syndrome, the blood vessels constrict more than they should, which allows less blood to get through. That not only makes your extremities cold, it makes them extremely difficult to warm up. The most commonly affected body parts are the fingers and toes, but your lips, nose, ear lobes, knees, and nipples may also be involved.</blockquote><blockquote>Raynaud's isn't all about the cold, though. The diminished blood flow can cause pain in the affected areas, and it may also cause the skin there to turn blue. Skin ulcers (sores) are possible, since prolonged episodes of low blood flow can damage your tissues.<ref name=":04" /></blockquote>

*[[Sleep dysfunction]]
**[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648619/ Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia]<ref name=":23">{{Cite journal|last=Vatthauer|first=Karlyn E|last2=Craggs|first2=Jason G|last3=Robinson|first3=Michael E|last4=Staud|first4=Roland|last5=Berry|first5=Richard B|last6=Perlstein|first6=William M|last7=McCrae|first7=Christina S|date=2015-11-12|title=Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648619/|journal=Journal of Pain Research|volume=8|pages=819–827|doi=10.2147/JPR.S87501|issn=1178-7090|pmc=|pmid=26648751|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=Roland Staud|author-link5=}}</ref>

:<blockquote>The present results of this study suggest that long-term, comorbid pain and sleep disturbance may be associated with increased activation in core default mode brain areas that is above and beyond long-term pain disturbance alone.<ref name=":23" /></blockquote>

:*[http://www.prohealth.com/library/showarticle.cfm?libid=22344 Fibromyalgia and Sleep]<ref name=":8">{{Cite news|url=https://www.prohealth.com/library/fibromyalgia-and-sleep-38954|title=Fibromyalgia and Sleep - Prohealth|date=2016-01-11|work=Prohealth|access-date=2018-08-09|language=en-US}}</ref> "Most people with fibromyalgia have an associated sleep disorder that makes it difficult for them to get the deep, restorative sleep they need."<ref name=":8" />

[[File:Skull_diagram.png|350px|thumb|right|The [[wikipedia:Temporomandibular_joint#Disorders|temporomandibular joint]] is the joint between the mandible (light blue) and the temporal bone (orange) of the skull]]
* [[Temporomandibular joint disorder]] (TMJ/TMD)

:* [https://www.sciencedirect.com/science/article/pii/S2255502114001758 Temporomandibular disorders in fibromyalgia syndrome: a short-communication]<ref>{{Cite journal|last=Soares Gui|first=Maisa|last2=Pimentel|first2=Marcele Jardim|last3=Rizzatti-Barbosa|first3=C'elia Marisa|date=2015-03-01|title=Temporomandibular disorders in fibromyalgia syndrome: a short-communication|url=https://www.sciencedirect.com/science/article/pii/S2255502114001758|journal=Revista Brasileira de Reumatologia (English Edition)|language=en|volume=55|issue=2|pages=189–194|doi=10.1016/j.rbre.2014.07.004|issn=2255-5021|via=ScienceDirect}}</ref><ref>{{Cite news|url=https://www.whitesmilesforlife.com/blog/study-probes-pain-link-between-tmj-fibromyalgia/|title=Study Probes Pain Link Between TMJ, Fibromyalgia|date=2016-05-03|work=Kent E. White, DDS|access-date=2018-08-19|language=en-US}}</ref>

:Other than headaches, the symptoms are quite distinct from symptoms of FMS and ME/CFS.

::They include:
::*Jaw pain
::*Discomfort or difficulty chewing
::*Painful clicking in the jaw
::*Difficulty opening or closing the mouth
::*Headaches
::*Locking jaw
::*Teeth that don't come together properly<ref>{{Cite news|url=https://www.verywellhealth.com/tmj-in-fibromyalgia-chronic-fatigue-syndrome-716175|title=TMJ in Fibromyalgia and Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Mar 31, 2018|work=Verywell Health|access-date=2018-08-22|archive-url=|archive-date=|dead-url=}}</ref>

*[[Thyroid disease]]
**[https://www.verywellhealth.com/relationship-between-cfs-fibromyalgia-and-aitd-3231677 Chronic Fatigue Syndrome, Fibromyalgia, and Autoimmune Thyroid Disease]<ref name=":9">{{Cite news|url=https://www.verywellhealth.com/relationship-between-cfs-fibromyalgia-and-aitd-3231677|title=A Comparison of Chronic Fatigue, Fibromyalgia, and Thyroid Disease|last=Shomon|first=Mary|date=Feb 21, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>

:<blockquote>People with Hashimoto's autoimmune thyroid disease often experience significant fatigue and body aches. While these symptoms are common in Hashimoto's, they can also be markers of other diseases, like chronic fatigue syndrome or fibromyalgia.<ref name=":9" /></blockquote>

*Other symptoms
**[http://chronicfatigue.about.com/od/whatisfibromyalgia/a/fibrosymptoms.htm Symptoms of Fibromyalgia]<ref>{{Cite news|url=https://www.verywellhealth.com/fibromyalgia-symptoms-716139|title=Symptoms of Fibromyalgia|last=Dellwo|first=Adrienne|date=May 16, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref> (On all the many symptoms and conditions of and related to fibromyalgia.)
**''Fibromyalgia Syndrome: An Overview of Pathophysiology, Diagnosis and Management'' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394355/ Conditions associated with fibromyalgia. (Table 1)]<ref name=":21" />

==Treatment==

===United States===
'''Rheumatology and primary care providers: Diagnosing and treatment'''

*2012, [https://www.mayoclinicproceedings.org/article/S0025-6196(12)00299-6/abstract A Framework for Fibromyalgia Management for Primary Care Providers]<ref>{{Cite journal|last=Arnold|first=Lesley M.|last2=Clauw|first2=Daniel J.|last3=Dunegan|first3=L. Jean|last4=Turk|first4=Dennis C.|date=2012|title=A Framework for Fibromyalgia Management for Primary Care Providers|url=https://www.mayoclinicproceedings.org/article/S0025-6196(12)00299-6/abstract|journal=Mayo Clinic Proceedings|language=English|volume=87|issue=5|pages=488–496|doi=10.1016/j.mayocp.2012.02.010|issn=0025-6196|via=}}</ref> Rheumatologists stopped treating fibromyalgia patients and primary care providers began treatment managment although rheumatologists are most often the specialist to diagnose. (Please see [http://me-pedia.org/wiki/Fibromyalgia#Disability disability] heading about ''primary provider'' and ''specialists'' for disability cases.)

=== '''Drugs (See main article link below)''' ===

{{Main article |page_name = Fibromyalgia drugs}}

=== Therapies ===

==== Exercise ====
''Please Note'': These treatments are for fibromyalgia patients and '''not''' [[ME/CFS]] sufferers due to it's hallmark symptom of [[post-exertional malaise]].
[[File:Warm water exercise.JPG|200px|thumb|left|Warm water exercise is best for fibromyalgia. Start slow and don't push through the pain<ref name=":11" />]]

*[https://www.verywellhealth.com/warm-water-exercise-for-fibromyalgia-716059 Warm Water Exercise for Fibromyalgia]<ref name=":11">{{Cite news|url=http://chronicfatigue.about.com/od/treatingfmscfs/a/warmwaterFMS.htm|title=Warm Water Exercise for Fibromyalgia|last=Dellwo|first=Adrienne|date=Nov 19, 2017|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite journal|last=Munguía-Izquierdo|first=D.|last2=Legaz-Arrese|first2=A.|date=2007|title=Exercise in warm water decreases pain and improves cognitive function in middle-aged women with fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pubmed/18173915|journal=Clinical and Experimental Rheumatology|volume=25|issue=6|pages=823–830|issn=0392-856X|pmid=18173915|via=}}</ref><ref>{{Cite news|url=https://www.prohealth.com/fibromyalgia/library/aquatic-exercise-training-fibromyalgia-85081?utm_campaign=Social%20Media%20-%20Fibromyalgia&utm_content=76595810&utm_medium=social&utm_source=twitter|title=Aquatic exercise training for fibromyalgia. - Prohealth|date=2018-08-29|work=Prohealth|access-date=2018-09-01|language=en-US}}</ref><ref>{{Cite journal|last=Bidonde|first=Julia|last2=Busch|first2=Angela J.|last3=Webber|first3=Sandra C.|last4=Schachter|first4=Candice L.|last5=Danyliw|first5=Adrienne|last6=Overend|first6=Tom J.|last7=Richards|first7=Rachel S.|last8=Rader|first8=Tamara|date=2014-10-28|title=Aquatic exercise training for fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pubmed/25350761|journal=The Cochrane Database of Systematic Reviews|issue=10|pages=CD011336|doi=10.1002/14651858.CD011336|issn=1469-493X|pmid=25350761}}</ref>

<blockquote>Several studies have found that warm-water pool exercise is a beneficial treatment for fibromyalgia. A very large survey of patients found that 26% have used pool therapy, rating it as very effective.<ref name=":45">{{Cite journal|last=Bennett|first=Robert M.|author-link=Robert Bennett|last2=Jones|first2=Jessie|author-link2=Jessie Jones|last3=Turk|first3=Dennis C.|author-link3=Dennis Turk|last4=Russell|first4=I. Jon|author-link4=I. Jon Russell|last5=Matallana|first5=Lynne|author-link5=Lynne Matallana|date=Mar 9, 2007|title=An internet survey of 2,596 people with fibromyalgia|url=https://doi.org/10.1186/1471-2474-8-27|journal=BMC Musculoskeletal Disorders|volume=8|issue=1|pages=27|doi=10.1186/1471-2474-8-27|issn=1471-2474|pmc=1829161|pmid=17349056|quote=|via=}}</ref> The same survey found 74% of patients found heat helpful - either warm water or heat packs.<ref name=":45" /> Warm water especially important in FMS because many people with the condition are intolerant of cold. A warm-water pool is one that's kept around 89.6 degrees Fahrenheit (32 Celsius), which is several degrees warmer than most heated pools.<ref name=":11" /></blockquote>

* Moderate aerobic exercise and weights with six to eight reps and then a day or two of rest in between. Do not start a program if you are in a flare.<ref>{{Cite web|url=http://www.arthritis.org/living-with-arthritis/tools-resources/expert-q-a/fibromyalgia-questions/fibromyalgia-exercise.php|title=Fibromyalgia Exercise {{!}} Exercising with Fibromyalgia|last=Ronenn|first=Roubenoff|date=|website=www.arthritis.org|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref>

*[https://www.youtube.com/watch?v=BauJYuJwFsI Easy fibromyalgia exercises and motivation to keep you healthy!]<ref>{{Cite web|url=https://www.youtube.com/watch?v=BauJYuJwFsI|title=Easy Fibromyalgia exercises and motivation to keep you healthy!|last=Suarez|first=Eric|date=Jun 21, 2011|website=YouTube|archive-url=|archive-date=|dead-url=|access-date=Aug 9, 2018}}</ref> Video

*[http://chronicfatigue.about.com/od/whatisfibromyalgia/a/Fibromyalgia-Myth-Vs-Fact.htm Fibromyalgia Myth vs. Fact]<ref name=":15">{{Cite news|url=https://www.verywellhealth.com/fibromyalgia-myth-vs-fact-716131|title=Fibromyalgia: What's Myth, What's Fact?|last=Dellwo|first=Adrienne|date=Jun 8, 2016|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|at=Myth #3 People With Fibromyalgia Need More Exercise}}</ref> Heading: ''Myth #3: People With Fibromyalgia Need More Exercise''. Appropriate exercise, which each patient needs to gauge for themselves.<ref name=":15" />

==== Massage ====

*2014, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930706/ Massage Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials]<ref>{{Cite journal|last=Li|first=Yan-hui|last2=Wang|first2=Feng-yun|last3=Feng|first3=Chun-qing|last4=Yang|first4=Xia-feng|last5=Sun|first5=Yi-hua|date=2014-02-20|title=Massage Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930706/|journal=PLoS ONE|volume=9|issue=2|doi=10.1371/journal.pone.0089304|issn=1932-6203|pmc=|pmid=24586677|pages=|via=}}</ref>

*2016, [http://chronicfatigue.about.com/od/alternativetreatments/a/bodywork.htm Massage, Rolfing & Other Bodywork - Are They Effective Fibromyalgia & Chronic Fatigue Syndrome Treatments?]<ref>{{Cite news|url=https://www.verywellhealth.com/massage-rolfing-other-bodywork-715645|title=Massage, Rolfing, Reiki: Do They Work for Fibromyalgia & ME/CFS?|last=Dellwo|first=Adrienne|date=Aug 10, 2017|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>

==== Acupuncture ====

*2004, [[U.S. Department of Health and Human Services]] (HHS) and [https://en.wikipedia.org/wiki/Centers_for_Medicare_and_Medicaid_Services Centers for Medicare and Medicaid Services] (CMS) ruled April 16, 2004, a noncoverage determination for acupuncture.<ref>{{Cite web|url=https://www.cms.gov/Regulations-and-Guidance/Guidance/Transmittals/downloads/R11NCD.pdf|title=CMS Manual System Pub. 100-03 Medicare National Coverage Determinations|last=|first=|date=Apr 16, 2004|website=CMS.gov|format=PDF|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

*2005, [http://acupunctureschoolonline.com/acupuncture-good-for-fibromyalgia.html Acupuncture Good for Fibromyalgia?] <ref name=":16">{{Cite web|url=http://acupunctureschoolonline.com/acupuncture-good-for-fibromyalgia.html|title=Acupuncture Good for Fibromyalgia?|last=|first=|date=Oct 2, 2012|website=Acupuncture School Online|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref> "Acupuncture gave no significant pain relief to fibromyalgia patients."<ref name=":16" />

*2016, [http://www.sciencedirect.com/science/article/pii/S2095496416602352 Short-term complementary and alternative medicine on quality of life in women with fibromyalgia] <ref name=":25">{{Cite journal|date=2016-01-01|title=Short-term complementary and alternative medicine on quality of life in women with fibromyalgia|url=https://www.sciencedirect.com/science/article/pii/S2095496416602352|journal=Journal of Integrative Medicine|language=en|volume=14|issue=1|pages=29–35|doi=10.1016/S2095-4964(16)60235-2|issn=2095-4964}}</ref> "There was no significant improvement in pain or reduction of tender points in any of the groups studied, at the end of the 8th session."<ref name=":25" />

*2016, [https://fibromyalgianewstoday.com/2016/02/01/acupuncture-does-not-reduce-pain-for-women-with-fibromyalgia/ Acupuncture Does Not Appear to Relieve Pain in Fibromyalgia Patients]<ref>{{Cite news|url=https://fibromyalgianewstoday.com/2016/02/01/acupuncture-does-not-reduce-pain-for-women-with-fibromyalgia/|title=Acupuncture Does Not Appear to Relieve Pain in Fibromyalgia Patients - Fibromyalgia News Today|last=Semedo|first=Daniela|date=2016-02-01|work=Fibromyalgia News Today|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== '''Disability: SSI/SSD and LTD (See main article link below)''' ==
{{Main article |page_name = Fibromyalgia disability process}}

== '''Notable studies (See main article link below)''' ==
{{Main article |page_name = Fibromyalgia notable studies}}

== Controversy ==
=== Dr. Frederick Wolfe ===
Dr. [http://rheummd.org/members/fwolfe Frederick Wolfe], the director of the [https://www.arthritis-research.org/ National Databank for Rheumatic Diseases] and the lead author of the 1990 paper that first defined the diagnostic guidelines for fibromyalgia, says he has become cynical and discouraged about the diagnosis. He now considers the condition a physical response to stress, depression, and economic and social anxiety.<ref>{{Cite news|url=http://www.nytimes.com/2008/01/14/health/14pain.html?_r=0|title=Drug Approved. Is Disease Real?|last=Berenson|first=Alex|date=Jan 14, 2008|work=The Wall Street Journal|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref><ref>{{Cite journal|last=Wolfe|first=Frederick|last2=Walitt|first2=Brian|date=2016|title=Fibromyalgia: A Short Commentary|url=http://headache.imedpub.com/fibromyalgia-a-short-commentary.pdf|journal=Journal of Headache & Pain Management|volume=1|issue=No. 3:27|pages=|via=iMedPubJournals}}</ref><ref>{{Cite news|url=https://www.news-medical.net/news/20130322/Fibromyalgia-an-interview-with-Dr-Frederick-Wolfe-University-of-Kansas-School-of-Medicine.aspx|title=Fibromyalgia: an interview with Dr Frederick Wolfe, University of Kansas School of Medicine|last=Cashin-Garbutt|first=April|date=2013-03-22|work=News-Medical.net|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref>

=== Fibromyalgia vs Chiari malformation ===
Some individuals diagnosed with FMS were undergoing surgery for [[chiari malformation]] (CM). These are two separate conditions; FMS cannot be resolved by undergoing a risky CM surgery.

*2011, [https://www.ncbi.nlm.nih.gov/pubmed/21135714 Is Chiari I malformation associated with fibromyalgia?]<ref>{{Cite journal|last=Watson|first=Nathaniel F.|last2=Buchwald|first2=Dedra|last3=Goldberg|first3=Jack|last4=Maravilla|first4=Kenneth R.|last5=Noonan|first5=Carolyn|last6=Guan|first6=Qingyan|last7=Ellenbogen|first7=Richard G.|date=2011|title=Is Chiari I malformation associated with fibromyalgia?|url=https://www.ncbi.nlm.nih.gov/pubmed/21135714|journal=Neurosurgery|volume=68|issue=2|pages=443–448; discussion 448–449|doi=10.1227/NEU.0b013e3182039a31|issn=1524-4040|pmid=21135714|via=}}</ref>
::Conclusion: Most patients with FM do not have [[CIM]] pathology. Future studies should focus on dynamic neuroimaging of craniocervical neuroanatomy in patients with FM.
*2015, [https://www.massmecfs.org/resource-library/9-treatment/172-cfidsfm-and-chiari-malformation-surgery CFS/FM and Chiari Malformation Surgery]<ref>{{Cite web|url=https://www.massmecfs.org/resource-library/9-treatment/172-cfidsfm-and-chiari-malformation-surgery|title=CFS/FM and Chiari Malformation Surgery|last=Casanova|first=Ken|date=Nov 15, 2015|website=www.massmecfs.org|language=en-GB|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref>

==See also==
*[[Fibromyalgia disability process]]
* [[Fibromyalgia drugs]]
* [[Fibromyalgia notable studies]]
* [[Influenza vaccine]]
*[[Lady Gaga]]

== Learn more ==
*[https://dx.doi.org/10.4065%2Fmcp.2011.0206 The Science of Fibromyalgia] - Daniel Clauw, Lesley Arnold, and Bill McCarber for the FibroCollaborative
*[https://www.s4me.info/forums/fibromyalgia-and-connective-tissue-disorders.35/ Forum: Fibromyalgia and Connective Tissue Disorders] at [[Science for ME]]
*[[Verywell FMS/CFS]]

=== Ongoing process of diagnosing and categorizing ===

*2014, [http://www.medpagetoday.com/Rheumatology/Fibromyalgia/49114 Lyme Disease, Fibromyalgia Link Evaporates]<ref>{{Cite news|url=https://www.medpagetoday.com/Rheumatology/Fibromyalgia/49114|title=Lyme Disease, Fibromylagia Link Evaporates|last=Kuznar|first=Wayne|date=2014-12-14|work=|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref> (See also: [[Chronic lyme disease]])

*2015, [http://www.news-medical.net/news/20150518/Fibromyalgia-now-considered-as-a-lifelong-central-nervous-system-disorder.aspx Fibromyalgia now considered as a lifelong central nervous system disorder]<ref>{{Cite news|url=https://www.news-medical.net/news/20150518/Fibromyalgia-now-considered-as-a-lifelong-central-nervous-system-disorder.aspx|title=Fibromyalgia now considered as a lifelong central nervous system disorder|date=2015-05-18|work=News-Medical.net|access-date=2018-08-09|language=en}}</ref>

*2015, [http://nationalpainreport.com/foundation-of-fibromyalgia-is-altered-central-nervous-system-new-study-validates-8827896.html Foundation of Fibromyalgia Is Altered Central Nervous System, New Study Validates]<ref>{{Cite news|url=http://nationalpainreport.com/foundation-of-fibromyalgia-is-altered-central-nervous-system-new-study-validates-8827896.html|title=Foundation of Fibromyalgia Is Altered Central Nervous System, New Study Validates|date=2015-10-24|work=National Pain Report|access-date=2018-08-09|language=en-US}}</ref>

*2015, ''Question:'' [http://fmcfstriggerpoints.blogspot.com/2015/09/is-fibromyalgia-psychosomatic-illness.html 'Is Fibromyalgia a Psychosomatic Illness?'] ''Answer:'' "Fibromyalgia is NOT a psychosomatic illness."<ref>{{Cite web|url=http://fmcfstriggerpoints.blogspot.com/2015/09/is-fibromyalgia-psychosomatic-illness.html|title=Is Fibromyalgia a Psychosomatic Illness? Med Student Asks Celeste Cooper|last=Cooper|first=Celeste|date=Sep 4, 2015|website=fmcfstriggerpoints.blogspot.com|archive-url=|archive-date=|dead-url=|access-date=2018-09-15}}</ref>

*2016, [http://fibromyalgianewstoday.com/2016/09/09/fibromyalgia-diagnosis-using-noninvasive-eye-examination Diagnosing Fibromyalgia May Be Possible Using Noninvasive Eye Examination]<ref>{{Cite news|url=https://fibromyalgianewstoday.com/2016/09/09/fibromyalgia-diagnosis-using-noninvasive-eye-examination|title=Diagnosing Fibromyalgia May Be Possible with Noninvasive Eye Exam|date=2016-09-09|work=Fibromyalgia News Today|access-date=2018-08-09|language=en-US}}</ref>

*2016, [https://www.verywellhealth.com/microglia-in-fibromyalgia-chronic-fatigue-syndrome-3862780 Microglia in Fibromyalgia & Chronic Fatigue Syndrome]<ref>{{Cite news|url=https://www.verywellhealth.com/microglia-in-fibromyalgia-chronic-fatigue-syndrome-3862780|title=Microglia in Fibromyalgia and Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Feb 21, 2018|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>

*2016, [http://simmaronresearch.com/2016/03/are-chronic-fatigue-syndrome-mecfs-and-fibromyalgia-immune-exhaustion-disorders/ Are Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Immune Exhaustion Disorders?]<ref>{{Cite news|url=http://simmaronresearch.com/2016/03/are-chronic-fatigue-syndrome-mecfs-and-fibromyalgia-immune-exhaustion-disorders/|title=Are Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Immune Exhaustion Disorders? - Simmaron Research|date=2016-03-21|work=Simmaron Research|access-date=2018-08-09|language=en-US}}</ref>

*2016, [https://consultqd.clevelandclinic.org/2016/03/why-fibromyalgia-is-neuropathic/?utm_campaign=qd+tweets&utm_medium=social&utm_source=twitter&utm_content=160308+fibromyalgia+neuropathic&dynid=twitter-_-qd+tweets-_-social-_-social-_-160308+fibromyalgia+neuropathic Why Fibromyalgia Is Neuropathic]<ref>{{Cite news|url=https://consultqd.clevelandclinic.org/why-fibromyalgia-is-neuropathic/?utm_campaign=qd+tweets&utm_medium=social&utm_source=twitter&utm_content=160308+fibromyalgia+neuropathic&dynid=twitter-_-qd+tweets-_-social-_-social-_-160308+fibromyalgia+neuropathic|title=Why Fibromyalgia Is Neuropathic|date=2016-03-08|work=Consult QD|access-date=2018-08-09|language=en-US}}</ref>

*2017, [http://nationalpainreport.com/study-reveals-new-treatment-target-for-fibromyalgia-inflammation-in-the-brain-8833354.html Study Reveals New Treatment Target for Fibromyalgia: Inflammation in the Brain]<ref>{{Cite news|url=http://nationalpainreport.com/study-reveals-new-treatment-target-for-fibromyalgia-inflammation-in-the-brain-8833354.html|title=Study Reveals New Treatment Target for Fibromyalgia: Inflammation in the Brain|last=Liptan|first=Ginevra|date=2017-04-11|work=National Pain Report|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*2017, [https://qz.com/1349854/ai-can-spot-the-pain-from-a-disease-some-doctors-still-think-is-fake/?mc_cid=669d3db241&mc_eid=c75cd86947 AI can spot the pain from a disease some doctors still think is fake]<ref>{{Cite news|url=https://qz.com/1349854/ai-can-spot-the-pain-from-a-disease-some-doctors-still-think-is-fake/?mc_cid=669d3db241&mc_eid=c75cd86947|title=AI can spot the pain from a disease some doctors still think is fake|last=Goldhill|first=Olivia|date=Aug 9, 2018|work=Quartz|access-date=2018-08-15|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*2018, [https://www.verywellhealth.com/fibromyalgia-pain-physiological-evidence-716141 Understanding the Pathophysiology of Fibromyalgia]<ref>{{Cite news|url=https://www.verywellhealth.com/fibromyalgia-pain-physiological-evidence-716141|title=What Is the Pathophysiology of Fibromyalgia?|last=Dellwo|first=Adrienne|date=Sep 18, 2018|work=Verywell Health|access-date=2018-09-19|archive-url=|archive-date=|dead-url=}}</ref>
*2018, [https://www.prohealth.com/fibromyalgia/library/fibromyalgia-central-sensitization-syndrome-87957?utm_campaign=Social%20Media%20-%20Fibromyalgia&utm_content=80329422&utm_medium=social&utm_source=twitter Fibromyalgia: Central Sensitization Syndrome - Characterizing classes of fibromyalgia within the continuum of central sensitization syndrome.]<ref>{{Cite news|url=https://www.prohealth.com/fibromyalgia/library/fibromyalgia-central-sensitization-syndrome-87957?utm_campaign=Social%20Media%20-%20Fibromyalgia&utm_content=80329422&utm_medium=social&utm_source=twitter|title=Fibromyalgia: Central Sensitization Syndrome - Prohealth|last=Davis|first=F|date=2018-11-18|work=Prohealth|access-date=2018-11-25|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

=== Blood tests ===

*2013, [http://nationalpainreport.com/new-fibromyalgia-blood-test-is-99-accurate-8821072.html New Fibromyalgia Blood Test is 99% Accurate]<ref>{{Cite news|url=http://nationalpainreport.com/new-fibromyalgia-blood-test-is-99-accurate-8821072.html|title=New Fibromyalgia Blood Test is 99% Accurate|date=2013-07-31|work=National Pain Report|access-date=2018-08-09|language=en-US}}</ref>

*2014, [http://www.prohealth.com/library/showarticle.cfm?libid=18837 Pridgen Reports Fibromyalgia Antiviral Trial Results “Very Positive”: Predicts New Approach Will Be “Game-Changer”]<ref>{{Cite news|url=https://www.prohealth.com/library/pridgen-reports-fibromyalgia-antiviral-trial-results-very-positive-predicts-new-approach-will-be-game-changer-32620|title=Pridgen Reports Fibromyalgia Antiviral Trial Results “Very Positive”: Predicts New Approach Will Be “Game-Changer”|last=|first=|date=2014-03-25|work=Prohealth|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

*2016, [https://www.celestecooper.com/2016/05/blood-test-for-fibromyalgia-fma-test-is.html Blood Test for Fibromyalgia: FM/a Test Ⓡ is now available, Q&A]<ref>{{Cite web|url=https://www.celestecooper.com/2016/05/blood-test-for-fibromyalgia-fma-test-is.html|title=Blood Test for Fibromyalgia: FM/a Test ® Is Real, Q&A|last=Cooper|first=Celeste|date=May 3, 2016|website=www.celestecooper.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref>

*2016, [http://www.liveinsurancenews.com/fibromyalgia-blood-testing-covered-rising-number-insurance-companies/ Fibromyalgia blood testing covered by rising number of insurance companies]<ref>{{Cite news|url=http://www.liveinsurancenews.com/fibromyalgia-blood-testing-covered-rising-number-insurance-companies/|title=Fibromyalgia blood testing covered more of insurance companies|last=Campbell|first=Julie|date=2016-04-08|work=Live Insurance News|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

*2017, [http://www.businesswire.com/news/home/20170419005324/en/EpicGenetics-Assistance-Leading-Medical-Centers-Expands-Clinical EpicGenetics, with the Assistance of Leading Medical Centers, Expands Clinical Study of FM/a® Test to Diagnose Fibromyalgia, Identify Genetic Markers Unique to the Disorder and Explore Direct Treatment Approaches]<ref>{{Cite news|url=https://www.businesswire.com/news/home/20170419005324/en/EpicGenetics-Assistance-Leading-Medical-Centers-Expands-Clinical|title=EpicGenetics, with the Assistance of Leading Medical Centers, Expands Clinical Study of FM/a® Test to Diagnose Fibromyalgia, Identify Genetic Markers Unique to the Disorder and Explore Direct Treatment Approaches|last=|first=|date=Apr 19, 2017|work=Business Wire|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref>

=== Brain scans ===

*2002, [http://www.anapsid.org/cnd/diagnosis/brainpain.html Fibromyalgia Pain Isn't All In Patient's Heads, New Brain Study Finds]<ref>{{Cite web|url=http://www.anapsid.org/cnd/diagnosis/brainpain.html|title=Fibromyalgia Pain Isn't All In Patient's Heads, New Brain Study Finds|last=Kaplan|first=Melissa|date=Jan 1, 2014|website=www.anapsid.org|publisher=ANAPSID|via=Chronic Neuroimmune Diseases|archive-url=|archive-date=|dead-url=|access-date=2018-08-09}}</ref>

*2012, [https://www.sciencedaily.com/releases/2012/11/121111153426.htm Fibromyalgia and the brain: New clues reveal how pain and therapies are processed]<ref>{{Cite news|url=https://www.sciencedaily.com/releases/2012/11/121111153426.htm|title=Fibromyalgia and the brain: New clues reveal how pain and therapies are processed|last=|first=|date=Nov 11, 2012|work=ScienceDaily|access-date=2018-08-09|archive-url=|archive-date=|dead-url=|language=en}}</ref>

*2015, [https://www.verywellhealth.com/how-lyrica-changes-the-fibromyalgia-brain-715767 How Lyrica Changes the Fibromyalgia Brain]<ref>{{Cite news|url=https://www.verywellhealth.com/how-lyrica-changes-the-fibromyalgia-brain-715767|title=How Lyrica Changes the Fibromyalgia Brain|last=Dellwo|first=Adrienne|date=Apr 30, 2016|work=Verywell Health|access-date=2018-08-09|archive-url=|archive-date=|dead-url=}}</ref>
*2018, [https://ki.se/en/news/people-with-fibromyalgia-have-inflammation-of-the-brain People with fibromyalgia have inflammation of the brain]<ref>{{Cite web|url=https://ki.se/en/news/people-with-fibromyalgia-have-inflammation-of-the-brain|title=People with fibromyalgia have inflammation of the brain|last=|first=|date=Sep 25, 2018|website=ki.se|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-26}}</ref>
*2018, [https://fibromyalgianewstoday.com/2018/10/11/brain-inflammation-imaged-first-time-fibromyalgia-patients-study/ Brain Inflammation Imaged for First Time in Fibromyalgia Patients, Study Reports]<ref>{{Cite news|url=https://fibromyalgianewstoday.com/2018/10/11/brain-inflammation-imaged-first-time-fibromyalgia-patients-study/|title=In Fibromyalgia Patients, Brain Inflammation Imaged for First Time in Study|last=Inacio|first=Patricia|date=2018-10-11|work=Fibromyalgia News Today|access-date=2018-10-30|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

==References==
<references />

[[Category:Diagnoses]]
[[Category:Comorbidities]]
[[Category:Musculoskeletal disorders]]

Post-exertional malaise

2019-04-19T13:51:28Z

MEandCFS:caption edit

'''Post-exertional malaise (PEM)''' refers to a ''worsening'' of [[List of symptoms in ME CFS|ME/CFS symptoms]] after minimal ''physical'' or ''mental'' [[exertion]],<ref name=":14" /><ref name=":32" /> which can be delayed 24-72 hours or more.<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15" /><ref name=":28">{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=137|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=2018-10-16|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.}}</ref><ref name=":30">{{Cite journal|last=|first=|date=2018|title=SAGE Journals: Your gateway to world-class journal research|url=http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf|journal=Sage Pub|language=en|volume=|pages=4-5|doi=10.1177/1359105318805819/suppl_file/appendix.__the_development_of_a_comprehensive_measure_of_post-exertional_malaise.8.20.2018.pdf|via=}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref> PEM is considered to be the hallmark symptom of [[ME/CFS]].<ref name=":0">{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK274235/|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|last=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations|last3=Institute of Medicine|date=2015|publisher=National Academies Press (US)|isbn=9780309316897|series=The National Academies Collection: Reports funded by National Institutes of Health|location=Washington (DC)|pmid=25695122}}</ref><ref>{{Cite web|url=https://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|website=www.medscape.com|access-date=2018-10-10}}</ref><ref>{{Cite web|url=https://ammes.org/2018/06/04/deconstructing-post-exertional-malaise-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-a-patient-centered-cross-sectional-survey/|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-10-16}}</ref> While in most diseases patients experience symptom relief after [[exercise|exercise,]]<ref>{{Cite journal|last=Loy|first=Bryan D.|last2=O'Connor|first2=Patrick J.|last3=Dishman|first3=Rodney K.|date=Oct 2013|title=The effect of a single bout of exercise on energy and fatigue states: a systematic review and meta-analysis|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2013.843266?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=1|issue=4|pages=223–242|doi=10.1080/21641846.2013.843266|issn=2164-1846}}</ref><ref>{{Cite journal|last=Robb-Nicholson|first=L. C.|last2=Daltroy|first2=L.|last3=Eaton|first3=H.|last4=Gall|first4=V.|last5=Wright|first5=E.|last6=Hartley|first6=L. H.|last7=Schur|first7=P. H.|last8=Liang|first8=M. H.|date=Dec 1989|title=Effects of aerobic conditioning in lupus fatigue: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/2590802|journal=British Journal of Rheumatology|volume=28|issue=6|pages=500–505|issn=0263-7103|pmid=2590802}}</ref><ref>{{Cite journal|last=Mostert|first=S.|last2=Kesselring|first2=J.|date=Apr 2002|title=Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis|url=https://www.ncbi.nlm.nih.gov/pubmed/11990874|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=8|issue=2|pages=161–168|doi=10.1191/1352458502ms779oa|issn=1352-4585|pmid=11990874}}</ref><ref>{{Cite news|url=https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise-and-chronic-disease/art-20046049|title=What you need to know about exercise and chronic disease|work=Mayo Clinic|access-date=2018-10-10|language=en}}</ref><ref>{{Cite journal|last=Dunn|first=A. L.|last2=Trivedi|first2=M. H.|last3=O'Neal|first3=H. A.|date=June 2001|title=Physical activity dose-response effects on outcomes of depression and anxiety|url=https://www.ncbi.nlm.nih.gov/pubmed/11427783|journal=Medicine and Science in Sports and Exercise|volume=33|issue=6 Suppl|pages=S587–597; discussion 609–610|issn=0195-9131|pmid=11427783}}</ref> the opposite is true for ME/CFS patients for whom even minimal exertion can cause a symptom flare-up.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Almond|first2=Freya|last3=De Becker|first3=Pascale|last4=Truijen|first4=Steven|last5=Paul|first5=Lorna|date=May 2008|title=Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial|url=https://www.ncbi.nlm.nih.gov/pubmed/18441039|journal=Clinical Rehabilitation|volume=22|issue=5|pages=426–435|doi=10.1177/0269215507084410|issn=0269-2155|pmid=18441039}}</ref> Because recovery is often prolonged,<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> lasting days or sometimes weeks to months,<ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> patients refer to these post-exertional setbacks as ‘crashes’.<ref>{{Cite news|url=https://www.healthrising.org/the-community-reports-best-practices-on-managing-thriving-with-or-just-surviving-chronic-fatigue-syndrome-mecfs/how-to-best-recover-from-a-crash-the-mecfs-community-reports/|title=How to Best Recover From a Crash: the ME/CFS Community Reports|work=Health Rising|access-date=2018-10-10|language=en-US}}</ref><ref name=":28" /> Depending on the criteria a patient meets ([[Systemic Exertion Intolerance Disease]] (SEID) for ME/CFS's [[Systemic Exertion Intolerance Disease#Diagnostic criteria| minimum core symptoms]], the [[Canadian Consensus Criteria]] (CCC) for [[Canadian Consensus Criteria#Definition| this criterion's ME/CFS symptoms]], or the [[International Consensus Criteria]] (ICC) for [[myalgic encephalomyelitis]] (ME) and [[International Consensus Criteria#Criteria|its ME symptoms]]) will correlate with the patient's symptoms that will worsen.

PEM can be caused by [[Exertion#Exertion in ME.2FCFS|physical as well as mental exertion]]<ref name=":14" /> and the symptom complex it invokes does not necessarily relate to the initial trigger.<ref name=":3" /> ME/CFS patients suffer from a post-exertional [[Flu-like symptoms|flu-like feeling,]]<ref name=":1" /> with [[brain fog|brain fog,]]<ref name=":13" /> [[photophobia]] and other symptoms not usually reported after exertion.<ref name=":3" /> In contrast to most forms of exercise intolerance, the onset of PEM is frequently delayed<ref name=":15" /> with many patients reporting the height of their symptom flare-up, two<ref name=":13" /> or several days after the initial trigger.

It is important to understand that in [[pediatric]] cases of ME/CFS, children do not describe having PEM. They can experience a relapse from exertion, perhaps from just taking the school bus, having to spend prolonged periods in bed.<ref>[https://www.me-pedia.org/wiki/Pediatric_myalgic_encephalomyelitis_and_chronic_fatigue_syndrome ME/CFS in Children - by David S. Bell - David Bell - Open Medicine Foundation - June 25, 2016]</ref>

[[File:Cfs woman sketch.jpg|435x435px|thumb|Post-exertional malaise (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]
The distinctive characteristics of post-exertional malaise are confirmed by scientific research. Exertion induces abnormalities in [[Cognitive dysfunction|cognitive functioning,]]<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=October 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781|via=}}</ref><ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref> [[immune activation|immune activation,]]<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723|issue=|quote=|author-link=Jo Nijs|author-link2=Andrea Nees|author-link3=Lorna Paul|author-link4=Margot De Kooning|author-link5=Kelly Ickmans|via=|author-link6=Mira Meeus|author-link7=Jessica Van Oosterwijck}}</ref> [[gene expression]]<ref name=":20">{{Cite journal|last=Light|first=Alan R.|last2=White|first2=Andrea T.|last3=Hughen|first3=Ronald W.|last4=Light|first4=Kathleen C.|date=Oct 2009|title=Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects|url=http://dx.doi.org/10.1016/j.jpain.2009.06.003|journal=The Journal of Pain|volume=10|issue=10|pages=1099–1112|doi=10.1016/j.jpain.2009.06.003|issn=1526-5900}}</ref><ref name=":21">{{Cite journal|last=Light|first=A. R.|last2=Bateman|first2=L.|last3=Jo|first3=D.|last4=Hughen|first4=R. W.|last5=VanHaitsma|first5=T. A.|last6=White|first6=A. T.|last7=Light|first7=K. C.|date=2011-07-13|title=Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome|url=http://dx.doi.org/10.1111/j.1365-2796.2011.02405.x|journal=Journal of Internal Medicine|volume=271|issue=1|pages=64–81|doi=10.1111/j.1365-2796.2011.02405.x|issn=0954-6820}}</ref><ref>{{Cite journal|last=Meyer|first=Jacob D.|last2=Light|first2=Alan R.|last3=Shukla|first3=Sanjay K.|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron J.|last7=Cook|first7=Dane B.|date=Oct 2013|title=Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression|url=http://dx.doi.org/10.1080/21641846.2013.838444|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|issue=4|pages=190–209|doi=10.1080/21641846.2013.838444|issn=2164-1846}}</ref><ref>{{Cite journal|last=White|first=A. T.|last2=Light|first2=A. R.|last3=Hughen|first3=R. W.|last4=VanHaitsma|first4=T. A.|last5=Light|first5=K. C.|date=2011-12-30|title=Differences in Metabolite-Detecting, Adrenergic, and Immune Gene Expression After Moderate Exercise in Patients With Chronic Fatigue Syndrome, Patients With Multiple Sclerosis, and Healthy Controls|url=http://dx.doi.org/10.1097/psy.0b013e31824152ed|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/psy.0b013e31824152ed|issn=0033-3174}}</ref> and [[endogenous pain inhibition]]<ref name=":22">{{Cite journal|last=Whiteside|first=Alan|last2=Hansen|first2=Stig|last3=Chaudhuri|first3=Abhijit|date=Jun 2004|title=Exercise lowers pain threshold in chronic fatigue syndrome|url=http://dx.doi.org/10.1016/j.pain.2004.02.029|journal=Pain|volume=109|issue=3|pages=497–499|doi=10.1016/j.pain.2004.02.029|issn=0304-3959}}</ref><ref name=":23">{{Cite journal|last=Meeus|first=M|last2=Roussel|first2=NA|last3=Truijen|first3=S|date=2010|title=Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: An experimental study|url=http://dx.doi.org/10.2340/16501977-0595|journal=Journal of Rehabilitation Medicine|volume=42|issue=9|pages=884–890|doi=10.2340/16501977-0595|issn=1650-1977}}</ref><ref name=":24">{{Cite journal|last=Van Oosterwijck|first=J.|last2=Nijs|first2=J.|last3=Meeus|first3=M.|last4=Lefever|first4=I.|last5=Huybrechts|first5=L.|last6=Lambrecht|first6=L.|last7=Paul|first7=L.|date=2010-03-03|title=Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: An experimental study|url=http://dx.doi.org/10.1111/j.1365-2796.2010.02228.x|journal=Journal of Internal Medicine|volume=268|issue=3|pages=265–278|doi=10.1111/j.1365-2796.2010.02228.x|issn=0954-6820|quote=|author-link=Jessica Van Oosterwijck|author-link2=Jo Nijs|author-link3=Mira Meeus|author-link4=|author-link5=|via=|author-link7=Lorna Paul}}</ref> in ME/CFS patients that were not seen before exertion or in healthy controls. Most importantly PEM can be demonstrated by a [[Two-day cardiopulmonary exercise test|2-day cardiopulmonary exercise test]] (CPET) procedure.<ref name=":16" /><ref name=":28" /> On the second day [[Two-day cardiopulmonary exercise test|CPET]], ME/CFS patients display a significant drop in [[VO2 max]] and [[maximal workload]], that is not seen in healthy controls or other diseases.<ref>{{Cite journal|last=Snell|first=C. R.|last2=Stevens|first2=S. R.|last3=Davenport|first3=T. E.|last4=Van Ness|first4=J. M.|date=2013-06-27|title=Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome|url=http://dx.doi.org/10.2522/ptj.20110368|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=0031-9023}}</ref><ref>{{Cite journal|last=Vermeulen|first=Ruud CW|last2=Kurk|first2=Ruud M|last3=Visser|first3=Frans C|last4=Sluiter|first4=Wim|last5=Scholte|first5=Hans R|date=2010|title=Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity|url=http://dx.doi.org/10.1186/1479-5876-8-93|journal=Journal of Translational Medicine|volume=8|issue=1|pages=93|doi=10.1186/1479-5876-8-93|issn=1479-5876}}</ref><ref name=":17" /><ref>{{Cite journal|last=Vanness|first=J. Mark|last2=Snell|first2=Christopher R.|last3=Stevens|first3=Staci R.|date=Jan 2007|title=Diminished Cardiopulmonary Capacity During Post-Exertional Malaise|url=http://dx.doi.org/10.1300/j092v14n02_07|journal=Journal of Chronic Fatigue Syndrome|volume=14|issue=2|pages=77–85|doi=10.1300/j092v14n02_07|issn=1057-3321}}</ref><ref name=":18" /> These objective measures track strongly with the presence, severity and duration of PEM.<ref name=":0" /> [[Brian Vastag]] won a groundbreaking long term disability (LTD) claim using CPET to prove his PEM was a severe disabling symptom.<ref>[US District Court of NJ: Brian Vastag v. Prudential Insurance Company of America, Civ.15-6197 (KSH), (CLW) https://t.co/Vq9GXo4VEI]</ref><ref>{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-02}}</ref>

A 2015 review of the literature by the [[National Academy of Medicine]] (NAM) concluded there to be “sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS from other conditions.”<ref name=":0" /> Disagreement exists however on the precise nature of PEM and how it should be defined,<ref name=":19">{{Cite journal|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth|last3=So|first3=Suzanna|last4=Scott|first4=Jilian|last5=Brown|first5=Abigail|date=2015|title=Problems in Defining Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295644/|journal=Journal of prevention & intervention in the community|volume=43|issue=1|pages=20–31|doi=10.1080/10852352.2014.973239|issn=1085-2352|pmc=4295644|pmid=25584525}}</ref> with some diagnostic criteria emphasizing [[Paresis|muscle weakness]] and others a more a general form of [[fatigue]] and exhaustion.<ref name=":8">{{Cite journal|last=McManimen|first=Stephanie L.|last2=Sunnquist|first2=Madison L.|last3=Jason|first3=Leonard A.|date=2016-08-24|title=Deconstructing post-exertional malaise: An exploratory factor analysis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/|journal=Journal of health psychology|doi=10.1177/1359105316664139|issn=1359-1053|pmc=5325824|pmid=27557649}}</ref>

The [[Centers for Disease Control and Prevention]] (CDC) outline different types of exertion that may trigger PEM and how it impacts patients noting some may be house-bound or completely bed-bound during a crash. "People with ME/CFS may not be able to predict what will cause a crash or how long it will last."<ref name=":32">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-11-21}}</ref> Examples of PEM given by the CDC are: attending a child’s school event may leave a patient house-bound for a couple of days unable to do needed tasks, like laundry; grocery shopping may cause a crash that requires a nap in the car before driving home or a call for a ride home; a shower may leave a patient bed-bound and unable to do anything for days; keeping up with work may lead to spending evenings and weekends recovering.<ref name=":32" />

== PEM described by Dr. David Kaufman ==
{{#ev:youtube|https://www.youtube.com/watch?v=RC9TjgE_PlU|400|right|'''PEM described by Dr. David Kaufman''' (2018) Kaufman/''Unrest'' Video begins @2:16 and PEM is described until @3:35|frame|start=136&rel=0&autoplay=0}}

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

(Video begins @2:16 and PEM is described until @3:35. View entire 11:47 for a full description of ME/CFS)

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Patients' description==
[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]
[[File:PEM.JPG|300px|thumb|right|#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with [[Neurally mediated hypotension|high pulse and very low energy]]. Even though you sometimes can see the exhaustion in someone's face, most [[List of symptoms in ME CFS|ME symptoms]] are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaise<ref>{{Cite web|url=https://twitter.com/ezchili/status/1085927134248488965|title=#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with high pulse and very low energy. Even though you sometimes can see the exhaustion in someone's face, most ME symptoms are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaisepic.twitter.com/FKSTo8W0hH|last=ez 📎|date=2019-01-17|website=@ezchili|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM2.JPG|300px|thumb|right|#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.<ref>{{Cite web|url=https://twitter.com/kaisecam/status/1085886323276349440|title=#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.pic.twitter.com/nTJVG63jRm|last=Kaise 🥄|first=Mx|date=2019-01-17|website=@kaisecam|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM3.JPG|300px|thumb|right|#TwoFacesofME Workday me v’s weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.<ref>{{Cite web|url=https://twitter.com/RachelFrancis/status/1085940724774912000|title=#TwoFacesofME Workday me vs weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.pic.twitter.com/qZNiQaVHyD|last=Francis|first=Rachel|date=2019-01-17|website=@RachelFrancis|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

[[File:PEM6.JPG|300px|thumb|right|What the [world] don’t [see] two faces of M.E.<ref>{{Cite web|url=https://twitter.com/SharonTiday/status/1085122891220430848|title=What the don’t two faces of M.E.pic.twitter.com/DYZVhtyrG5|last=Awareness|first=CFDA #|date=2019-01-15|website=@SharonTiday|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM7.JPG|300px|thumb|right|Joining #pwME sharing #TwoFacesofME for #MEAwareness 1: a fall day when I got outside (but ended up in bed a week) 2: what no one sees (constant [[Chronic pain|pain]], post exertional malaise & [[Sleep dysfunction|sleep deprivation]]) Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)<ref>{{Cite web|url=https://twitter.com/ceibakoru/status/1085894325832040448|title=Joining #pwME sharing #TwoFacesofME for #MEAwareness, 1: a fall day when I got outside (but ended up in bed a week), 2: what no one sees (constant pain, post exertional malaise & sleep deprivation). Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)pic.twitter.com/EpsMLT8E11|last=Ceiba 🌳Koru 🌀|date=2019-01-17|website=@ceibakoru|language=en|access-date=2019-01-17}}</ref>]]

=== An illness within an illness ===

PEM refers to a worsening of many ME/CFS symptoms as a result of physical or mental exertion. It consists of more than post-exertional fatigue and can cause severe debility. As one patient described it: <blockquote>“When I do any activity that goes beyond what I can do—I literally collapse—my body is in major pain, it hurts to lay in bed, it hurts to think, I can’t hardly talk—I can’t find the words, I feel my insides are at war.”<ref name=":0" /></blockquote> Another patient emphasized that the feeling of PEM is very different from what one experiences as a healthy person: <blockquote>"PEM is like nothing else you will experience in healthy life; a combination of a hangover, the flu, finishing a 10k run, all at the same time at varying levels of severity."<ref>{{Cite news|url=https://twitter.com/Fatigo_MECFS/status/1050305665565102080|title=Fatigo_MECFS on Twitter|work=Twitter|access-date=2018-10-11|language=en}}</ref></blockquote>Considering the serious but fluctuating debility PEM causes, ME/CFS expert Dr. [[Anthony Komaroff]] described it as “an illness within an illness”.<ref>{{Cite news|url=https://phoenixrising.me/archives/11884|title=Post-Exertional Malaise II: Perception and Reality By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref>

=== Energy conservation and pacing ===
Patients often report the feeling of a red line, an energy level that if exceeded, will result in a relapse. As one [[Norway|Norwegian]] patient described: <blockquote>“....And suddenly it is just too much. The body turns itself off, as if it has gone on strike. You have pushed too much for too long, it repeats itself, and the body stops functioning.”<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>Energy conservation strategies such as [[pacing]] and the [[Energy Envelope Theory|envelope theory]] have been developed to minimize PEM while allowing patients to stay as active as possible.<ref>{{Cite journal|last=Goudsmit|first=Ellen M.|last2=Nijs|first2=Jo|last3=Jason|first3=Leonard A.|last4=Wallman|first4=Karen E.|date=2012|title=Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document|url=https://www.ncbi.nlm.nih.gov/pubmed/22181560|journal=Disability and Rehabilitation|volume=34|issue=13|pages=1140–1147|doi=10.3109/09638288.2011.635746|issn=1464-5165|pmid=22181560}}</ref> These techniques advise patients to balance energy availability and expenditure and to recognize early signs of PEM so they can reduce activity levels before a relapse occurs.

== History ==

=== Case definitions ===
Early descriptions of symptom exacerbation in [[Myalgic encephalomyelitis|ME]] focused on post-exertional muscle weakness. Renowned ME-expert [[Melvin Ramsay]] for example wrote: <blockquote>"[[Muscle fatigability]] whereby, even after a minor degree of physical effort, three, four or five days or longer elapse before full [[muscle]] power is restored is unique and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME."<ref name=":10">Ramsay M. (1988). Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease. Gower Medical Publishing. Second edition.</ref> </blockquote>In a 1985 study [[Peter Behan|Behan]] et al. noted that all of their patients “had the same primary symptom that of gross fatigue made worse by exercise".<ref>{{Cite journal|last=Behan|first=P. O.|last2=Behan|first2=W. M.|last3=Bell|first3=E. J.|date=May 1985|title=The postviral fatigue syndrome - an analysis of the findings in 50 cases|url=https://www.ncbi.nlm.nih.gov/pubmed/2993423|journal=The Journal of Infection|volume=10|issue=3|pages=211–222|issn=0163-4453|pmid=2993423}}</ref>

'''Formerly used to define Chronic fatigue syndrome'''

In the 1988 [[Holmes criteria|Holmes definition]] of [[Chronic fatigue syndrome|CFS]], unexplained generalized muscle weakness was one of the 11 minor symptoms, yet it was fatigue that set the tone. Another minor symptom referred to “prolonged (24 hours or greater) generalized fatigue after levels of [[exercise]] that would have been easily tolerated in the patient’s premorbid state”.<ref>{{Cite journal|last=Holmes|first=G. P.|last2=Kaplan|first2=J. E.|last3=Gantz|first3=N. M.|last4=Komaroff|first4=A. L.|last5=Schonberger|first5=L. B.|last6=Straus|first6=S. E.|last7=Jones|first7=J. F.|last8=Dubois|first8=R. E.|last9=Cunningham-Rundles|first9=C.|date=Mar 1988|title=Chronic fatigue syndrome: a working case definition|url=https://www.ncbi.nlm.nih.gov/pubmed/2829679|journal=Annals of Internal Medicine|volume=108|issue=3|pages=387–389|issn=0003-4819|pmid=2829679}}</ref> PEM is not a mandatory symptom under the Holmes definition.

The wording post-exertional malaise was first used in one of the 8 minor symptoms in the 1994 [[Fukuda criteria]], but without further clarification of the term, except that it lasts more than 24 hours. PEM is not a mandatory symptom under the Fukuda criterion.

'''Currently disputed to define Chronic fatigue syndrome'''

The [[Oxford criteria]] is flawed as it does not list PEM as a symptom. Patients with the symptom of [[fatigue]], which many illnesses and diseases have, are swept into the diagnosis and research studies. ''The Argus Report'' article ''US NIH Report Calls for UK Definition of ME/CFS to be Scrapped'' wrote the following:<blockquote> The [[United States]] [[National Institutes of Health]] (NIH) has issued a draft report that highlights the dire need for scientific research that will help find a cure for the millions of people suffering from [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS) worldwide. The report also highlights the fact that the decades-old UK Royal Society of Medicine’s Oxford criteria for ME/CFS are severely “flawed,” and that continuing to use these criteria may “cause harm.” Further, the NIH report says that the Royal Society definition should “be retired” and replaced with a single case definition agreed to by the ME/CFS community.<ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref></blockquote>There are further criticisms [https://www.me-pedia.org/wiki/Oxford_criteria#Criticisms here].

'''Currently used to define ME/CFS'''

In 2003, [[Canadian Consensus Criteria]] (CCC) PEM became a recognized symptom for the diagnosis of ME/CFS. The CCC were the first criteria to stress that the onset of PEM could be delayed and to describe its debility as a flu-like distress.<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|last2=Jain|first2=Anil Kumar|last3=De Meirleir|first3=Kenny L.|last4=Peterson|first4=Daniel L.|last5=Klimas|first5=Nancy G.|last6=Lerner|first6=A. Martin|last7=Bested|first7=Alison C.|last8=Flor-Henry|first8=Pierre|last9=Joshi|first9=Pradip|date=Jan 2003|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v11n01_02|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=11|issue=1|pages=7–115|doi=10.1300/j092v11n01_02|issn=1057-3321}}</ref> [[Canadian Consensus Criteria#Definition|PEM and/or post-exertional fatigue]] is a mandatory symptom under the CCC criterion.<ref>{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|date=|website=investinme.org|page=4|type=|archive-url=|archive-date=|dead-url=|access-date=|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref>

The 2015 report of the [[National Academy of Medicine]] (NAM) describes PEM more generally as “an exacerbation of some or all of an individual’s ME/CFS symptoms that occurs after physical or cognitive exertion and leads to a reduction in functional ability.” The report confirmed PEM as the hallmark symptom of ME/CFS and advised to rename the disease accordingly to [[Systemic Exertion Intolerance Disease]] (SEID).<ref name=":0" /> PEM is a mandatory symptom under the SEID criterion.

'''Currently used to define Myalgic encephalomyelitis'''

In 2011, the [[International Consensus Criteria]] (ICC) introduced the new term '''Post-Exertional Neuro-immune Exhaustion (PENE)''' to refer to the characteristic exercise and exertion intolerance of [[myalgic encephalomyelitis]] (ME) patients. It notes a delayed onset and prolonged recovery, and uses acute [[flu-like symptoms]] to describe PENE. By definition PENE results in a substantial reduction in functioning, as even simple activities of daily living can cause a relapse.<ref name=":2">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> PENE is a mandatory symptom under the ICC criterion.

===Dismissed as disturbed effort perceptions or kinesiophobia ===
[[File:Brian vastag.png|thumb|right|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]
The existence of PEM as a distinctive and complex symptom of ME/CFS has been dismissed in early research into the disease. Some interpreted it as just fatigue after exercise<ref>https://www.cdc.gov/me-cfs/pdfs/symptom-inventory-questionnaire-508.pdf</ref>, while others saw it as an artifact of disturbed effort perceptions<ref>{{Cite journal|last=Lawrie|first=S. M.|last2=Machale|first2=S. M.|last3=Power|first3=M. J.|last4=Goodwin|first4=G. M.|date=Sep 1997|title=Is the chronic fatigue syndrome best understood as a primary disturbance of the sense of effort?|url=https://www.cambridge.org/core/journals/psychological-medicine/article/editorial-is-the-chronic-fatigue-syndrome-best-understood-as-a-primary-disturbance-of-the-sense-of-effort/434A5EB2C5B4F971A4A36C1DC3400A7E|journal=Psychological Medicine|language=en|volume=27|issue=5|pages=995–999|issn=1469-8978}}</ref><ref>{{Cite journal|last=Rosen|first=S D|last2=King|first2=J C|last3=Wilkinson|first3=J B|last4=Nixon|first4=P G|date=Dec 1990|title=Is chronic fatigue syndrome synonymous with effort syndrome?|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292947/|journal=Journal of the Royal Society of Medicine|volume=83|issue=12|pages=761–764|issn=0141-0768|pmc=1292947|pmid=2125315}}</ref><ref>{{Cite journal|last=Wallman|first=Karen E.|last2=Sacco|first2=Paul|date=Jan 2007|title=Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17365951|journal=Research in Sports Medicine|volume=15|issue=1|pages=47–59|doi=10.1080/15438620601184331|issn=1543-8627|pmid=17365951}}</ref> or an irrational fear of movement<ref>{{Cite journal|last=Silver|first=A.|last2=Haeney|first2=M.|last3=Vijayadurai|first3=P.|last4=Wilks|first4=D.|last5=Pattrick|first5=M.|last6=Main|first6=C. J.|date=Jun 2002|title=The role of fear of physical movement and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12069873|journal=Journal of Psychosomatic Research|volume=52|issue=6|pages=485–493|issn=0022-3999|pmid=12069873}}</ref><ref>{{Cite journal|last=Fischler|first=B.|last2=Dendale|first2=P.|last3=Michiels|first3=V.|last4=Cluydts|first4=R.|last5=Kaufman|first5=L.|last6=De Meirleir|first6=K.|date=Apr 1997|title=Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology|url=https://www.ncbi.nlm.nih.gov/pubmed/9160276|journal=Journal of Psychosomatic Research|volume=42|issue=4|pages=369–378|issn=0022-3999|pmid=9160276}}</ref>. One example of this is the [http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf Tampa scale kinesiophobia], adapted for [[chronic fatigue syndrome]]. Some of the questions in this scale ask about the experience of PEM such as: “If I were to try to overcome it, my symptoms would increase” or “my symptoms let me know when to stop exercising so that I do not harm myself”. Yet these symptoms are classified as an indicator of irrational fear of movement and exercise, instead of PEM.<ref>{{Cite web|url=http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf|title=Tampa Scale Kinesiophobia - Version Chronic Fatigue Syndrome|last=Nijs|first=J|last2=De Meirleir|first2=K|date=2004|website=painmotion.be|publisher=Archives of Physical Medicine and Rehabilitation|archive-url=|archive-date=|dead-url=|access-date=|last3=Duquet|first3=W}}</ref>

=== Critique of the term ===
The name post-exertional malaise was introduced by the 1994 Fukuda criteria and had no prior medical meaning attached to it.<ref name=":3">{{Cite journal|last=Chu|first=Lily|last2=Valencia|first2=Ian J.|last3=Garvert|first3=Donn W.|last4=Montoya|first4=Jose G.|date=2018|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey|url=https://www.ncbi.nlm.nih.gov/pubmed/29856774|journal=PloS One|volume=13|issue=6|pages=e0197811|doi=10.1371/journal.pone.0197811|issn=1932-6203|pmc=5983853|pmid=29856774|quote=|author-link=Lily Chu|author-link2=Ian Valencia|author-link3=Donn Gavert|author-link4=Jose Montoya|author-link5=|via=}}</ref> While in the scientific literature, the term has become the standard to describe the relapses ME/CFS patients suffer after exertion, patients argue that it trivializes their experience. The term malaise after all refers to “a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify”<ref>{{Cite web|url=https://en.oxforddictionaries.com/definition/malaise|title=Definition of malaise in English by Oxford Dictionaries|website=Oxford Dictionaries {{!}} English|access-date=2018-10-13}}</ref>. Doctor of [http://sph.berkeley.edu/ Public Health at Berkely], [[David Tuller]], calls post-exertional malaise a “complete misnomer” arguing what ME/CFS patients experience "is much closer to a serious crash or relapse than a Victorian fainting spell.”<ref>{{Cite web|url=http://www.virology.ws/2011/11/23/chronic-fatigue-syndrome-and-the-cdc-a-long-tangled-tale/|title=Chronic Fatigue Syndrome and the CDC: A Long, Tangled Tale|website=www.virology.ws|language=en-US|access-date=2018-10-10}}</ref> ME/CFS patients usually use the abbreviation PEM or the term ‘crash’ to describe their relapses.

== The distinctive characteristics of PEM ==
Four aspects differentiate the post-exertional malaise of ME/CFS patients from the exercise intolerance commonly reported in patients suffering from [[deconditioning]] or other conditions.

=== Timing ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertional Malaise: History, Characteristics, Evidence'' (2015) By Dr. Lily Chu/Solve CFS">https://www.youtube.com/watch?v=hxJPrkWHcBo</embedvideo>
First of all, there is the time lapse. While physical complaints are usually reported during or shortly after exercise, PEM often has a delayed onset, hours or sometimes even days after the original trigger. Yoshiuchi et al. for example wrote that: “after a briefer maximal exercise task, reports of worsening CFS symptoms were inconsistent or absent until 5 days after the challenge, a pattern not typically observed in real life.”<ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> The authors noted that this delay could be used to distinguish ME/CFS from other fatiguing illness. Another study from Stanford University showed that in up to 37% of the 150 ME/CFS patients studied, PEM may not begin until a day or more after an [[Exertion|exertional]] trigger.<ref name=":3" />

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about PEM and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

Patients may not be familiar with this characteristic of their relapses, since it is very counter-intuitive. As one patient noted:<blockquote>"It's really counter-intuitive to feel bad after a delay of 24 hours after exertion. It may take quite some time before people even make that connection, if ever. I only noticed it about three years in, and I hesitated to mention to others because I thought it might make me sound nuts."<ref name=":5">{{Cite news|url=https://www.s4me.info/threads/s4me-submission-to-the-public-review-on-common-data-elements-for-me-cfs-concerns-with-the-proposed-measure-of-post-exertional-malaise.2220/|title=S4ME: Submission to the public review on Common Data Elements for ME/CFS: Concerns with the proposed measure of post-exertional malaise|work=Science for ME|access-date=2018-10-10|language=en-US}}</ref></blockquote>Another time-related characteristic of PEM is a prolonged recovery period. In a 2010 study 25 M/CFS patients and 23 matched controls were followed up for seven days after performing a maximal cardiopulmonary exercise test. After two days, all controls subjects were recovered while only one ME/CFS patient was. Most (60%) of the ME/CFS participants reported that it took more than five days to fully recover from the test and many reported feeling at their worst 24 to 48 hours after the test.<ref name=":9">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health |volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> Other studies have found the same prolonged recovery period in ME/CFS patients after exertion. A Dutch study for example noted: <blockquote>"For CFS patients, daily observed fatigue was increased up to 2 days after the exercise test. For controls, self-observed fatigue returned to baseline after 2 h."<ref>{{Cite journal|last=Bazelmans|first=Ellen|last2=Bleijenberg|first2=Gijs|last3=Voeten|first3=Marinus J. M.|last4=van der Meer|first4=Jos W. M.|last5=Folgering|first5=Hans|date=Oct 2005|title=Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16223622|journal=Journal of Psychosomatic Research|volume=59|issue=4|pages=201–208|doi=10.1016/j.jpsychores.2005.04.003|issn=0022-3999|pmid=16223622|quote=|author-link=Ellen Bazelmans|author-link2=Gijs Bleijenberg|author-link3=Marinus Voeten|author-link4=Jos van der Meer|author-link5=Hans Folgering|via=}}</ref></blockquote>[[Charles Lapp|Lapp]] et al. followed 31 ME/CFS patients for 12 days after performing a maximal exercise test of 8-10 minutes. The average relapse lasted 8,82 days, although 22% of patients were still in relapse when the study ended at 12 days.<ref>{{Cite journal|last=Lapp|first=C. W.|date=Jul 1997|title=Exercise limits in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9236491|journal=The American Journal of Medicine|volume=103|issue=1|pages=83–84|issn=0002-9343|pmid=9236491}}</ref> In the Stanford study by [[Lily Chu|Chu]] et al. 87% of respondents indicated that they endure PEM for 24 hours or more. The authors concluded: <blockquote>"In many medical conditions, exertion-exacerbated symptoms usually start during exertion or immediately after and usually resolve immediately or shortly after exertion stops. In contrast, PEM may not start until hours or even days after the trigger starts or has been removed, may peak after the first day, and may not stop until hours to months later. This characteristic of PEM often leads patients and clinicians to believe that symptom exacerbations are random rather than associated with a trigger; most people will not intuit that symptoms are caused by a trigger that occurred hours to days prior unless specifically asked by their clinicians to pay attention."<ref name=":3" /> </blockquote>

=== Type of symptoms ===
The second characteristic of PEM is the [[List of symptoms in ME CFS|type of symptoms reported]]. The [[Canadian Consensus Criteria]], a 2003 clinical guideline formed by experts in the field, underlines that many PEM symptoms are [[Immune system|immune-related]]: <blockquote>"The [[malaise]] that follows exertion is difficult to describe but is often reported to be similar to the generalized [[pain]], discomfort and fatigue associated with the acute phase of [[influenza]]. Delayed malaise and fatigue may be associated with signs of immune activation: [[sore throat]], lymph glandular tenderness and/or [[Swollen lymph nodes|swelling]], general malaise, increased pain or [[Brain fog|cognitive fog]]."<ref name=":1" /> </blockquote>[[Mark VanNess|Van Ness]] et al. noted how [[Cognitive dysfunction|cognitive difficulties]] after exertion differentiate ME/CFS patients from healthy controls: <blockquote>"Another interesting difference between groups was the reported symptom of [[cognitive dysfunction]], for example, ‘‘[[Brain fog|brain-fog]]’’ or ‘‘difficulty concentrating.’’ Problems of this nature were not reported by any of the control subjects, whereas 12 patients (48%) experienced these problems: “Carrying on conversations was hard.” “Can’t think straight.” “My mind was not clear.”<ref name=":9" /></blockquote>This was elaborated by [[Lily Chu|Chu]] et al., the research team who conducted the first in-depth investigation on how ME/CFS patients describe their PEM: <blockquote>"There exists no medical condition the authors are familiar with where exertion or emotional distress causes immune/ [[Inflammation|inflammatory]]-related symptoms like sore throat, tender lymph nodes, or flu-like feelings, yet 60% and 36% of our subjects, respectively, reported these symptoms with either stimuli and about a quarter experienced all 3 with exertion. Conversely, symptoms typically associated with physical exertion in other conditions, like [[Dyspnea|shortness of breath]] or [[chest pain]] in [[chronic lung]] or [[heart disease]], are rarely reported in ME/CFS. Furthermore, it is well-established that physical activity improves [[Mood swings|mood]], [[Sleep dysfunction|sleep]], and pain in both healthy people as well those with chronic illnesses like depression or anxiety yet our subjects report worsened sleep, mood, and pain with physical activity."<ref name=":3" /></blockquote>

=== Triggers ===
A third characteristic of PEM is that it can be elicited by multiple triggers. Research has shown that ME/CFS patients experience PEM after both [[Exertion#Exertion in ME.2FCFS|physical and cognitive exertion]]. A 2014 study for example followed up on 32 ME/CFS patients after completing a battery of neurocognitive tests. As the authors concluded: “following a challenging cognitive demand, fatigue significantly increased two days after testing”, which was “suggestive of post-exertional symptom exacerbation following mental effort.”<ref name=":14">{{Cite journal|last=Arroll|first=Megan A.|last2=Attree|first2=Elizabeth A.|last3=O'Leary|first3=John M.|last4=Dancey|first4=Christine P.|date=2014-04-03|title=The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2014.892755|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=2|issue=2|pages=57–63|doi=10.1080/21641846.2014.892755|issn=2164-1846}}</ref> Commenting on the [https://www.me-pedia.org/wiki/1980-81_Ayrshire_outbreak outbreak in West Kilbride, Ayrshire], Ramsay remarked: <blockquote>“Once the disease was established the most characteristic symptom was extreme exhaustion, particularly after exercise. The exhaustion also occurred after emotional or mental strain.”<ref name=":10" /> </blockquote>Some other precipitants of PEM that have been reported include positional changes and exposure to excessive light or sounds<ref>{{Cite web|url=http://anilvanderzee.com/dance-hermit-16-vs-sumo-baby-part-1/|title=Dance hermit ’16 vs. Sumo Baby (part 1) {{!}} Anil van der Zee|website=anilvanderzee.com|language=en-GB|access-date=2018-10-13}}</ref>. While PEM was often thought of as symptom exacerbation after exercise, it is clear that for some ME/CFS patients even basic activities of daily living such as toileting, bathing, dressing, communicating, and reading can trigger relapses.<ref name=":11" /> As long time ME/CFS expert [[Jennie Spotila|Jennifer Spotila]] explained in a four-piece exploration of the phenomenon post-exertional malaise:<blockquote>“The use of the word ‘exertion’ may create the impression that PEM is triggered by strenuous or intense activity, but this is not the case […] Some patients need only attempt to make a simple meal or get dressed before PEM descends.”<ref>{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref></blockquote>This was confirmed by Chu et al. <blockquote>"[…] our results provide formal evidence supporting patient narratives, clinician experiences, and current case definitions which assert that even tasks like walking, cooking, or reading can provoke PEM."<ref name=":3" /> </blockquote>In some instances, the specific trigger of PEM cannot be identified.<ref name=":11">NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Post-Exertional Malaise Subgroup Draft Recommendations Public Review Comments Due January 31, 2018</ref>

=== Loss of functional capacity ===
A fourth distinctive element of PEM is often described as a loss of stamina and/or functional capacity. This refers to the results of the 2-day cardiopulmonary exercise test (CPET) procedure. A CPET is usually reproducible and normally has a test-retest difference of 7-12%<ref name=":16">{{Cite journal|last=Stevens|first=Staci|last2=Snell|first2=Chris|last3=Stevens|first3=Jared|last4=Keller|first4=Betsy|last5=VanNess|first5=J. Mark|date=2018|title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00242/full|journal=Frontiers in Pediatrics|language=English|volume=6|doi=10.3389/fped.2018.00242|issn=2296-2360}}</ref>. ME/CFS patients however show strikingly lower results on several measures at the second CPET compared to the first, despite meeting objective markers of maximal effort. These results have been replicated by several research teams, though there is inconsistency on which measure ([[VO2]] or maximal workload, at peak or ventilatory threshold), the decline in functional capacity is best represented.

{| class="wikitable"
! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS
|-
|
|Number of ME/CFS patients
|VO2 peak
|VO2 at VT
|Workload peak
|Workload at VT
|HR peak
|O2pulse at VT
|-
|[[Mark VanNess|VanNess]] et al. 2007.
|6
| -22%
| -26%
|?
|?
|?
|?
|-
|[[Vemeulen]] et al. 2010.
|15
| -6.3%
| -7.0%
| -5.3%
| -7.0%
| -1.9%
| -8.8%
|-
|[[Christopher Snell|Snell]] et al. 2013.
|51
| -5%
| -10.8%
| -7.2%
| -55.2%
|?
|?
|-
|[[Betsy Keller|Keller]] et al. 2014.
|22
| -13.8%
| -15.8%
| -12.5%
| -21.3%
| -5.9%
| -12.6%
|-
|[[Hodges]] et al. 2018.
|10
| +5.3%
| +6.1%
| -6.7%
| -11.4%
| -0.6%
|?
|}
The drop in functional capacity on the second CPET is usually not seen in other diseases. According to [[Betsy Keller|Keller]] et al. "ME/CFS patients currently represent a unique class of ill patients who do not reproduce maximal CPET measures, unlike individuals with cardiovascular disease, lung disease, end-stage renal disease pulmonary arterial hypertension and cystic fibrosis".<ref name=":17">{{Cite journal|last=Keller|first=Betsy A.|last2=Pryor|first2=John Luke|last3=Giloteaux|first3=Ludovic|date=2014-04-23|title=Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref> A preliminary study from [[New Zealand]] suggests that patients with MS do not display the same decline on the second day of exercise testing, as do patients with ME/CFS.<ref name=":18">{{Cite journal|last=Hodges|first=L. D.|last2=Nielsen|first2=T.|last3=Baken|first3=D.|date=Jul 2018|title=Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4|pages=639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref>

Questions have however been raised about the clinical use of the 2-day CPET procedure. [[Christopher Snell|Snell]] et al. suggested it might be unethical to use this method since many ME/CFS patients might suffer a serious relapse as a result of exercise performance.<ref>{{Cite journal|last=Snell|first=Christopher R.|last2=Stevens|first2=Staci R.|last3=Davenport|first3=Todd E.|last4=Van Ness|first4=J. Mark|date=Nov 2013|title=Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23813081|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=1538-6724|pmid=23813081}}</ref> Others have noted that the CPET- procedure is not practical either. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, may not be available to most clinicians.<ref name=":11" /> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref name=":7">{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref> For these reasons PEM is usually assessed using self-reporting questionnaires.

== Differentiation ==
Several studies have shown that PEM is the symptom of ME/CFS that best differentiates it from other diseases.

=== Healthy controls and idiopathic chronic fatigue ===
PEM was one of the symptoms in the CDC symptom inventory list that differentiated subjects with ME/CFS from those without the disease.<ref>{{Cite journal|last=Wagner|first=Dieter|last2=Nisenbaum|first2=Rosane|last3=Heim|first3=Christine|last4=Jones|first4=James F.|last5=Unger|first5=Elizabeth R.|last6=Reeves|first6=William C.|date=2005-07-22|title=Psychometric properties of the CDC Symptom Inventory for assessment of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16042777|journal=Population Health Metrics|volume=3|pages=8|doi=10.1186/1478-7954-3-8|issn=1478-7954|pmc=1183246|pmid=16042777}}</ref> It was also the highest loading factor among a data set of 38 measurements used for a principal component analysis of unexplained chronic fatigue.<ref>{{Cite journal|last=Vollmer-Conna|first=Uté|last2=Aslakson|first2=Eric|last3=White|first3=Peter D|date=Apr 2006|title=An empirical delineation of the heterogeneity of chronic unexplained fatigue in women|url=https://www.futuremedicine.com/doi/abs/10.2217/14622416.7.3.355|journal=Pharmacogenomics|language=en|volume=7|issue=3|pages=355–364|doi=10.2217/14622416.7.3.355|issn=1462-2416}}</ref> Data for this study came from the epidemiological study in Wichita, Kansas.

The other major epidemiological study, carried out in Chicago, also identified PEM as the hallmark symptom of ME/CFS. In a 10 year follow-up study on the 32 patients originally identified as having ME/CFS, all of the contacted patients reported post-exertional malaise at some point in time. This symptom was able to differentiate ME/CFS patients with those with [[idiopathic chronic fatigue]], those with exclusionary illnesses and healthy controls. According to the author: <blockquote>"Among all the variables in this study, only for post-exertional malaise did the CFS group significantly differ from the other three conditions. This reaffirms the importance of this being a cardinal and critical symptom for CFS."<ref>{{Cite journal|last=Jason|first=Leonard A.|date=Feb 2011|title=Natural History of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171164/|journal=Rehabilitation psychology|volume=56|issue=1|pages=32–42|doi=10.1037/a0022595|issn=0090-5550|pmc=3171164|pmid=21401284}}</ref> </blockquote>Using a large sample of ME/CFS patients from Newcastle, [[Norway]] and the [https://www.me-pedia.org/wiki/Solve_ME/CFS_Initiative#Biobank Solve ME/CFS Biobank], Jason et al. conducted an analysis of different case definitions and symptoms. The domain of post-exertional malaise was found to be most adequate at differentiating ME/CFS patients from controls. As the authors noted: <blockquote>Using the latent variables from the empiric criteria, only one factor (PEM) was needed to reach a sensitivity of 90.8%, specificity of 92.5% and accuracy of 91.6%, and this was the only data mining where all percentages were over 90%. […] the fact that PEM came out in all analyses supports the importance of this domain in the case definition.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Reed|first5=Jordan|last6=Furst|first6=Jacob|last7=Newton|first7=Julia L.|last8=Strand|first8=Elin Bolle|last9=Vernon|first9=Suzanne D.|date=2014-04-01|title=Comparing and Contrasting Consensus versus Empirical Domains|url=https://www.ncbi.nlm.nih.gov/pubmed/26977374|journal=Fatigue: Biomedicine, Health & Behavior|volume=3|issue=2|pages=63–74|doi=10.1080/21641846.2015.1017344|issn=2164-1846|pmc=4788637|pmid=26977374}}</ref> </blockquote>A 2014 examination, using 236 patients and 86 controls, showed that three symptoms accurately classified 95.4% of participants as patient or control: fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Sunnquist|first2=Madison|last3=Brown|first3=Abigail|last4=Evans|first4=Meredyth|last5=Vernon|first5=Suzanne D.|last6=Furst|first6=Jacob|last7=Simonis|first7=Valerie|date=2014-01-01|title=Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24511456|journal=Fatigue: Biomedicine, Health & Behavior|volume=2|issue=1|pages=40–56|doi=10.1080/21641846.2013.862993|issn=2164-1846|pmc=3912876|pmid=24511456}}</ref> Another data mining study by the same research group, suggested the selection of four symptoms: next to extreme tiredness, unrefreshing sleep and [[Word-finding problems|difficulty finding the right word to say]] or [[Aphasia|expressing thoughts]], PEM was once again represented with the item “physically drained/sick after mild activity.”<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Evans|first5=Meredyth|last6=Jantke|first6=Rachel|last7=Williams|first7=Yolonda|last8=Furst|first8=Jacob|last9=Vernon|first9=Suzanne D.|date=2015|title=Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Toward An Empirical Case Definition|url=https://www.ncbi.nlm.nih.gov/pubmed/26029488|journal=Health Psychology and Behavioral Medicine|volume=3|issue=1|pages=82–93|doi=10.1080/21642850.2015.1014489|issn=2164-2850|pmc=4443921|pmid=26029488}}</ref>

[[Michael Maes|Maes]] et al. divided ME/CFS patients into two groups: those with or without PEM lasting for more than 24 hours. Analysis showed this to be a meaningful division as the former group (45% of the sample) not only had higher symptom scores on concentration difficulties and a subjective experience of infection, but also higher markers of immune-activation such as [[Interleukin 1|IL-1]], [[TNFa]], [[lysozyme]] and [[neopterin]], than the CFS group without PEM. According to the authors their findings, "underscore the relevance of post-exertional malaise to identify a subgroup of CFS patients that should be diagnosed as ME".<ref>{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Johnson|first3=Cort|date=2012-12-30|title=Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data|url=https://www.ncbi.nlm.nih.gov/pubmed/22521895|journal=Psychiatry Research|volume=200|issue=2-3|pages=754–760|doi=10.1016/j.psychres.2012.03.031|issn=1872-7123|pmid=22521895}}</ref>

=== Multiple sclerosis ===
According to a 2015 report by the National Academy of Medicine, the prevalence of PEM among ME/CFS patients varies from 69 to 100%, which is much higher than in other disease groups.<ref name=":0" /> In a 1996 study by Komaroff et al. 13 of 25 MS-patients (52%) reported PEM<ref name=":12">{{Cite journal|last=Komaroff|first=A. L.|last2=Fagioli|first2=L. R.|last3=Geiger|first3=A. M.|last4=Doolittle|first4=T. H.|last5=Lee|first5=J.|last6=Kornish|first6=R. J.|last7=Gleit|first7=M. A.|last8=Guerriero|first8=R. T.|date=Jan 1996|title=An examination of the working case definition of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8579088|journal=The American Journal of Medicine|volume=100|issue=1|pages=56–64|issn=0002-9343|pmid=8579088}}</ref>, a figure similar to what Jason et al. found with the DSQ PEM subscale in a cohort of 106 MS-patients.<ref>{{Cite journal|last=Jason|first=L. A.|last2=Ohanian|first2=D.|last3=Brown|first3=A.|last4=Sunnquist|first4=M.|last5=McManimen|first5=S.|last6=Klebek|first6=L.|last7=Fox|first7=P.|last8=Sorenson|first8=M.|date=2017|title=Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29430570|journal=Insights in Biomedicine|volume=2|issue=2|doi=10.21767/2572-5610.10027|issn=2572-5610|pmc=5800741|pmid=29430570}}</ref> Both studies used a broad definition of PEM which focused on fatigue after exercise. Preliminary research suggests that adding more specific questions, for example about the prolonged recovery and various type of triggers, PEM might be able to differentiate ME/CFS from [[multiple sclerosis]]. A 2018 study for example showed that ME/CFS patients reported to experience PEM more often through mental exertion and to recover more slowly from PEM compared to multiple sclerosis patients.<ref name=":7" />
=== Major Depressive disorder ===
In the 1996 study by Komaroff et al., only 19% of patients with major [[depression]] reported PEM.<ref name=":12" /> A similar figure was found by Hawk et al., who found PEM in 3 patients in their sample of 15 with major depressive disorder.<ref>{{Cite journal|last=Hawk|first=Caroline|last2=Jason|first2=Leonard A.|last3=Torres-Harding|first3=Susan|date=2006|title=Differential diagnosis of chronic fatigue syndrome and major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/17078775|journal=International Journal of Behavioral Medicine|volume=13|issue=3|pages=244–251|doi=10.1207/s15327558ijbm1303_8|issn=1070-5503|pmid=17078775}}</ref> In contrast all of the 15 studied ME/CFS patients reported PEM, making it the largest discriminant function for all investigated symptoms. White et al. studied patients with persistent symptoms of fatigue and poor concentration after glandular fever. According to the authors "the complaint of post-exertional physical fatigue may help to differentiate post-viral fatigue states from psychiatric disorders."<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmed/8588010|title=The validity and reliability of the fatigue syndrome that follows glandular fever. - PubMed - NCBI|last=White|first=PD|website=www.ncbi.nlm.nih.gov|language=en|access-date=2018-10-24}}</ref>

=== Gulf war illness ===
[[James Baraniuk|Baraniuk]] and Shivapurkar (2017) looked at [[MicroRNA]]<nowiki/>s (miRNA) in the [[cerebrospinal fluid]] of ME/CFS patients, healthy controls and patients with [[Gulf War Illness]] before and after an exercise challenge (a submaximal bicycle exercise). While there were no differences in miRNA between the groups at baseline, a distinct signature appeared after exercise. According to the authors, "exercise caused distinct patterns of [[miRNA]] changes in CFS and […] [[Gulf War Illness|GWI]] indicating significant pathophysiological differences between conditions."<ref>{{Cite journal|last=Baraniuk|first=James N.|last2=Shivapurkar|first2=Narayan|date=2017-11-10|title=Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects|url=https://www.nature.com/articles/s41598-017-15383-9|journal=Scientific Reports|language=En|volume=7|issue=1|doi=10.1038/s41598-017-15383-9|issn=2045-2322}}</ref> A 2013 study under the guidance of [[Nancy Klimas]] compared the immune signature in 30 Gulf war patients, 22 ME/CFS patients and 30 controls, after an graded exercise test. Results indicated the importance of physical exercise for differentiating these different groups: <blockquote>"Common to both GWI and CFS illness signatures were the direct or indirect contributions of IL-10 and IL-23 expression though these occurred at very different times. While levels measured at rest supported an illness signature in GWI, their impact in CFS was only observable during and after exercise, again emphasizing the importance of a challenge and response timeline in distinguishing these illnesses."<ref>{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23800166|journal=BMC immunology|volume=14|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=3698072|pmid=23800166}}</ref></blockquote>

== Objective findings after exertion: ==
In the 1980s Melvin A. Ramsay stressed the use of assessing ME-patients after exertion. Regarding muscle weakness – what he regarded as the hallmark symptom of the disease –he noted: <blockquote>"If muscle power is found to be satisfactory, a re-examination should be made after exercise; a walk of half a mile is sufficient, as very few ME case can manage more. […] It is most important to stress the fact that cases of ME of mild or even moderate severity may have normal muscle power in a remission. In such cases, test for muscle power should be repeated after exercise."<ref name=":10" /> </blockquote>Though the definition of PEM has been expended far beyond muscle weakness, modern day research has confirmed the utility of testing ME/CFS after exertion. Many markers that are normal in resting state in ME/CFS patients turn out to be abnormal after a physical or cognitive stressor.<ref name=":0" />

=== Gene expression ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''72. Gene-expression and exercise / Gen-expressie en inspanning – dr. Lucinda Bateman'' (2015) By Dr. Lucinda Bateman/Wetenschap voor Patienten - ME/cvs Vereniging">https://https://www.youtube.com/watch?v=F1PP21TmUPs</embedvideo>

One example is gene expression. In a 2009 study Light et al. showed that after a moderate exercise test, the [[Leucocyte|leukocytes]] of ME/CFS patients showed an increase in expression of [[Adrenergic receptor|adrenergic]], [[metabolite]] detecting and [[immune-related genes]] that was not seen in healthy controls. Before the exercise test there were no abnormalities in the expression of these genes of ME/CFS patients. The authors speculated this to be evidence for sensitization of fatigue pathways in ME/CFS.<ref name=":20" /> The research team was able to confirm their results in a subsequent study using a larger sample of 48 patients.<ref name=":21" /> In a 2012 comparison MS patients also displayed an increase in post-exercise gene expression, but only ME/CFS patients showed increases in metabolite-detecting sensory receptors. According to the authors:<blockquote>"Because only the CFS patients showed increases in these metabolite-detecting receptors, the sensory receptor elements of this gene profile seem particularly specific to CFS and may reflect dysregulated pathways that directly contribute to increased effort sense during exercise and postexertional malaise."<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=VanHaitsma|first4=Timothy A.|last5=Light|first5=Kathleen C.|date=Jan 2012|title=Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/PSY.0b013e31824152ed|issn=0033-3174|pmc=3256093|pmid=22210239}}</ref></blockquote>Attempts at replication by other research teams have produced contradictory results. Meyer et al. were unable to confirm most of the post-exertional increases in gene expression, except for some in the adrenergic and glucocorticoid pathway.<ref>{{Cite journal|last=Meyer|first=Jacob|last2=R. Light|first2=Alan|last3=Shukla|first3=Sanjay|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron|last7=Cook|first7=Dane|date=2013-10-01|title=Post-exertion malaise in chronic fatigue syndrome: Symptoms and gene expression|url=https://www.researchgate.net/publication/258165434_Post-exertion_malaise_in_chronic_fatigue_syndrome_Symptoms_and_gene_expression|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|pages=190–209|doi=10.1080/21641846.2013.838444}}</ref> An [[Australia|Australian]] team under the guidance of [[Andrew Lloyd]] failed to find any significant exercise-induced changes in leucocyte gene expression, though the patient sample used (n = 10) was rather small and did not include any patients with severe [[functional disability]].<ref>{{Cite journal|last=Keech|first=Andrew|last2=Vollmer-Conna|first2=Ute|last3=Barry|first3=Benjamin K.|last4=Lloyd|first4=Andrew R.|date=2016|title=Gene Expression in Response to Exercise in Patients with Chronic Fatigue Syndrome: A Pilot Study|url=https://www.ncbi.nlm.nih.gov/pubmed/27713703|journal=Frontiers in Physiology|volume=7|pages=421|doi=10.3389/fphys.2016.00421|issn=1664-042X|pmc=5031769|pmid=27713703}}</ref>

=== Immune activation ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Inducing Post-Exertional Malaise in ME/CFS: A Look at the Research Evidence'' (2015) By Dr. Peter Rowe/Solve CFS">https://www.youtube.com/watch?v=ux93w7yGQ5g</embedvideo>
There are many studies demonstrating exercise-induced immunological abnormalities in ME/CFS patients.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723}}</ref> Most findings however still have to be replicated by other research groups, using larger samples.

==== Oxidative stress ====
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertion Malaise: The Intersection of Biology and Behavior'' (2015) By Dr. Dane B. Cook/Solve CFS">https://www.youtube.com/watch?v=vfmrPd4-rIE</embedvideo>
In 2005 the French team Yammes et al. found a lengthened and accentuated oxidative stress response in ME/CFS patients after a cycling exercise until exhaustion. At baseline markers of [[oxidative stress]] (thiobarbituric acidreactiv substances and ascorbic acid) did not differ significantly from healthy controls. After the exercise challenge however, the oxidative stress response occurred sooner and lasted longer in the ME/CFS group. This was associated with alterations in muscle excitability (lengthened [[M-wave]] duration) in ME/CFS-patients, which were not seen in controls.<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Mambrini|first3=O.|last4=Brégeon|first4=F.|last5=Delliaux|first5=S.|date=Mar 2005|title=Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/15715687|journal=Journal of Internal Medicine|volume=257|issue=3|pages=299–310|doi=10.1111/j.1365-2796.2005.01452.x|issn=0954-6820|pmid=15715687}}</ref> A small 2009 follow-up study confirmed these results and associated it with a post-exertional reduction of [[Heat shock protein|heat shock proteins]] HSP 27 and HSP 70 after exercise.<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=Aug 2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://www.ncbi.nlm.nih.gov/pubmed/19457057|journal=Journal of Internal Medicine|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796|pmid=19457057}}</ref> According to the authors, this is another indication of an impaired redox status in ME/CFS patients. A 2011 study confirmed most of these results in a larger cohort of 43 ME/CFS patients and 23 healthy controls. Again the data indicated an increased exercise-induced oxidative stress and a reduced Hsp response. Though it is know that deconditioning can increase oxidative stress, the authors argued this to be unlikely in their study population, for several reasons: <blockquote>“…deconditioning can be ruled out in our study because (i) it induces carbohydrate and lipid disorders that were not observed during routine biochemical check-up in these CFS patients, (ii) CFS patients did not have reduced maximal exercise performance or an accentuated lactic acid response and (iii) we found no correlation between the duration of CFS symptoms […] and the resting levels of oxidant–antioxidant status and HSPs.”<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|date=Jul 2012|title=Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins|url=https://www.ncbi.nlm.nih.gov/pubmed/22112145|journal=Journal of Internal Medicine|volume=272|issue=1|pages=74–84|doi=10.1111/j.1365-2796.2011.02488.x|issn=1365-2796|pmid=22112145}}</ref></blockquote>A [[Canada|Canadian]] research team had already reported a marked decline of HSP 27 during the post-exercise period of six ME/CFS patients in 2002.<ref>{{Cite journal|last=Thambirajah|first=Anita A.|last2=Sleigh|first2=Kenna|last3=Stiver|first3=H. Grant|last4=Chow|first4=Anthony W.|date=2008-12-01|title=Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/19032901|journal=Clinical and Investigative Medicine. Medecine Clinique Et Experimentale|volume=31|issue=6|pages=E319–327|issn=1488-2353|pmid=19032901}}</ref>

==== Complement C4a ====
In 2003 Sorensen et al. found that the [[Complement C4a|complement split product C4a]] was increased after exercise in the 20 ME/CFS patients, but not in controls. Furthermore a significant correlation was found between the increase in C4a and total symptom score.<ref>{{Cite journal|last=Sorensen|first=Bristol|last2=Streib|first2=Joanne E.|last3=Strand|first3=Matthew|last4=Make|first4=Barry|last5=Giclas|first5=Patricia C.|last6=Fleshner|first6=Monika|last7=Jones|first7=James F.|date=Aug 2003|title=Complement activation in a model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12897748|journal=The Journal of Allergy and Clinical Immunology|volume=112|issue=2|pages=397–403|issn=0091-6749|pmid=12897748}}</ref> C4a is generated from the cleavage of the native complement protein C4 via the classical and lectin pathways. A follow up study, published in 2009, found that other elements of the lectin pathway also responded differently to an exercise challenge in ME/CFS patients compared to controls. Both C4 and mannan-binding lectin serine protease 2 (MASP2) were observed at higher levels in ME/CFS subjects 1 hour post-exercise.<ref>{{Cite journal|last=Sorensen|first=Bristol|author-link=|last2=Jones|first2=James F|author-link2=|last3=Vernon|first3=Suzanne D|author-link3=Suzanne Vernon|last4=Rajeevan|first4=Mangalathu S|author-link4=Mangalathu Rajeevan|author-link5=|date=Jan 2009|title=Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/|journal=Molecular Medicine|volume=15|issue=1-2|pages=34–42|doi=10.2119/molmed.2008.00098|pmc=2583111|pmid=19015737|quote=|via=}}</ref> The authors speculated this to contribute to the increased C4a split product 6 hours after the exercise challenge. In a 2010 study by Nijs et al. there was no increase in C4a after exercise in ME/CFS patients, though a significant correlation with post-exertional pain and fatigue was found.<ref>{{Cite journal|last=Nijs|first=J.|last2=Van Oosterwijck|first2=J.|last3=Meeus|first3=M.|last4=Lambrecht|first4=L.|last5=Metzger|first5=K.|last6=Frémont|first6=M.|last7=Paul|first7=L.|date=Apr 2010|title=Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1β|url=https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2009.02178.x|journal=Journal of Internal Medicine|volume=267|issue=4|pages=418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=0954-6820}}</ref>
==== Cytokines ====
The expression of cytokines after physical exercise has been researched in ME/CFS patients since the mid-1990s. Most of these studies have found negative results (see table below).

{| class="wikitable"
|Study
|Number of participants
|Exercise challenge
|Cytokines tested:
|Results:
|-
|[[Daniel Peterson|Peterson]] et al. (1994)<ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=Mar 1994|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7496949|journal=Clinical and Diagnostic Laboratory Immunology|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>
|10 ([[Holmes criteria]], all cases were post-infectious)
|Walking 1 mile per hour for 30 min
|[[Interleukin 1 beta|IL-1 β]], [[Interleukin 6|IL-6]], and [[TNF-alpha|TNF-α]], [[TGF beta|TGF-β]]
|Negative results
|-
|[[Andrew Lloyd|Lloyd]] et al. (1994)<ref>{{Cite journal|last=Lloyd|first=A.|last2=Gandevia|first2=S.|last3=Brockman|first3=A.|last4=Hales|first4=J.|last5=Wakefield|first5=D.|date=Jan 1994|title=Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/8148442|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S142–146|issn=1058-4838|pmid=8148442}}</ref>
|12 ([[Australian criteria]])
|30 min hand grip exercises
|[[Interferon gamma|IFN-γ]], [[Interferon alpha |IFN-α]], [[Interleukin 1 beta|IL-1 β]], [[TNF-alpha|TNF-α]]
|Negative results
|-
|[[La Manca]] et al. (1999)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=Zhou|first3=X. D.|last4=Ottenweller|first4=J. E.|last5=Cook|first5=S.|last6=Peckerman|first6=A.|last7=Zhang|first7=Q.|last8=Denny|first8=T. N.|last9=Gause|first9=W. C.|date=Mar 1999|title=Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion|url=https://www.ncbi.nlm.nih.gov/pubmed/10226888|journal=Journal of Clinical Immunology|volume=19|issue=2|pages=135–142|issn=0271-9142|pmid=10226888}}</ref>
|20 ([[Fukuda criteria]]) "only patients with an illness duration of less than 6 years, who reported at least substantial intensity on symptom severity scales in the month prior to recruitment and who had no major psychiatric diagnosis in the 5 years prior to illness onset" were included
|An exhaustive treadmill exercise test
|[[Interleukin 2|IL-2]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]]<nowiki>, [[Interferon gamma|IFN-γ, </nowiki>[[TNF-alpha|TNF-α]]
|Negative results
|-
|Cannon et al. (1997)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Abad|first3=L. W.|last4=Vannier|first4=E.|last5=Mileno|first5=M. D.|last6=Fagioli|first6=L.|last7=Wolff|first7=S. M.|last8=Komaroff|first8=A. L.|date=May 1997|title=Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9168406|journal=Journal of Clinical Immunology|volume=17|issue=3|pages=253–261|issn=0271-9142|pmid=9168406}}</ref>
|8 (Holmes criteria) “their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]], [[interleukin-1 receptor antagonist]] (IL-1Ra), and [[soluble interleukin-1 receptor type II]] (IL-lsRII).
|Negative results
|-
|Gupta et al. (1998)<ref>{{Cite journal|last=Gupta|first=S.|last2=Aggarwal|first2=S.|last3=Starr|first3=A.|date=Feb 1999|title=Increased production of interleukin-6 by adherent and non-adherent mononuclear cells during 'natural fatigue' but not following 'experimental fatigue' in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9917531|journal=International Journal of Molecular Medicine|volume=3|issue=2|pages=209–213|issn=1107-3756|pmid=9917531}}</ref>
|5 (Holmes criteria)
|30 min hand grip exercises
|[[Interleukin 6|IL-6]]
|Negative results
|-
|Cannon et al. (1999)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Ball|first3=R. W.|last4=Abad|first4=L. W.|last5=Fagioli|first5=L.|last6=Komaroff|first6=A. L.|date=Nov 1999|title=Acute phase responses and cytokine secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10634215|journal=Journal of Clinical Immunology|volume=19|issue=6|pages=414–421|issn=0271-9142|pmid=10634215}}</ref>
|10 (Holmes criteria) their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]],[[IL-6]]
|Negative results
|-
|Yammes et al. (2009)<ref name=":25" />
|9 ([[Fukuda criteria]]) 6/9 had practiced sport at high levelxxxxxxxx, for more than 4 years before the symptoms occurred.
|Cycling test until maximal work load
|[[IL-6]], [[TNF-a]]
|Negative results
|-
|Robinson et al (2010)<ref>{{Cite journal|last=Robinson|first=M.|last2=Gray|first2=S. R.|last3=Watson|first3=M. S.|last4=Kennedy|first4=G.|last5=Hill|first5=A.|last6=Belch|first6=J. J. F.|last7=Nimmo|first7=M. A.|date=Apr 2010|title=Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19422646|journal=Scandinavian Journal of Medicine & Science in Sports|volume=20|issue=2|pages=282–290|doi=10.1111/j.1600-0838.2009.00895.x|issn=1600-0838|pmid=19422646}}</ref>
|6 (Fukuda criteria)
|Incremental exercise test to exhaustion
|IL-6, [[sIL-6R]] and [[sgp130]]
|Negative results
|-
|[[Andrea White]] et al. (2010)<ref name=":26">{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010-07-01|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20230500|journal=Psychophysiology|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1540-5958|pmc=4378647|pmid=20230500}}</ref>
|19 (Fukuda criteria)
|The authors used "a moderate whole-body exercise task (working both arms and legs) for 25 min that was mild enough that all CFS patients were able to complete it successfully but did induce a flare of fatigue and pain symptoms that remained above pre-exercise levels for 48 h post-exercise in the majority of patients."
|[[Interleukin 1 beta |IL-1β]], [[Interleukin 2 |IL-2]], [[Interleukin 12|IL-12]], [[TNF-alpha |TNFα]], soluble [[CD40L]], [[Interferon gamma |IFN-γ]], [[Interleukin 4|IL-4]], [[Interleukin 10 |IL-10]], [[Interleukin 13|IL-13]], [[Interleukin 6|IL-6]] and [[Interleukin 8|IL-8]]

 
|Positive results for a subgroup (11/19) of patients with high PEM

 
|-
|Andrew Lloyd et al. (2018)<ref name=":27">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=En|volume=8|issue=1|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|24 ([[Fukuda criteria]]) “we used the 1994 Centers for Disease Control (CDC)/Fukuda international diagnostic criteria for ME/CFS, but required participants to have post exertional malaise. Terefore, in labeling our patients this refers to the revised [[International Consensus Criteria|international consensus criteria]] from 2011”
|Symptom limited exercise on an ergocycle.
|Growth factors: [[FGF beta|FGF-β]], [[HGF]], [[NGF]], [[PDGF-BB]], [[TGF alpha|TGFα]], [[TGF-β1]], [[Vascular endothelial growth factor|VEGF]]

 

[[Colony stimulating factors]] and [[stem cell factors]]: [[G-CSF]], [[GM-CSF]], [[M-CSF]], [[SCF]]

 

Interleukins: [[Interleukin 1alpha|IL-1α]], [[Interleukin 1beta|IL-1β]], [[Interleukin 1RA|IL-1RA]], [[Interleukin 2|IL-2]], [[IL-4]], [[IL-5]], [[IL-6]], [[Interleukin 7|IL-7]], [[Interleukin |IL-8]], [[Interleukin 10|IL-10]], [[Interleukin 12p40|IL12p40]], [[Interleukin 12p70|IL12p70]], [[Interleukin 13|IL-13]], [[Interleukin 15|IL-15]], [[Interleukin 17|IL-17]], [[Interleukin 17f|IL-17F]], [[Interleukin 18|IL-18]] and [[LIF]]

 

[[Chemokine|Chemokines]]: [[CCL2]] ([[MCP-1]]), [[CCL3]] ([[MIP-1α]]), [[CCL4]] ([[MIP-1β]]), [[CCL5]] ([[RANTES]]) [[CCL7]] ([[MCP-3]]), [[CXCL1]] ([[Gro alpha|Gro-α]]), [[CXCL5]] ([[ENA78]]), [[CXCL9]] ([[MIG]]), [[CXCL10]] ([[IP-10]]), [[CCL11]] ([[Eotaxin]])

 

[[Interferon|Interferons]]: [[Interferon alpha |INF-α]], [[Interferon beta |INF-β]], [[Interferon gamma|INF-γ]]

 

[[Adhesion Molecule|Adhesion Molecules]] : [[ICAM-1]], [[VCAM-1]]

 

Other factors: [[CD40L]], [[FASL]], [[Leptin]], [[PAI-1]], [[Resistin]], [[TNF-α]], [[TNF-β]], [[TRAIL]]
|Positive results: ME/CFS had a distinct [[cytokine profile]] post-exercise.
|}
Moneghetti et al. took a different approach and looked at the cytokine profiling after exercise, as this may differentiate patients with ME/CFS from sedentary controls. Of the 51 [[cytokine]]s and growth factors tested, 10 significantly changed after exercise in both groups, a further 7 only changed in controls and five only changed in ME/CFS (namely, [[CXCL10]], [[IL-8]], [[CCL4]], [[TNF-β]] and [[ICAM-1]]). This suggests a distinct [[cytokine inflammatory signature]] in ME/CFS.<ref name=":27" /> White et al. (2010) differentiated their 19 ME/CFS patients with a high or low post-exertional malaise (called symptom flare SF, in the study). While the cytokine expression after exercise of patients with low PEM was similar to those of healthy controls, patients with high PEM showed opposite results. As the authors noted:<blockquote>"In sum, low SF patients and controls showed a pattern of post-exercise decreases in both pro and anti-inflammatory cytokines (with the exception of increases in IL-8), whereas the high SF patients showed a pattern of increases in both cytokine types at 8 h and no decreases at any time."<ref name=":26" /></blockquote>

=== Autonomic response ===
Several research teams have noted post-exertional abnormalities in the [[Autonomic nervous system|autonomic]] function of ME/CFS patients, though the exact meaning of these results is not yet clear.

A Canadian team under the guidance of [[Terrence Montague]] noted that during a maximal exercise test, ME/CFS patients have a lower maximal heart rate than controls. The authors noted that: <blockquote>“...patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.”<ref>{{Cite journal|last=Montague|first=T.J.|last2=Marrie|first2=T.J.|last3=Klassen|first3=G.A.|last4=Bewick|first4=D.J.|last5=Horacek|first5=B.M.|date=Apr 1989|title=Cardiac function at rest and with exercise in the chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/2924607|journal=Chest|volume=95|issue=4|pages=779–784|issn=0012-3692|pmid=2924607}}</ref> </blockquote>A significantly lower peak heart rate has been repeatedly observed in CPET-studies with ME/CFS patients.<ref>{{Cite journal|last=Gibson|first=H|last2=Carroll|first2=N|last3=Clague|first3=J E|last4=Edwards|first4=R H|date=Sep 1993|title=Exercise performance and fatiguability in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC489735/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=56|issue=9|pages=993–998|issn=0022-3050|pmid=8410041}}</ref><ref>{{Cite journal|last=Sisto|first=Sue Ann|last2=LaManca|first2=John|last3=Cordero|first3=Douglas L.|last4=Bergen|first4=Michael T.|last5=Ellis|first5=Steven P.|last6=Drastal|first6=Susan|last7=Boda|first7=Wanda L.|last8=Tapp|first8=Walter N.|last9=Natelson|first9=Benjamin H.|date=Jun 1996|title=Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome|url=https://www.amjmed.com/article/S0002-9343(96)00041-1/pdf|journal=The American Journal of Medicine|language=English|volume=100|issue=6|pages=634–640|doi=10.1016/S0002-9343(96)00041-1|issn=0002-9343}}</ref><ref>{{Cite journal|last=Rowbottom|first=David|last2=Keast|first2=David|last3=Pervan|first3=Zhukov|last4=Morton|first4=Alan|date=Jan 1998|title=The Physiological Response to Exercise in Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v04n02_04|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=4|issue=2|pages=33–49|doi=10.1300/j092v04n02_04|issn=1057-3321}}</ref> In one of the largest of these into exercise performance, the authors noted the same phenomenon as Montague et al. <blockquote>“The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects.”<ref>{{Cite journal|last=De Becker|first=P.|last2=Roeykens|first2=J.|last3=Reynders|first3=M.|last4=McGregor|first4=N.|last5=De Meirleir|first5=K.|date=2000-11-27|title=Exercise capacity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11088089|journal=Archives of Internal Medicine|volume=160|issue=21|pages=3270–3277|issn=0003-9926|pmid=11088089}}</ref></blockquote>The Belgium team Van Oosterwijck et al. reported an impaired heart rate recovery in 20 female ME/CFS patients following exercise.<ref>{{Cite journal|last=Van Oosterwijck|first=J.|last2=Marusic|first2=U.|last3=De Wandele|first3=I.|last4=Meeus|first4=M.|last5=Paul|first5=L.|last6=Lambrecht|first6=L.|last7=Moorkens|first7=G.|last8=Nijs|first8=J.|date=May 2015|title=Reduced parasympathetic reactivation during recovery from exercise in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)|url=https://www.physiotherapyjournal.com/article/S0031-9406(15)02014-3/fulltext|journal=Physiotherapy|language=English|volume=101|pages=e1091–e1092|doi=10.1016/j.physio.2015.03.1984|issn=0031-9406|issue=|quote=|author-link=Jessica Van Oosterwijck|author-link2=|author-link3=|author-link4=|author-link5=|via=|author-link8=Jo Nijs}}</ref> In other disease groups this is associated with risk for cardiac events and sudden death. Cordero et al. did not find a significant difference in mean heart rate between 11 ME/CFS patients and six healthy controls after walking on a treadmill, but they did find patients to have significantly less ‘vagal power’, a measure for respiratory-related parasympathetic contributions to heart rate.<ref>{{Cite journal|last=Cordero|first=D. L.|last2=Sisto|first2=S. A.|last3=Tapp|first3=W. N.|last4=LaManca|first4=J. J.|last5=Pareja|first5=J. G.|last6=Natelson|first6=B. H.|date=Dec 1996|title=Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8985621|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=6|issue=6|pages=329–333|issn=0959-9851|pmid=8985621}}</ref> Soetekouw et al. noted that during a handgrip exercise, the hemodynamics response was lower in the ME/CFS group than in the control group, although this could be attributed to the lower level of muscle exertion in the ME/CFS group.<ref>{{Cite journal|last=Soetekouw|first=P. M.|last2=Lenders|first2=J. W.|last3=Bleijenberg|first3=G.|last4=Thien|first4=T.|last5=van der Meer|first5=J. W.|date=Dec 1999|title=Autonomic function in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10638807|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=9|issue=6|pages=334–340|issn=0959-9851|pmid=10638807}}</ref> LaManca et al. studied 19 ME/CFS (Holmes criteria) and found that they had a diminished heart rate and blood pressure in response to a cognitive test compared to healthy controls, though exercise did not magnify this effect.<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Peckerman|first2=A.|last3=Sisto|first3=S. A.|last4=DeLuca|first4=J.|last5=Cook|first5=S.|last6=Natelson|first6=B. H.|date=Sep 2001|title=Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/11573024|journal=Psychosomatic Medicine|volume=63|issue=5|pages=756–764|issn=0033-3174|pmid=11573024}}</ref> Similar results were found by a Norwegian research team. They studied 13 adolescents with ME/CFS and 53 age-matched controls after a mental stress test (arithmetic questions). Though heart rate was significantly higher in patients at baseline, there were no meaningful differences during the arithmetic challenge.<ref>{{Cite journal|last=Egge|first=Caroline|last2=Wyller|first2=Vegard Bruun|date=2010-12-14|title=No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/21156045|journal=BioPsychoSocial Medicine|volume=4|pages=22|doi=10.1186/1751-0759-4-22|issn=1751-0759|pmc=3012010|pmid=21156045}}</ref> Finally, Ocon et al. (2012) studied 16 patients with both the diagnosis of ME/CFS and POTS after increased orthostatic stress and a cognitive challenge. An impairment of the neurocognitive abilities was noted, that was not seen in healthy controls.<ref>{{Cite journal|last=Ocon|first=Anthony J.|last2=Messer|first2=Zachary R.|last3=Medow|first3=Marvin S.|last4=Stewart|first4=Julian M.|date=Mar 2012|title=Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/21919887|journal=Clinical Science (London, England: 1979)|volume=122|issue=5|pages=227–238|doi=10.1042/CS20110241|issn=1470-8736|pmc=3368269|pmid=21919887}}</ref>

=== Sleep ===
A first study into the effects of exercise on sleep in ME/CFS found a beneficial effect: approximately half the patients slept better after exercise.<ref>{{Cite journal|last=Togo|first=Fumiharu|last2=Natelson|first2=Benjamin H.|last3=Cherniack|first3=Neil S.|last4=Klapholz|first4=Marc|last5=Rapoport|first5=David M.|last6=Cook|first6=Dane B.|date=Jan 2010|title=Sleep is not disrupted by exercise in patients with chronic fatigue syndromes|url=https://www.ncbi.nlm.nih.gov/pubmed/20010134|journal=Medicine and Science in Sports and Exercise|volume=42|issue=1|pages=16–22|doi=10.1249/MSS.0b013e3181b11bc7|issn=1530-0315|pmc=2796587|pmid=20010134}}</ref> A follow-up study by the same research team (under the guidance of Benjamin Natelson) found more post-exercise improvement (transitions to deeper [[sleep stages]]) of sleep in ME/CFS patients than in controls. The patients, however, reported more fatigue in the morning after exercise while healthy controls showed significant improvement in sleepiness and fatigue. The authors speculated this to be due to a disruption of the [[REM]] sleep: ME/CFS showed, both at baseline and post-exercise, an increased rate of transition from REM to wake compared to controls and this correlated with symptoms of fatigue, pain and sleepiness.<ref>{{Cite journal|last=Kishi|first=Akifumi|last2=Togo|first2=Fumiharu|last3=Cook|first3=Dane B|last4=Klapholz|first4=Marc|last5=Yamamoto|first5=Yoshiharu|last6=Rapoport|first6=David M|last7=Natelson|first7=Benjamin H|date=Nov 2013|title=The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871467/|journal=Physiological Reports|volume=1|issue=6|doi=10.1002/phy2.152|issn=2051-817X|pmc=3871467|pmid=24400154}}</ref> An Australian study followed up on 35 ME/CFS patients after performing a physical (stationary cycling) or cognitive (stimulated driving) challenge. While patients spent a greater proportion of wakeful hours lying down, they did not report significant changes in sleep quality or sleep duration. The authors did however note that the expected increase in [[heart rate variability]] (HRV) between wake and sleep, was significantly reduced in ME/CFS patients after completing the challenges. These changes in HRV have been associated with the falling asleep, and might be related to the unfreshed sleep of ME/CFS patients.<ref>{{Cite journal|last=Cvejic|first=Erin|last2=Sandler|first2=Carolina X.|last3=Keech|first3=Andrew|last4=Barry|first4=Benjamin K.|last5=Lloyd|first5=Andrew R.|last6=Vollmer-Conna|first6=Uté|date=Dec 2017|title=Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29167053|journal=Journal of Psychosomatic Research|volume=103|pages=91–94|doi=10.1016/j.jpsychores.2017.10.010|issn=1879-1360|pmid=29167053}}</ref> Finally, Ohashi et al. recorded physical activity for 6-days in 10 patients with ME/CFS and 6 controls before and after performing a maximal treadmill test. Their results indicate an increase in [[circadian]] rest-activity in ME/CFS patients after exercise as the activity pattern of patients shifted toward later hours in the day.<ref>{{Cite journal|last=Ohashi|first=Kyoko|last2=Yamamoto|first2=Yoshiharu|last3=Natelson|first3=Benjamin H.|date=Sep 2002|title=Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12213500|journal=Physiology & Behavior|volume=77|issue=1|pages=39–44|issn=0031-9384|pmid=12213500}}</ref>
=== Cognitive performance ===
While some studies have found a decreased cognitive performance after exercise in ME/CFS, others have not (see table below).<ref name=":0" /> This difference may be due to heterogeneity of the patient sample and methods used.

{| class="wikitable"
|Study
|Number of ME/CFS subjects
|Neurocognitive tests
|Results
|-
|[[Marshall]] et al. (1997)<ref>{{Cite journal|last=Marshall|first=P. S.|last2=Forstot|first2=M.|last3=Callies|first3=A.|last4=Peterson|first4=P. K.|last5=Schenck|first5=C. H.|date=Jan 1997|title=Cognitive slowing and working memory difficulties in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9021867|journal=Psychosomatic Medicine|volume=59|issue=1|pages=58–66|issn=0033-3174|pmid=9021867}}</ref>
|8
|Buschke Selective Reminding Test, Continuous-Performance Test-Identical Pairs Version (CPTIP), Paced Auditory Serial Addition Task (PASAT), Stroop Color Word Test, Reaction-Time Tests, Salthouse Reading Span Task (SRST), Verbal Scholastic Aptitude Test (SAT).
|Negative
|-
|[[Blackwood]] et al. (1998)<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=Oct 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781}}</ref>
|10
|"The following aspects of cognitive function were examined (in order): working memory/auditory attention (digit span, from WAIS-R); psychomotor speed (digit symbol, also from WAIS-R); word fluency (FAS test, using the letters F and S only); and selective attention and sustained attention (telephone search and lottery tasks respectively, both from the test of everyday attention)”
|Positive
|-
|[[La Manca]] et al. (1998)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=DeLuca|first3=J.|last4=Johnson|first4=S. K.|last5=Lange|first5=G.|last6=Pareja|first6=J.|last7=Cook|first7=S.|last8=Natelson|first8=B. H.|date=1998-09-28|title=Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9790484|journal=The American Journal of Medicine|volume=105|issue=3A|pages=59S–65S|issn=0002-9343|pmid=9790484}}</ref>
|19
|The Stroop Color and Word Test, the Symbol Digit Modalities Test (SDMT), an oral version of the Trail Making Test (TMT) and the Serial 13s Test (STT)
|Positive
|-
|[[Claypoole]] et al. (2001)<ref>{{Cite journal|last=Claypoole|first=Keith|last2=Mahurin|first2=Roderick|last3=Fischer|first3=Mary E.|last4=Goldberg|first4=Jack|last5=Schmaling|first5=Karen B.|last6=Schoene|first6=Robert B.|last7=Ashton|first7=Suzanne|last8=Buchwald|first8=Dedra|date=Mar 2001|title=Cognitive Compromise Following Exercise in Monozygotic Twins Discordant for Chronic Fatigue Syndrome: Fact or Artifact?|url=http://dx.doi.org/10.1207/s15324826an0801_5|journal=Applied Neuropsychology|volume=8|issue=1|pages=31–40|doi=10.1207/s15324826an0801_5|issn=0908-4282}}</ref>
|21
|The Wechsler Adult Intelligence Scale–Revised, Digit Span Forward and Backward subtests, The Hopkins Verbal Learning Test, . The Digit Vigilance Test, the Lafayette Clinic Repeatable Neuropsychological Test Battery, Controlled Oral Word Association Test (COWAT)
|Negative
|-
|[[Dane Cook|Cook]] et al. (2005)<ref>{{Cite journal|last=Cook|first=Dane B.|last2=Nagelkirk|first2=Paul R.|last3=Peckerman|first3=Arnold|last4=Poluri|first4=Ashok|last5=Mores|first5=John|last6=Natelson|first6=Benjamin H.|date=Sep 2005|title=Exercise and cognitive performance in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16177595|journal=Medicine and Science in Sports and Exercise|volume=37|issue=9|pages=1460–1467|issn=0195-9131|pmid=16177595}}</ref>
|20 ME/CFS only and 19 ME/CFS with comorbid fibromyalgia
|Participants completed cognitive testing using the automated neuropsychological assessment matrices (ANAM)
|Negative
|-
|[[Yoshiuchi]] et al. (2007)<ref>{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref>
|9
|A one-back memory task
|Negative
|-
|Cook et al. (2017)<ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref>
|15
|The Paced Auditory Serial Addition Task (PASAT) and a simple number recognition task
|Positive
|}

=== Pain modulation ===
Another post-exertional abnormality reported in ME/CFS is pain modulation. When healthy people exercise, their brain produces [[endorphins]] that increase pain thresholds. In some chronic pain patients like [[fibromyalgia]] and whiplash associated disorders, this endogenous pain inhibition response is defect and pain thresholds decrease shortly after exercise (i.e. they experience more pain while they should be feeling less). In 2004 Whiteside et al. first showed this defect in ME/CFS patients.<ref name=":22" /> These results were confirmed by two studies by the Belgium pain in motion team: while pain thresholds increased in normal controls they decreased in the ME/CFS patient group.<ref name=":23" /><ref name=":24" /> As a caveat, one must note that these studies only included ME/CFS patients that were suffering from chronic pain, while comorbid FM was not assessed. So it remains unclear if these results will also show up in ME/CFS patients that do not have comorbid FM.<ref>{{Cite journal|last=Yunus|first=Muhammad|date=2015-07-02|title=Editorial Review (Thematic Issue: An Update on Central Sensitivity Syndromes and the Issues of Nosology and Psychobiology)|url=http://dx.doi.org/10.2174/157339711102150702112236|journal=Current Rheumatology Reviews|language=en|volume=11|issue=2|pages=70–85|doi=10.2174/157339711102150702112236|issn=1573-3971}}</ref>

=== Other ===

==== The gut microbiome ====
Shukla et al. (2015) found post-exertional changes in the gut microbiome in ME/CFS patients that were not seen in healthy controls. Increased clearance of bacteria in the blood was also noted, which made the authors speculate that exercise induced a bacterial translocation in ME/CFS patients.<ref>{{Cite journal|last=Shukla|first=Sanjay K.|last2=Cook|first2=Dane|last3=Meyer|first3=Jacob|last4=Vernon|first4=Suzanne D.|last5=Le|first5=Thao|last6=Clevidence|first6=Derek|last7=Robertson|first7=Charles E.|last8=Schrodi|first8=Steven J.|last9=Yale|first9=Steven|date=2015-12-18|title=Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=http://dx.doi.org/10.1371/journal.pone.0145453|journal=PLOS ONE|volume=10|issue=12|pages=e0145453|doi=10.1371/journal.pone.0145453|issn=1932-6203}}</ref>

==== Catecholaminergic hyporeactivity ====
Strahler et al. found that ME/CFS patients showed an attenuated response (lower increases) of epinephrine to an exercise challenge, compared to heathy controls. This ‘catecholaminergic hyporeactivity’ was however subtle and short-lived.<ref>{{Cite journal|last=Strahler|first=Jana|last2=Fischer|first2=Susanne|last3=Nater|first3=Urs M.|last4=Ehlert|first4=Ulrike|last5=Gaab|first5=Jens|date=Sep 2013|title=Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23770415|journal=Biological Psychology|volume=94|issue=1|pages=160–166|doi=10.1016/j.biopsycho.2013.06.002|issn=1873-6246|pmid=23770415}}</ref>

==== Nitric oxide metabolites ====
A [[Spain|Spanish]] research team found much higher increases of nitric oxide metabolites (nitrates) after a maximal exercise test in 44 ME/CFS patients compared to 25 healthy controls while there were no differences between the groups at baseline.<ref>{{Cite journal|last=Suárez|first=Andrea|last2=Guillamó|first2=Elisabet|last3=Roig|first3=Teresa|last4=Blázquez|first4=Alicia|last5=Alegre|first5=José|last6=Bermúdez|first6=Jordi|last7=Ventura|first7=José Luis|last8=García-Quintana|first8=Ana María|last9=Comella|first9=Agustí|date=Jun 2010|title=Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study|url=http://dx.doi.org/10.1089/jwh.2008.1255|journal=Journal of Women's Health|volume=19|issue=6|pages=1073–1077|doi=10.1089/jwh.2008.1255|issn=1540-9996}}</ref>

== Problems in defining PEM ==

=== Asking the right questions ===
[[Leonard Jason|Jason]] et al. (1999) reported that in a group of ME/CFS patients, the percentage endorsing PEM ranged from 40,6 to 93,8% depending on how the question assessed this symptom.<ref>{{Cite web|url=https://www.meassociation.org.uk/2012/04/to-pem-or-not-to-pem-that-is-the-question-for-case-definition-research-1st-website-27-april-2012/|title=To PEM or not to PEM? That is the question for case definition {{!}} Research 1st website|date=27 April 2012|website=www.meassociation.org.uk|language=en-US|access-date=2018-10-10}}</ref> The report of the National Academy of Medicine noted that “the prevalence of PEM among ME/CFS patients as diagnosed by existing criteria varies from 69 to 100 percent.”<ref name=":0" />

Some patients try to reduce post-exertional relapses by pacing themselves and reducing exertion that exceeds their energy limits. Questionnaires assessing PEM by frequency instead of propensity, might erroneously label these patients as not having PEM. In a 2015 study, Jason et al. measured ME/CFS patients’ responses to the PEM-criterion in the [[Keiji Fukida|Fukuda]] et al. (1994) definition: ‘Do you feel generally worse than usual or fatigued for 24 hours or more after you have exercised?’ Although the majority (75%) endorsed this item, a notable percentage (25%) did not. Yet when the question was framed differently, leaving out the 24 hours’ time period and substituting exercise with normal daily activity, these participants also agreed they experienced high levels of fatigue after normal daily activity.<ref name=":19" /> This clearly shows that patients who have already modified their activities to avoid or reduce PEM may potentially show up as false negatives.

Another issue is the definition of PEM in the Fukuda-criteria. While the wording used here is vague, the time criterion is rather strict requiring PEM to last more than 24 hours. Some patients do not endorse this item because they only have post-exertional malaise for less than 24 hours.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=King|first2=Caroline P.|last3=Richman|first3=Judith A.|last4=Taylor|first4=Renee R.|last5=Torres|first5=Susan R.|last6=Song|first6=Sharon|date=Jan 1999|title=U.S. Case Definition of Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v05n03_02?journalCode=icfs20|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=5|issue=3-4|pages=3–33|doi=10.1300/j092v05n03_02|issn=1057-3321}}</ref> A 2018 study concluded that setting the criterion at 24 hours would exclude almost 30% of ME/CFS patients. It advises that this definition might be useful in research settings but that in a clinical context, a 14-23 hour time period might be more appropriate.<ref>{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref>

These observations point to the need of a more precise definition of PEM and several attempts to this end have been made.
=== More than just fatigue ===
Few instruments have assessed PEM adequately. The [[CDC 2005 Symptom Inventory for CFS|CDC symptom inventory]] for example, only asks about fatigue after exertion, while PEM entails much more than that. An [[Australia|Australian]] group at the University of New South Wales tried to better define PEM, using 19 ME/CFS patients after exposure to different stressors.<ref>{{Cite journal|last=Keech|first=Andrew|last2=Sandler|first2=Carolina X.|last3=Vollmer-Conna|first3=Ute|last4=Cvejic|first4=Erin|last5=Lloyd|first5=Andrew R.|last6=Barry|first6=Benjamin K.|date=Dec 2015|title=Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26359713|journal=Journal of Psychosomatic Research|volume=79|issue=6|pages=537–549|doi=10.1016/j.jpsychores.2015.08.008|issn=1879-1360|pmid=26359713}}</ref> Participants indicated that the term fatigue did not adequately describe the sensation they experienced on a daily basis. A word frequency analysis of descriptors nominated by these patients indicated 5 themes:
# Exhausted or tired.
# Heaviness in the limbs or whole-body.
# Fogginess in the head.
# Weakness in the muscles.
# Drained of energy.
===The DePaul Symptom Questionnaire (DSQ) subscale ===
The instrument most commonly used to assess PEM is a subscale from the [[DePaul Symptom Questionnaire]] (DSQ). The DSQ is a 54-item questionnaire was developed in 2010 to operationalize the Canadian Consensus Criteria, providing concrete directives to assess ME/CFS-symptoms with their frequency and severity.<ref>{{Cite web|url=https://www.semanticscholar.org/paper/The-Development-of-a-Revised-Canadian-Myalgic-Case-Jason-Evans/b2a2564f55daa57721d24502df6bd6c161238ff0|title=The Development of a Revised Canadian Myalgic Encephalomyelitis Chronic Fatigue Syndrome Case Definition|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth Anne|date=2010|language=en|access-date=2018-10-10|last3=Porter|first3=Nicole|last4=Brown|first4=Molly|last5=Brown|first5=Abigail A.|last6=Hunnell|first6=Jessica|last7=Anderson|first7=Valerie C.|last8=Lerch|first8=Athena|last9=Meirleir|first9=Kenny de}}</ref> In a Norwegian comparison with physician assessments, The DSQ scored a sensitivity of 92% and a specificity of 75%.<ref>{{Cite journal|last=Strand|first=Elin B.|last2=Lillestøl|first2=Kristine|last3=Jason|first3=Leonard A.|last4=Tveito|first4=Kari|last5=Diep|first5=Lien My|last6=Valla|first6=Simen Strand|last7=Sunnquist|first7=Madison|last8=Helland|first8=Ingrid B.|last9=Herder|first9=Ingrid|date=2016-01-02|title=Comparing the DePaul Symptom Questionnaire with physician assessments: a preliminary study|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1126026|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=4|issue=1|pages=52–62|doi=10.1080/21641846.2015.1126026|issn=2164-1846}}</ref> This indicated that the DSQ is a useful tool in detecting and screening symptoms, but that a follow-up medical examination is necessarily to confirm the diagnosis and identify possible exclusionary medical and psychiatric disorders.

The post-exertional malaise subscale on the DSQ particularly demonstrated excellent clinical utility as it was able to differentiate between ME/CFS patients and controls.<ref>{{Cite journal|last=Murdock|first=Kyle W.|last2=Wang|first2=Xin Shelley|last3=Shi|first3=Qiuling|last4=Cleeland|first4=Charles S.|last5=Fagundes|first5=Christopher P.|last6=Vernon|first6=Suzanne D.|date=Apr 2017|title=The utility of patient-reported outcome measures among patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/27600520|journal=Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation|volume=26|issue=4|pages=913–921|doi=10.1007/s11136-016-1406-3|issn=1573-2649|pmc=5336422|pmid=27600520}}</ref> In early 2018 the Common Data Elements working group on PEM formed by [[National Institute of Neurological Disorders and Stroke|NINDS]] and the CDC, recommended the use of 5 items from the DSQ to measure PEM.<ref name=":4">https://www.commondataelements.ninds.nih.gov/Doc/MECFS/PEM_Subgroup_Summary.pdf</ref>
# Dead, heavy feeling after starting to exercise.
# Next day soreness after non-strenuous, everyday activities.
# Mentally tired after the slightest effort.
# Minimum exercise makes physically tired.
# Physically drained or sick after mild activity.
To meet criteria for post-exertional malaise, one of these items need to be endorsed at sufficient frequency and severity (2 or greater on a scale of 0-4).

Although the DSQ has good test-retest reliability and is regarded as a useful tool in making the diagnosis of ME/CFS, its ability to capture PEM accurately has been questioned. Originally these five items formed one of the five subdomains of the ME/CFS Fatigue Types Questionnaire (MFTQ)<ref>{{Cite journal|last=Jason|first=Leonard|last2=Jessen|first2=Tricia|last3=Porter|first3=Nicole|last4=Boulton|first4=Aaron|last5=Gloria-Njoku|first5=Mary|date=2009-07-16|title=Examining Types of Fatigue Among Individuals with ME/CFS|url=http://dsq-sds.org/article/view/938|journal=Disability Studies Quarterly|language=en|volume=29|issue=3|doi=10.18061/dsq.v29i3.938|issn=2159-8371}}</ref><ref>{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> and critics argue that these items are focused too much on fatigue/tiredness to be an adequate measure of PEM. A document formulated by the Science for ME PEM working group to address these issues, explained:<blockquote>"The DSQ PEM items focus largely on feeling fatigue or tiredness, and, apart from one item, do not mention that post-exertional symptoms may be delayed. There is no mention of prolonged recovery or the loss of functional capacity."<ref name=":5" /></blockquote>The NINDS/CDC common data elements PEM subgroup also noted about the DSQ: <blockquote>"...the instrument does not assess the full range of symptoms that could be exacerbated by PEM and only one item addresses the sometimes delayed onset/ prolonged duration of PEM.<ref>https://www.commondataelements.ninds.nih.gov/Doc/MECFS/F2771_Guidance_for_Core_PEM_Assessment.pdf</ref> </blockquote>In an online poll to which 783 people responded, 68% answered that the DSQ PEM did not reflect their experience of post-exertional malaise<ref name=":5" />, though questions have been raised about the neutrality of the wording used.<ref name=":6">{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> In response Jason et al. noted that the DSQ PEM items were developed and selected to screen for the presence of PEM, rather than to comprehensively measure all aspects and variations of PEM. A 2018 analysis, using a large patient sample (n = 704), showed that screening items from the DSQ PEM subscale, were able to identify 97% of patients, which was higher than any other item to describe PEM.<ref name=":6" />

Furthermore, the authors have recently revised the DSQ PEM subscale to include new items, some based on Ramsay’s writings.<ref name=":7" /> An extra 5 questions can be used after the initial screening with the DSQ PEM subscale, to better differentiate ME/CFS from other, comparable conditions:
# Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?
# Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?
# If you feel worse after activities, how long does this last?
# If you were to become exhausted after actively participating in extracurricular activities, sports, or outings with friends, would you recover within an hour or two after the activity ended?
# If you do not exercise, is it because exercise makes your symptoms worse?
An analysis showed that these questions (the duration of PEM in particular) helped to differentiate ME/CFS patients from controls with [[Multiple sclerosis|MS]] or [[post-polio syndrome]].<ref name=":7" />

=== The DePaul Post-Exertional Malaise Questionnaire (DPEMQ) ===
The DPEMQ is a [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf questionnaire] based on input from hundreds of patients.<ref name=":29">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref><blockquote>Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.<ref name=":29" /></blockquote>

=== PENE ===
Of all case definitions, the 2011 International Consensus Criteria (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> offered the most precise and elaborated definition of the post-exertional relapses that characterize ME. To differentiate it with post-exertional malaise, the term used in the Fukuda-criteria, the authors introduced a new name: Post-Exertional Neuroimmune Exhaustion (PENE). PENE is described as “a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions”<ref name=":2" /> and has the following characteristics:
# Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
# Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
# Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
# Recovery period is prolonged, usually taking 24 hours or longer. A relapse can last days, weeks or longer.
# Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.
The definition fails however to make clear how many of these characteristics are necessary to diagnose PENE.
=== Muscle weakness ===
A more prominent criticism of PENE came from a 2016 factor analysis of PEM, using a large sample of 704 participants. Results suggested that “PEM is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue.”<ref name=":8" /> The latter refers to the description of ME by Ramsay, where post-exertional muscle weakness was highlighted. This element of PEM was confirmed in a study by the [[Workwell Foundation]] where the symptoms of 25 ME/CFS patients and 23 age-matched controls were followed up. As the report noted: <blockquote>"The two groups also differed with respect to the experience of physical weakness or instability immediately after testing. This was reported by 16 patients (64%) as opposed to 5 controls (22%). Weakness persisted into the next day in 10 patients (40%) but in only 1 control (4%). However, distinct differences can be observed in the severity of the weakness between groups when analyzing their reports. The sole report of weakness from a control stated: '[I had] tired legs when going up stairs—fine overall.' In contrast, statements from CFS patients included: 'Unable to walk without assistance.' '[I experienced] falling from muscle weakness.'<ref name=":13" /></blockquote>A Norwegian in depth-report of ME/CFS-patients relationship to exercise also highlighted muscle weakness: <blockquote>"Some related how they would struggle to get home after exercise – one had to stop her car on her way from the fitness centre. Another was walking in the woods and suddenly felt it would be impossible to make his way back home. They described feeling that something completely wrong had happened to their bodies, without understanding what was going on. Thought processes did not work as usual, motor abilities were reduced, or the legs would not move them as they would usually expect. Some participants described a paralyzed feeling subsequent to activity, where a lot of energy would be needed to be able to move."<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>While many descriptions of PEM like the DSQ subscale assess this element indirectly by asking patients about a dead heavy feeling after exercise or next day soreness, it is fully lacking in the ICC definition of PENE.<ref name=":8" />
=== Common data elements PEM working group ===
The NINDS/CDC Common Data Elements (CDE) PEM working group emphasized the need of a better definition of PEM. Its draft recommendations highlighted that <blockquote>"The definition of PEM is based primarily on clinician experience, patient reports and a few formal studies. There is a dearth of studies asking participants about their experiences of PEM in an openended manner, which is needed."<ref name=":4" /> </blockquote>A 2018 analysis showed that patients' preferences to describe PEM are generally not well-represented within present case definition criteria or descriptions.<ref>{{Cite journal|last=Jason|first=Leonard|last2=McManimen|first2=Stephanie|last3=Sunnquist|first3=Madison|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.researchgate.net/publication/323916016_Patient_perceptions_of_post_exertional_malaise|journal=Fatigue: Biomedicine, Health & Behavior|doi=10.1080/21641846.2018.1453265}}</ref> Although the CDE working group acknowledged the need to device a better instrument to assess PEM, it currently promotes the use of the DSQ PEM subscale as a screening tool, after which a clinician’s assessment is advised to diagnose PEM. The CDE PEM working group also provided a description of PEM, based on the 2015 literature review by the National Academy of Medicine: <blockquote>"PEM is defined as an abnormal response to minimal amounts of physical or cognitive exertion that is characterized by:</blockquote>
# Exacerbation of some or all of an individual study participant's ME/CFS symptoms. Symptoms exacerbated can include physical fatigue, cognitive fatigue, problems thinking (e.g. slowed information processing speed, memory, concentration), [[unrefreshing sleep]], [[Myalgia|muscle pain]], [[Arthralgia|joint pain]], [[Headache|headaches]], weakness/instability, light-headedness, flu-like symptoms, sore throat, [[nausea]], and other symptoms. Study participants can experience new or non-typical symptoms as well as exacerbation of their more typical symptoms.
# Loss of stamina and/or functional capacity.
# An onset that can be immediate or delayed after the exertional stimulus by hours, days or even longer.
# A prolonged, unpredictable recovery period that may last days, weeks, or even months.
# Severity and duration of symptoms that is often out-of-proportion to the type, intensity, frequency, and/or duration of the exertion. For some study participants, even basic activities of daily living like toileting, bathing, dressing, communicating, and reading can trigger PEM."<ref name=":4" />

==Notable studies==
* 1999, Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome<ref>{{Cite journal|last=Paul|first=L.|last2=Wood|first2=L.|last3=Behan|first3=W. M.|last4=Maclaren|first4=W. M.|date=1999|title=Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10209352|journal=European Journal of Neurology|volume=6|issue=1|pages=63–69|issn=1351-5101|pmid=10209352|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/10209352 (Abstract)]
* 2010, Postexertional Malaise in Women with Chronic Fatigue Syndrome<ref name="VanNess2010" /> [https://www.liebertpub.com/doi/10.1089/jwh.2009.1507 (Abstract)]

[[File:2010 VanNess Post exertional worsening of symptoms chart.png|center|frame|Post-exertional worsening of symptoms<ref name="VanNess2010" />]]
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Top 10 Things You Should Know About Post-Exertional Relapse'' (2012) By University of the Pacific/Solve CFS - 2010 study, ''PEM in Women w/ CFS'' is discussed in this video">https://www.youtube.com/watch?v=B20H1u1LjCE</embedvideo>

* 2013, Post-exertion malaise in chronic fatigue syndrome: symptoms and [[gene expression]]<ref name="MeyerJ2013" /> [http://www.tandfonline.com/doi/abs/10.1080/21641846.2013.838444 (Abstract)]
* 2015, Myalgic Encephalomyelitis: Symptoms and [[Biomarker]]s<ref name="JasonL2015bio" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/#!po=2.51799 (Full Text)]
*2015, Changes in Gut and Plasma [[Microbiome]] following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="ShuklaS2015" /> [http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0145453 (Full Text)]
*2016, Deconstructing post-exertional malaise: An exploratory factor analysis<ref name="McManimen, 2016" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/ (Full Text)]

*2018, Comparing Post-Exertional Symptoms Following Serial Exercise Tests<ref>{{Cite journal|last=Mateo|first=Lariel J.|date=2018|title=Comparing Post-Exertional Symptoms Following Serial Exercise Tests|url=https://scholarlycommons.pacific.edu/purcc/2018/events/87/|journal=PURCC|language=en|volume=|pages=|via=Scholarly Commons}}</ref> [https://scholarlycommons.pacific.edu/purcc/2018/events/87/ (Abstract)]

* 2018, The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome<ref name=":31" /><ref name=":30" /> [http://journals.sagepub.com/doi/abs/10.1177/1359105318805819?journalCode=hpqa& (Abstract)] [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf (Questionnaire)]

==Notable articles==
* Dec 30, 2015 [http://me-cfs.se/blogg/suggestion-to-replace-pem-by-par/ Suggestion to replace PEM (Post Exertional Malaise) with PAR (Post Activity Relapse)]<ref name="MEBlogg2015" />

*Nov 4, 2016 [http://www.medscape.com/viewarticle/871482#vp_1 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome]<ref>{{Cite web|url=http://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|last=Tucker|first=Miriam|date=|website=www.medscape.com|type=Login Required|archive-url=|archive-date=|dead-url=|access-date=2018-09-06}}</ref>

==Talks & interviews==
* 2013, [https://www.youtube.com/watch?v=zZ8aPYihkpQ CFS gene expression after exercise (part 1)]<ref>{{Cite web|url=https://www.youtube.com/watch?v=zZ8aPYihkpQ|title=CFS gene expression after exercise (part 1)|last=|first=|date=May 26, 2013|website=YouTube|publisher=Jw N|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

==See also==

*[[Exercise]]
*[[Exertion]]
*[[Flu-like symptoms]]
*[[Malaise]]
==Learn more==

*[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html International CFS/ME Awareness Day - What Health]<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-08-17}}</ref> (PEM Definition Included)
*[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf Post-Exertional Malaise in Chronic Fatigue Syndrome]<ref name="SpotilaJ2010" />
*[http://solvecfs.org/post-exertional-malaise-cause-and-effect/ Post-Exertional Malaise: Cause and Effect]<ref name="SpotilaJ20120523" />
*[https://www.verywellhealth.com/what-is-post-exertional-malaise-716023 What is Post-Exertional Malaise]<ref name="AboutHealthPEM" />
*[http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/ The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained?]<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/|title=The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained? - Health Rising|last=Johnson|first=Cort|date=2016-07-04|work=Health Rising|access-date=2018-08-17|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== References ==
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}}</ref>
<ref name="VanNess2010">{{Citation
| last1 = VanNess | first1 = M | authorlink1 = Mark VanNess
| last2 = Stevens | first2 = S | authorlink2 = Staci Stevens
| last3 = Bateman | first3 = L | authorlink3 = Lucinda Bateman
| last4 = Stiles | first4 = TL | authorlink4 = TL Stiles
| last5 = Snell | first5 = CR | authorlink5 = Christopher Snell
| display-authors =
| title = Postexertional malaise in women with chronic fatigue syndrome
| journal = Journal of Women's Health | volume = | issue = | page =
| date = February 2010
| pmid = 20095909
| doi = 10.1089/jwh.2009.1507
}}
</ref>
</references>

[[Category:Signs and symptoms]]

Post-exertional malaise

2019-04-19T13:39:40Z

MEandCFS:/* History */ c/e

'''Post-exertional malaise (PEM)''' refers to a ''worsening'' of [[List of symptoms in ME CFS|ME/CFS symptoms]] after minimal ''physical'' or ''mental'' [[exertion]],<ref name=":14" /><ref name=":32" /> which can be delayed 24-72 hours or more.<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15" /><ref name=":28">{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=137|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=2018-10-16|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.}}</ref><ref name=":30">{{Cite journal|last=|first=|date=2018|title=SAGE Journals: Your gateway to world-class journal research|url=http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf|journal=Sage Pub|language=en|volume=|pages=4-5|doi=10.1177/1359105318805819/suppl_file/appendix.__the_development_of_a_comprehensive_measure_of_post-exertional_malaise.8.20.2018.pdf|via=}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref> PEM is considered to be the hallmark symptom of [[ME/CFS]].<ref name=":0">{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK274235/|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|last=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations|last3=Institute of Medicine|date=2015|publisher=National Academies Press (US)|isbn=9780309316897|series=The National Academies Collection: Reports funded by National Institutes of Health|location=Washington (DC)|pmid=25695122}}</ref><ref>{{Cite web|url=https://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|website=www.medscape.com|access-date=2018-10-10}}</ref><ref>{{Cite web|url=https://ammes.org/2018/06/04/deconstructing-post-exertional-malaise-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-a-patient-centered-cross-sectional-survey/|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-10-16}}</ref> While in most diseases patients experience symptom relief after [[exercise|exercise,]]<ref>{{Cite journal|last=Loy|first=Bryan D.|last2=O'Connor|first2=Patrick J.|last3=Dishman|first3=Rodney K.|date=Oct 2013|title=The effect of a single bout of exercise on energy and fatigue states: a systematic review and meta-analysis|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2013.843266?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=1|issue=4|pages=223–242|doi=10.1080/21641846.2013.843266|issn=2164-1846}}</ref><ref>{{Cite journal|last=Robb-Nicholson|first=L. C.|last2=Daltroy|first2=L.|last3=Eaton|first3=H.|last4=Gall|first4=V.|last5=Wright|first5=E.|last6=Hartley|first6=L. H.|last7=Schur|first7=P. H.|last8=Liang|first8=M. H.|date=Dec 1989|title=Effects of aerobic conditioning in lupus fatigue: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/2590802|journal=British Journal of Rheumatology|volume=28|issue=6|pages=500–505|issn=0263-7103|pmid=2590802}}</ref><ref>{{Cite journal|last=Mostert|first=S.|last2=Kesselring|first2=J.|date=Apr 2002|title=Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis|url=https://www.ncbi.nlm.nih.gov/pubmed/11990874|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=8|issue=2|pages=161–168|doi=10.1191/1352458502ms779oa|issn=1352-4585|pmid=11990874}}</ref><ref>{{Cite news|url=https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise-and-chronic-disease/art-20046049|title=What you need to know about exercise and chronic disease|work=Mayo Clinic|access-date=2018-10-10|language=en}}</ref><ref>{{Cite journal|last=Dunn|first=A. L.|last2=Trivedi|first2=M. H.|last3=O'Neal|first3=H. A.|date=June 2001|title=Physical activity dose-response effects on outcomes of depression and anxiety|url=https://www.ncbi.nlm.nih.gov/pubmed/11427783|journal=Medicine and Science in Sports and Exercise|volume=33|issue=6 Suppl|pages=S587–597; discussion 609–610|issn=0195-9131|pmid=11427783}}</ref> the opposite is true for ME/CFS patients for whom even minimal exertion can cause a symptom flare-up.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Almond|first2=Freya|last3=De Becker|first3=Pascale|last4=Truijen|first4=Steven|last5=Paul|first5=Lorna|date=May 2008|title=Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial|url=https://www.ncbi.nlm.nih.gov/pubmed/18441039|journal=Clinical Rehabilitation|volume=22|issue=5|pages=426–435|doi=10.1177/0269215507084410|issn=0269-2155|pmid=18441039}}</ref> Because recovery is often prolonged,<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> lasting days or sometimes weeks to months,<ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> patients refer to these post-exertional setbacks as ‘crashes’.<ref>{{Cite news|url=https://www.healthrising.org/the-community-reports-best-practices-on-managing-thriving-with-or-just-surviving-chronic-fatigue-syndrome-mecfs/how-to-best-recover-from-a-crash-the-mecfs-community-reports/|title=How to Best Recover From a Crash: the ME/CFS Community Reports|work=Health Rising|access-date=2018-10-10|language=en-US}}</ref><ref name=":28" /> Depending on the criteria a patient meets ([[Systemic Exertion Intolerance Disease]] (SEID) for ME/CFS's [[Systemic Exertion Intolerance Disease#Diagnostic criteria| minimum core symptoms]], the [[Canadian Consensus Criteria]] (CCC) for [[Canadian Consensus Criteria#Definition| this criterion's ME/CFS symptoms]], or the [[International Consensus Criteria]] (ICC) for [[myalgic encephalomyelitis]] (ME) and [[International Consensus Criteria#Criteria|its ME symptoms]]) will correlate with the patient's symptoms that will worsen.

PEM can be caused by [[Exertion#Exertion in ME.2FCFS|physical as well as mental exertion]]<ref name=":14" /> and the symptom complex it invokes does not necessarily relate to the initial trigger.<ref name=":3" /> ME/CFS patients suffer from a post-exertional [[Flu-like symptoms|flu-like feeling,]]<ref name=":1" /> with [[brain fog|brain fog,]]<ref name=":13" /> [[photophobia]] and other symptoms not usually reported after exertion.<ref name=":3" /> In contrast to most forms of exercise intolerance, the onset of PEM is frequently delayed<ref name=":15" /> with many patients reporting the height of their symptom flare-up, two<ref name=":13" /> or several days after the initial trigger.

It is important to understand that in [[pediatric]] cases of ME/CFS, children do not describe having PEM. They can experience a relapse from exertion, perhaps from just taking the school bus, having to spend prolonged periods in bed.<ref>[https://www.me-pedia.org/wiki/Pediatric_myalgic_encephalomyelitis_and_chronic_fatigue_syndrome ME/CFS in Children - by David S. Bell - David Bell - Open Medicine Foundation - June 25, 2016]</ref>

[[File:Cfs woman sketch.jpg|435x435px|thumb|Post-exertional malaise (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]
The distinctive characteristics of post-exertional malaise are confirmed by scientific research. Exertion induces abnormalities in [[Cognitive dysfunction|cognitive functioning,]]<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=October 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781|via=}}</ref><ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref> [[immune activation|immune activation,]]<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723|issue=|quote=|author-link=Jo Nijs|author-link2=Andrea Nees|author-link3=Lorna Paul|author-link4=Margot De Kooning|author-link5=Kelly Ickmans|via=|author-link6=Mira Meeus|author-link7=Jessica Van Oosterwijck}}</ref> [[gene expression]]<ref name=":20">{{Cite journal|last=Light|first=Alan R.|last2=White|first2=Andrea T.|last3=Hughen|first3=Ronald W.|last4=Light|first4=Kathleen C.|date=Oct 2009|title=Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects|url=http://dx.doi.org/10.1016/j.jpain.2009.06.003|journal=The Journal of Pain|volume=10|issue=10|pages=1099–1112|doi=10.1016/j.jpain.2009.06.003|issn=1526-5900}}</ref><ref name=":21">{{Cite journal|last=Light|first=A. R.|last2=Bateman|first2=L.|last3=Jo|first3=D.|last4=Hughen|first4=R. W.|last5=VanHaitsma|first5=T. A.|last6=White|first6=A. T.|last7=Light|first7=K. C.|date=2011-07-13|title=Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome|url=http://dx.doi.org/10.1111/j.1365-2796.2011.02405.x|journal=Journal of Internal Medicine|volume=271|issue=1|pages=64–81|doi=10.1111/j.1365-2796.2011.02405.x|issn=0954-6820}}</ref><ref>{{Cite journal|last=Meyer|first=Jacob D.|last2=Light|first2=Alan R.|last3=Shukla|first3=Sanjay K.|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron J.|last7=Cook|first7=Dane B.|date=Oct 2013|title=Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression|url=http://dx.doi.org/10.1080/21641846.2013.838444|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|issue=4|pages=190–209|doi=10.1080/21641846.2013.838444|issn=2164-1846}}</ref><ref>{{Cite journal|last=White|first=A. T.|last2=Light|first2=A. R.|last3=Hughen|first3=R. W.|last4=VanHaitsma|first4=T. A.|last5=Light|first5=K. C.|date=2011-12-30|title=Differences in Metabolite-Detecting, Adrenergic, and Immune Gene Expression After Moderate Exercise in Patients With Chronic Fatigue Syndrome, Patients With Multiple Sclerosis, and Healthy Controls|url=http://dx.doi.org/10.1097/psy.0b013e31824152ed|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/psy.0b013e31824152ed|issn=0033-3174}}</ref> and [[endogenous pain inhibition]]<ref name=":22">{{Cite journal|last=Whiteside|first=Alan|last2=Hansen|first2=Stig|last3=Chaudhuri|first3=Abhijit|date=Jun 2004|title=Exercise lowers pain threshold in chronic fatigue syndrome|url=http://dx.doi.org/10.1016/j.pain.2004.02.029|journal=Pain|volume=109|issue=3|pages=497–499|doi=10.1016/j.pain.2004.02.029|issn=0304-3959}}</ref><ref name=":23">{{Cite journal|last=Meeus|first=M|last2=Roussel|first2=NA|last3=Truijen|first3=S|date=2010|title=Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: An experimental study|url=http://dx.doi.org/10.2340/16501977-0595|journal=Journal of Rehabilitation Medicine|volume=42|issue=9|pages=884–890|doi=10.2340/16501977-0595|issn=1650-1977}}</ref><ref name=":24">{{Cite journal|last=Van Oosterwijck|first=J.|last2=Nijs|first2=J.|last3=Meeus|first3=M.|last4=Lefever|first4=I.|last5=Huybrechts|first5=L.|last6=Lambrecht|first6=L.|last7=Paul|first7=L.|date=2010-03-03|title=Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: An experimental study|url=http://dx.doi.org/10.1111/j.1365-2796.2010.02228.x|journal=Journal of Internal Medicine|volume=268|issue=3|pages=265–278|doi=10.1111/j.1365-2796.2010.02228.x|issn=0954-6820|quote=|author-link=Jessica Van Oosterwijck|author-link2=Jo Nijs|author-link3=Mira Meeus|author-link4=|author-link5=|via=|author-link7=Lorna Paul}}</ref> in ME/CFS patients that were not seen before exertion or in healthy controls. Most importantly PEM can be demonstrated by a [[Two-day cardiopulmonary exercise test|2-day cardiopulmonary exercise test]] (CPET) procedure.<ref name=":16" /><ref name=":28" /> On the second day [[Two-day cardiopulmonary exercise test|CPET]], ME/CFS patients display a significant drop in [[VO2 max]] and [[maximal workload]], that is not seen in healthy controls or other diseases.<ref>{{Cite journal|last=Snell|first=C. R.|last2=Stevens|first2=S. R.|last3=Davenport|first3=T. E.|last4=Van Ness|first4=J. M.|date=2013-06-27|title=Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome|url=http://dx.doi.org/10.2522/ptj.20110368|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=0031-9023}}</ref><ref>{{Cite journal|last=Vermeulen|first=Ruud CW|last2=Kurk|first2=Ruud M|last3=Visser|first3=Frans C|last4=Sluiter|first4=Wim|last5=Scholte|first5=Hans R|date=2010|title=Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity|url=http://dx.doi.org/10.1186/1479-5876-8-93|journal=Journal of Translational Medicine|volume=8|issue=1|pages=93|doi=10.1186/1479-5876-8-93|issn=1479-5876}}</ref><ref name=":17" /><ref>{{Cite journal|last=Vanness|first=J. Mark|last2=Snell|first2=Christopher R.|last3=Stevens|first3=Staci R.|date=Jan 2007|title=Diminished Cardiopulmonary Capacity During Post-Exertional Malaise|url=http://dx.doi.org/10.1300/j092v14n02_07|journal=Journal of Chronic Fatigue Syndrome|volume=14|issue=2|pages=77–85|doi=10.1300/j092v14n02_07|issn=1057-3321}}</ref><ref name=":18" /> These objective measures track strongly with the presence, severity and duration of PEM.<ref name=":0" /> [[Brian Vastag]] won a groundbreaking long term disability (LTD) claim using CPET to prove his PEM was a severe disabling symptom.<ref>[US District Court of NJ: Brian Vastag v. Prudential Insurance Company of America, Civ.15-6197 (KSH), (CLW) https://t.co/Vq9GXo4VEI]</ref><ref>{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-02}}</ref>

A 2015 review of the literature by the [[National Academy of Medicine]] (NAM) concluded there to be “sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS from other conditions.”<ref name=":0" /> Disagreement exists however on the precise nature of PEM and how it should be defined,<ref name=":19">{{Cite journal|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth|last3=So|first3=Suzanna|last4=Scott|first4=Jilian|last5=Brown|first5=Abigail|date=2015|title=Problems in Defining Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295644/|journal=Journal of prevention & intervention in the community|volume=43|issue=1|pages=20–31|doi=10.1080/10852352.2014.973239|issn=1085-2352|pmc=4295644|pmid=25584525}}</ref> with some diagnostic criteria emphasizing [[Paresis|muscle weakness]] and others a more a general form of [[fatigue]] and exhaustion.<ref name=":8">{{Cite journal|last=McManimen|first=Stephanie L.|last2=Sunnquist|first2=Madison L.|last3=Jason|first3=Leonard A.|date=2016-08-24|title=Deconstructing post-exertional malaise: An exploratory factor analysis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/|journal=Journal of health psychology|doi=10.1177/1359105316664139|issn=1359-1053|pmc=5325824|pmid=27557649}}</ref>

The [[Centers for Disease Control and Prevention]] (CDC) outline different types of exertion that may trigger PEM and how it impacts patients noting some may be house-bound or completely bed-bound during a crash. "People with ME/CFS may not be able to predict what will cause a crash or how long it will last."<ref name=":32">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-11-21}}</ref> Examples of PEM given by the CDC are: attending a child’s school event may leave a patient house-bound for a couple of days unable to do needed tasks, like laundry; grocery shopping may cause a crash that requires a nap in the car before driving home or a call for a ride home; a shower may leave a patient bed-bound and unable to do anything for days; keeping up with work may lead to spending evenings and weekends recovering.<ref name=":32" />

== PEM described by Dr. David Kaufman ==
{{#ev:youtube|https://www.youtube.com/watch?v=RC9TjgE_PlU|400|right|'''PEM described by Dr. David Kaufman''' (2018) Kaufman/''Unrest'' Video begins @2:16 and PEM is described until @3:35|frame|start=136&rel=0&autoplay=0}}

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

(Video begins @2:16 and PEM is described until @3:35. View entire 11:47 for a full description of ME/CFS)

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Patients' description==
[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]
[[File:PEM.JPG|300px|thumb|right|#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with [[Neurally mediated hypotension|high pulse and very low energy]]. Even though you sometimes can see the exhaustion in someone's face, most [[List of symptoms in ME CFS|ME symptoms]] are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaise<ref>{{Cite web|url=https://twitter.com/ezchili/status/1085927134248488965|title=#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with high pulse and very low energy. Even though you sometimes can see the exhaustion in someone's face, most ME symptoms are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaisepic.twitter.com/FKSTo8W0hH|last=ez 📎|date=2019-01-17|website=@ezchili|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM2.JPG|300px|thumb|right|#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.<ref>{{Cite web|url=https://twitter.com/kaisecam/status/1085886323276349440|title=#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.pic.twitter.com/nTJVG63jRm|last=Kaise 🥄|first=Mx|date=2019-01-17|website=@kaisecam|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM3.JPG|300px|thumb|right|#TwoFacesofME Workday me v’s weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.<ref>{{Cite web|url=https://twitter.com/RachelFrancis/status/1085940724774912000|title=#TwoFacesofME Workday me vs weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.pic.twitter.com/qZNiQaVHyD|last=Francis|first=Rachel|date=2019-01-17|website=@RachelFrancis|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

[[File:PEM6.JPG|300px|thumb|right|What the [world] don’t [see] two faces of M.E.<ref>{{Cite web|url=https://twitter.com/SharonTiday/status/1085122891220430848|title=What the don’t two faces of M.E.pic.twitter.com/DYZVhtyrG5|last=Awareness|first=CFDA #|date=2019-01-15|website=@SharonTiday|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM7.JPG|300px|thumb|right|Joining #pwME sharing #TwoFacesofME for #MEAwareness 1: a fall day when I got outside (but ended up in bed a week) 2: what no one sees (constant [[Chronic pain|pain]], post exertional malaise & [[Sleep dysfunction|sleep deprivation]]) Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)<ref>{{Cite web|url=https://twitter.com/ceibakoru/status/1085894325832040448|title=Joining #pwME sharing #TwoFacesofME for #MEAwareness, 1: a fall day when I got outside (but ended up in bed a week), 2: what no one sees (constant pain, post exertional malaise & sleep deprivation). Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)pic.twitter.com/EpsMLT8E11|last=Ceiba 🌳Koru 🌀|date=2019-01-17|website=@ceibakoru|language=en|access-date=2019-01-17}}</ref>]]

=== An illness within an illness ===

PEM refers to a worsening of many ME/CFS symptoms as a result of physical or mental exertion. It consists of more than post-exertional fatigue and can cause severe debility. As one patient described it: <blockquote>“When I do any activity that goes beyond what I can do—I literally collapse—my body is in major pain, it hurts to lay in bed, it hurts to think, I can’t hardly talk—I can’t find the words, I feel my insides are at war.”<ref name=":0" /></blockquote> Another patient emphasized that the feeling of PEM is very different from what one experiences as a healthy person: <blockquote>"PEM is like nothing else you will experience in healthy life; a combination of a hangover, the flu, finishing a 10k run, all at the same time at varying levels of severity."<ref>{{Cite news|url=https://twitter.com/Fatigo_MECFS/status/1050305665565102080|title=Fatigo_MECFS on Twitter|work=Twitter|access-date=2018-10-11|language=en}}</ref></blockquote>Considering the serious but fluctuating debility PEM causes, ME/CFS expert Dr. [[Anthony Komaroff]] described it as “an illness within an illness”.<ref>{{Cite news|url=https://phoenixrising.me/archives/11884|title=Post-Exertional Malaise II: Perception and Reality By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref>

=== Energy conservation and pacing ===
Patients often report the feeling of a red line, an energy level that if exceeded, will result in a relapse. As one [[Norway|Norwegian]] patient described: <blockquote>“....And suddenly it is just too much. The body turns itself off, as if it has gone on strike. You have pushed too much for too long, it repeats itself, and the body stops functioning.”<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>Energy conservation strategies such as [[pacing]] and the [[Energy Envelope Theory|envelope theory]] have been developed to minimize PEM while allowing patients to stay as active as possible.<ref>{{Cite journal|last=Goudsmit|first=Ellen M.|last2=Nijs|first2=Jo|last3=Jason|first3=Leonard A.|last4=Wallman|first4=Karen E.|date=2012|title=Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document|url=https://www.ncbi.nlm.nih.gov/pubmed/22181560|journal=Disability and Rehabilitation|volume=34|issue=13|pages=1140–1147|doi=10.3109/09638288.2011.635746|issn=1464-5165|pmid=22181560}}</ref> These techniques advise patients to balance energy availability and expenditure and to recognize early signs of PEM so they can reduce activity levels before a relapse occurs.

== History ==

=== Case definitions ===
Early descriptions of symptom exacerbation in [[Myalgic encephalomyelitis|ME]] focused on post-exertional muscle weakness. Renowned ME-expert [[Melvin Ramsay]] for example wrote: <blockquote>"[[Muscle fatigability]] whereby, even after a minor degree of physical effort, three, four or five days or longer elapse before full [[muscle]] power is restored is unique and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME."<ref name=":10">Ramsay M. (1988). Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease. Gower Medical Publishing. Second edition.</ref> </blockquote>In a 1985 study [[Peter Behan|Behan]] et al. noted that all of their patients “had the same primary symptom that of gross fatigue made worse by exercise".<ref>{{Cite journal|last=Behan|first=P. O.|last2=Behan|first2=W. M.|last3=Bell|first3=E. J.|date=May 1985|title=The postviral fatigue syndrome - an analysis of the findings in 50 cases|url=https://www.ncbi.nlm.nih.gov/pubmed/2993423|journal=The Journal of Infection|volume=10|issue=3|pages=211–222|issn=0163-4453|pmid=2993423}}</ref>

'''Formerly used to define Chronic fatigue syndrome'''

In the 1988 [[Holmes criteria|Holmes definition]] of [[Chronic fatigue syndrome|CFS]], unexplained generalized muscle weakness was one of the 11 minor symptoms, yet it was fatigue that set the tone. Another minor symptom referred to “prolonged (24 hours or greater) generalized fatigue after levels of [[exercise]] that would have been easily tolerated in the patient’s premorbid state”.<ref>{{Cite journal|last=Holmes|first=G. P.|last2=Kaplan|first2=J. E.|last3=Gantz|first3=N. M.|last4=Komaroff|first4=A. L.|last5=Schonberger|first5=L. B.|last6=Straus|first6=S. E.|last7=Jones|first7=J. F.|last8=Dubois|first8=R. E.|last9=Cunningham-Rundles|first9=C.|date=Mar 1988|title=Chronic fatigue syndrome: a working case definition|url=https://www.ncbi.nlm.nih.gov/pubmed/2829679|journal=Annals of Internal Medicine|volume=108|issue=3|pages=387–389|issn=0003-4819|pmid=2829679}}</ref> PEM is not a mandatory symptom under the Holmes definition.

The wording post-exertional malaise was first used in one of the 8 minor symptoms in the 1994 [[Fukuda criteria]], but without further clarification of the term, except that it lasts more than 24 hours. PEM is not a mandatory symptom under the Fukuda criterion.

'''Currently disputed to define Chronic fatigue syndrome'''

The [[Oxford criteria]] is flawed as it does not list PEM as a symptom. Patients with the symptom of [[fatigue]], which many illnesses and diseases have, are swept into the diagnosis and research studies. ''The Argus Report'' article ''US NIH Report Calls for UK Definition of ME/CFS to be Scrapped'' wrote the following:<blockquote> The [[United States]] [[National Institutes of Health]] (NIH) has issued a draft report that highlights the dire need for scientific research that will help find a cure for the millions of people suffering from [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS) worldwide. The report also highlights the fact that the decades-old UK Royal Society of Medicine’s Oxford criteria for ME/CFS are severely “flawed,” and that continuing to use these criteria may “cause harm.” Further, the NIH report says that the Royal Society definition should “be retired” and replaced with a single case definition agreed to by the ME/CFS community.<ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref></blockquote>There are further criticisms [https://www.me-pedia.org/wiki/Oxford_criteria#Criticisms here].

'''Currently used to define ME/CFS'''

In 2003, [[Canadian Consensus Criteria]] (CCC) PEM became a recognized symptom for the diagnosis of ME/CFS. The CCC were the first criteria to stress that the onset of PEM could be delayed and to describe its debility as a flu-like distress.<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|last2=Jain|first2=Anil Kumar|last3=De Meirleir|first3=Kenny L.|last4=Peterson|first4=Daniel L.|last5=Klimas|first5=Nancy G.|last6=Lerner|first6=A. Martin|last7=Bested|first7=Alison C.|last8=Flor-Henry|first8=Pierre|last9=Joshi|first9=Pradip|date=Jan 2003|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v11n01_02|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=11|issue=1|pages=7–115|doi=10.1300/j092v11n01_02|issn=1057-3321}}</ref> [[Canadian Consensus Criteria#Definition|PEM and/or post-exertional fatigue]] is a mandatory symptom under the CCC criterion.<ref>{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|date=|website=investinme.org|page=4|type=|archive-url=|archive-date=|dead-url=|access-date=|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref>

The 2015 report of the [[National Academy of Medicine]] (NAM) describes PEM more generally as “an exacerbation of some or all of an individual’s ME/CFS symptoms that occurs after physical or cognitive exertion and leads to a reduction in functional ability.” The report confirmed PEM as the hallmark symptom of ME/CFS and advised to rename the disease accordingly to [[Systemic Exertion Intolerance Disease]] (SEID).<ref name=":0" /> PEM is a mandatory symptom under the SEID criterion.

'''Currently used to define Myalgic encephalomyelitis'''

In 2011, the [[International Consensus Criteria]] (ICC) introduced the new term '''Post-Exertional Neuro-immune Exhaustion (PENE)''' to refer to the characteristic exercise and exertion intolerance of [[myalgic encephalomyelitis]] (ME) patients. It notes a delayed onset and prolonged recovery, and uses acute [[flu-like symptoms]] to describe PENE. By definition PENE results in a substantial reduction in functioning, as even simple activities of daily living can cause a relapse.<ref name=":2">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> PENE is a mandatory symptom under the ICC criterion.

===Dismissed as disturbed effort perceptions or kinesiophobia ===
[[File:Brian vastag.png|thumb|right|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]
The existence of PEM as a distinctive and complex symptom of ME/CFS has been dismissed in early research into the disease. Some interpreted it as just fatigue after exercise<ref>https://www.cdc.gov/me-cfs/pdfs/symptom-inventory-questionnaire-508.pdf</ref>, while others saw it as an artifact of disturbed effort perceptions<ref>{{Cite journal|last=Lawrie|first=S. M.|last2=Machale|first2=S. M.|last3=Power|first3=M. J.|last4=Goodwin|first4=G. M.|date=Sep 1997|title=Is the chronic fatigue syndrome best understood as a primary disturbance of the sense of effort?|url=https://www.cambridge.org/core/journals/psychological-medicine/article/editorial-is-the-chronic-fatigue-syndrome-best-understood-as-a-primary-disturbance-of-the-sense-of-effort/434A5EB2C5B4F971A4A36C1DC3400A7E|journal=Psychological Medicine|language=en|volume=27|issue=5|pages=995–999|issn=1469-8978}}</ref><ref>{{Cite journal|last=Rosen|first=S D|last2=King|first2=J C|last3=Wilkinson|first3=J B|last4=Nixon|first4=P G|date=Dec 1990|title=Is chronic fatigue syndrome synonymous with effort syndrome?|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292947/|journal=Journal of the Royal Society of Medicine|volume=83|issue=12|pages=761–764|issn=0141-0768|pmc=1292947|pmid=2125315}}</ref><ref>{{Cite journal|last=Wallman|first=Karen E.|last2=Sacco|first2=Paul|date=Jan 2007|title=Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17365951|journal=Research in Sports Medicine|volume=15|issue=1|pages=47–59|doi=10.1080/15438620601184331|issn=1543-8627|pmid=17365951}}</ref> or an irrational fear of movement<ref>{{Cite journal|last=Silver|first=A.|last2=Haeney|first2=M.|last3=Vijayadurai|first3=P.|last4=Wilks|first4=D.|last5=Pattrick|first5=M.|last6=Main|first6=C. J.|date=Jun 2002|title=The role of fear of physical movement and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12069873|journal=Journal of Psychosomatic Research|volume=52|issue=6|pages=485–493|issn=0022-3999|pmid=12069873}}</ref><ref>{{Cite journal|last=Fischler|first=B.|last2=Dendale|first2=P.|last3=Michiels|first3=V.|last4=Cluydts|first4=R.|last5=Kaufman|first5=L.|last6=De Meirleir|first6=K.|date=Apr 1997|title=Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology|url=https://www.ncbi.nlm.nih.gov/pubmed/9160276|journal=Journal of Psychosomatic Research|volume=42|issue=4|pages=369–378|issn=0022-3999|pmid=9160276}}</ref>. One example of this is the [http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf Tampa scale kinesiophobia], adapted for [[chronic fatigue syndrome]]. Some of the questions in this scale ask about the experience of PEM such as: “If I were to try to overcome it, my symptoms would increase” or “my symptoms let me know when to stop exercising so that I do not harm myself”. Yet these symptoms are classified as an indicator of irrational fear of movement and exercise, instead of PEM.<ref>{{Cite web|url=http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf|title=Tampa Scale Kinesiophobia - Version Chronic Fatigue Syndrome|last=Nijs|first=J|last2=De Meirleir|first2=K|date=2004|website=painmotion.be|publisher=Archives of Physical Medicine and Rehabilitation|archive-url=|archive-date=|dead-url=|access-date=|last3=Duquet|first3=W}}</ref>

=== Critique of the term ===
The name post-exertional malaise was introduced by the 1994 Fukuda criteria and had no prior medical meaning attached to it.<ref name=":3">{{Cite journal|last=Chu|first=Lily|last2=Valencia|first2=Ian J.|last3=Garvert|first3=Donn W.|last4=Montoya|first4=Jose G.|date=2018|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey|url=https://www.ncbi.nlm.nih.gov/pubmed/29856774|journal=PloS One|volume=13|issue=6|pages=e0197811|doi=10.1371/journal.pone.0197811|issn=1932-6203|pmc=5983853|pmid=29856774|quote=|author-link=Lily Chu|author-link2=Ian Valencia|author-link3=Donn Gavert|author-link4=Jose Montoya|author-link5=|via=}}</ref> While in the scientific literature, the term has become the standard to describe the relapses ME/CFS patients suffer after exertion, patients argue that it trivializes their experience. The term malaise after all refers to “a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify”<ref>{{Cite web|url=https://en.oxforddictionaries.com/definition/malaise|title=Definition of malaise in English by Oxford Dictionaries|website=Oxford Dictionaries {{!}} English|access-date=2018-10-13}}</ref>. Doctor of [http://sph.berkeley.edu/ Public Health at Berkely], [[David Tuller]], calls post-exertional malaise a “complete misnomer” arguing what ME/CFS patients experience "is much closer to a serious crash or relapse than a Victorian fainting spell.”<ref>{{Cite web|url=http://www.virology.ws/2011/11/23/chronic-fatigue-syndrome-and-the-cdc-a-long-tangled-tale/|title=Chronic Fatigue Syndrome and the CDC: A Long, Tangled Tale|website=www.virology.ws|language=en-US|access-date=2018-10-10}}</ref> ME/CFS patients usually use the abbreviation PEM or the term ‘crash’ to describe their relapses.

== The distinctive characteristics of PEM ==
Four aspects differentiate the post-exertional malaise of ME/CFS patients from the exercise intolerance commonly reported in patients suffering from [[deconditioning]] or other conditions.

=== Timing ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertional Malaise: History, Characteristics, Evidence'' (2015) By Dr. Lily Chu/Solve CFS">https://www.youtube.com/watch?v=hxJPrkWHcBo</embedvideo>
First of all, there is the time lapse. While physical complaints are usually reported during or shortly after exercise, PEM often has a delayed onset, hours or sometimes even days after the original trigger. Yoshiuchi et al. for example wrote that: “after a briefer maximal exercise task, reports of worsening CFS symptoms were inconsistent or absent until 5 days after the challenge, a pattern not typically observed in real life.”<ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> The authors noted that this delay could be used to distinguish ME/CFS from other fatiguing illness. Another study from Stanford University showed that in up to 37% of the 150 ME/CFS patients studied, PEM may not begin until a day or more after an [[Exertion|exertional]] trigger.<ref name=":3" />

[[File:Rosa SEID.JPG|400px|thumb|Rosa age 25 in 1986. In 2015 the [[SEID]] criteria were released. Rosa read about PEM and how it is delayed and makes [[ME/CFS]] symptoms including [[chronic fatigue]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her [[List of symptoms in ME CFS|worsening symptoms]] with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled]]

Patients may not be familiar with this characteristic of their relapses, since it is very counter-intuitive. As one patient noted:<blockquote>"It's really counter-intuitive to feel bad after a delay of 24 hours after exertion. It may take quite some time before people even make that connection, if ever. I only noticed it about three years in, and I hesitated to mention to others because I thought it might make me sound nuts."<ref name=":5">{{Cite news|url=https://www.s4me.info/threads/s4me-submission-to-the-public-review-on-common-data-elements-for-me-cfs-concerns-with-the-proposed-measure-of-post-exertional-malaise.2220/|title=S4ME: Submission to the public review on Common Data Elements for ME/CFS: Concerns with the proposed measure of post-exertional malaise|work=Science for ME|access-date=2018-10-10|language=en-US}}</ref></blockquote>Another time-related characteristic of PEM is a prolonged recovery period. In a 2010 study 25 M/CFS patients and 23 matched controls were followed up for seven days after performing a maximal cardiopulmonary exercise test. After two days, all controls subjects were recovered while only one ME/CFS patient was. Most (60%) of the ME/CFS participants reported that it took more than five days to fully recover from the test and many reported feeling at their worst 24 to 48 hours after the test.<ref name=":9">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health |volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> Other studies have found the same prolonged recovery period in ME/CFS patients after exertion. A Dutch study for example noted: <blockquote>"For CFS patients, daily observed fatigue was increased up to 2 days after the exercise test. For controls, self-observed fatigue returned to baseline after 2 h."<ref>{{Cite journal|last=Bazelmans|first=Ellen|last2=Bleijenberg|first2=Gijs|last3=Voeten|first3=Marinus J. M.|last4=van der Meer|first4=Jos W. M.|last5=Folgering|first5=Hans|date=Oct 2005|title=Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16223622|journal=Journal of Psychosomatic Research|volume=59|issue=4|pages=201–208|doi=10.1016/j.jpsychores.2005.04.003|issn=0022-3999|pmid=16223622|quote=|author-link=Ellen Bazelmans|author-link2=Gijs Bleijenberg|author-link3=Marinus Voeten|author-link4=Jos van der Meer|author-link5=Hans Folgering|via=}}</ref></blockquote>[[Charles Lapp|Lapp]] et al. followed 31 ME/CFS patients for 12 days after performing a maximal exercise test of 8-10 minutes. The average relapse lasted 8,82 days, although 22% of patients were still in relapse when the study ended at 12 days.<ref>{{Cite journal|last=Lapp|first=C. W.|date=Jul 1997|title=Exercise limits in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9236491|journal=The American Journal of Medicine|volume=103|issue=1|pages=83–84|issn=0002-9343|pmid=9236491}}</ref> In the Stanford study by [[Lily Chu|Chu]] et al. 87% of respondents indicated that they endure PEM for 24 hours or more. The authors concluded: <blockquote>"In many medical conditions, exertion-exacerbated symptoms usually start during exertion or immediately after and usually resolve immediately or shortly after exertion stops. In contrast, PEM may not start until hours or even days after the trigger starts or has been removed, may peak after the first day, and may not stop until hours to months later. This characteristic of PEM often leads patients and clinicians to believe that symptom exacerbations are random rather than associated with a trigger; most people will not intuit that symptoms are caused by a trigger that occurred hours to days prior unless specifically asked by their clinicians to pay attention."<ref name=":3" /> </blockquote>

=== Type of symptoms ===
The second characteristic of PEM is the [[List of symptoms in ME CFS|type of symptoms reported]]. The [[Canadian Consensus Criteria]], a 2003 clinical guideline formed by experts in the field, underlines that many PEM symptoms are [[Immune system|immune-related]]: <blockquote>"The [[malaise]] that follows exertion is difficult to describe but is often reported to be similar to the generalized [[pain]], discomfort and fatigue associated with the acute phase of [[influenza]]. Delayed malaise and fatigue may be associated with signs of immune activation: [[sore throat]], lymph glandular tenderness and/or [[Swollen lymph nodes|swelling]], general malaise, increased pain or [[Brain fog|cognitive fog]]."<ref name=":1" /> </blockquote>[[Mark VanNess|Van Ness]] et al. noted how [[Cognitive dysfunction|cognitive difficulties]] after exertion differentiate ME/CFS patients from healthy controls: <blockquote>"Another interesting difference between groups was the reported symptom of [[cognitive dysfunction]], for example, ‘‘[[Brain fog|brain-fog]]’’ or ‘‘difficulty concentrating.’’ Problems of this nature were not reported by any of the control subjects, whereas 12 patients (48%) experienced these problems: “Carrying on conversations was hard.” “Can’t think straight.” “My mind was not clear.”<ref name=":9" /></blockquote>This was elaborated by [[Lily Chu|Chu]] et al., the research team who conducted the first in-depth investigation on how ME/CFS patients describe their PEM: <blockquote>"There exists no medical condition the authors are familiar with where exertion or emotional distress causes immune/ [[Inflammation|inflammatory]]-related symptoms like sore throat, tender lymph nodes, or flu-like feelings, yet 60% and 36% of our subjects, respectively, reported these symptoms with either stimuli and about a quarter experienced all 3 with exertion. Conversely, symptoms typically associated with physical exertion in other conditions, like [[Dyspnea|shortness of breath]] or [[chest pain]] in [[chronic lung]] or [[heart disease]], are rarely reported in ME/CFS. Furthermore, it is well-established that physical activity improves [[Mood swings|mood]], [[Sleep dysfunction|sleep]], and pain in both healthy people as well those with chronic illnesses like depression or anxiety yet our subjects report worsened sleep, mood, and pain with physical activity."<ref name=":3" /></blockquote>

=== Triggers ===
A third characteristic of PEM is that it can be elicited by multiple triggers. Research has shown that ME/CFS patients experience PEM after both [[Exertion#Exertion in ME.2FCFS|physical and cognitive exertion]]. A 2014 study for example followed up on 32 ME/CFS patients after completing a battery of neurocognitive tests. As the authors concluded: “following a challenging cognitive demand, fatigue significantly increased two days after testing”, which was “suggestive of post-exertional symptom exacerbation following mental effort.”<ref name=":14">{{Cite journal|last=Arroll|first=Megan A.|last2=Attree|first2=Elizabeth A.|last3=O'Leary|first3=John M.|last4=Dancey|first4=Christine P.|date=2014-04-03|title=The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2014.892755|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=2|issue=2|pages=57–63|doi=10.1080/21641846.2014.892755|issn=2164-1846}}</ref> Commenting on the [https://www.me-pedia.org/wiki/1980-81_Ayrshire_outbreak outbreak in West Kilbride, Ayrshire], Ramsay remarked: <blockquote>“Once the disease was established the most characteristic symptom was extreme exhaustion, particularly after exercise. The exhaustion also occurred after emotional or mental strain.”<ref name=":10" /> </blockquote>Some other precipitants of PEM that have been reported include positional changes and exposure to excessive light or sounds<ref>{{Cite web|url=http://anilvanderzee.com/dance-hermit-16-vs-sumo-baby-part-1/|title=Dance hermit ’16 vs. Sumo Baby (part 1) {{!}} Anil van der Zee|website=anilvanderzee.com|language=en-GB|access-date=2018-10-13}}</ref>. While PEM was often thought of as symptom exacerbation after exercise, it is clear that for some ME/CFS patients even basic activities of daily living such as toileting, bathing, dressing, communicating, and reading can trigger relapses.<ref name=":11" /> As long time ME/CFS expert [[Jennie Spotila|Jennifer Spotila]] explained in a four-piece exploration of the phenomenon post-exertional malaise:<blockquote>“The use of the word ‘exertion’ may create the impression that PEM is triggered by strenuous or intense activity, but this is not the case […] Some patients need only attempt to make a simple meal or get dressed before PEM descends.”<ref>{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref></blockquote>This was confirmed by Chu et al. <blockquote>"[…] our results provide formal evidence supporting patient narratives, clinician experiences, and current case definitions which assert that even tasks like walking, cooking, or reading can provoke PEM."<ref name=":3" /> </blockquote>In some instances, the specific trigger of PEM cannot be identified.<ref name=":11">NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Post-Exertional Malaise Subgroup Draft Recommendations Public Review Comments Due January 31, 2018</ref>

=== Loss of functional capacity ===
A fourth distinctive element of PEM is often described as a loss of stamina and/or functional capacity. This refers to the results of the 2-day cardiopulmonary exercise test (CPET) procedure. A CPET is usually reproducible and normally has a test-retest difference of 7-12%<ref name=":16">{{Cite journal|last=Stevens|first=Staci|last2=Snell|first2=Chris|last3=Stevens|first3=Jared|last4=Keller|first4=Betsy|last5=VanNess|first5=J. Mark|date=2018|title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00242/full|journal=Frontiers in Pediatrics|language=English|volume=6|doi=10.3389/fped.2018.00242|issn=2296-2360}}</ref>. ME/CFS patients however show strikingly lower results on several measures at the second CPET compared to the first, despite meeting objective markers of maximal effort. These results have been replicated by several research teams, though there is inconsistency on which measure ([[VO2]] or maximal workload, at peak or ventilatory threshold), the decline in functional capacity is best represented.

{| class="wikitable"
! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS
|-
|
|Number of ME/CFS patients
|VO2 peak
|VO2 at VT
|Workload peak
|Workload at VT
|HR peak
|O2pulse at VT
|-
|[[Mark VanNess|VanNess]] et al. 2007.
|6
| -22%
| -26%
|?
|?
|?
|?
|-
|[[Vemeulen]] et al. 2010.
|15
| -6.3%
| -7.0%
| -5.3%
| -7.0%
| -1.9%
| -8.8%
|-
|[[Christopher Snell|Snell]] et al. 2013.
|51
| -5%
| -10.8%
| -7.2%
| -55.2%
|?
|?
|-
|[[Betsy Keller|Keller]] et al. 2014.
|22
| -13.8%
| -15.8%
| -12.5%
| -21.3%
| -5.9%
| -12.6%
|-
|[[Hodges]] et al. 2018.
|10
| +5.3%
| +6.1%
| -6.7%
| -11.4%
| -0.6%
|?
|}
The drop in functional capacity on the second CPET is usually not seen in other diseases. According to [[Betsy Keller|Keller]] et al. "ME/CFS patients currently represent a unique class of ill patients who do not reproduce maximal CPET measures, unlike individuals with cardiovascular disease, lung disease, end-stage renal disease pulmonary arterial hypertension and cystic fibrosis".<ref name=":17">{{Cite journal|last=Keller|first=Betsy A.|last2=Pryor|first2=John Luke|last3=Giloteaux|first3=Ludovic|date=2014-04-23|title=Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref> A preliminary study from [[New Zealand]] suggests that patients with MS do not display the same decline on the second day of exercise testing, as do patients with ME/CFS.<ref name=":18">{{Cite journal|last=Hodges|first=L. D.|last2=Nielsen|first2=T.|last3=Baken|first3=D.|date=Jul 2018|title=Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4|pages=639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref>

Questions have however been raised about the clinical use of the 2-day CPET procedure. [[Christopher Snell|Snell]] et al. suggested it might be unethical to use this method since many ME/CFS patients might suffer a serious relapse as a result of exercise performance.<ref>{{Cite journal|last=Snell|first=Christopher R.|last2=Stevens|first2=Staci R.|last3=Davenport|first3=Todd E.|last4=Van Ness|first4=J. Mark|date=Nov 2013|title=Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23813081|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=1538-6724|pmid=23813081}}</ref> Others have noted that the CPET- procedure is not practical either. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, may not be available to most clinicians.<ref name=":11" /> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref name=":7">{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref> For these reasons PEM is usually assessed using self-reporting questionnaires.

== Differentiation ==
Several studies have shown that PEM is the symptom of ME/CFS that best differentiates it from other diseases.

=== Healthy controls and idiopathic chronic fatigue ===
PEM was one of the symptoms in the CDC symptom inventory list that differentiated subjects with ME/CFS from those without the disease.<ref>{{Cite journal|last=Wagner|first=Dieter|last2=Nisenbaum|first2=Rosane|last3=Heim|first3=Christine|last4=Jones|first4=James F.|last5=Unger|first5=Elizabeth R.|last6=Reeves|first6=William C.|date=2005-07-22|title=Psychometric properties of the CDC Symptom Inventory for assessment of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16042777|journal=Population Health Metrics|volume=3|pages=8|doi=10.1186/1478-7954-3-8|issn=1478-7954|pmc=1183246|pmid=16042777}}</ref> It was also the highest loading factor among a data set of 38 measurements used for a principal component analysis of unexplained chronic fatigue.<ref>{{Cite journal|last=Vollmer-Conna|first=Uté|last2=Aslakson|first2=Eric|last3=White|first3=Peter D|date=Apr 2006|title=An empirical delineation of the heterogeneity of chronic unexplained fatigue in women|url=https://www.futuremedicine.com/doi/abs/10.2217/14622416.7.3.355|journal=Pharmacogenomics|language=en|volume=7|issue=3|pages=355–364|doi=10.2217/14622416.7.3.355|issn=1462-2416}}</ref> Data for this study came from the epidemiological study in Wichita, Kansas.

The other major epidemiological study, carried out in Chicago, also identified PEM as the hallmark symptom of ME/CFS. In a 10 year follow-up study on the 32 patients originally identified as having ME/CFS, all of the contacted patients reported post-exertional malaise at some point in time. This symptom was able to differentiate ME/CFS patients with those with [[idiopathic chronic fatigue]], those with exclusionary illnesses and healthy controls. According to the author: <blockquote>"Among all the variables in this study, only for post-exertional malaise did the CFS group significantly differ from the other three conditions. This reaffirms the importance of this being a cardinal and critical symptom for CFS."<ref>{{Cite journal|last=Jason|first=Leonard A.|date=Feb 2011|title=Natural History of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171164/|journal=Rehabilitation psychology|volume=56|issue=1|pages=32–42|doi=10.1037/a0022595|issn=0090-5550|pmc=3171164|pmid=21401284}}</ref> </blockquote>Using a large sample of ME/CFS patients from Newcastle, [[Norway]] and the [https://www.me-pedia.org/wiki/Solve_ME/CFS_Initiative#Biobank Solve ME/CFS Biobank], Jason et al. conducted an analysis of different case definitions and symptoms. The domain of post-exertional malaise was found to be most adequate at differentiating ME/CFS patients from controls. As the authors noted: <blockquote>Using the latent variables from the empiric criteria, only one factor (PEM) was needed to reach a sensitivity of 90.8%, specificity of 92.5% and accuracy of 91.6%, and this was the only data mining where all percentages were over 90%. […] the fact that PEM came out in all analyses supports the importance of this domain in the case definition.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Reed|first5=Jordan|last6=Furst|first6=Jacob|last7=Newton|first7=Julia L.|last8=Strand|first8=Elin Bolle|last9=Vernon|first9=Suzanne D.|date=2014-04-01|title=Comparing and Contrasting Consensus versus Empirical Domains|url=https://www.ncbi.nlm.nih.gov/pubmed/26977374|journal=Fatigue: Biomedicine, Health & Behavior|volume=3|issue=2|pages=63–74|doi=10.1080/21641846.2015.1017344|issn=2164-1846|pmc=4788637|pmid=26977374}}</ref> </blockquote>A 2014 examination, using 236 patients and 86 controls, showed that three symptoms accurately classified 95.4% of participants as patient or control: fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Sunnquist|first2=Madison|last3=Brown|first3=Abigail|last4=Evans|first4=Meredyth|last5=Vernon|first5=Suzanne D.|last6=Furst|first6=Jacob|last7=Simonis|first7=Valerie|date=2014-01-01|title=Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24511456|journal=Fatigue: Biomedicine, Health & Behavior|volume=2|issue=1|pages=40–56|doi=10.1080/21641846.2013.862993|issn=2164-1846|pmc=3912876|pmid=24511456}}</ref> Another data mining study by the same research group, suggested the selection of four symptoms: next to extreme tiredness, unrefreshing sleep and [[Word-finding problems|difficulty finding the right word to say]] or [[Aphasia|expressing thoughts]], PEM was once again represented with the item “physically drained/sick after mild activity.”<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Evans|first5=Meredyth|last6=Jantke|first6=Rachel|last7=Williams|first7=Yolonda|last8=Furst|first8=Jacob|last9=Vernon|first9=Suzanne D.|date=2015|title=Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Toward An Empirical Case Definition|url=https://www.ncbi.nlm.nih.gov/pubmed/26029488|journal=Health Psychology and Behavioral Medicine|volume=3|issue=1|pages=82–93|doi=10.1080/21642850.2015.1014489|issn=2164-2850|pmc=4443921|pmid=26029488}}</ref>

[[Michael Maes|Maes]] et al. divided ME/CFS patients into two groups: those with or without PEM lasting for more than 24 hours. Analysis showed this to be a meaningful division as the former group (45% of the sample) not only had higher symptom scores on concentration difficulties and a subjective experience of infection, but also higher markers of immune-activation such as [[Interleukin 1|IL-1]], [[TNFa]], [[lysozyme]] and [[neopterin]], than the CFS group without PEM. According to the authors their findings, "underscore the relevance of post-exertional malaise to identify a subgroup of CFS patients that should be diagnosed as ME".<ref>{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Johnson|first3=Cort|date=2012-12-30|title=Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data|url=https://www.ncbi.nlm.nih.gov/pubmed/22521895|journal=Psychiatry Research|volume=200|issue=2-3|pages=754–760|doi=10.1016/j.psychres.2012.03.031|issn=1872-7123|pmid=22521895}}</ref>

=== Multiple sclerosis ===
According to a 2015 report by the National Academy of Medicine, the prevalence of PEM among ME/CFS patients varies from 69 to 100%, which is much higher than in other disease groups.<ref name=":0" /> In a 1996 study by Komaroff et al. 13 of 25 MS-patients (52%) reported PEM<ref name=":12">{{Cite journal|last=Komaroff|first=A. L.|last2=Fagioli|first2=L. R.|last3=Geiger|first3=A. M.|last4=Doolittle|first4=T. H.|last5=Lee|first5=J.|last6=Kornish|first6=R. J.|last7=Gleit|first7=M. A.|last8=Guerriero|first8=R. T.|date=Jan 1996|title=An examination of the working case definition of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8579088|journal=The American Journal of Medicine|volume=100|issue=1|pages=56–64|issn=0002-9343|pmid=8579088}}</ref>, a figure similar to what Jason et al. found with the DSQ PEM subscale in a cohort of 106 MS-patients.<ref>{{Cite journal|last=Jason|first=L. A.|last2=Ohanian|first2=D.|last3=Brown|first3=A.|last4=Sunnquist|first4=M.|last5=McManimen|first5=S.|last6=Klebek|first6=L.|last7=Fox|first7=P.|last8=Sorenson|first8=M.|date=2017|title=Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29430570|journal=Insights in Biomedicine|volume=2|issue=2|doi=10.21767/2572-5610.10027|issn=2572-5610|pmc=5800741|pmid=29430570}}</ref> Both studies used a broad definition of PEM which focused on fatigue after exercise. Preliminary research suggests that adding more specific questions, for example about the prolonged recovery and various type of triggers, PEM might be able to differentiate ME/CFS from [[multiple sclerosis]]. A 2018 study for example showed that ME/CFS patients reported to experience PEM more often through mental exertion and to recover more slowly from PEM compared to multiple sclerosis patients.<ref name=":7" />
=== Major Depressive disorder ===
In the 1996 study by Komaroff et al., only 19% of patients with major [[depression]] reported PEM.<ref name=":12" /> A similar figure was found by Hawk et al., who found PEM in 3 patients in their sample of 15 with major depressive disorder.<ref>{{Cite journal|last=Hawk|first=Caroline|last2=Jason|first2=Leonard A.|last3=Torres-Harding|first3=Susan|date=2006|title=Differential diagnosis of chronic fatigue syndrome and major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/17078775|journal=International Journal of Behavioral Medicine|volume=13|issue=3|pages=244–251|doi=10.1207/s15327558ijbm1303_8|issn=1070-5503|pmid=17078775}}</ref> In contrast all of the 15 studied ME/CFS patients reported PEM, making it the largest discriminant function for all investigated symptoms. White et al. studied patients with persistent symptoms of fatigue and poor concentration after glandular fever. According to the authors "the complaint of post-exertional physical fatigue may help to differentiate post-viral fatigue states from psychiatric disorders."<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmed/8588010|title=The validity and reliability of the fatigue syndrome that follows glandular fever. - PubMed - NCBI|last=White|first=PD|website=www.ncbi.nlm.nih.gov|language=en|access-date=2018-10-24}}</ref>

=== Gulf war illness ===
[[James Baraniuk|Baraniuk]] and Shivapurkar (2017) looked at [[MicroRNA]]<nowiki/>s (miRNA) in the [[cerebrospinal fluid]] of ME/CFS patients, healthy controls and patients with [[Gulf War Illness]] before and after an exercise challenge (a submaximal bicycle exercise). While there were no differences in miRNA between the groups at baseline, a distinct signature appeared after exercise. According to the authors, "exercise caused distinct patterns of [[miRNA]] changes in CFS and […] [[Gulf War Illness|GWI]] indicating significant pathophysiological differences between conditions."<ref>{{Cite journal|last=Baraniuk|first=James N.|last2=Shivapurkar|first2=Narayan|date=2017-11-10|title=Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects|url=https://www.nature.com/articles/s41598-017-15383-9|journal=Scientific Reports|language=En|volume=7|issue=1|doi=10.1038/s41598-017-15383-9|issn=2045-2322}}</ref> A 2013 study under the guidance of [[Nancy Klimas]] compared the immune signature in 30 Gulf war patients, 22 ME/CFS patients and 30 controls, after an graded exercise test. Results indicated the importance of physical exercise for differentiating these different groups: <blockquote>"Common to both GWI and CFS illness signatures were the direct or indirect contributions of IL-10 and IL-23 expression though these occurred at very different times. While levels measured at rest supported an illness signature in GWI, their impact in CFS was only observable during and after exercise, again emphasizing the importance of a challenge and response timeline in distinguishing these illnesses."<ref>{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23800166|journal=BMC immunology|volume=14|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=3698072|pmid=23800166}}</ref></blockquote>

== Objective findings after exertion: ==
In the 1980s Melvin A. Ramsay stressed the use of assessing ME-patients after exertion. Regarding muscle weakness – what he regarded as the hallmark symptom of the disease –he noted: <blockquote>"If muscle power is found to be satisfactory, a re-examination should be made after exercise; a walk of half a mile is sufficient, as very few ME case can manage more. […] It is most important to stress the fact that cases of ME of mild or even moderate severity may have normal muscle power in a remission. In such cases, test for muscle power should be repeated after exercise."<ref name=":10" /> </blockquote>Though the definition of PEM has been expended far beyond muscle weakness, modern day research has confirmed the utility of testing ME/CFS after exertion. Many markers that are normal in resting state in ME/CFS patients turn out to be abnormal after a physical or cognitive stressor.<ref name=":0" />

=== Gene expression ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''72. Gene-expression and exercise / Gen-expressie en inspanning – dr. Lucinda Bateman'' (2015) By Dr. Lucinda Bateman/Wetenschap voor Patienten - ME/cvs Vereniging">https://https://www.youtube.com/watch?v=F1PP21TmUPs</embedvideo>

One example is gene expression. In a 2009 study Light et al. showed that after a moderate exercise test, the [[Leucocyte|leukocytes]] of ME/CFS patients showed an increase in expression of [[Adrenergic receptor|adrenergic]], [[metabolite]] detecting and [[immune-related genes]] that was not seen in healthy controls. Before the exercise test there were no abnormalities in the expression of these genes of ME/CFS patients. The authors speculated this to be evidence for sensitization of fatigue pathways in ME/CFS.<ref name=":20" /> The research team was able to confirm their results in a subsequent study using a larger sample of 48 patients.<ref name=":21" /> In a 2012 comparison MS patients also displayed an increase in post-exercise gene expression, but only ME/CFS patients showed increases in metabolite-detecting sensory receptors. According to the authors:<blockquote>"Because only the CFS patients showed increases in these metabolite-detecting receptors, the sensory receptor elements of this gene profile seem particularly specific to CFS and may reflect dysregulated pathways that directly contribute to increased effort sense during exercise and postexertional malaise."<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=VanHaitsma|first4=Timothy A.|last5=Light|first5=Kathleen C.|date=Jan 2012|title=Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/PSY.0b013e31824152ed|issn=0033-3174|pmc=3256093|pmid=22210239}}</ref></blockquote>Attempts at replication by other research teams have produced contradictory results. Meyer et al. were unable to confirm most of the post-exertional increases in gene expression, except for some in the adrenergic and glucocorticoid pathway.<ref>{{Cite journal|last=Meyer|first=Jacob|last2=R. Light|first2=Alan|last3=Shukla|first3=Sanjay|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron|last7=Cook|first7=Dane|date=2013-10-01|title=Post-exertion malaise in chronic fatigue syndrome: Symptoms and gene expression|url=https://www.researchgate.net/publication/258165434_Post-exertion_malaise_in_chronic_fatigue_syndrome_Symptoms_and_gene_expression|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|pages=190–209|doi=10.1080/21641846.2013.838444}}</ref> An [[Australia|Australian]] team under the guidance of [[Andrew Lloyd]] failed to find any significant exercise-induced changes in leucocyte gene expression, though the patient sample used (n = 10) was rather small and did not include any patients with severe [[functional disability]].<ref>{{Cite journal|last=Keech|first=Andrew|last2=Vollmer-Conna|first2=Ute|last3=Barry|first3=Benjamin K.|last4=Lloyd|first4=Andrew R.|date=2016|title=Gene Expression in Response to Exercise in Patients with Chronic Fatigue Syndrome: A Pilot Study|url=https://www.ncbi.nlm.nih.gov/pubmed/27713703|journal=Frontiers in Physiology|volume=7|pages=421|doi=10.3389/fphys.2016.00421|issn=1664-042X|pmc=5031769|pmid=27713703}}</ref>

=== Immune activation ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Inducing Post-Exertional Malaise in ME/CFS: A Look at the Research Evidence'' (2015) By Dr. Peter Rowe/Solve CFS">https://www.youtube.com/watch?v=ux93w7yGQ5g</embedvideo>
There are many studies demonstrating exercise-induced immunological abnormalities in ME/CFS patients.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723}}</ref> Most findings however still have to be replicated by other research groups, using larger samples.

==== Oxidative stress ====
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertion Malaise: The Intersection of Biology and Behavior'' (2015) By Dr. Dane B. Cook/Solve CFS">https://www.youtube.com/watch?v=vfmrPd4-rIE</embedvideo>
In 2005 the French team Yammes et al. found a lengthened and accentuated oxidative stress response in ME/CFS patients after a cycling exercise until exhaustion. At baseline markers of [[oxidative stress]] (thiobarbituric acidreactiv substances and ascorbic acid) did not differ significantly from healthy controls. After the exercise challenge however, the oxidative stress response occurred sooner and lasted longer in the ME/CFS group. This was associated with alterations in muscle excitability (lengthened [[M-wave]] duration) in ME/CFS-patients, which were not seen in controls.<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Mambrini|first3=O.|last4=Brégeon|first4=F.|last5=Delliaux|first5=S.|date=Mar 2005|title=Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/15715687|journal=Journal of Internal Medicine|volume=257|issue=3|pages=299–310|doi=10.1111/j.1365-2796.2005.01452.x|issn=0954-6820|pmid=15715687}}</ref> A small 2009 follow-up study confirmed these results and associated it with a post-exertional reduction of [[Heat shock protein|heat shock proteins]] HSP 27 and HSP 70 after exercise.<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=Aug 2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://www.ncbi.nlm.nih.gov/pubmed/19457057|journal=Journal of Internal Medicine|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796|pmid=19457057}}</ref> According to the authors, this is another indication of an impaired redox status in ME/CFS patients. A 2011 study confirmed most of these results in a larger cohort of 43 ME/CFS patients and 23 healthy controls. Again the data indicated an increased exercise-induced oxidative stress and a reduced Hsp response. Though it is know that deconditioning can increase oxidative stress, the authors argued this to be unlikely in their study population, for several reasons: <blockquote>“…deconditioning can be ruled out in our study because (i) it induces carbohydrate and lipid disorders that were not observed during routine biochemical check-up in these CFS patients, (ii) CFS patients did not have reduced maximal exercise performance or an accentuated lactic acid response and (iii) we found no correlation between the duration of CFS symptoms […] and the resting levels of oxidant–antioxidant status and HSPs.”<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|date=Jul 2012|title=Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins|url=https://www.ncbi.nlm.nih.gov/pubmed/22112145|journal=Journal of Internal Medicine|volume=272|issue=1|pages=74–84|doi=10.1111/j.1365-2796.2011.02488.x|issn=1365-2796|pmid=22112145}}</ref></blockquote>A [[Canada|Canadian]] research team had already reported a marked decline of HSP 27 during the post-exercise period of six ME/CFS patients in 2002.<ref>{{Cite journal|last=Thambirajah|first=Anita A.|last2=Sleigh|first2=Kenna|last3=Stiver|first3=H. Grant|last4=Chow|first4=Anthony W.|date=2008-12-01|title=Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/19032901|journal=Clinical and Investigative Medicine. Medecine Clinique Et Experimentale|volume=31|issue=6|pages=E319–327|issn=1488-2353|pmid=19032901}}</ref>

==== Complement C4a ====
In 2003 Sorensen et al. found that the [[Complement C4a|complement split product C4a]] was increased after exercise in the 20 ME/CFS patients, but not in controls. Furthermore a significant correlation was found between the increase in C4a and total symptom score.<ref>{{Cite journal|last=Sorensen|first=Bristol|last2=Streib|first2=Joanne E.|last3=Strand|first3=Matthew|last4=Make|first4=Barry|last5=Giclas|first5=Patricia C.|last6=Fleshner|first6=Monika|last7=Jones|first7=James F.|date=Aug 2003|title=Complement activation in a model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12897748|journal=The Journal of Allergy and Clinical Immunology|volume=112|issue=2|pages=397–403|issn=0091-6749|pmid=12897748}}</ref> C4a is generated from the cleavage of the native complement protein C4 via the classical and lectin pathways. A follow up study, published in 2009, found that other elements of the lectin pathway also responded differently to an exercise challenge in ME/CFS patients compared to controls. Both C4 and mannan-binding lectin serine protease 2 (MASP2) were observed at higher levels in ME/CFS subjects 1 hour post-exercise.<ref>{{Cite journal|last=Sorensen|first=Bristol|author-link=|last2=Jones|first2=James F|author-link2=|last3=Vernon|first3=Suzanne D|author-link3=Suzanne Vernon|last4=Rajeevan|first4=Mangalathu S|author-link4=Mangalathu Rajeevan|author-link5=|date=Jan 2009|title=Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/|journal=Molecular Medicine|volume=15|issue=1-2|pages=34–42|doi=10.2119/molmed.2008.00098|pmc=2583111|pmid=19015737|quote=|via=}}</ref> The authors speculated this to contribute to the increased C4a split product 6 hours after the exercise challenge. In a 2010 study by Nijs et al. there was no increase in C4a after exercise in ME/CFS patients, though a significant correlation with post-exertional pain and fatigue was found.<ref>{{Cite journal|last=Nijs|first=J.|last2=Van Oosterwijck|first2=J.|last3=Meeus|first3=M.|last4=Lambrecht|first4=L.|last5=Metzger|first5=K.|last6=Frémont|first6=M.|last7=Paul|first7=L.|date=Apr 2010|title=Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1β|url=https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2009.02178.x|journal=Journal of Internal Medicine|volume=267|issue=4|pages=418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=0954-6820}}</ref>
==== Cytokines ====
The expression of cytokines after physical exercise has been researched in ME/CFS patients since the mid-1990s. Most of these studies have found negative results (see table below).

{| class="wikitable"
|Study
|Number of participants
|Exercise challenge
|Cytokines tested:
|Results:
|-
|[[Daniel Peterson|Peterson]] et al. (1994)<ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=Mar 1994|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7496949|journal=Clinical and Diagnostic Laboratory Immunology|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>
|10 ([[Holmes criteria]], all cases were post-infectious)
|Walking 1 mile per hour for 30 min
|[[Interleukin 1 beta|IL-1 β]], [[Interleukin 6|IL-6]], and [[TNF-alpha|TNF-α]], [[TGF beta|TGF-β]]
|Negative results
|-
|[[Andrew Lloyd|Lloyd]] et al. (1994)<ref>{{Cite journal|last=Lloyd|first=A.|last2=Gandevia|first2=S.|last3=Brockman|first3=A.|last4=Hales|first4=J.|last5=Wakefield|first5=D.|date=Jan 1994|title=Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/8148442|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S142–146|issn=1058-4838|pmid=8148442}}</ref>
|12 ([[Australian criteria]])
|30 min hand grip exercises
|[[Interferon gamma|IFN-γ]], [[Interferon alpha |IFN-α]], [[Interleukin 1 beta|IL-1 β]], [[TNF-alpha|TNF-α]]
|Negative results
|-
|[[La Manca]] et al. (1999)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=Zhou|first3=X. D.|last4=Ottenweller|first4=J. E.|last5=Cook|first5=S.|last6=Peckerman|first6=A.|last7=Zhang|first7=Q.|last8=Denny|first8=T. N.|last9=Gause|first9=W. C.|date=Mar 1999|title=Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion|url=https://www.ncbi.nlm.nih.gov/pubmed/10226888|journal=Journal of Clinical Immunology|volume=19|issue=2|pages=135–142|issn=0271-9142|pmid=10226888}}</ref>
|20 ([[Fukuda criteria]]) "only patients with an illness duration of less than 6 years, who reported at least substantial intensity on symptom severity scales in the month prior to recruitment and who had no major psychiatric diagnosis in the 5 years prior to illness onset" were included
|An exhaustive treadmill exercise test
|[[Interleukin 2|IL-2]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]]<nowiki>, [[Interferon gamma|IFN-γ, </nowiki>[[TNF-alpha|TNF-α]]
|Negative results
|-
|Cannon et al. (1997)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Abad|first3=L. W.|last4=Vannier|first4=E.|last5=Mileno|first5=M. D.|last6=Fagioli|first6=L.|last7=Wolff|first7=S. M.|last8=Komaroff|first8=A. L.|date=May 1997|title=Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9168406|journal=Journal of Clinical Immunology|volume=17|issue=3|pages=253–261|issn=0271-9142|pmid=9168406}}</ref>
|8 (Holmes criteria) “their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]], [[interleukin-1 receptor antagonist]] (IL-1Ra), and [[soluble interleukin-1 receptor type II]] (IL-lsRII).
|Negative results
|-
|Gupta et al. (1998)<ref>{{Cite journal|last=Gupta|first=S.|last2=Aggarwal|first2=S.|last3=Starr|first3=A.|date=Feb 1999|title=Increased production of interleukin-6 by adherent and non-adherent mononuclear cells during 'natural fatigue' but not following 'experimental fatigue' in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9917531|journal=International Journal of Molecular Medicine|volume=3|issue=2|pages=209–213|issn=1107-3756|pmid=9917531}}</ref>
|5 (Holmes criteria)
|30 min hand grip exercises
|[[Interleukin 6|IL-6]]
|Negative results
|-
|Cannon et al. (1999)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Ball|first3=R. W.|last4=Abad|first4=L. W.|last5=Fagioli|first5=L.|last6=Komaroff|first6=A. L.|date=Nov 1999|title=Acute phase responses and cytokine secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10634215|journal=Journal of Clinical Immunology|volume=19|issue=6|pages=414–421|issn=0271-9142|pmid=10634215}}</ref>
|10 (Holmes criteria) their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]],[[IL-6]]
|Negative results
|-
|Yammes et al. (2009)<ref name=":25" />
|9 ([[Fukuda criteria]]) 6/9 had practiced sport at high levelxxxxxxxx, for more than 4 years before the symptoms occurred.
|Cycling test until maximal work load
|[[IL-6]], [[TNF-a]]
|Negative results
|-
|Robinson et al (2010)<ref>{{Cite journal|last=Robinson|first=M.|last2=Gray|first2=S. R.|last3=Watson|first3=M. S.|last4=Kennedy|first4=G.|last5=Hill|first5=A.|last6=Belch|first6=J. J. F.|last7=Nimmo|first7=M. A.|date=Apr 2010|title=Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19422646|journal=Scandinavian Journal of Medicine & Science in Sports|volume=20|issue=2|pages=282–290|doi=10.1111/j.1600-0838.2009.00895.x|issn=1600-0838|pmid=19422646}}</ref>
|6 (Fukuda criteria)
|Incremental exercise test to exhaustion
|IL-6, [[sIL-6R]] and [[sgp130]]
|Negative results
|-
|[[Andrea White]] et al. (2010)<ref name=":26">{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010-07-01|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20230500|journal=Psychophysiology|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1540-5958|pmc=4378647|pmid=20230500}}</ref>
|19 (Fukuda criteria)
|The authors used "a moderate whole-body exercise task (working both arms and legs) for 25 min that was mild enough that all CFS patients were able to complete it successfully but did induce a flare of fatigue and pain symptoms that remained above pre-exercise levels for 48 h post-exercise in the majority of patients."
|[[Interleukin 1 beta |IL-1β]], [[Interleukin 2 |IL-2]], [[Interleukin 12|IL-12]], [[TNF-alpha |TNFα]], soluble [[CD40L]], [[Interferon gamma |IFN-γ]], [[Interleukin 4|IL-4]], [[Interleukin 10 |IL-10]], [[Interleukin 13|IL-13]], [[Interleukin 6|IL-6]] and [[Interleukin 8|IL-8]]

 
|Positive results for a subgroup (11/19) of patients with high PEM

 
|-
|Andrew Lloyd et al. (2018)<ref name=":27">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=En|volume=8|issue=1|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|24 ([[Fukuda criteria]]) “we used the 1994 Centers for Disease Control (CDC)/Fukuda international diagnostic criteria for ME/CFS, but required participants to have post exertional malaise. Terefore, in labeling our patients this refers to the revised [[International Consensus Criteria|international consensus criteria]] from 2011”
|Symptom limited exercise on an ergocycle.
|Growth factors: [[FGF beta|FGF-β]], [[HGF]], [[NGF]], [[PDGF-BB]], [[TGF alpha|TGFα]], [[TGF-β1]], [[Vascular endothelial growth factor|VEGF]]

 

[[Colony stimulating factors]] and [[stem cell factors]]: [[G-CSF]], [[GM-CSF]], [[M-CSF]], [[SCF]]

 

Interleukins: [[Interleukin 1alpha|IL-1α]], [[Interleukin 1beta|IL-1β]], [[Interleukin 1RA|IL-1RA]], [[Interleukin 2|IL-2]], [[IL-4]], [[IL-5]], [[IL-6]], [[Interleukin 7|IL-7]], [[Interleukin |IL-8]], [[Interleukin 10|IL-10]], [[Interleukin 12p40|IL12p40]], [[Interleukin 12p70|IL12p70]], [[Interleukin 13|IL-13]], [[Interleukin 15|IL-15]], [[Interleukin 17|IL-17]], [[Interleukin 17f|IL-17F]], [[Interleukin 18|IL-18]] and [[LIF]]

 

[[Chemokine|Chemokines]]: [[CCL2]] ([[MCP-1]]), [[CCL3]] ([[MIP-1α]]), [[CCL4]] ([[MIP-1β]]), [[CCL5]] ([[RANTES]]) [[CCL7]] ([[MCP-3]]), [[CXCL1]] ([[Gro alpha|Gro-α]]), [[CXCL5]] ([[ENA78]]), [[CXCL9]] ([[MIG]]), [[CXCL10]] ([[IP-10]]), [[CCL11]] ([[Eotaxin]])

 

[[Interferon|Interferons]]: [[Interferon alpha |INF-α]], [[Interferon beta |INF-β]], [[Interferon gamma|INF-γ]]

 

[[Adhesion Molecule|Adhesion Molecules]] : [[ICAM-1]], [[VCAM-1]]

 

Other factors: [[CD40L]], [[FASL]], [[Leptin]], [[PAI-1]], [[Resistin]], [[TNF-α]], [[TNF-β]], [[TRAIL]]
|Positive results: ME/CFS had a distinct [[cytokine profile]] post-exercise.
|}
Moneghetti et al. took a different approach and looked at the cytokine profiling after exercise, as this may differentiate patients with ME/CFS from sedentary controls. Of the 51 [[cytokine]]s and growth factors tested, 10 significantly changed after exercise in both groups, a further 7 only changed in controls and five only changed in ME/CFS (namely, [[CXCL10]], [[IL-8]], [[CCL4]], [[TNF-β]] and [[ICAM-1]]). This suggests a distinct [[cytokine inflammatory signature]] in ME/CFS.<ref name=":27" /> White et al. (2010) differentiated their 19 ME/CFS patients with a high or low post-exertional malaise (called symptom flare SF, in the study). While the cytokine expression after exercise of patients with low PEM was similar to those of healthy controls, patients with high PEM showed opposite results. As the authors noted:<blockquote>"In sum, low SF patients and controls showed a pattern of post-exercise decreases in both pro and anti-inflammatory cytokines (with the exception of increases in IL-8), whereas the high SF patients showed a pattern of increases in both cytokine types at 8 h and no decreases at any time."<ref name=":26" /></blockquote>

=== Autonomic response ===
Several research teams have noted post-exertional abnormalities in the [[Autonomic nervous system|autonomic]] function of ME/CFS patients, though the exact meaning of these results is not yet clear.

A Canadian team under the guidance of [[Terrence Montague]] noted that during a maximal exercise test, ME/CFS patients have a lower maximal heart rate than controls. The authors noted that: <blockquote>“...patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.”<ref>{{Cite journal|last=Montague|first=T.J.|last2=Marrie|first2=T.J.|last3=Klassen|first3=G.A.|last4=Bewick|first4=D.J.|last5=Horacek|first5=B.M.|date=Apr 1989|title=Cardiac function at rest and with exercise in the chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/2924607|journal=Chest|volume=95|issue=4|pages=779–784|issn=0012-3692|pmid=2924607}}</ref> </blockquote>A significantly lower peak heart rate has been repeatedly observed in CPET-studies with ME/CFS patients.<ref>{{Cite journal|last=Gibson|first=H|last2=Carroll|first2=N|last3=Clague|first3=J E|last4=Edwards|first4=R H|date=Sep 1993|title=Exercise performance and fatiguability in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC489735/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=56|issue=9|pages=993–998|issn=0022-3050|pmid=8410041}}</ref><ref>{{Cite journal|last=Sisto|first=Sue Ann|last2=LaManca|first2=John|last3=Cordero|first3=Douglas L.|last4=Bergen|first4=Michael T.|last5=Ellis|first5=Steven P.|last6=Drastal|first6=Susan|last7=Boda|first7=Wanda L.|last8=Tapp|first8=Walter N.|last9=Natelson|first9=Benjamin H.|date=Jun 1996|title=Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome|url=https://www.amjmed.com/article/S0002-9343(96)00041-1/pdf|journal=The American Journal of Medicine|language=English|volume=100|issue=6|pages=634–640|doi=10.1016/S0002-9343(96)00041-1|issn=0002-9343}}</ref><ref>{{Cite journal|last=Rowbottom|first=David|last2=Keast|first2=David|last3=Pervan|first3=Zhukov|last4=Morton|first4=Alan|date=Jan 1998|title=The Physiological Response to Exercise in Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v04n02_04|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=4|issue=2|pages=33–49|doi=10.1300/j092v04n02_04|issn=1057-3321}}</ref> In one of the largest of these into exercise performance, the authors noted the same phenomenon as Montague et al. <blockquote>“The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects.”<ref>{{Cite journal|last=De Becker|first=P.|last2=Roeykens|first2=J.|last3=Reynders|first3=M.|last4=McGregor|first4=N.|last5=De Meirleir|first5=K.|date=2000-11-27|title=Exercise capacity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11088089|journal=Archives of Internal Medicine|volume=160|issue=21|pages=3270–3277|issn=0003-9926|pmid=11088089}}</ref></blockquote>The Belgium team Van Oosterwijck et al. reported an impaired heart rate recovery in 20 female ME/CFS patients following exercise.<ref>{{Cite journal|last=Van Oosterwijck|first=J.|last2=Marusic|first2=U.|last3=De Wandele|first3=I.|last4=Meeus|first4=M.|last5=Paul|first5=L.|last6=Lambrecht|first6=L.|last7=Moorkens|first7=G.|last8=Nijs|first8=J.|date=May 2015|title=Reduced parasympathetic reactivation during recovery from exercise in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)|url=https://www.physiotherapyjournal.com/article/S0031-9406(15)02014-3/fulltext|journal=Physiotherapy|language=English|volume=101|pages=e1091–e1092|doi=10.1016/j.physio.2015.03.1984|issn=0031-9406|issue=|quote=|author-link=Jessica Van Oosterwijck|author-link2=|author-link3=|author-link4=|author-link5=|via=|author-link8=Jo Nijs}}</ref> In other disease groups this is associated with risk for cardiac events and sudden death. Cordero et al. did not find a significant difference in mean heart rate between 11 ME/CFS patients and six healthy controls after walking on a treadmill, but they did find patients to have significantly less ‘vagal power’, a measure for respiratory-related parasympathetic contributions to heart rate.<ref>{{Cite journal|last=Cordero|first=D. L.|last2=Sisto|first2=S. A.|last3=Tapp|first3=W. N.|last4=LaManca|first4=J. J.|last5=Pareja|first5=J. G.|last6=Natelson|first6=B. H.|date=Dec 1996|title=Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8985621|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=6|issue=6|pages=329–333|issn=0959-9851|pmid=8985621}}</ref> Soetekouw et al. noted that during a handgrip exercise, the hemodynamics response was lower in the ME/CFS group than in the control group, although this could be attributed to the lower level of muscle exertion in the ME/CFS group.<ref>{{Cite journal|last=Soetekouw|first=P. M.|last2=Lenders|first2=J. W.|last3=Bleijenberg|first3=G.|last4=Thien|first4=T.|last5=van der Meer|first5=J. W.|date=Dec 1999|title=Autonomic function in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10638807|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=9|issue=6|pages=334–340|issn=0959-9851|pmid=10638807}}</ref> LaManca et al. studied 19 ME/CFS (Holmes criteria) and found that they had a diminished heart rate and blood pressure in response to a cognitive test compared to healthy controls, though exercise did not magnify this effect.<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Peckerman|first2=A.|last3=Sisto|first3=S. A.|last4=DeLuca|first4=J.|last5=Cook|first5=S.|last6=Natelson|first6=B. H.|date=Sep 2001|title=Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/11573024|journal=Psychosomatic Medicine|volume=63|issue=5|pages=756–764|issn=0033-3174|pmid=11573024}}</ref> Similar results were found by a Norwegian research team. They studied 13 adolescents with ME/CFS and 53 age-matched controls after a mental stress test (arithmetic questions). Though heart rate was significantly higher in patients at baseline, there were no meaningful differences during the arithmetic challenge.<ref>{{Cite journal|last=Egge|first=Caroline|last2=Wyller|first2=Vegard Bruun|date=2010-12-14|title=No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/21156045|journal=BioPsychoSocial Medicine|volume=4|pages=22|doi=10.1186/1751-0759-4-22|issn=1751-0759|pmc=3012010|pmid=21156045}}</ref> Finally, Ocon et al. (2012) studied 16 patients with both the diagnosis of ME/CFS and POTS after increased orthostatic stress and a cognitive challenge. An impairment of the neurocognitive abilities was noted, that was not seen in healthy controls.<ref>{{Cite journal|last=Ocon|first=Anthony J.|last2=Messer|first2=Zachary R.|last3=Medow|first3=Marvin S.|last4=Stewart|first4=Julian M.|date=Mar 2012|title=Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/21919887|journal=Clinical Science (London, England: 1979)|volume=122|issue=5|pages=227–238|doi=10.1042/CS20110241|issn=1470-8736|pmc=3368269|pmid=21919887}}</ref>

=== Sleep ===
A first study into the effects of exercise on sleep in ME/CFS found a beneficial effect: approximately half the patients slept better after exercise.<ref>{{Cite journal|last=Togo|first=Fumiharu|last2=Natelson|first2=Benjamin H.|last3=Cherniack|first3=Neil S.|last4=Klapholz|first4=Marc|last5=Rapoport|first5=David M.|last6=Cook|first6=Dane B.|date=Jan 2010|title=Sleep is not disrupted by exercise in patients with chronic fatigue syndromes|url=https://www.ncbi.nlm.nih.gov/pubmed/20010134|journal=Medicine and Science in Sports and Exercise|volume=42|issue=1|pages=16–22|doi=10.1249/MSS.0b013e3181b11bc7|issn=1530-0315|pmc=2796587|pmid=20010134}}</ref> A follow-up study by the same research team (under the guidance of Benjamin Natelson) found more post-exercise improvement (transitions to deeper [[sleep stages]]) of sleep in ME/CFS patients than in controls. The patients, however, reported more fatigue in the morning after exercise while healthy controls showed significant improvement in sleepiness and fatigue. The authors speculated this to be due to a disruption of the [[REM]] sleep: ME/CFS showed, both at baseline and post-exercise, an increased rate of transition from REM to wake compared to controls and this correlated with symptoms of fatigue, pain and sleepiness.<ref>{{Cite journal|last=Kishi|first=Akifumi|last2=Togo|first2=Fumiharu|last3=Cook|first3=Dane B|last4=Klapholz|first4=Marc|last5=Yamamoto|first5=Yoshiharu|last6=Rapoport|first6=David M|last7=Natelson|first7=Benjamin H|date=Nov 2013|title=The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871467/|journal=Physiological Reports|volume=1|issue=6|doi=10.1002/phy2.152|issn=2051-817X|pmc=3871467|pmid=24400154}}</ref> An Australian study followed up on 35 ME/CFS patients after performing a physical (stationary cycling) or cognitive (stimulated driving) challenge. While patients spent a greater proportion of wakeful hours lying down, they did not report significant changes in sleep quality or sleep duration. The authors did however note that the expected increase in [[heart rate variability]] (HRV) between wake and sleep, was significantly reduced in ME/CFS patients after completing the challenges. These changes in HRV have been associated with the falling asleep, and might be related to the unfreshed sleep of ME/CFS patients.<ref>{{Cite journal|last=Cvejic|first=Erin|last2=Sandler|first2=Carolina X.|last3=Keech|first3=Andrew|last4=Barry|first4=Benjamin K.|last5=Lloyd|first5=Andrew R.|last6=Vollmer-Conna|first6=Uté|date=Dec 2017|title=Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29167053|journal=Journal of Psychosomatic Research|volume=103|pages=91–94|doi=10.1016/j.jpsychores.2017.10.010|issn=1879-1360|pmid=29167053}}</ref> Finally, Ohashi et al. recorded physical activity for 6-days in 10 patients with ME/CFS and 6 controls before and after performing a maximal treadmill test. Their results indicate an increase in [[circadian]] rest-activity in ME/CFS patients after exercise as the activity pattern of patients shifted toward later hours in the day.<ref>{{Cite journal|last=Ohashi|first=Kyoko|last2=Yamamoto|first2=Yoshiharu|last3=Natelson|first3=Benjamin H.|date=Sep 2002|title=Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12213500|journal=Physiology & Behavior|volume=77|issue=1|pages=39–44|issn=0031-9384|pmid=12213500}}</ref>
=== Cognitive performance ===
While some studies have found a decreased cognitive performance after exercise in ME/CFS, others have not (see table below).<ref name=":0" /> This difference may be due to heterogeneity of the patient sample and methods used.

{| class="wikitable"
|Study
|Number of ME/CFS subjects
|Neurocognitive tests
|Results
|-
|[[Marshall]] et al. (1997)<ref>{{Cite journal|last=Marshall|first=P. S.|last2=Forstot|first2=M.|last3=Callies|first3=A.|last4=Peterson|first4=P. K.|last5=Schenck|first5=C. H.|date=Jan 1997|title=Cognitive slowing and working memory difficulties in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9021867|journal=Psychosomatic Medicine|volume=59|issue=1|pages=58–66|issn=0033-3174|pmid=9021867}}</ref>
|8
|Buschke Selective Reminding Test, Continuous-Performance Test-Identical Pairs Version (CPTIP), Paced Auditory Serial Addition Task (PASAT), Stroop Color Word Test, Reaction-Time Tests, Salthouse Reading Span Task (SRST), Verbal Scholastic Aptitude Test (SAT).
|Negative
|-
|[[Blackwood]] et al. (1998)<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=Oct 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781}}</ref>
|10
|"The following aspects of cognitive function were examined (in order): working memory/auditory attention (digit span, from WAIS-R); psychomotor speed (digit symbol, also from WAIS-R); word fluency (FAS test, using the letters F and S only); and selective attention and sustained attention (telephone search and lottery tasks respectively, both from the test of everyday attention)”
|Positive
|-
|[[La Manca]] et al. (1998)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=DeLuca|first3=J.|last4=Johnson|first4=S. K.|last5=Lange|first5=G.|last6=Pareja|first6=J.|last7=Cook|first7=S.|last8=Natelson|first8=B. H.|date=1998-09-28|title=Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9790484|journal=The American Journal of Medicine|volume=105|issue=3A|pages=59S–65S|issn=0002-9343|pmid=9790484}}</ref>
|19
|The Stroop Color and Word Test, the Symbol Digit Modalities Test (SDMT), an oral version of the Trail Making Test (TMT) and the Serial 13s Test (STT)
|Positive
|-
|[[Claypoole]] et al. (2001)<ref>{{Cite journal|last=Claypoole|first=Keith|last2=Mahurin|first2=Roderick|last3=Fischer|first3=Mary E.|last4=Goldberg|first4=Jack|last5=Schmaling|first5=Karen B.|last6=Schoene|first6=Robert B.|last7=Ashton|first7=Suzanne|last8=Buchwald|first8=Dedra|date=Mar 2001|title=Cognitive Compromise Following Exercise in Monozygotic Twins Discordant for Chronic Fatigue Syndrome: Fact or Artifact?|url=http://dx.doi.org/10.1207/s15324826an0801_5|journal=Applied Neuropsychology|volume=8|issue=1|pages=31–40|doi=10.1207/s15324826an0801_5|issn=0908-4282}}</ref>
|21
|The Wechsler Adult Intelligence Scale–Revised, Digit Span Forward and Backward subtests, The Hopkins Verbal Learning Test, . The Digit Vigilance Test, the Lafayette Clinic Repeatable Neuropsychological Test Battery, Controlled Oral Word Association Test (COWAT)
|Negative
|-
|[[Dane Cook|Cook]] et al. (2005)<ref>{{Cite journal|last=Cook|first=Dane B.|last2=Nagelkirk|first2=Paul R.|last3=Peckerman|first3=Arnold|last4=Poluri|first4=Ashok|last5=Mores|first5=John|last6=Natelson|first6=Benjamin H.|date=Sep 2005|title=Exercise and cognitive performance in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16177595|journal=Medicine and Science in Sports and Exercise|volume=37|issue=9|pages=1460–1467|issn=0195-9131|pmid=16177595}}</ref>
|20 ME/CFS only and 19 ME/CFS with comorbid fibromyalgia
|Participants completed cognitive testing using the automated neuropsychological assessment matrices (ANAM)
|Negative
|-
|[[Yoshiuchi]] et al. (2007)<ref>{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref>
|9
|A one-back memory task
|Negative
|-
|Cook et al. (2017)<ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref>
|15
|The Paced Auditory Serial Addition Task (PASAT) and a simple number recognition task
|Positive
|}

=== Pain modulation ===
Another post-exertional abnormality reported in ME/CFS is pain modulation. When healthy people exercise, their brain produces [[endorphins]] that increase pain thresholds. In some chronic pain patients like [[fibromyalgia]] and whiplash associated disorders, this endogenous pain inhibition response is defect and pain thresholds decrease shortly after exercise (i.e. they experience more pain while they should be feeling less). In 2004 Whiteside et al. first showed this defect in ME/CFS patients.<ref name=":22" /> These results were confirmed by two studies by the Belgium pain in motion team: while pain thresholds increased in normal controls they decreased in the ME/CFS patient group.<ref name=":23" /><ref name=":24" /> As a caveat, one must note that these studies only included ME/CFS patients that were suffering from chronic pain, while comorbid FM was not assessed. So it remains unclear if these results will also show up in ME/CFS patients that do not have comorbid FM.<ref>{{Cite journal|last=Yunus|first=Muhammad|date=2015-07-02|title=Editorial Review (Thematic Issue: An Update on Central Sensitivity Syndromes and the Issues of Nosology and Psychobiology)|url=http://dx.doi.org/10.2174/157339711102150702112236|journal=Current Rheumatology Reviews|language=en|volume=11|issue=2|pages=70–85|doi=10.2174/157339711102150702112236|issn=1573-3971}}</ref>

=== Other ===

==== The gut microbiome ====
Shukla et al. (2015) found post-exertional changes in the gut microbiome in ME/CFS patients that were not seen in healthy controls. Increased clearance of bacteria in the blood was also noted, which made the authors speculate that exercise induced a bacterial translocation in ME/CFS patients.<ref>{{Cite journal|last=Shukla|first=Sanjay K.|last2=Cook|first2=Dane|last3=Meyer|first3=Jacob|last4=Vernon|first4=Suzanne D.|last5=Le|first5=Thao|last6=Clevidence|first6=Derek|last7=Robertson|first7=Charles E.|last8=Schrodi|first8=Steven J.|last9=Yale|first9=Steven|date=2015-12-18|title=Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=http://dx.doi.org/10.1371/journal.pone.0145453|journal=PLOS ONE|volume=10|issue=12|pages=e0145453|doi=10.1371/journal.pone.0145453|issn=1932-6203}}</ref>

==== Catecholaminergic hyporeactivity ====
Strahler et al. found that ME/CFS patients showed an attenuated response (lower increases) of epinephrine to an exercise challenge, compared to heathy controls. This ‘catecholaminergic hyporeactivity’ was however subtle and short-lived.<ref>{{Cite journal|last=Strahler|first=Jana|last2=Fischer|first2=Susanne|last3=Nater|first3=Urs M.|last4=Ehlert|first4=Ulrike|last5=Gaab|first5=Jens|date=Sep 2013|title=Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23770415|journal=Biological Psychology|volume=94|issue=1|pages=160–166|doi=10.1016/j.biopsycho.2013.06.002|issn=1873-6246|pmid=23770415}}</ref>

==== Nitric oxide metabolites ====
A [[Spain|Spanish]] research team found much higher increases of nitric oxide metabolites (nitrates) after a maximal exercise test in 44 ME/CFS patients compared to 25 healthy controls while there were no differences between the groups at baseline.<ref>{{Cite journal|last=Suárez|first=Andrea|last2=Guillamó|first2=Elisabet|last3=Roig|first3=Teresa|last4=Blázquez|first4=Alicia|last5=Alegre|first5=José|last6=Bermúdez|first6=Jordi|last7=Ventura|first7=José Luis|last8=García-Quintana|first8=Ana María|last9=Comella|first9=Agustí|date=Jun 2010|title=Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study|url=http://dx.doi.org/10.1089/jwh.2008.1255|journal=Journal of Women's Health|volume=19|issue=6|pages=1073–1077|doi=10.1089/jwh.2008.1255|issn=1540-9996}}</ref>

== Problems in defining PEM ==

=== Asking the right questions ===
[[Leonard Jason|Jason]] et al. (1999) reported that in a group of ME/CFS patients, the percentage endorsing PEM ranged from 40,6 to 93,8% depending on how the question assessed this symptom.<ref>{{Cite web|url=https://www.meassociation.org.uk/2012/04/to-pem-or-not-to-pem-that-is-the-question-for-case-definition-research-1st-website-27-april-2012/|title=To PEM or not to PEM? That is the question for case definition {{!}} Research 1st website|date=27 April 2012|website=www.meassociation.org.uk|language=en-US|access-date=2018-10-10}}</ref> The report of the National Academy of Medicine noted that “the prevalence of PEM among ME/CFS patients as diagnosed by existing criteria varies from 69 to 100 percent.”<ref name=":0" />

Some patients try to reduce post-exertional relapses by pacing themselves and reducing exertion that exceeds their energy limits. Questionnaires assessing PEM by frequency instead of propensity, might erroneously label these patients as not having PEM. In a 2015 study, Jason et al. measured ME/CFS patients’ responses to the PEM-criterion in the [[Keiji Fukida|Fukuda]] et al. (1994) definition: ‘Do you feel generally worse than usual or fatigued for 24 hours or more after you have exercised?’ Although the majority (75%) endorsed this item, a notable percentage (25%) did not. Yet when the question was framed differently, leaving out the 24 hours’ time period and substituting exercise with normal daily activity, these participants also agreed they experienced high levels of fatigue after normal daily activity.<ref name=":19" /> This clearly shows that patients who have already modified their activities to avoid or reduce PEM may potentially show up as false negatives.

Another issue is the definition of PEM in the Fukuda-criteria. While the wording used here is vague, the time criterion is rather strict requiring PEM to last more than 24 hours. Some patients do not endorse this item because they only have post-exertional malaise for less than 24 hours.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=King|first2=Caroline P.|last3=Richman|first3=Judith A.|last4=Taylor|first4=Renee R.|last5=Torres|first5=Susan R.|last6=Song|first6=Sharon|date=Jan 1999|title=U.S. Case Definition of Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v05n03_02?journalCode=icfs20|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=5|issue=3-4|pages=3–33|doi=10.1300/j092v05n03_02|issn=1057-3321}}</ref> A 2018 study concluded that setting the criterion at 24 hours would exclude almost 30% of ME/CFS patients. It advises that this definition might be useful in research settings but that in a clinical context, a 14-23 hour time period might be more appropriate.<ref>{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref>

These observations point to the need of a more precise definition of PEM and several attempts to this end have been made.
=== More than just fatigue ===
Few instruments have assessed PEM adequately. The [[CDC 2005 Symptom Inventory for CFS|CDC symptom inventory]] for example, only asks about fatigue after exertion, while PEM entails much more than that. An [[Australia|Australian]] group at the University of New South Wales tried to better define PEM, using 19 ME/CFS patients after exposure to different stressors.<ref>{{Cite journal|last=Keech|first=Andrew|last2=Sandler|first2=Carolina X.|last3=Vollmer-Conna|first3=Ute|last4=Cvejic|first4=Erin|last5=Lloyd|first5=Andrew R.|last6=Barry|first6=Benjamin K.|date=Dec 2015|title=Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26359713|journal=Journal of Psychosomatic Research|volume=79|issue=6|pages=537–549|doi=10.1016/j.jpsychores.2015.08.008|issn=1879-1360|pmid=26359713}}</ref> Participants indicated that the term fatigue did not adequately describe the sensation they experienced on a daily basis. A word frequency analysis of descriptors nominated by these patients indicated 5 themes:
# Exhausted or tired.
# Heaviness in the limbs or whole-body.
# Fogginess in the head.
# Weakness in the muscles.
# Drained of energy.
===The DePaul Symptom Questionnaire (DSQ) subscale ===
The instrument most commonly used to assess PEM is a subscale from the [[DePaul Symptom Questionnaire]] (DSQ). The DSQ is a 54-item questionnaire was developed in 2010 to operationalize the Canadian Consensus Criteria, providing concrete directives to assess ME/CFS-symptoms with their frequency and severity.<ref>{{Cite web|url=https://www.semanticscholar.org/paper/The-Development-of-a-Revised-Canadian-Myalgic-Case-Jason-Evans/b2a2564f55daa57721d24502df6bd6c161238ff0|title=The Development of a Revised Canadian Myalgic Encephalomyelitis Chronic Fatigue Syndrome Case Definition|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth Anne|date=2010|language=en|access-date=2018-10-10|last3=Porter|first3=Nicole|last4=Brown|first4=Molly|last5=Brown|first5=Abigail A.|last6=Hunnell|first6=Jessica|last7=Anderson|first7=Valerie C.|last8=Lerch|first8=Athena|last9=Meirleir|first9=Kenny de}}</ref> In a Norwegian comparison with physician assessments, The DSQ scored a sensitivity of 92% and a specificity of 75%.<ref>{{Cite journal|last=Strand|first=Elin B.|last2=Lillestøl|first2=Kristine|last3=Jason|first3=Leonard A.|last4=Tveito|first4=Kari|last5=Diep|first5=Lien My|last6=Valla|first6=Simen Strand|last7=Sunnquist|first7=Madison|last8=Helland|first8=Ingrid B.|last9=Herder|first9=Ingrid|date=2016-01-02|title=Comparing the DePaul Symptom Questionnaire with physician assessments: a preliminary study|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1126026|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=4|issue=1|pages=52–62|doi=10.1080/21641846.2015.1126026|issn=2164-1846}}</ref> This indicated that the DSQ is a useful tool in detecting and screening symptoms, but that a follow-up medical examination is necessarily to confirm the diagnosis and identify possible exclusionary medical and psychiatric disorders.

The post-exertional malaise subscale on the DSQ particularly demonstrated excellent clinical utility as it was able to differentiate between ME/CFS patients and controls.<ref>{{Cite journal|last=Murdock|first=Kyle W.|last2=Wang|first2=Xin Shelley|last3=Shi|first3=Qiuling|last4=Cleeland|first4=Charles S.|last5=Fagundes|first5=Christopher P.|last6=Vernon|first6=Suzanne D.|date=Apr 2017|title=The utility of patient-reported outcome measures among patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/27600520|journal=Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation|volume=26|issue=4|pages=913–921|doi=10.1007/s11136-016-1406-3|issn=1573-2649|pmc=5336422|pmid=27600520}}</ref> In early 2018 the Common Data Elements working group on PEM formed by [[National Institute of Neurological Disorders and Stroke|NINDS]] and the CDC, recommended the use of 5 items from the DSQ to measure PEM.<ref name=":4">https://www.commondataelements.ninds.nih.gov/Doc/MECFS/PEM_Subgroup_Summary.pdf</ref>
# Dead, heavy feeling after starting to exercise.
# Next day soreness after non-strenuous, everyday activities.
# Mentally tired after the slightest effort.
# Minimum exercise makes physically tired.
# Physically drained or sick after mild activity.
To meet criteria for post-exertional malaise, one of these items need to be endorsed at sufficient frequency and severity (2 or greater on a scale of 0-4).

Although the DSQ has good test-retest reliability and is regarded as a useful tool in making the diagnosis of ME/CFS, its ability to capture PEM accurately has been questioned. Originally these five items formed one of the five subdomains of the ME/CFS Fatigue Types Questionnaire (MFTQ)<ref>{{Cite journal|last=Jason|first=Leonard|last2=Jessen|first2=Tricia|last3=Porter|first3=Nicole|last4=Boulton|first4=Aaron|last5=Gloria-Njoku|first5=Mary|date=2009-07-16|title=Examining Types of Fatigue Among Individuals with ME/CFS|url=http://dsq-sds.org/article/view/938|journal=Disability Studies Quarterly|language=en|volume=29|issue=3|doi=10.18061/dsq.v29i3.938|issn=2159-8371}}</ref><ref>{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> and critics argue that these items are focused too much on fatigue/tiredness to be an adequate measure of PEM. A document formulated by the Science for ME PEM working group to address these issues, explained:<blockquote>"The DSQ PEM items focus largely on feeling fatigue or tiredness, and, apart from one item, do not mention that post-exertional symptoms may be delayed. There is no mention of prolonged recovery or the loss of functional capacity."<ref name=":5" /></blockquote>The NINDS/CDC common data elements PEM subgroup also noted about the DSQ: <blockquote>"...the instrument does not assess the full range of symptoms that could be exacerbated by PEM and only one item addresses the sometimes delayed onset/ prolonged duration of PEM.<ref>https://www.commondataelements.ninds.nih.gov/Doc/MECFS/F2771_Guidance_for_Core_PEM_Assessment.pdf</ref> </blockquote>In an online poll to which 783 people responded, 68% answered that the DSQ PEM did not reflect their experience of post-exertional malaise<ref name=":5" />, though questions have been raised about the neutrality of the wording used.<ref name=":6">{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> In response Jason et al. noted that the DSQ PEM items were developed and selected to screen for the presence of PEM, rather than to comprehensively measure all aspects and variations of PEM. A 2018 analysis, using a large patient sample (n = 704), showed that screening items from the DSQ PEM subscale, were able to identify 97% of patients, which was higher than any other item to describe PEM.<ref name=":6" />

Furthermore, the authors have recently revised the DSQ PEM subscale to include new items, some based on Ramsay’s writings.<ref name=":7" /> An extra 5 questions can be used after the initial screening with the DSQ PEM subscale, to better differentiate ME/CFS from other, comparable conditions:
# Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?
# Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?
# If you feel worse after activities, how long does this last?
# If you were to become exhausted after actively participating in extracurricular activities, sports, or outings with friends, would you recover within an hour or two after the activity ended?
# If you do not exercise, is it because exercise makes your symptoms worse?
An analysis showed that these questions (the duration of PEM in particular) helped to differentiate ME/CFS patients from controls with [[Multiple sclerosis|MS]] or [[post-polio syndrome]].<ref name=":7" />

=== The DePaul Post-Exertional Malaise Questionnaire (DPEMQ) ===
The DPEMQ is a [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf questionnaire] based on input from hundreds of patients.<ref name=":29">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref><blockquote>Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.<ref name=":29" /></blockquote>

=== PENE ===
Of all case definitions, the 2011 International Consensus Criteria (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> offered the most precise and elaborated definition of the post-exertional relapses that characterize ME. To differentiate it with post-exertional malaise, the term used in the Fukuda-criteria, the authors introduced a new name: Post-Exertional Neuroimmune Exhaustion (PENE). PENE is described as “a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions”<ref name=":2" /> and has the following characteristics:
# Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
# Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
# Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
# Recovery period is prolonged, usually taking 24 hours or longer. A relapse can last days, weeks or longer.
# Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.
The definition fails however to make clear how many of these characteristics are necessary to diagnose PENE.
=== Muscle weakness ===
A more prominent criticism of PENE came from a 2016 factor analysis of PEM, using a large sample of 704 participants. Results suggested that “PEM is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue.”<ref name=":8" /> The latter refers to the description of ME by Ramsay, where post-exertional muscle weakness was highlighted. This element of PEM was confirmed in a study by the [[Workwell Foundation]] where the symptoms of 25 ME/CFS patients and 23 age-matched controls were followed up. As the report noted: <blockquote>"The two groups also differed with respect to the experience of physical weakness or instability immediately after testing. This was reported by 16 patients (64%) as opposed to 5 controls (22%). Weakness persisted into the next day in 10 patients (40%) but in only 1 control (4%). However, distinct differences can be observed in the severity of the weakness between groups when analyzing their reports. The sole report of weakness from a control stated: '[I had] tired legs when going up stairs—fine overall.' In contrast, statements from CFS patients included: 'Unable to walk without assistance.' '[I experienced] falling from muscle weakness.'<ref name=":13" /></blockquote>A Norwegian in depth-report of ME/CFS-patients relationship to exercise also highlighted muscle weakness: <blockquote>"Some related how they would struggle to get home after exercise – one had to stop her car on her way from the fitness centre. Another was walking in the woods and suddenly felt it would be impossible to make his way back home. They described feeling that something completely wrong had happened to their bodies, without understanding what was going on. Thought processes did not work as usual, motor abilities were reduced, or the legs would not move them as they would usually expect. Some participants described a paralyzed feeling subsequent to activity, where a lot of energy would be needed to be able to move."<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>While many descriptions of PEM like the DSQ subscale assess this element indirectly by asking patients about a dead heavy feeling after exercise or next day soreness, it is fully lacking in the ICC definition of PENE.<ref name=":8" />
=== Common data elements PEM working group ===
The NINDS/CDC Common Data Elements (CDE) PEM working group emphasized the need of a better definition of PEM. Its draft recommendations highlighted that <blockquote>"The definition of PEM is based primarily on clinician experience, patient reports and a few formal studies. There is a dearth of studies asking participants about their experiences of PEM in an openended manner, which is needed."<ref name=":4" /> </blockquote>A 2018 analysis showed that patients' preferences to describe PEM are generally not well-represented within present case definition criteria or descriptions.<ref>{{Cite journal|last=Jason|first=Leonard|last2=McManimen|first2=Stephanie|last3=Sunnquist|first3=Madison|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.researchgate.net/publication/323916016_Patient_perceptions_of_post_exertional_malaise|journal=Fatigue: Biomedicine, Health & Behavior|doi=10.1080/21641846.2018.1453265}}</ref> Although the CDE working group acknowledged the need to device a better instrument to assess PEM, it currently promotes the use of the DSQ PEM subscale as a screening tool, after which a clinician’s assessment is advised to diagnose PEM. The CDE PEM working group also provided a description of PEM, based on the 2015 literature review by the National Academy of Medicine: <blockquote>"PEM is defined as an abnormal response to minimal amounts of physical or cognitive exertion that is characterized by:</blockquote>
# Exacerbation of some or all of an individual study participant's ME/CFS symptoms. Symptoms exacerbated can include physical fatigue, cognitive fatigue, problems thinking (e.g. slowed information processing speed, memory, concentration), [[unrefreshing sleep]], [[Myalgia|muscle pain]], [[Arthralgia|joint pain]], [[Headache|headaches]], weakness/instability, light-headedness, flu-like symptoms, sore throat, [[nausea]], and other symptoms. Study participants can experience new or non-typical symptoms as well as exacerbation of their more typical symptoms.
# Loss of stamina and/or functional capacity.
# An onset that can be immediate or delayed after the exertional stimulus by hours, days or even longer.
# A prolonged, unpredictable recovery period that may last days, weeks, or even months.
# Severity and duration of symptoms that is often out-of-proportion to the type, intensity, frequency, and/or duration of the exertion. For some study participants, even basic activities of daily living like toileting, bathing, dressing, communicating, and reading can trigger PEM."<ref name=":4" />

==Notable studies==
* 1999, Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome<ref>{{Cite journal|last=Paul|first=L.|last2=Wood|first2=L.|last3=Behan|first3=W. M.|last4=Maclaren|first4=W. M.|date=1999|title=Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10209352|journal=European Journal of Neurology|volume=6|issue=1|pages=63–69|issn=1351-5101|pmid=10209352|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/10209352 (Abstract)]
* 2010, Postexertional Malaise in Women with Chronic Fatigue Syndrome<ref name="VanNess2010" /> [https://www.liebertpub.com/doi/10.1089/jwh.2009.1507 (Abstract)]

[[File:2010 VanNess Post exertional worsening of symptoms chart.png|center|frame|Post-exertional worsening of symptoms<ref name="VanNess2010" />]]
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Top 10 Things You Should Know About Post-Exertional Relapse'' (2012) By University of the Pacific/Solve CFS - 2010 study, ''PEM in Women w/ CFS'' is discussed in this video">https://www.youtube.com/watch?v=B20H1u1LjCE</embedvideo>

* 2013, Post-exertion malaise in chronic fatigue syndrome: symptoms and [[gene expression]]<ref name="MeyerJ2013" /> [http://www.tandfonline.com/doi/abs/10.1080/21641846.2013.838444 (Abstract)]
* 2015, Myalgic Encephalomyelitis: Symptoms and [[Biomarker]]s<ref name="JasonL2015bio" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/#!po=2.51799 (Full Text)]
*2015, Changes in Gut and Plasma [[Microbiome]] following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="ShuklaS2015" /> [http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0145453 (Full Text)]
*2016, Deconstructing post-exertional malaise: An exploratory factor analysis<ref name="McManimen, 2016" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/ (Full Text)]

*2018, Comparing Post-Exertional Symptoms Following Serial Exercise Tests<ref>{{Cite journal|last=Mateo|first=Lariel J.|date=2018|title=Comparing Post-Exertional Symptoms Following Serial Exercise Tests|url=https://scholarlycommons.pacific.edu/purcc/2018/events/87/|journal=PURCC|language=en|volume=|pages=|via=Scholarly Commons}}</ref> [https://scholarlycommons.pacific.edu/purcc/2018/events/87/ (Abstract)]

* 2018, The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome<ref name=":31" /><ref name=":30" /> [http://journals.sagepub.com/doi/abs/10.1177/1359105318805819?journalCode=hpqa& (Abstract)] [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf (Questionnaire)]

==Notable articles==
* Dec 30, 2015 [http://me-cfs.se/blogg/suggestion-to-replace-pem-by-par/ Suggestion to replace PEM (Post Exertional Malaise) with PAR (Post Activity Relapse)]<ref name="MEBlogg2015" />

*Nov 4, 2016 [http://www.medscape.com/viewarticle/871482#vp_1 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome]<ref>{{Cite web|url=http://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|last=Tucker|first=Miriam|date=|website=www.medscape.com|type=Login Required|archive-url=|archive-date=|dead-url=|access-date=2018-09-06}}</ref>

==Talks & interviews==
* 2013, [https://www.youtube.com/watch?v=zZ8aPYihkpQ CFS gene expression after exercise (part 1)]<ref>{{Cite web|url=https://www.youtube.com/watch?v=zZ8aPYihkpQ|title=CFS gene expression after exercise (part 1)|last=|first=|date=May 26, 2013|website=YouTube|publisher=Jw N|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

==See also==

*[[Exercise]]
*[[Exertion]]
*[[Flu-like symptoms]]
*[[Malaise]]
==Learn more==

*[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html International CFS/ME Awareness Day - What Health]<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-08-17}}</ref> (PEM Definition Included)
*[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf Post-Exertional Malaise in Chronic Fatigue Syndrome]<ref name="SpotilaJ2010" />
*[http://solvecfs.org/post-exertional-malaise-cause-and-effect/ Post-Exertional Malaise: Cause and Effect]<ref name="SpotilaJ20120523" />
*[https://www.verywellhealth.com/what-is-post-exertional-malaise-716023 What is Post-Exertional Malaise]<ref name="AboutHealthPEM" />
*[http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/ The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained?]<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/|title=The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained? - Health Rising|last=Johnson|first=Cort|date=2016-07-04|work=Health Rising|access-date=2018-08-17|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== References ==
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}}</ref>
<ref name="VanNess2010">{{Citation
| last1 = VanNess | first1 = M | authorlink1 = Mark VanNess
| last2 = Stevens | first2 = S | authorlink2 = Staci Stevens
| last3 = Bateman | first3 = L | authorlink3 = Lucinda Bateman
| last4 = Stiles | first4 = TL | authorlink4 = TL Stiles
| last5 = Snell | first5 = CR | authorlink5 = Christopher Snell
| display-authors =
| title = Postexertional malaise in women with chronic fatigue syndrome
| journal = Journal of Women's Health | volume = | issue = | page =
| date = February 2010
| pmid = 20095909
| doi = 10.1089/jwh.2009.1507
}}
</ref>
</references>

[[Category:Signs and symptoms]]

List of symptoms in ME CFS

2019-04-19T13:34:10Z

MEandCFS:/* Canadian consensus criteria (CCC) symptom list */ citation

{{Cleanup|date=January 2019|reason= International Consensus Criteria Pediatric symptoms missing}}
{{stub}}

{{mbox|text= Except for introduction information and SEID criteria symptoms, this page draws symptoms from subpages.}}

The '''list of symptoms in ME CFS''' can be extensive and most patients will not have every symptom possible

A minimum list of core symptoms of [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]; [[Cognitive dysfunction|cognitive impairment]]; and/or [[orthostatic intolerance]] (OI) can [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnose]] a person with [[Systemic Exertion Intolerance Disease]] (SEID), an [[ME/CFS]] definition. Other symptoms can be present but a diagnosis of the SEID criterion for ME/CFS requires less symptoms than the [[Canadian Consensus Criteria]] (CCC) or the [[International Consensus Criteria]] (ICC). The CCC is another ME/CFS definition which includes the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet its [[Canadian Consensus Criteria#Definition|diagnostic criteria]]. The ICC is for [[International Consensus Criteria#Criteria|diagnosing]] the [[Nervous system|neurological]] disease [[myalgic encephalomyelitis]] (ME) which was defined by the [[World Health Organization]] (WHO) in 1969.<ref name=":3">{{Cite book|url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y|title=International Classification of Diseases|last=World Health Organization|first=|publisher=WHO|year=1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic), (myalgic, benign) 323|editor-last2=|editor-link2=}}</ref>

It includes the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment.
== Systemic Exertion Intolerance Disease (SEID) symptom list ==
These are the minimum of core symptoms necessary to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with SEID]], an ME/CFS criteria. Patients can have more symptoms<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/7|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academy of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=141|language=en|chapter=5|quote=|editor-last2=|editor-link2=}}</ref> and they are outlined in the [[Institute of Medicine report]].

These core symptoms are also part of the [[Canadian Consensus Criteria|CCC]] and [[International Consensus Criteria|ICC]] criteria below. However, the CCC lists PEM as optional with Post-exertional fatigue. ICC refers to PEM as [[Post-exertional malaise|Postexertional neuroimmune exhaustion]] (PENE) and instead of CF the term "[[lack of stamina]]" is used. ME/CFS and ME patients will always have the core symptoms and the SEID diagnostic criteria can be used to diagnose these patients also. However, the SEID diagnostic criteria cannot speak to the number of symptoms and their severity all ME/CFS and ME patients experience. The IOM report authors who created the SEID diagnostic criteria did include some other symptoms in chapters 4 and 5.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/6|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academy of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=|language=en|chapter=4 and 5|quote=|editor-last2=|editor-link2=}}</ref>

=== Core symptoms ===
* [[chronic fatigue]] and

* [[post-exertional malaise]] (PEM) and

* [[unrefreshing sleep]]
and at least one of the following:
* [[Cognitive dysfunction|cognitive impairment]]
or
* [[orthostatic intolerance]] (OI)
<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

=== Pediatric ===
[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]] cases have the same symptoms.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/8|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=181|language=en|chapter=6|quote=|editor-last2=|editor-link2=}}</ref> However, the CDC notes some differences: OI ([[dizziness]] and lightheadedness) is experienced more often making their other ME/CFS symptoms worse. [[Sleep dysfunction|Sleep problems]] may be harder to detect; they will experience [[insomnia]], daytime sleepiness, and intense and vidid dreaming. Children and adolescents do not usually have [[muscle]] and [[Arthralgia|joint pain]] but [[Headache|headaches]] and stomach pain are more common.<ref name=":5">{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/children-symptoms-diagnosis.html|title=Symptoms and Diagnosis of ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref> Dr. [[David Bell]] agrees the symptoms for children can be different noting abdominal pain is more common and in teens there can be facial flushing. Although children do not describe having PEM, a hallmark symptom used in diagnosing ME/CFS, they can experience a relapse from exertion, perhaps from just taking the school bus, having to spend prolonged periods in bed.<ref name=":6">{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref>

Children, particularly adolescents, will more likely have an acute illness like the [[Influenza|flu]] or [[mononucleosis]] as their onset.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/children-symptoms-diagnosis.html|title=Symptoms and Diagnosis of ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref>

==Canadian consensus criteria (CCC) symptom list ==

The [[Canadian Consensus Criteria]] (CCC), an ME/CFS criteria, includes a list of recognized signs and symptoms in the appendix. Only some of these symptoms within the categories below are needed to be diagnosed under the [[Canadian Consensus Criteria#Definition|Canadian Consensus Criteria diagnostic criteria]]. PEM is an and/or option with post-exertional fatigue.<ref name=":0">{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|date=|access-date=|website=investinme.org|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|archive-url=|archive-date=|dead-url=|type=|page=4|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref> Pediatric cases have the same symptoms; please note the information for the "Pediatric" heading under "Systemic Exertion Intolerance Disease (SEID) symptom list" above.
=== Cognitive ===
{{:List of symptoms in ME CFS/Canadian/Cognitive}}<div style="clear: both"></div><hr />
=== Motor (movement) and balance ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Motor_and_balance}} <div style="clear: both"></div><hr />
=== Sleep disruption ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Sleep}} <div style="clear: both"></div><hr />
=== Visual and auditory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Visual_and_auditory}} <div style="clear: both"></div><hr />
=== Neuropsychological ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neuropsychological}} <div style="clear: both"></div><hr />
=== Immune system ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Immune_system}} <div style="clear: both"></div><hr />
=== Reproductive ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Reproductive}} <div style="clear: both"></div><hr/>
=== Respiratory (breathing)===
{{:List_of_symptoms_in_ME_CFS/Canadian/Respiratory}} <div style="clear: both"></div><hr />
=== Urinary ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Urinary}} <div style="clear: both"></div><hr />
=== Circulatory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Circulatory}} <div style="clear: both"></div><hr />
=== Digestive ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Digestive}} <div style="clear: both"></div><hr />
=== Neuroendocrine ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neuroendocrine}} <div style="clear: both"></div><hr />
=== Musculoskeletal ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Musculoskeletal}} <div style="clear: both"></div><hr />
=== Neurological (nervous system) ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neurological}} <div style="clear: both"></div><hr />
===Sensory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Sensory}}<div style="clear: both"></div><ref name="canadianconsensus" /> 

==International consensus criteria (ICC) symptom list ==
The [[International Consensus Criteria]] (ICC) will diagnose [[myalgic encephalomyelitis]] (ME). See the [[International Consensus Criteria#Criteria|International Consensus Criteria diagnostic criteria]] for diagnostic guidance. Not every symptom listed is necessary to diagnose ME but having symptoms within categories is necessary. The ICC refers to "[[lack of stamina]]" instead of CF.

=== Post-exertional Neuroimmune Exhaustion (PENE) ===

''Previously known as [[Post-exertional malaise]].''
{{:List_of_symptoms_in_ME_CFS/ICC/PENE}} <div style="clear: both"></div><hr />

=== Neurological ===
'''Neurocognitive Impairments'''
{{:List of symptoms in ME CFS/ICC/Neurological/Neurocognitive}}
'''Pain'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Pain}}
'''Sleep disturbances'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Sleep}} <div style="clear: both"></div>
'''Neurosensory, Perceptual and Motor Disturbances'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Neurosensory_and_perceptual}} <div style="clear: both"></div>
{{:List of symptoms in ME CFS/ICC/Neurological/Motor}} <div style="clear: both"><hr />

=== Immune, Gastro-intestinal and Genitourinary ===
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Immune}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Gastro}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Urinary}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/MCS}} <div style="clear: both"><hr />

=== Energy Metabolism/Ion Transportation ===
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Cardiovascular}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Respiratory}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Metabolism}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Extreme_Temperature}} <div style="clear: both">
<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref><hr />

===Children's symptoms===
* {{:List_of_symptoms_in_ME_CFS/ICC/Pediatric}} <div style="clear: both"></div>
<div style="clear: both"></div><ref name="ICC2011primer" /><hr />

==See also==

* [[Common symptoms in ME/CFS|Common symptoms]]
* [[Rare and uncommon symptoms]]
* [[Canadian Consensus Criteria]]

* [[International Consensus Criteria]]

* [[Institute of Medicine report]]

==Learn more==

* [http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf International Consensus Primer for medical practitioners]<ref name="ICC2011primer" />

* [http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx IOM report] - Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

* [http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf Canadian Consensus Criteria]

==References==
<references>
<ref name="ICC2011primer"><cite id="CITEREFCarruthersvan_de_SandeDe_MeirleirKlimas2012" class="citation">[[Bruce Carruthers|Carruthers, BM]]; [[Marjorie van de Sande|van de Sande, MI]]; [[Kenny de Meirleir|De Meirleir, KL]]; [[Nancy Klimas|Klimas, NG]]; [[Gordon Broderick|Broderick, G]]; [[Terry Mitchell|Mitchell, T]]; [[Donald Staines|Staines, D]]; [[A C Peter Powles|Powles, ACP]]; [[Nigel Speight|Speight, N]]; [[Rosamund Vallings|Vallings, R]]; [[Lucinda Bateman|Bateman, L]]; [[David Bell|Bell, DS]]; [[Nicoletta Carlo-Stella|Carlo-Stella, N]]; [[John Chia|Chia, J]]; [[Austin Darragh|Darragh, A]]; [[Anne Gerken|Gerken, A]]; [[Daehyun Jo|Jo, D]]; [[Donald Lewis|Lewis, DP]]; [[Alan Light|Light, AR]]; [[Kathleen Light|Light, KC]]; [[Sonya Marshall-Gradisnik|Marshall-Gradisnik, S]]; [[John McLaren-Howard|McLaren-Howard, J]]; [[Ismael Mena|Mena, I]]; [[Kunihisa Miwa|Miwa, K]]; [[Modra Murovska|Murovska, M]]; [[Staci Stevens|Stevens, SR]] (2012), [http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf ''Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners''] (PDF), [[International Standard Book Number|ISBN]] [[Special:BookSources/978-0-9739335-3-6|978-0-9739335-3-6]]</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Myalgic+encephalomyelitis%3A+Adult+%26+Paediatric%3A+International+Consensus+Primer+for+Medical+Practitioners&rft.date=2012&rft.isbn=978-0-9739335-3-6&rft.aulast=Carruthers&rft.aufirst=BM&rft.au=van+de+Sande%2C+MI&rft.au=De+Meirleir%2C+KL&rft.au=Klimas%2C+NG&rft.au=Broderick%2C+G&rft.au=Mitchell%2C+T&rft.au=Staines%2C+D&rft.au=Powles%2C+ACP&rft.au=Speight%2C+N&rft.au=Vallings%2C+R&rft.au=Bateman%2C+L&rft.au=Bell%2C+DS&rft.au=Carlo-Stella%2C+N&rft.au=Chia%2C+J&rft.au=Darragh%2C+A&rft.au=Gerken%2C+A&rft.au=Jo%2C+D&rft.au=Lewis%2C+DP&rft.au=Light%2C+AR&rft.au=Light%2C+KC&rft.au=Marshall-Gradisnik%2C+S&rft.au=McLaren-Howard%2C+J&rft.au=Mena%2C+I&rft.au=Miwa%2C+K&rft.au=Murovska%2C+M&rft.au=Stevens%2C+SR&rft_id=http%3A%2F%2Fwww.investinme.org%2FDocuments%2FGuidelines%2FMyalgic%2520Encephalomyelitis%2520International%2520Consensus%2520Primer%2520-2012-11-26.pdf&rfr_id=info%3Asid%2Fwww.me-pedia.org%3AList+of+symptoms+in+ME+CFS" class="Z3988"> </ref>
<ref name="canadianconsensus"><cite id="CITEREFCarruthersJainDe_MeirleirPeterson2003" class="citation">[[Bruce Carruthers|Carruthers, Bruce M.]]; [[Anil Kumar Jain|Jain, Anil Kumar]]; [[Kenny De Meirleir|De Meirleir, Kenny L.]]; [[Daniel Peterson|Peterson, Daniel L.]]; [[Nancy Klimas|Klimas, Nancy G.]]; [[Martin Lerner|Lerner, A. Martin]]; [[Alison Bested|Bested, Alison C.]]; [[Pierre Flor-Henry|Flor-Henry, Pierre]]; [[Pradip Joshi|Joshi, Pradip]]; [[A C Peter Powles|Powles, A C Peter]]; [[Jeffrey Sherkey|Sherkey, Jeffrey A.]]; [[Marjorie van de Sande|van de Sande, Marjorie I.]] (2003), [http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols"] (PDF), ''Journal of Chronic Fatigue Syndrome'', 11 (2): 7-115, [[Digital object identifier|doi]]:[//doi.org/10.1300%2FJ092v11n01_02 10.1300/J092v11n01_02]</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Chronic+Fatigue+Syndrome&rft.atitle=Myalgic+Encephalomyelitis%2FChronic+Fatigue+Syndrome%3A+Clinical+Working+Case+Definition%2C+Diagnostic+and+Treatment+Protocols&rft.volume=11&rft.issue=2&rft.pages=7-115&rft.date=2003&rft_id=info%3Adoi%2F10.1300%2FJ092v11n01_02&rft.aulast=Carruthers&rft.aufirst=Bruce+M.&rft.au=Jain%2C+Anil+Kumar&rft.au=De+Meirleir%2C+Kenny+L.&rft.au=Peterson%2C+Daniel+L.&rft.au=Klimas%2C+Nancy+G.&rft.au=Lerner%2C+A.+Martin&rft.au=Bested%2C+Alison+C.&rft.au=Flor-Henry%2C+Pierre&rft.au=Joshi%2C+Pradip&rft.au=Powles%2C+A+C+Peter&rft.au=Sherkey%2C+Jeffrey+A.&rft.au=van+de+Sande%2C+Marjorie+I.&rft_id=http%3A%2F%2Fwww.investinme.org%2FDocuments%2FPDFdocuments%2FCanadianDefinitionME-CFS.pdf&rfr_id=info%3Asid%2Fwww.me-pedia.org%3AList+of+symptoms+in+ME+CFS" class="Z3988"> </ref>
</references>

List of symptoms in ME CFS

2019-04-19T13:32:47Z

MEandCFS:/* Canadian consensus criteria (CCC) symptom list */ c/e

{{Cleanup|date=January 2019|reason= International Consensus Criteria Pediatric symptoms missing}}
{{stub}}

{{mbox|text= Except for introduction information and SEID criteria symptoms, this page draws symptoms from subpages.}}

The '''list of symptoms in ME CFS''' can be extensive and most patients will not have every symptom possible

A minimum list of core symptoms of [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]; [[Cognitive dysfunction|cognitive impairment]]; and/or [[orthostatic intolerance]] (OI) can [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnose]] a person with [[Systemic Exertion Intolerance Disease]] (SEID), an [[ME/CFS]] definition. Other symptoms can be present but a diagnosis of the SEID criterion for ME/CFS requires less symptoms than the [[Canadian Consensus Criteria]] (CCC) or the [[International Consensus Criteria]] (ICC). The CCC is another ME/CFS definition which includes the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet its [[Canadian Consensus Criteria#Definition|diagnostic criteria]]. The ICC is for [[International Consensus Criteria#Criteria|diagnosing]] the [[Nervous system|neurological]] disease [[myalgic encephalomyelitis]] (ME) which was defined by the [[World Health Organization]] (WHO) in 1969.<ref name=":3">{{Cite book|url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y|title=International Classification of Diseases|last=World Health Organization|first=|publisher=WHO|year=1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic), (myalgic, benign) 323|editor-last2=|editor-link2=}}</ref>

It includes the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment.
== Systemic Exertion Intolerance Disease (SEID) symptom list ==
These are the minimum of core symptoms necessary to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with SEID]], an ME/CFS criteria. Patients can have more symptoms<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/7|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academy of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=141|language=en|chapter=5|quote=|editor-last2=|editor-link2=}}</ref> and they are outlined in the [[Institute of Medicine report]].

These core symptoms are also part of the [[Canadian Consensus Criteria|CCC]] and [[International Consensus Criteria|ICC]] criteria below. However, the CCC lists PEM as optional with Post-exertional fatigue. ICC refers to PEM as [[Post-exertional malaise|Postexertional neuroimmune exhaustion]] (PENE) and instead of CF the term "[[lack of stamina]]" is used. ME/CFS and ME patients will always have the core symptoms and the SEID diagnostic criteria can be used to diagnose these patients also. However, the SEID diagnostic criteria cannot speak to the number of symptoms and their severity all ME/CFS and ME patients experience. The IOM report authors who created the SEID diagnostic criteria did include some other symptoms in chapters 4 and 5.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/6|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academy of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=|language=en|chapter=4 and 5|quote=|editor-last2=|editor-link2=}}</ref>

=== Core symptoms ===
* [[chronic fatigue]] and

* [[post-exertional malaise]] (PEM) and

* [[unrefreshing sleep]]
and at least one of the following:
* [[Cognitive dysfunction|cognitive impairment]]
or
* [[orthostatic intolerance]] (OI)
<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

=== Pediatric ===
[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]] cases have the same symptoms.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/8|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=181|language=en|chapter=6|quote=|editor-last2=|editor-link2=}}</ref> However, the CDC notes some differences: OI ([[dizziness]] and lightheadedness) is experienced more often making their other ME/CFS symptoms worse. [[Sleep dysfunction|Sleep problems]] may be harder to detect; they will experience [[insomnia]], daytime sleepiness, and intense and vidid dreaming. Children and adolescents do not usually have [[muscle]] and [[Arthralgia|joint pain]] but [[Headache|headaches]] and stomach pain are more common.<ref name=":5">{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/children-symptoms-diagnosis.html|title=Symptoms and Diagnosis of ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref> Dr. [[David Bell]] agrees the symptoms for children can be different noting abdominal pain is more common and in teens there can be facial flushing. Although children do not describe having PEM, a hallmark symptom used in diagnosing ME/CFS, they can experience a relapse from exertion, perhaps from just taking the school bus, having to spend prolonged periods in bed.<ref name=":6">{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref>

Children, particularly adolescents, will more likely have an acute illness like the [[Influenza|flu]] or [[mononucleosis]] as their onset.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/children-symptoms-diagnosis.html|title=Symptoms and Diagnosis of ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref>

==Canadian consensus criteria (CCC) symptom list ==

The [[Canadian Consensus Criteria]] (CCC), an ME/CFS criteria, includes a list of recognized signs and symptoms in the appendix. Only some of these symptoms within the categories below are needed to be diagnosed under the [[Canadian Consensus Criteria#Definition|Canadian Consensus Criteria diagnostic criteria]]. PEM is an and/or option with post-exertional fatigue. Pediatric cases have the same symptoms; please note the information for the "Pediatric" heading under "Systemic Exertion Intolerance Disease (SEID) symptom list" above.
=== Cognitive ===
{{:List of symptoms in ME CFS/Canadian/Cognitive}}<div style="clear: both"></div><hr />
=== Motor (movement) and balance ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Motor_and_balance}} <div style="clear: both"></div><hr />
=== Sleep disruption ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Sleep}} <div style="clear: both"></div><hr />
=== Visual and auditory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Visual_and_auditory}} <div style="clear: both"></div><hr />
=== Neuropsychological ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neuropsychological}} <div style="clear: both"></div><hr />
=== Immune system ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Immune_system}} <div style="clear: both"></div><hr />
=== Reproductive ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Reproductive}} <div style="clear: both"></div><hr/>
=== Respiratory (breathing)===
{{:List_of_symptoms_in_ME_CFS/Canadian/Respiratory}} <div style="clear: both"></div><hr />
=== Urinary ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Urinary}} <div style="clear: both"></div><hr />
=== Circulatory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Circulatory}} <div style="clear: both"></div><hr />
=== Digestive ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Digestive}} <div style="clear: both"></div><hr />
=== Neuroendocrine ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neuroendocrine}} <div style="clear: both"></div><hr />
=== Musculoskeletal ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Musculoskeletal}} <div style="clear: both"></div><hr />
=== Neurological (nervous system) ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neurological}} <div style="clear: both"></div><hr />
===Sensory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Sensory}}<div style="clear: both"></div><ref name="canadianconsensus" /> 

==International consensus criteria (ICC) symptom list ==
The [[International Consensus Criteria]] (ICC) will diagnose [[myalgic encephalomyelitis]] (ME). See the [[International Consensus Criteria#Criteria|International Consensus Criteria diagnostic criteria]] for diagnostic guidance. Not every symptom listed is necessary to diagnose ME but having symptoms within categories is necessary. The ICC refers to "[[lack of stamina]]" instead of CF.

=== Post-exertional Neuroimmune Exhaustion (PENE) ===

''Previously known as [[Post-exertional malaise]].''
{{:List_of_symptoms_in_ME_CFS/ICC/PENE}} <div style="clear: both"></div><hr />

=== Neurological ===
'''Neurocognitive Impairments'''
{{:List of symptoms in ME CFS/ICC/Neurological/Neurocognitive}}
'''Pain'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Pain}}
'''Sleep disturbances'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Sleep}} <div style="clear: both"></div>
'''Neurosensory, Perceptual and Motor Disturbances'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Neurosensory_and_perceptual}} <div style="clear: both"></div>
{{:List of symptoms in ME CFS/ICC/Neurological/Motor}} <div style="clear: both"><hr />

=== Immune, Gastro-intestinal and Genitourinary ===
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Immune}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Gastro}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Urinary}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/MCS}} <div style="clear: both"><hr />

=== Energy Metabolism/Ion Transportation ===
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Cardiovascular}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Respiratory}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Metabolism}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Extreme_Temperature}} <div style="clear: both">
<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref><hr />

===Children's symptoms===
* {{:List_of_symptoms_in_ME_CFS/ICC/Pediatric}} <div style="clear: both"></div>
<div style="clear: both"></div><ref name="ICC2011primer" /><hr />

==See also==

* [[Common symptoms in ME/CFS|Common symptoms]]
* [[Rare and uncommon symptoms]]
* [[Canadian Consensus Criteria]]

* [[International Consensus Criteria]]

* [[Institute of Medicine report]]

==Learn more==

* [http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf International Consensus Primer for medical practitioners]<ref name="ICC2011primer" />

* [http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx IOM report] - Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

* [http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf Canadian Consensus Criteria]

==References==
<references>
<ref name="ICC2011primer"><cite id="CITEREFCarruthersvan_de_SandeDe_MeirleirKlimas2012" class="citation">[[Bruce Carruthers|Carruthers, BM]]; [[Marjorie van de Sande|van de Sande, MI]]; [[Kenny de Meirleir|De Meirleir, KL]]; [[Nancy Klimas|Klimas, NG]]; [[Gordon Broderick|Broderick, G]]; [[Terry Mitchell|Mitchell, T]]; [[Donald Staines|Staines, D]]; [[A C Peter Powles|Powles, ACP]]; [[Nigel Speight|Speight, N]]; [[Rosamund Vallings|Vallings, R]]; [[Lucinda Bateman|Bateman, L]]; [[David Bell|Bell, DS]]; [[Nicoletta Carlo-Stella|Carlo-Stella, N]]; [[John Chia|Chia, J]]; [[Austin Darragh|Darragh, A]]; [[Anne Gerken|Gerken, A]]; [[Daehyun Jo|Jo, D]]; [[Donald Lewis|Lewis, DP]]; [[Alan Light|Light, AR]]; [[Kathleen Light|Light, KC]]; [[Sonya Marshall-Gradisnik|Marshall-Gradisnik, S]]; [[John McLaren-Howard|McLaren-Howard, J]]; [[Ismael Mena|Mena, I]]; [[Kunihisa Miwa|Miwa, K]]; [[Modra Murovska|Murovska, M]]; [[Staci Stevens|Stevens, SR]] (2012), [http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf ''Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners''] (PDF), [[International Standard Book Number|ISBN]] [[Special:BookSources/978-0-9739335-3-6|978-0-9739335-3-6]]</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Myalgic+encephalomyelitis%3A+Adult+%26+Paediatric%3A+International+Consensus+Primer+for+Medical+Practitioners&rft.date=2012&rft.isbn=978-0-9739335-3-6&rft.aulast=Carruthers&rft.aufirst=BM&rft.au=van+de+Sande%2C+MI&rft.au=De+Meirleir%2C+KL&rft.au=Klimas%2C+NG&rft.au=Broderick%2C+G&rft.au=Mitchell%2C+T&rft.au=Staines%2C+D&rft.au=Powles%2C+ACP&rft.au=Speight%2C+N&rft.au=Vallings%2C+R&rft.au=Bateman%2C+L&rft.au=Bell%2C+DS&rft.au=Carlo-Stella%2C+N&rft.au=Chia%2C+J&rft.au=Darragh%2C+A&rft.au=Gerken%2C+A&rft.au=Jo%2C+D&rft.au=Lewis%2C+DP&rft.au=Light%2C+AR&rft.au=Light%2C+KC&rft.au=Marshall-Gradisnik%2C+S&rft.au=McLaren-Howard%2C+J&rft.au=Mena%2C+I&rft.au=Miwa%2C+K&rft.au=Murovska%2C+M&rft.au=Stevens%2C+SR&rft_id=http%3A%2F%2Fwww.investinme.org%2FDocuments%2FGuidelines%2FMyalgic%2520Encephalomyelitis%2520International%2520Consensus%2520Primer%2520-2012-11-26.pdf&rfr_id=info%3Asid%2Fwww.me-pedia.org%3AList+of+symptoms+in+ME+CFS" class="Z3988"> </ref>
<ref name="canadianconsensus"><cite id="CITEREFCarruthersJainDe_MeirleirPeterson2003" class="citation">[[Bruce Carruthers|Carruthers, Bruce M.]]; [[Anil Kumar Jain|Jain, Anil Kumar]]; [[Kenny De Meirleir|De Meirleir, Kenny L.]]; [[Daniel Peterson|Peterson, Daniel L.]]; [[Nancy Klimas|Klimas, Nancy G.]]; [[Martin Lerner|Lerner, A. Martin]]; [[Alison Bested|Bested, Alison C.]]; [[Pierre Flor-Henry|Flor-Henry, Pierre]]; [[Pradip Joshi|Joshi, Pradip]]; [[A C Peter Powles|Powles, A C Peter]]; [[Jeffrey Sherkey|Sherkey, Jeffrey A.]]; [[Marjorie van de Sande|van de Sande, Marjorie I.]] (2003), [http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols"] (PDF), ''Journal of Chronic Fatigue Syndrome'', 11 (2): 7-115, [[Digital object identifier|doi]]:[//doi.org/10.1300%2FJ092v11n01_02 10.1300/J092v11n01_02]</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Chronic+Fatigue+Syndrome&rft.atitle=Myalgic+Encephalomyelitis%2FChronic+Fatigue+Syndrome%3A+Clinical+Working+Case+Definition%2C+Diagnostic+and+Treatment+Protocols&rft.volume=11&rft.issue=2&rft.pages=7-115&rft.date=2003&rft_id=info%3Adoi%2F10.1300%2FJ092v11n01_02&rft.aulast=Carruthers&rft.aufirst=Bruce+M.&rft.au=Jain%2C+Anil+Kumar&rft.au=De+Meirleir%2C+Kenny+L.&rft.au=Peterson%2C+Daniel+L.&rft.au=Klimas%2C+Nancy+G.&rft.au=Lerner%2C+A.+Martin&rft.au=Bested%2C+Alison+C.&rft.au=Flor-Henry%2C+Pierre&rft.au=Joshi%2C+Pradip&rft.au=Powles%2C+A+C+Peter&rft.au=Sherkey%2C+Jeffrey+A.&rft.au=van+de+Sande%2C+Marjorie+I.&rft_id=http%3A%2F%2Fwww.investinme.org%2FDocuments%2FPDFdocuments%2FCanadianDefinitionME-CFS.pdf&rfr_id=info%3Asid%2Fwww.me-pedia.org%3AList+of+symptoms+in+ME+CFS" class="Z3988"> </ref>
</references>

Post-exertional malaise

2019-04-19T13:30:00Z

MEandCFS:/* History */ il

'''Post-exertional malaise (PEM)''' refers to a ''worsening'' of [[List of symptoms in ME CFS|ME/CFS symptoms]] after minimal ''physical'' or ''mental'' [[exertion]],<ref name=":14" /><ref name=":32" /> which can be delayed 24-72 hours or more.<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15" /><ref name=":28">{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=137|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=2018-10-16|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.}}</ref><ref name=":30">{{Cite journal|last=|first=|date=2018|title=SAGE Journals: Your gateway to world-class journal research|url=http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf|journal=Sage Pub|language=en|volume=|pages=4-5|doi=10.1177/1359105318805819/suppl_file/appendix.__the_development_of_a_comprehensive_measure_of_post-exertional_malaise.8.20.2018.pdf|via=}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref> PEM is considered to be the hallmark symptom of [[ME/CFS]].<ref name=":0">{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK274235/|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|last=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations|last3=Institute of Medicine|date=2015|publisher=National Academies Press (US)|isbn=9780309316897|series=The National Academies Collection: Reports funded by National Institutes of Health|location=Washington (DC)|pmid=25695122}}</ref><ref>{{Cite web|url=https://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|website=www.medscape.com|access-date=2018-10-10}}</ref><ref>{{Cite web|url=https://ammes.org/2018/06/04/deconstructing-post-exertional-malaise-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-a-patient-centered-cross-sectional-survey/|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-10-16}}</ref> While in most diseases patients experience symptom relief after [[exercise|exercise,]]<ref>{{Cite journal|last=Loy|first=Bryan D.|last2=O'Connor|first2=Patrick J.|last3=Dishman|first3=Rodney K.|date=Oct 2013|title=The effect of a single bout of exercise on energy and fatigue states: a systematic review and meta-analysis|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2013.843266?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=1|issue=4|pages=223–242|doi=10.1080/21641846.2013.843266|issn=2164-1846}}</ref><ref>{{Cite journal|last=Robb-Nicholson|first=L. C.|last2=Daltroy|first2=L.|last3=Eaton|first3=H.|last4=Gall|first4=V.|last5=Wright|first5=E.|last6=Hartley|first6=L. H.|last7=Schur|first7=P. H.|last8=Liang|first8=M. H.|date=Dec 1989|title=Effects of aerobic conditioning in lupus fatigue: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/2590802|journal=British Journal of Rheumatology|volume=28|issue=6|pages=500–505|issn=0263-7103|pmid=2590802}}</ref><ref>{{Cite journal|last=Mostert|first=S.|last2=Kesselring|first2=J.|date=Apr 2002|title=Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis|url=https://www.ncbi.nlm.nih.gov/pubmed/11990874|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=8|issue=2|pages=161–168|doi=10.1191/1352458502ms779oa|issn=1352-4585|pmid=11990874}}</ref><ref>{{Cite news|url=https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise-and-chronic-disease/art-20046049|title=What you need to know about exercise and chronic disease|work=Mayo Clinic|access-date=2018-10-10|language=en}}</ref><ref>{{Cite journal|last=Dunn|first=A. L.|last2=Trivedi|first2=M. H.|last3=O'Neal|first3=H. A.|date=June 2001|title=Physical activity dose-response effects on outcomes of depression and anxiety|url=https://www.ncbi.nlm.nih.gov/pubmed/11427783|journal=Medicine and Science in Sports and Exercise|volume=33|issue=6 Suppl|pages=S587–597; discussion 609–610|issn=0195-9131|pmid=11427783}}</ref> the opposite is true for ME/CFS patients for whom even minimal exertion can cause a symptom flare-up.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Almond|first2=Freya|last3=De Becker|first3=Pascale|last4=Truijen|first4=Steven|last5=Paul|first5=Lorna|date=May 2008|title=Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial|url=https://www.ncbi.nlm.nih.gov/pubmed/18441039|journal=Clinical Rehabilitation|volume=22|issue=5|pages=426–435|doi=10.1177/0269215507084410|issn=0269-2155|pmid=18441039}}</ref> Because recovery is often prolonged,<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> lasting days or sometimes weeks to months,<ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> patients refer to these post-exertional setbacks as ‘crashes’.<ref>{{Cite news|url=https://www.healthrising.org/the-community-reports-best-practices-on-managing-thriving-with-or-just-surviving-chronic-fatigue-syndrome-mecfs/how-to-best-recover-from-a-crash-the-mecfs-community-reports/|title=How to Best Recover From a Crash: the ME/CFS Community Reports|work=Health Rising|access-date=2018-10-10|language=en-US}}</ref><ref name=":28" /> Depending on the criteria a patient meets ([[Systemic Exertion Intolerance Disease]] (SEID) for ME/CFS's [[Systemic Exertion Intolerance Disease#Diagnostic criteria| minimum core symptoms]], the [[Canadian Consensus Criteria]] (CCC) for [[Canadian Consensus Criteria#Definition| this criterion's ME/CFS symptoms]], or the [[International Consensus Criteria]] (ICC) for [[myalgic encephalomyelitis]] (ME) and [[International Consensus Criteria#Criteria|its ME symptoms]]) will correlate with the patient's symptoms that will worsen.

PEM can be caused by [[Exertion#Exertion in ME.2FCFS|physical as well as mental exertion]]<ref name=":14" /> and the symptom complex it invokes does not necessarily relate to the initial trigger.<ref name=":3" /> ME/CFS patients suffer from a post-exertional [[Flu-like symptoms|flu-like feeling,]]<ref name=":1" /> with [[brain fog|brain fog,]]<ref name=":13" /> [[photophobia]] and other symptoms not usually reported after exertion.<ref name=":3" /> In contrast to most forms of exercise intolerance, the onset of PEM is frequently delayed<ref name=":15" /> with many patients reporting the height of their symptom flare-up, two<ref name=":13" /> or several days after the initial trigger.

It is important to understand that in [[pediatric]] cases of ME/CFS, children do not describe having PEM. They can experience a relapse from exertion, perhaps from just taking the school bus, having to spend prolonged periods in bed.<ref>[https://www.me-pedia.org/wiki/Pediatric_myalgic_encephalomyelitis_and_chronic_fatigue_syndrome ME/CFS in Children - by David S. Bell - David Bell - Open Medicine Foundation - June 25, 2016]</ref>

[[File:Cfs woman sketch.jpg|435x435px|thumb|Post-exertional malaise (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]
The distinctive characteristics of post-exertional malaise are confirmed by scientific research. Exertion induces abnormalities in [[Cognitive dysfunction|cognitive functioning,]]<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=October 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781|via=}}</ref><ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref> [[immune activation|immune activation,]]<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723|issue=|quote=|author-link=Jo Nijs|author-link2=Andrea Nees|author-link3=Lorna Paul|author-link4=Margot De Kooning|author-link5=Kelly Ickmans|via=|author-link6=Mira Meeus|author-link7=Jessica Van Oosterwijck}}</ref> [[gene expression]]<ref name=":20">{{Cite journal|last=Light|first=Alan R.|last2=White|first2=Andrea T.|last3=Hughen|first3=Ronald W.|last4=Light|first4=Kathleen C.|date=Oct 2009|title=Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects|url=http://dx.doi.org/10.1016/j.jpain.2009.06.003|journal=The Journal of Pain|volume=10|issue=10|pages=1099–1112|doi=10.1016/j.jpain.2009.06.003|issn=1526-5900}}</ref><ref name=":21">{{Cite journal|last=Light|first=A. R.|last2=Bateman|first2=L.|last3=Jo|first3=D.|last4=Hughen|first4=R. W.|last5=VanHaitsma|first5=T. A.|last6=White|first6=A. T.|last7=Light|first7=K. C.|date=2011-07-13|title=Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome|url=http://dx.doi.org/10.1111/j.1365-2796.2011.02405.x|journal=Journal of Internal Medicine|volume=271|issue=1|pages=64–81|doi=10.1111/j.1365-2796.2011.02405.x|issn=0954-6820}}</ref><ref>{{Cite journal|last=Meyer|first=Jacob D.|last2=Light|first2=Alan R.|last3=Shukla|first3=Sanjay K.|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron J.|last7=Cook|first7=Dane B.|date=Oct 2013|title=Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression|url=http://dx.doi.org/10.1080/21641846.2013.838444|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|issue=4|pages=190–209|doi=10.1080/21641846.2013.838444|issn=2164-1846}}</ref><ref>{{Cite journal|last=White|first=A. T.|last2=Light|first2=A. R.|last3=Hughen|first3=R. W.|last4=VanHaitsma|first4=T. A.|last5=Light|first5=K. C.|date=2011-12-30|title=Differences in Metabolite-Detecting, Adrenergic, and Immune Gene Expression After Moderate Exercise in Patients With Chronic Fatigue Syndrome, Patients With Multiple Sclerosis, and Healthy Controls|url=http://dx.doi.org/10.1097/psy.0b013e31824152ed|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/psy.0b013e31824152ed|issn=0033-3174}}</ref> and [[endogenous pain inhibition]]<ref name=":22">{{Cite journal|last=Whiteside|first=Alan|last2=Hansen|first2=Stig|last3=Chaudhuri|first3=Abhijit|date=Jun 2004|title=Exercise lowers pain threshold in chronic fatigue syndrome|url=http://dx.doi.org/10.1016/j.pain.2004.02.029|journal=Pain|volume=109|issue=3|pages=497–499|doi=10.1016/j.pain.2004.02.029|issn=0304-3959}}</ref><ref name=":23">{{Cite journal|last=Meeus|first=M|last2=Roussel|first2=NA|last3=Truijen|first3=S|date=2010|title=Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: An experimental study|url=http://dx.doi.org/10.2340/16501977-0595|journal=Journal of Rehabilitation Medicine|volume=42|issue=9|pages=884–890|doi=10.2340/16501977-0595|issn=1650-1977}}</ref><ref name=":24">{{Cite journal|last=Van Oosterwijck|first=J.|last2=Nijs|first2=J.|last3=Meeus|first3=M.|last4=Lefever|first4=I.|last5=Huybrechts|first5=L.|last6=Lambrecht|first6=L.|last7=Paul|first7=L.|date=2010-03-03|title=Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: An experimental study|url=http://dx.doi.org/10.1111/j.1365-2796.2010.02228.x|journal=Journal of Internal Medicine|volume=268|issue=3|pages=265–278|doi=10.1111/j.1365-2796.2010.02228.x|issn=0954-6820|quote=|author-link=Jessica Van Oosterwijck|author-link2=Jo Nijs|author-link3=Mira Meeus|author-link4=|author-link5=|via=|author-link7=Lorna Paul}}</ref> in ME/CFS patients that were not seen before exertion or in healthy controls. Most importantly PEM can be demonstrated by a [[Two-day cardiopulmonary exercise test|2-day cardiopulmonary exercise test]] (CPET) procedure.<ref name=":16" /><ref name=":28" /> On the second day [[Two-day cardiopulmonary exercise test|CPET]], ME/CFS patients display a significant drop in [[VO2 max]] and [[maximal workload]], that is not seen in healthy controls or other diseases.<ref>{{Cite journal|last=Snell|first=C. R.|last2=Stevens|first2=S. R.|last3=Davenport|first3=T. E.|last4=Van Ness|first4=J. M.|date=2013-06-27|title=Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome|url=http://dx.doi.org/10.2522/ptj.20110368|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=0031-9023}}</ref><ref>{{Cite journal|last=Vermeulen|first=Ruud CW|last2=Kurk|first2=Ruud M|last3=Visser|first3=Frans C|last4=Sluiter|first4=Wim|last5=Scholte|first5=Hans R|date=2010|title=Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity|url=http://dx.doi.org/10.1186/1479-5876-8-93|journal=Journal of Translational Medicine|volume=8|issue=1|pages=93|doi=10.1186/1479-5876-8-93|issn=1479-5876}}</ref><ref name=":17" /><ref>{{Cite journal|last=Vanness|first=J. Mark|last2=Snell|first2=Christopher R.|last3=Stevens|first3=Staci R.|date=Jan 2007|title=Diminished Cardiopulmonary Capacity During Post-Exertional Malaise|url=http://dx.doi.org/10.1300/j092v14n02_07|journal=Journal of Chronic Fatigue Syndrome|volume=14|issue=2|pages=77–85|doi=10.1300/j092v14n02_07|issn=1057-3321}}</ref><ref name=":18" /> These objective measures track strongly with the presence, severity and duration of PEM.<ref name=":0" /> [[Brian Vastag]] won a groundbreaking long term disability (LTD) claim using CPET to prove his PEM was a severe disabling symptom.<ref>[US District Court of NJ: Brian Vastag v. Prudential Insurance Company of America, Civ.15-6197 (KSH), (CLW) https://t.co/Vq9GXo4VEI]</ref><ref>{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-02}}</ref>

A 2015 review of the literature by the [[National Academy of Medicine]] (NAM) concluded there to be “sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS from other conditions.”<ref name=":0" /> Disagreement exists however on the precise nature of PEM and how it should be defined,<ref name=":19">{{Cite journal|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth|last3=So|first3=Suzanna|last4=Scott|first4=Jilian|last5=Brown|first5=Abigail|date=2015|title=Problems in Defining Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295644/|journal=Journal of prevention & intervention in the community|volume=43|issue=1|pages=20–31|doi=10.1080/10852352.2014.973239|issn=1085-2352|pmc=4295644|pmid=25584525}}</ref> with some diagnostic criteria emphasizing [[Paresis|muscle weakness]] and others a more a general form of [[fatigue]] and exhaustion.<ref name=":8">{{Cite journal|last=McManimen|first=Stephanie L.|last2=Sunnquist|first2=Madison L.|last3=Jason|first3=Leonard A.|date=2016-08-24|title=Deconstructing post-exertional malaise: An exploratory factor analysis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/|journal=Journal of health psychology|doi=10.1177/1359105316664139|issn=1359-1053|pmc=5325824|pmid=27557649}}</ref>

The [[Centers for Disease Control and Prevention]] (CDC) outline different types of exertion that may trigger PEM and how it impacts patients noting some may be house-bound or completely bed-bound during a crash. "People with ME/CFS may not be able to predict what will cause a crash or how long it will last."<ref name=":32">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-11-21}}</ref> Examples of PEM given by the CDC are: attending a child’s school event may leave a patient house-bound for a couple of days unable to do needed tasks, like laundry; grocery shopping may cause a crash that requires a nap in the car before driving home or a call for a ride home; a shower may leave a patient bed-bound and unable to do anything for days; keeping up with work may lead to spending evenings and weekends recovering.<ref name=":32" />

== PEM described by Dr. David Kaufman ==
{{#ev:youtube|https://www.youtube.com/watch?v=RC9TjgE_PlU|400|right|'''PEM described by Dr. David Kaufman''' (2018) Kaufman/''Unrest'' Video begins @2:16 and PEM is described until @3:35|frame|start=136&rel=0&autoplay=0}}

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

(Video begins @2:16 and PEM is described until @3:35. View entire 11:47 for a full description of ME/CFS)

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Patients' description==
[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]
[[File:PEM.JPG|300px|thumb|right|#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with [[Neurally mediated hypotension|high pulse and very low energy]]. Even though you sometimes can see the exhaustion in someone's face, most [[List of symptoms in ME CFS|ME symptoms]] are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaise<ref>{{Cite web|url=https://twitter.com/ezchili/status/1085927134248488965|title=#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with high pulse and very low energy. Even though you sometimes can see the exhaustion in someone's face, most ME symptoms are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaisepic.twitter.com/FKSTo8W0hH|last=ez 📎|date=2019-01-17|website=@ezchili|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM2.JPG|300px|thumb|right|#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.<ref>{{Cite web|url=https://twitter.com/kaisecam/status/1085886323276349440|title=#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.pic.twitter.com/nTJVG63jRm|last=Kaise 🥄|first=Mx|date=2019-01-17|website=@kaisecam|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM3.JPG|300px|thumb|right|#TwoFacesofME Workday me v’s weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.<ref>{{Cite web|url=https://twitter.com/RachelFrancis/status/1085940724774912000|title=#TwoFacesofME Workday me vs weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.pic.twitter.com/qZNiQaVHyD|last=Francis|first=Rachel|date=2019-01-17|website=@RachelFrancis|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

[[File:PEM6.JPG|300px|thumb|right|What the [world] don’t [see] two faces of M.E.<ref>{{Cite web|url=https://twitter.com/SharonTiday/status/1085122891220430848|title=What the don’t two faces of M.E.pic.twitter.com/DYZVhtyrG5|last=Awareness|first=CFDA #|date=2019-01-15|website=@SharonTiday|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM7.JPG|300px|thumb|right|Joining #pwME sharing #TwoFacesofME for #MEAwareness 1: a fall day when I got outside (but ended up in bed a week) 2: what no one sees (constant [[Chronic pain|pain]], post exertional malaise & [[Sleep dysfunction|sleep deprivation]]) Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)<ref>{{Cite web|url=https://twitter.com/ceibakoru/status/1085894325832040448|title=Joining #pwME sharing #TwoFacesofME for #MEAwareness, 1: a fall day when I got outside (but ended up in bed a week), 2: what no one sees (constant pain, post exertional malaise & sleep deprivation). Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)pic.twitter.com/EpsMLT8E11|last=Ceiba 🌳Koru 🌀|date=2019-01-17|website=@ceibakoru|language=en|access-date=2019-01-17}}</ref>]]

=== An illness within an illness ===

PEM refers to a worsening of many ME/CFS symptoms as a result of physical or mental exertion. It consists of more than post-exertional fatigue and can cause severe debility. As one patient described it: <blockquote>“When I do any activity that goes beyond what I can do—I literally collapse—my body is in major pain, it hurts to lay in bed, it hurts to think, I can’t hardly talk—I can’t find the words, I feel my insides are at war.”<ref name=":0" /></blockquote> Another patient emphasized that the feeling of PEM is very different from what one experiences as a healthy person: <blockquote>"PEM is like nothing else you will experience in healthy life; a combination of a hangover, the flu, finishing a 10k run, all at the same time at varying levels of severity."<ref>{{Cite news|url=https://twitter.com/Fatigo_MECFS/status/1050305665565102080|title=Fatigo_MECFS on Twitter|work=Twitter|access-date=2018-10-11|language=en}}</ref></blockquote>Considering the serious but fluctuating debility PEM causes, ME/CFS expert Dr. [[Anthony Komaroff]] described it as “an illness within an illness”.<ref>{{Cite news|url=https://phoenixrising.me/archives/11884|title=Post-Exertional Malaise II: Perception and Reality By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref>

=== Energy conservation and pacing ===
Patients often report the feeling of a red line, an energy level that if exceeded, will result in a relapse. As one [[Norway|Norwegian]] patient described: <blockquote>“....And suddenly it is just too much. The body turns itself off, as if it has gone on strike. You have pushed too much for too long, it repeats itself, and the body stops functioning.”<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>Energy conservation strategies such as [[pacing]] and the [[Energy Envelope Theory|envelope theory]] have been developed to minimize PEM while allowing patients to stay as active as possible.<ref>{{Cite journal|last=Goudsmit|first=Ellen M.|last2=Nijs|first2=Jo|last3=Jason|first3=Leonard A.|last4=Wallman|first4=Karen E.|date=2012|title=Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document|url=https://www.ncbi.nlm.nih.gov/pubmed/22181560|journal=Disability and Rehabilitation|volume=34|issue=13|pages=1140–1147|doi=10.3109/09638288.2011.635746|issn=1464-5165|pmid=22181560}}</ref> These techniques advise patients to balance energy availability and expenditure and to recognize early signs of PEM so they can reduce activity levels before a relapse occurs.

== History ==

=== Case definitions ===
Early descriptions of symptom exacerbation in [[Myalgic encephalomyelitis|ME]] focused on post-exertional muscle weakness. Renowned ME-expert [[Melvin Ramsay]] for example wrote: <blockquote>"[[Muscle fatigability]] whereby, even after a minor degree of physical effort, three, four or five days or longer elapse before full [[muscle]] power is restored is unique and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME."<ref name=":10">Ramsay M. (1988). Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease. Gower Medical Publishing. Second edition.</ref> </blockquote>In a 1985 study [[Peter Behan|Behan]] et al. noted that all of their patients “had the same primary symptom that of gross fatigue made worse by exercise".<ref>{{Cite journal|last=Behan|first=P. O.|last2=Behan|first2=W. M.|last3=Bell|first3=E. J.|date=May 1985|title=The postviral fatigue syndrome - an analysis of the findings in 50 cases|url=https://www.ncbi.nlm.nih.gov/pubmed/2993423|journal=The Journal of Infection|volume=10|issue=3|pages=211–222|issn=0163-4453|pmid=2993423}}</ref>

'''Formerly used to define Chronic fatigue syndrome'''

In the 1988 [[Holmes criteria|Holmes definition]] of [[Chronic fatigue syndrome|CFS]], unexplained generalized muscle weakness was one of the 11 minor symptoms, yet it was fatigue that set the tone. Another minor symptom referred to “prolonged (24 hours or greater) generalized fatigue after levels of [[exercise]] that would have been easily tolerated in the patient’s premorbid state”.<ref>{{Cite journal|last=Holmes|first=G. P.|last2=Kaplan|first2=J. E.|last3=Gantz|first3=N. M.|last4=Komaroff|first4=A. L.|last5=Schonberger|first5=L. B.|last6=Straus|first6=S. E.|last7=Jones|first7=J. F.|last8=Dubois|first8=R. E.|last9=Cunningham-Rundles|first9=C.|date=Mar 1988|title=Chronic fatigue syndrome: a working case definition|url=https://www.ncbi.nlm.nih.gov/pubmed/2829679|journal=Annals of Internal Medicine|volume=108|issue=3|pages=387–389|issn=0003-4819|pmid=2829679}}</ref> PEM is not a mandatory symptom under the Holmes definition.

The wording post-exertional malaise was first used in one of the 8 minor symptoms in the 1994 [[Fukuda criteria]], but without further clarification of the term, except that it lasts more than 24 hours. PEM is not a mandatory symptom under the Fukuda criterion.

'''Currently disputed to define Chronic fatigue syndrome'''

The [[Oxford criteria]] is flawed as it does not list PEM as a symptom. Patients with the symptom of [[fatigue]], which many illnesses and diseases have, are swept into the diagnosis and research studies. ''The Argus Report'' article ''US NIH Report Calls for UK Definition of ME/CFS to be Scrapped'' wrote the following:<blockquote> The [[United States]] [[National Institutes of Health]] (NIH) has issued a draft report that highlights the dire need for scientific research that will help find a cure for the millions of people suffering from [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS) worldwide. The report also highlights the fact that the decades-old UK Royal Society of Medicine’s Oxford criteria for ME/CFS are severely “flawed,” and that continuing to use these criteria may “cause harm.” Further, the NIH report says that the Royal Society definition should “be retired” and replaced with a single case definition agreed to by the ME/CFS community.<ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref></blockquote>There are further criticisms [https://www.me-pedia.org/wiki/Oxford_criteria#Criticisms here].

'''Currently used to define ME/CFS'''

In 2003, [[Canadian Consensus Criteria]] (CCC) PEM became a recognized symptom for the diagnosis of ME/CFS. The CCC were the first criteria to stress that the onset of PEM could be delayed and to describe its debility as a flu-like distress.<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|last2=Jain|first2=Anil Kumar|last3=De Meirleir|first3=Kenny L.|last4=Peterson|first4=Daniel L.|last5=Klimas|first5=Nancy G.|last6=Lerner|first6=A. Martin|last7=Bested|first7=Alison C.|last8=Flor-Henry|first8=Pierre|last9=Joshi|first9=Pradip|date=Jan 2003|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v11n01_02|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=11|issue=1|pages=7–115|doi=10.1300/j092v11n01_02|issn=1057-3321}}</ref> [[Canadian Consensus Criteria#Definition|PEM and/or post-exertional fatigue]] is used for the CCC criterion.<ref>{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|date=|website=investinme.org|page=4|type=|archive-url=|archive-date=|dead-url=|access-date=|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref>

The 2015 report of the [[National Academy of Medicine]] (NAM) describes PEM more generally as “an exacerbation of some or all of an individual’s ME/CFS symptoms that occurs after physical or cognitive exertion and leads to a reduction in functional ability.” The report confirmed PEM as the hallmark symptom of ME/CFS and advised to rename the disease accordingly to [[Systemic Exertion Intolerance Disease]] (SEID).<ref name=":0" /> PEM is a mandatory symptom under the SEID criterion.

'''Currently used to define Myalgic encephalomyelitis'''

In 2011, the [[International Consensus Criteria]] (ICC) introduced the new term '''Post-Exertional Neuro-immune Exhaustion (PENE)''' to refer to the characteristic exercise and exertion intolerance of [[myalgic encephalomyelitis]] (ME) patients. It notes a delayed onset and prolonged recovery, and uses acute [[flu-like symptoms]] to describe PENE. By definition PENE results in a substantial reduction in functioning, as even simple activities of daily living can cause a relapse.<ref name=":2">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> PENE is a mandatory symptom under the ICC criterion.

===Dismissed as disturbed effort perceptions or kinesiophobia ===
[[File:Brian vastag.png|thumb|right|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]
The existence of PEM as a distinctive and complex symptom of ME/CFS has been dismissed in early research into the disease. Some interpreted it as just fatigue after exercise<ref>https://www.cdc.gov/me-cfs/pdfs/symptom-inventory-questionnaire-508.pdf</ref>, while others saw it as an artifact of disturbed effort perceptions<ref>{{Cite journal|last=Lawrie|first=S. M.|last2=Machale|first2=S. M.|last3=Power|first3=M. J.|last4=Goodwin|first4=G. M.|date=Sep 1997|title=Is the chronic fatigue syndrome best understood as a primary disturbance of the sense of effort?|url=https://www.cambridge.org/core/journals/psychological-medicine/article/editorial-is-the-chronic-fatigue-syndrome-best-understood-as-a-primary-disturbance-of-the-sense-of-effort/434A5EB2C5B4F971A4A36C1DC3400A7E|journal=Psychological Medicine|language=en|volume=27|issue=5|pages=995–999|issn=1469-8978}}</ref><ref>{{Cite journal|last=Rosen|first=S D|last2=King|first2=J C|last3=Wilkinson|first3=J B|last4=Nixon|first4=P G|date=Dec 1990|title=Is chronic fatigue syndrome synonymous with effort syndrome?|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292947/|journal=Journal of the Royal Society of Medicine|volume=83|issue=12|pages=761–764|issn=0141-0768|pmc=1292947|pmid=2125315}}</ref><ref>{{Cite journal|last=Wallman|first=Karen E.|last2=Sacco|first2=Paul|date=Jan 2007|title=Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17365951|journal=Research in Sports Medicine|volume=15|issue=1|pages=47–59|doi=10.1080/15438620601184331|issn=1543-8627|pmid=17365951}}</ref> or an irrational fear of movement<ref>{{Cite journal|last=Silver|first=A.|last2=Haeney|first2=M.|last3=Vijayadurai|first3=P.|last4=Wilks|first4=D.|last5=Pattrick|first5=M.|last6=Main|first6=C. J.|date=Jun 2002|title=The role of fear of physical movement and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12069873|journal=Journal of Psychosomatic Research|volume=52|issue=6|pages=485–493|issn=0022-3999|pmid=12069873}}</ref><ref>{{Cite journal|last=Fischler|first=B.|last2=Dendale|first2=P.|last3=Michiels|first3=V.|last4=Cluydts|first4=R.|last5=Kaufman|first5=L.|last6=De Meirleir|first6=K.|date=Apr 1997|title=Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology|url=https://www.ncbi.nlm.nih.gov/pubmed/9160276|journal=Journal of Psychosomatic Research|volume=42|issue=4|pages=369–378|issn=0022-3999|pmid=9160276}}</ref>. One example of this is the [http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf Tampa scale kinesiophobia], adapted for [[chronic fatigue syndrome]]. Some of the questions in this scale ask about the experience of PEM such as: “If I were to try to overcome it, my symptoms would increase” or “my symptoms let me know when to stop exercising so that I do not harm myself”. Yet these symptoms are classified as an indicator of irrational fear of movement and exercise, instead of PEM.<ref>{{Cite web|url=http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf|title=Tampa Scale Kinesiophobia - Version Chronic Fatigue Syndrome|last=Nijs|first=J|last2=De Meirleir|first2=K|date=2004|website=painmotion.be|publisher=Archives of Physical Medicine and Rehabilitation|archive-url=|archive-date=|dead-url=|access-date=|last3=Duquet|first3=W}}</ref>

=== Critique of the term ===
The name post-exertional malaise was introduced by the 1994 Fukuda criteria and had no prior medical meaning attached to it.<ref name=":3">{{Cite journal|last=Chu|first=Lily|last2=Valencia|first2=Ian J.|last3=Garvert|first3=Donn W.|last4=Montoya|first4=Jose G.|date=2018|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey|url=https://www.ncbi.nlm.nih.gov/pubmed/29856774|journal=PloS One|volume=13|issue=6|pages=e0197811|doi=10.1371/journal.pone.0197811|issn=1932-6203|pmc=5983853|pmid=29856774|quote=|author-link=Lily Chu|author-link2=Ian Valencia|author-link3=Donn Gavert|author-link4=Jose Montoya|author-link5=|via=}}</ref> While in the scientific literature, the term has become the standard to describe the relapses ME/CFS patients suffer after exertion, patients argue that it trivializes their experience. The term malaise after all refers to “a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify”<ref>{{Cite web|url=https://en.oxforddictionaries.com/definition/malaise|title=Definition of malaise in English by Oxford Dictionaries|website=Oxford Dictionaries {{!}} English|access-date=2018-10-13}}</ref>. Doctor of [http://sph.berkeley.edu/ Public Health at Berkely], [[David Tuller]], calls post-exertional malaise a “complete misnomer” arguing what ME/CFS patients experience "is much closer to a serious crash or relapse than a Victorian fainting spell.”<ref>{{Cite web|url=http://www.virology.ws/2011/11/23/chronic-fatigue-syndrome-and-the-cdc-a-long-tangled-tale/|title=Chronic Fatigue Syndrome and the CDC: A Long, Tangled Tale|website=www.virology.ws|language=en-US|access-date=2018-10-10}}</ref> ME/CFS patients usually use the abbreviation PEM or the term ‘crash’ to describe their relapses.

== The distinctive characteristics of PEM ==
Four aspects differentiate the post-exertional malaise of ME/CFS patients from the exercise intolerance commonly reported in patients suffering from [[deconditioning]] or other conditions.

=== Timing ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertional Malaise: History, Characteristics, Evidence'' (2015) By Dr. Lily Chu/Solve CFS">https://www.youtube.com/watch?v=hxJPrkWHcBo</embedvideo>
First of all, there is the time lapse. While physical complaints are usually reported during or shortly after exercise, PEM often has a delayed onset, hours or sometimes even days after the original trigger. Yoshiuchi et al. for example wrote that: “after a briefer maximal exercise task, reports of worsening CFS symptoms were inconsistent or absent until 5 days after the challenge, a pattern not typically observed in real life.”<ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> The authors noted that this delay could be used to distinguish ME/CFS from other fatiguing illness. Another study from Stanford University showed that in up to 37% of the 150 ME/CFS patients studied, PEM may not begin until a day or more after an [[Exertion|exertional]] trigger.<ref name=":3" />

[[File:Rosa SEID.JPG|400px|thumb|Rosa age 25 in 1986. In 2015 the [[SEID]] criteria were released. Rosa read about PEM and how it is delayed and makes [[ME/CFS]] symptoms including [[chronic fatigue]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her [[List of symptoms in ME CFS|worsening symptoms]] with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled]]

Patients may not be familiar with this characteristic of their relapses, since it is very counter-intuitive. As one patient noted:<blockquote>"It's really counter-intuitive to feel bad after a delay of 24 hours after exertion. It may take quite some time before people even make that connection, if ever. I only noticed it about three years in, and I hesitated to mention to others because I thought it might make me sound nuts."<ref name=":5">{{Cite news|url=https://www.s4me.info/threads/s4me-submission-to-the-public-review-on-common-data-elements-for-me-cfs-concerns-with-the-proposed-measure-of-post-exertional-malaise.2220/|title=S4ME: Submission to the public review on Common Data Elements for ME/CFS: Concerns with the proposed measure of post-exertional malaise|work=Science for ME|access-date=2018-10-10|language=en-US}}</ref></blockquote>Another time-related characteristic of PEM is a prolonged recovery period. In a 2010 study 25 M/CFS patients and 23 matched controls were followed up for seven days after performing a maximal cardiopulmonary exercise test. After two days, all controls subjects were recovered while only one ME/CFS patient was. Most (60%) of the ME/CFS participants reported that it took more than five days to fully recover from the test and many reported feeling at their worst 24 to 48 hours after the test.<ref name=":9">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health |volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> Other studies have found the same prolonged recovery period in ME/CFS patients after exertion. A Dutch study for example noted: <blockquote>"For CFS patients, daily observed fatigue was increased up to 2 days after the exercise test. For controls, self-observed fatigue returned to baseline after 2 h."<ref>{{Cite journal|last=Bazelmans|first=Ellen|last2=Bleijenberg|first2=Gijs|last3=Voeten|first3=Marinus J. M.|last4=van der Meer|first4=Jos W. M.|last5=Folgering|first5=Hans|date=Oct 2005|title=Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16223622|journal=Journal of Psychosomatic Research|volume=59|issue=4|pages=201–208|doi=10.1016/j.jpsychores.2005.04.003|issn=0022-3999|pmid=16223622|quote=|author-link=Ellen Bazelmans|author-link2=Gijs Bleijenberg|author-link3=Marinus Voeten|author-link4=Jos van der Meer|author-link5=Hans Folgering|via=}}</ref></blockquote>[[Charles Lapp|Lapp]] et al. followed 31 ME/CFS patients for 12 days after performing a maximal exercise test of 8-10 minutes. The average relapse lasted 8,82 days, although 22% of patients were still in relapse when the study ended at 12 days.<ref>{{Cite journal|last=Lapp|first=C. W.|date=Jul 1997|title=Exercise limits in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9236491|journal=The American Journal of Medicine|volume=103|issue=1|pages=83–84|issn=0002-9343|pmid=9236491}}</ref> In the Stanford study by [[Lily Chu|Chu]] et al. 87% of respondents indicated that they endure PEM for 24 hours or more. The authors concluded: <blockquote>"In many medical conditions, exertion-exacerbated symptoms usually start during exertion or immediately after and usually resolve immediately or shortly after exertion stops. In contrast, PEM may not start until hours or even days after the trigger starts or has been removed, may peak after the first day, and may not stop until hours to months later. This characteristic of PEM often leads patients and clinicians to believe that symptom exacerbations are random rather than associated with a trigger; most people will not intuit that symptoms are caused by a trigger that occurred hours to days prior unless specifically asked by their clinicians to pay attention."<ref name=":3" /> </blockquote>

=== Type of symptoms ===
The second characteristic of PEM is the [[List of symptoms in ME CFS|type of symptoms reported]]. The [[Canadian Consensus Criteria]], a 2003 clinical guideline formed by experts in the field, underlines that many PEM symptoms are [[Immune system|immune-related]]: <blockquote>"The [[malaise]] that follows exertion is difficult to describe but is often reported to be similar to the generalized [[pain]], discomfort and fatigue associated with the acute phase of [[influenza]]. Delayed malaise and fatigue may be associated with signs of immune activation: [[sore throat]], lymph glandular tenderness and/or [[Swollen lymph nodes|swelling]], general malaise, increased pain or [[Brain fog|cognitive fog]]."<ref name=":1" /> </blockquote>[[Mark VanNess|Van Ness]] et al. noted how [[Cognitive dysfunction|cognitive difficulties]] after exertion differentiate ME/CFS patients from healthy controls: <blockquote>"Another interesting difference between groups was the reported symptom of [[cognitive dysfunction]], for example, ‘‘[[Brain fog|brain-fog]]’’ or ‘‘difficulty concentrating.’’ Problems of this nature were not reported by any of the control subjects, whereas 12 patients (48%) experienced these problems: “Carrying on conversations was hard.” “Can’t think straight.” “My mind was not clear.”<ref name=":9" /></blockquote>This was elaborated by [[Lily Chu|Chu]] et al., the research team who conducted the first in-depth investigation on how ME/CFS patients describe their PEM: <blockquote>"There exists no medical condition the authors are familiar with where exertion or emotional distress causes immune/ [[Inflammation|inflammatory]]-related symptoms like sore throat, tender lymph nodes, or flu-like feelings, yet 60% and 36% of our subjects, respectively, reported these symptoms with either stimuli and about a quarter experienced all 3 with exertion. Conversely, symptoms typically associated with physical exertion in other conditions, like [[Dyspnea|shortness of breath]] or [[chest pain]] in [[chronic lung]] or [[heart disease]], are rarely reported in ME/CFS. Furthermore, it is well-established that physical activity improves [[Mood swings|mood]], [[Sleep dysfunction|sleep]], and pain in both healthy people as well those with chronic illnesses like depression or anxiety yet our subjects report worsened sleep, mood, and pain with physical activity."<ref name=":3" /></blockquote>

=== Triggers ===
A third characteristic of PEM is that it can be elicited by multiple triggers. Research has shown that ME/CFS patients experience PEM after both [[Exertion#Exertion in ME.2FCFS|physical and cognitive exertion]]. A 2014 study for example followed up on 32 ME/CFS patients after completing a battery of neurocognitive tests. As the authors concluded: “following a challenging cognitive demand, fatigue significantly increased two days after testing”, which was “suggestive of post-exertional symptom exacerbation following mental effort.”<ref name=":14">{{Cite journal|last=Arroll|first=Megan A.|last2=Attree|first2=Elizabeth A.|last3=O'Leary|first3=John M.|last4=Dancey|first4=Christine P.|date=2014-04-03|title=The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2014.892755|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=2|issue=2|pages=57–63|doi=10.1080/21641846.2014.892755|issn=2164-1846}}</ref> Commenting on the [https://www.me-pedia.org/wiki/1980-81_Ayrshire_outbreak outbreak in West Kilbride, Ayrshire], Ramsay remarked: <blockquote>“Once the disease was established the most characteristic symptom was extreme exhaustion, particularly after exercise. The exhaustion also occurred after emotional or mental strain.”<ref name=":10" /> </blockquote>Some other precipitants of PEM that have been reported include positional changes and exposure to excessive light or sounds<ref>{{Cite web|url=http://anilvanderzee.com/dance-hermit-16-vs-sumo-baby-part-1/|title=Dance hermit ’16 vs. Sumo Baby (part 1) {{!}} Anil van der Zee|website=anilvanderzee.com|language=en-GB|access-date=2018-10-13}}</ref>. While PEM was often thought of as symptom exacerbation after exercise, it is clear that for some ME/CFS patients even basic activities of daily living such as toileting, bathing, dressing, communicating, and reading can trigger relapses.<ref name=":11" /> As long time ME/CFS expert [[Jennie Spotila|Jennifer Spotila]] explained in a four-piece exploration of the phenomenon post-exertional malaise:<blockquote>“The use of the word ‘exertion’ may create the impression that PEM is triggered by strenuous or intense activity, but this is not the case […] Some patients need only attempt to make a simple meal or get dressed before PEM descends.”<ref>{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref></blockquote>This was confirmed by Chu et al. <blockquote>"[…] our results provide formal evidence supporting patient narratives, clinician experiences, and current case definitions which assert that even tasks like walking, cooking, or reading can provoke PEM."<ref name=":3" /> </blockquote>In some instances, the specific trigger of PEM cannot be identified.<ref name=":11">NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Post-Exertional Malaise Subgroup Draft Recommendations Public Review Comments Due January 31, 2018</ref>

=== Loss of functional capacity ===
A fourth distinctive element of PEM is often described as a loss of stamina and/or functional capacity. This refers to the results of the 2-day cardiopulmonary exercise test (CPET) procedure. A CPET is usually reproducible and normally has a test-retest difference of 7-12%<ref name=":16">{{Cite journal|last=Stevens|first=Staci|last2=Snell|first2=Chris|last3=Stevens|first3=Jared|last4=Keller|first4=Betsy|last5=VanNess|first5=J. Mark|date=2018|title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00242/full|journal=Frontiers in Pediatrics|language=English|volume=6|doi=10.3389/fped.2018.00242|issn=2296-2360}}</ref>. ME/CFS patients however show strikingly lower results on several measures at the second CPET compared to the first, despite meeting objective markers of maximal effort. These results have been replicated by several research teams, though there is inconsistency on which measure ([[VO2]] or maximal workload, at peak or ventilatory threshold), the decline in functional capacity is best represented.

{| class="wikitable"
! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS
|-
|
|Number of ME/CFS patients
|VO2 peak
|VO2 at VT
|Workload peak
|Workload at VT
|HR peak
|O2pulse at VT
|-
|[[Mark VanNess|VanNess]] et al. 2007.
|6
| -22%
| -26%
|?
|?
|?
|?
|-
|[[Vemeulen]] et al. 2010.
|15
| -6.3%
| -7.0%
| -5.3%
| -7.0%
| -1.9%
| -8.8%
|-
|[[Christopher Snell|Snell]] et al. 2013.
|51
| -5%
| -10.8%
| -7.2%
| -55.2%
|?
|?
|-
|[[Betsy Keller|Keller]] et al. 2014.
|22
| -13.8%
| -15.8%
| -12.5%
| -21.3%
| -5.9%
| -12.6%
|-
|[[Hodges]] et al. 2018.
|10
| +5.3%
| +6.1%
| -6.7%
| -11.4%
| -0.6%
|?
|}
The drop in functional capacity on the second CPET is usually not seen in other diseases. According to [[Betsy Keller|Keller]] et al. "ME/CFS patients currently represent a unique class of ill patients who do not reproduce maximal CPET measures, unlike individuals with cardiovascular disease, lung disease, end-stage renal disease pulmonary arterial hypertension and cystic fibrosis".<ref name=":17">{{Cite journal|last=Keller|first=Betsy A.|last2=Pryor|first2=John Luke|last3=Giloteaux|first3=Ludovic|date=2014-04-23|title=Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref> A preliminary study from [[New Zealand]] suggests that patients with MS do not display the same decline on the second day of exercise testing, as do patients with ME/CFS.<ref name=":18">{{Cite journal|last=Hodges|first=L. D.|last2=Nielsen|first2=T.|last3=Baken|first3=D.|date=Jul 2018|title=Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4|pages=639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref>

Questions have however been raised about the clinical use of the 2-day CPET procedure. [[Christopher Snell|Snell]] et al. suggested it might be unethical to use this method since many ME/CFS patients might suffer a serious relapse as a result of exercise performance.<ref>{{Cite journal|last=Snell|first=Christopher R.|last2=Stevens|first2=Staci R.|last3=Davenport|first3=Todd E.|last4=Van Ness|first4=J. Mark|date=Nov 2013|title=Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23813081|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=1538-6724|pmid=23813081}}</ref> Others have noted that the CPET- procedure is not practical either. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, may not be available to most clinicians.<ref name=":11" /> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref name=":7">{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref> For these reasons PEM is usually assessed using self-reporting questionnaires.

== Differentiation ==
Several studies have shown that PEM is the symptom of ME/CFS that best differentiates it from other diseases.

=== Healthy controls and idiopathic chronic fatigue ===
PEM was one of the symptoms in the CDC symptom inventory list that differentiated subjects with ME/CFS from those without the disease.<ref>{{Cite journal|last=Wagner|first=Dieter|last2=Nisenbaum|first2=Rosane|last3=Heim|first3=Christine|last4=Jones|first4=James F.|last5=Unger|first5=Elizabeth R.|last6=Reeves|first6=William C.|date=2005-07-22|title=Psychometric properties of the CDC Symptom Inventory for assessment of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16042777|journal=Population Health Metrics|volume=3|pages=8|doi=10.1186/1478-7954-3-8|issn=1478-7954|pmc=1183246|pmid=16042777}}</ref> It was also the highest loading factor among a data set of 38 measurements used for a principal component analysis of unexplained chronic fatigue.<ref>{{Cite journal|last=Vollmer-Conna|first=Uté|last2=Aslakson|first2=Eric|last3=White|first3=Peter D|date=Apr 2006|title=An empirical delineation of the heterogeneity of chronic unexplained fatigue in women|url=https://www.futuremedicine.com/doi/abs/10.2217/14622416.7.3.355|journal=Pharmacogenomics|language=en|volume=7|issue=3|pages=355–364|doi=10.2217/14622416.7.3.355|issn=1462-2416}}</ref> Data for this study came from the epidemiological study in Wichita, Kansas.

The other major epidemiological study, carried out in Chicago, also identified PEM as the hallmark symptom of ME/CFS. In a 10 year follow-up study on the 32 patients originally identified as having ME/CFS, all of the contacted patients reported post-exertional malaise at some point in time. This symptom was able to differentiate ME/CFS patients with those with [[idiopathic chronic fatigue]], those with exclusionary illnesses and healthy controls. According to the author: <blockquote>"Among all the variables in this study, only for post-exertional malaise did the CFS group significantly differ from the other three conditions. This reaffirms the importance of this being a cardinal and critical symptom for CFS."<ref>{{Cite journal|last=Jason|first=Leonard A.|date=Feb 2011|title=Natural History of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171164/|journal=Rehabilitation psychology|volume=56|issue=1|pages=32–42|doi=10.1037/a0022595|issn=0090-5550|pmc=3171164|pmid=21401284}}</ref> </blockquote>Using a large sample of ME/CFS patients from Newcastle, [[Norway]] and the [https://www.me-pedia.org/wiki/Solve_ME/CFS_Initiative#Biobank Solve ME/CFS Biobank], Jason et al. conducted an analysis of different case definitions and symptoms. The domain of post-exertional malaise was found to be most adequate at differentiating ME/CFS patients from controls. As the authors noted: <blockquote>Using the latent variables from the empiric criteria, only one factor (PEM) was needed to reach a sensitivity of 90.8%, specificity of 92.5% and accuracy of 91.6%, and this was the only data mining where all percentages were over 90%. […] the fact that PEM came out in all analyses supports the importance of this domain in the case definition.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Reed|first5=Jordan|last6=Furst|first6=Jacob|last7=Newton|first7=Julia L.|last8=Strand|first8=Elin Bolle|last9=Vernon|first9=Suzanne D.|date=2014-04-01|title=Comparing and Contrasting Consensus versus Empirical Domains|url=https://www.ncbi.nlm.nih.gov/pubmed/26977374|journal=Fatigue: Biomedicine, Health & Behavior|volume=3|issue=2|pages=63–74|doi=10.1080/21641846.2015.1017344|issn=2164-1846|pmc=4788637|pmid=26977374}}</ref> </blockquote>A 2014 examination, using 236 patients and 86 controls, showed that three symptoms accurately classified 95.4% of participants as patient or control: fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Sunnquist|first2=Madison|last3=Brown|first3=Abigail|last4=Evans|first4=Meredyth|last5=Vernon|first5=Suzanne D.|last6=Furst|first6=Jacob|last7=Simonis|first7=Valerie|date=2014-01-01|title=Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24511456|journal=Fatigue: Biomedicine, Health & Behavior|volume=2|issue=1|pages=40–56|doi=10.1080/21641846.2013.862993|issn=2164-1846|pmc=3912876|pmid=24511456}}</ref> Another data mining study by the same research group, suggested the selection of four symptoms: next to extreme tiredness, unrefreshing sleep and [[Word-finding problems|difficulty finding the right word to say]] or [[Aphasia|expressing thoughts]], PEM was once again represented with the item “physically drained/sick after mild activity.”<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Evans|first5=Meredyth|last6=Jantke|first6=Rachel|last7=Williams|first7=Yolonda|last8=Furst|first8=Jacob|last9=Vernon|first9=Suzanne D.|date=2015|title=Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Toward An Empirical Case Definition|url=https://www.ncbi.nlm.nih.gov/pubmed/26029488|journal=Health Psychology and Behavioral Medicine|volume=3|issue=1|pages=82–93|doi=10.1080/21642850.2015.1014489|issn=2164-2850|pmc=4443921|pmid=26029488}}</ref>

[[Michael Maes|Maes]] et al. divided ME/CFS patients into two groups: those with or without PEM lasting for more than 24 hours. Analysis showed this to be a meaningful division as the former group (45% of the sample) not only had higher symptom scores on concentration difficulties and a subjective experience of infection, but also higher markers of immune-activation such as [[Interleukin 1|IL-1]], [[TNFa]], [[lysozyme]] and [[neopterin]], than the CFS group without PEM. According to the authors their findings, "underscore the relevance of post-exertional malaise to identify a subgroup of CFS patients that should be diagnosed as ME".<ref>{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Johnson|first3=Cort|date=2012-12-30|title=Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data|url=https://www.ncbi.nlm.nih.gov/pubmed/22521895|journal=Psychiatry Research|volume=200|issue=2-3|pages=754–760|doi=10.1016/j.psychres.2012.03.031|issn=1872-7123|pmid=22521895}}</ref>

=== Multiple sclerosis ===
According to a 2015 report by the National Academy of Medicine, the prevalence of PEM among ME/CFS patients varies from 69 to 100%, which is much higher than in other disease groups.<ref name=":0" /> In a 1996 study by Komaroff et al. 13 of 25 MS-patients (52%) reported PEM<ref name=":12">{{Cite journal|last=Komaroff|first=A. L.|last2=Fagioli|first2=L. R.|last3=Geiger|first3=A. M.|last4=Doolittle|first4=T. H.|last5=Lee|first5=J.|last6=Kornish|first6=R. J.|last7=Gleit|first7=M. A.|last8=Guerriero|first8=R. T.|date=Jan 1996|title=An examination of the working case definition of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8579088|journal=The American Journal of Medicine|volume=100|issue=1|pages=56–64|issn=0002-9343|pmid=8579088}}</ref>, a figure similar to what Jason et al. found with the DSQ PEM subscale in a cohort of 106 MS-patients.<ref>{{Cite journal|last=Jason|first=L. A.|last2=Ohanian|first2=D.|last3=Brown|first3=A.|last4=Sunnquist|first4=M.|last5=McManimen|first5=S.|last6=Klebek|first6=L.|last7=Fox|first7=P.|last8=Sorenson|first8=M.|date=2017|title=Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29430570|journal=Insights in Biomedicine|volume=2|issue=2|doi=10.21767/2572-5610.10027|issn=2572-5610|pmc=5800741|pmid=29430570}}</ref> Both studies used a broad definition of PEM which focused on fatigue after exercise. Preliminary research suggests that adding more specific questions, for example about the prolonged recovery and various type of triggers, PEM might be able to differentiate ME/CFS from [[multiple sclerosis]]. A 2018 study for example showed that ME/CFS patients reported to experience PEM more often through mental exertion and to recover more slowly from PEM compared to multiple sclerosis patients.<ref name=":7" />
=== Major Depressive disorder ===
In the 1996 study by Komaroff et al., only 19% of patients with major [[depression]] reported PEM.<ref name=":12" /> A similar figure was found by Hawk et al., who found PEM in 3 patients in their sample of 15 with major depressive disorder.<ref>{{Cite journal|last=Hawk|first=Caroline|last2=Jason|first2=Leonard A.|last3=Torres-Harding|first3=Susan|date=2006|title=Differential diagnosis of chronic fatigue syndrome and major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/17078775|journal=International Journal of Behavioral Medicine|volume=13|issue=3|pages=244–251|doi=10.1207/s15327558ijbm1303_8|issn=1070-5503|pmid=17078775}}</ref> In contrast all of the 15 studied ME/CFS patients reported PEM, making it the largest discriminant function for all investigated symptoms. White et al. studied patients with persistent symptoms of fatigue and poor concentration after glandular fever. According to the authors "the complaint of post-exertional physical fatigue may help to differentiate post-viral fatigue states from psychiatric disorders."<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmed/8588010|title=The validity and reliability of the fatigue syndrome that follows glandular fever. - PubMed - NCBI|last=White|first=PD|website=www.ncbi.nlm.nih.gov|language=en|access-date=2018-10-24}}</ref>

=== Gulf war illness ===
[[James Baraniuk|Baraniuk]] and Shivapurkar (2017) looked at [[MicroRNA]]<nowiki/>s (miRNA) in the [[cerebrospinal fluid]] of ME/CFS patients, healthy controls and patients with [[Gulf War Illness]] before and after an exercise challenge (a submaximal bicycle exercise). While there were no differences in miRNA between the groups at baseline, a distinct signature appeared after exercise. According to the authors, "exercise caused distinct patterns of [[miRNA]] changes in CFS and […] [[Gulf War Illness|GWI]] indicating significant pathophysiological differences between conditions."<ref>{{Cite journal|last=Baraniuk|first=James N.|last2=Shivapurkar|first2=Narayan|date=2017-11-10|title=Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects|url=https://www.nature.com/articles/s41598-017-15383-9|journal=Scientific Reports|language=En|volume=7|issue=1|doi=10.1038/s41598-017-15383-9|issn=2045-2322}}</ref> A 2013 study under the guidance of [[Nancy Klimas]] compared the immune signature in 30 Gulf war patients, 22 ME/CFS patients and 30 controls, after an graded exercise test. Results indicated the importance of physical exercise for differentiating these different groups: <blockquote>"Common to both GWI and CFS illness signatures were the direct or indirect contributions of IL-10 and IL-23 expression though these occurred at very different times. While levels measured at rest supported an illness signature in GWI, their impact in CFS was only observable during and after exercise, again emphasizing the importance of a challenge and response timeline in distinguishing these illnesses."<ref>{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23800166|journal=BMC immunology|volume=14|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=3698072|pmid=23800166}}</ref></blockquote>

== Objective findings after exertion: ==
In the 1980s Melvin A. Ramsay stressed the use of assessing ME-patients after exertion. Regarding muscle weakness – what he regarded as the hallmark symptom of the disease –he noted: <blockquote>"If muscle power is found to be satisfactory, a re-examination should be made after exercise; a walk of half a mile is sufficient, as very few ME case can manage more. […] It is most important to stress the fact that cases of ME of mild or even moderate severity may have normal muscle power in a remission. In such cases, test for muscle power should be repeated after exercise."<ref name=":10" /> </blockquote>Though the definition of PEM has been expended far beyond muscle weakness, modern day research has confirmed the utility of testing ME/CFS after exertion. Many markers that are normal in resting state in ME/CFS patients turn out to be abnormal after a physical or cognitive stressor.<ref name=":0" />

=== Gene expression ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''72. Gene-expression and exercise / Gen-expressie en inspanning – dr. Lucinda Bateman'' (2015) By Dr. Lucinda Bateman/Wetenschap voor Patienten - ME/cvs Vereniging">https://https://www.youtube.com/watch?v=F1PP21TmUPs</embedvideo>

One example is gene expression. In a 2009 study Light et al. showed that after a moderate exercise test, the [[Leucocyte|leukocytes]] of ME/CFS patients showed an increase in expression of [[Adrenergic receptor|adrenergic]], [[metabolite]] detecting and [[immune-related genes]] that was not seen in healthy controls. Before the exercise test there were no abnormalities in the expression of these genes of ME/CFS patients. The authors speculated this to be evidence for sensitization of fatigue pathways in ME/CFS.<ref name=":20" /> The research team was able to confirm their results in a subsequent study using a larger sample of 48 patients.<ref name=":21" /> In a 2012 comparison MS patients also displayed an increase in post-exercise gene expression, but only ME/CFS patients showed increases in metabolite-detecting sensory receptors. According to the authors:<blockquote>"Because only the CFS patients showed increases in these metabolite-detecting receptors, the sensory receptor elements of this gene profile seem particularly specific to CFS and may reflect dysregulated pathways that directly contribute to increased effort sense during exercise and postexertional malaise."<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=VanHaitsma|first4=Timothy A.|last5=Light|first5=Kathleen C.|date=Jan 2012|title=Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/PSY.0b013e31824152ed|issn=0033-3174|pmc=3256093|pmid=22210239}}</ref></blockquote>Attempts at replication by other research teams have produced contradictory results. Meyer et al. were unable to confirm most of the post-exertional increases in gene expression, except for some in the adrenergic and glucocorticoid pathway.<ref>{{Cite journal|last=Meyer|first=Jacob|last2=R. Light|first2=Alan|last3=Shukla|first3=Sanjay|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron|last7=Cook|first7=Dane|date=2013-10-01|title=Post-exertion malaise in chronic fatigue syndrome: Symptoms and gene expression|url=https://www.researchgate.net/publication/258165434_Post-exertion_malaise_in_chronic_fatigue_syndrome_Symptoms_and_gene_expression|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|pages=190–209|doi=10.1080/21641846.2013.838444}}</ref> An [[Australia|Australian]] team under the guidance of [[Andrew Lloyd]] failed to find any significant exercise-induced changes in leucocyte gene expression, though the patient sample used (n = 10) was rather small and did not include any patients with severe [[functional disability]].<ref>{{Cite journal|last=Keech|first=Andrew|last2=Vollmer-Conna|first2=Ute|last3=Barry|first3=Benjamin K.|last4=Lloyd|first4=Andrew R.|date=2016|title=Gene Expression in Response to Exercise in Patients with Chronic Fatigue Syndrome: A Pilot Study|url=https://www.ncbi.nlm.nih.gov/pubmed/27713703|journal=Frontiers in Physiology|volume=7|pages=421|doi=10.3389/fphys.2016.00421|issn=1664-042X|pmc=5031769|pmid=27713703}}</ref>

=== Immune activation ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Inducing Post-Exertional Malaise in ME/CFS: A Look at the Research Evidence'' (2015) By Dr. Peter Rowe/Solve CFS">https://www.youtube.com/watch?v=ux93w7yGQ5g</embedvideo>
There are many studies demonstrating exercise-induced immunological abnormalities in ME/CFS patients.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723}}</ref> Most findings however still have to be replicated by other research groups, using larger samples.

==== Oxidative stress ====
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertion Malaise: The Intersection of Biology and Behavior'' (2015) By Dr. Dane B. Cook/Solve CFS">https://www.youtube.com/watch?v=vfmrPd4-rIE</embedvideo>
In 2005 the French team Yammes et al. found a lengthened and accentuated oxidative stress response in ME/CFS patients after a cycling exercise until exhaustion. At baseline markers of [[oxidative stress]] (thiobarbituric acidreactiv substances and ascorbic acid) did not differ significantly from healthy controls. After the exercise challenge however, the oxidative stress response occurred sooner and lasted longer in the ME/CFS group. This was associated with alterations in muscle excitability (lengthened [[M-wave]] duration) in ME/CFS-patients, which were not seen in controls.<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Mambrini|first3=O.|last4=Brégeon|first4=F.|last5=Delliaux|first5=S.|date=Mar 2005|title=Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/15715687|journal=Journal of Internal Medicine|volume=257|issue=3|pages=299–310|doi=10.1111/j.1365-2796.2005.01452.x|issn=0954-6820|pmid=15715687}}</ref> A small 2009 follow-up study confirmed these results and associated it with a post-exertional reduction of [[Heat shock protein|heat shock proteins]] HSP 27 and HSP 70 after exercise.<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=Aug 2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://www.ncbi.nlm.nih.gov/pubmed/19457057|journal=Journal of Internal Medicine|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796|pmid=19457057}}</ref> According to the authors, this is another indication of an impaired redox status in ME/CFS patients. A 2011 study confirmed most of these results in a larger cohort of 43 ME/CFS patients and 23 healthy controls. Again the data indicated an increased exercise-induced oxidative stress and a reduced Hsp response. Though it is know that deconditioning can increase oxidative stress, the authors argued this to be unlikely in their study population, for several reasons: <blockquote>“…deconditioning can be ruled out in our study because (i) it induces carbohydrate and lipid disorders that were not observed during routine biochemical check-up in these CFS patients, (ii) CFS patients did not have reduced maximal exercise performance or an accentuated lactic acid response and (iii) we found no correlation between the duration of CFS symptoms […] and the resting levels of oxidant–antioxidant status and HSPs.”<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|date=Jul 2012|title=Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins|url=https://www.ncbi.nlm.nih.gov/pubmed/22112145|journal=Journal of Internal Medicine|volume=272|issue=1|pages=74–84|doi=10.1111/j.1365-2796.2011.02488.x|issn=1365-2796|pmid=22112145}}</ref></blockquote>A [[Canada|Canadian]] research team had already reported a marked decline of HSP 27 during the post-exercise period of six ME/CFS patients in 2002.<ref>{{Cite journal|last=Thambirajah|first=Anita A.|last2=Sleigh|first2=Kenna|last3=Stiver|first3=H. Grant|last4=Chow|first4=Anthony W.|date=2008-12-01|title=Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/19032901|journal=Clinical and Investigative Medicine. Medecine Clinique Et Experimentale|volume=31|issue=6|pages=E319–327|issn=1488-2353|pmid=19032901}}</ref>

==== Complement C4a ====
In 2003 Sorensen et al. found that the [[Complement C4a|complement split product C4a]] was increased after exercise in the 20 ME/CFS patients, but not in controls. Furthermore a significant correlation was found between the increase in C4a and total symptom score.<ref>{{Cite journal|last=Sorensen|first=Bristol|last2=Streib|first2=Joanne E.|last3=Strand|first3=Matthew|last4=Make|first4=Barry|last5=Giclas|first5=Patricia C.|last6=Fleshner|first6=Monika|last7=Jones|first7=James F.|date=Aug 2003|title=Complement activation in a model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12897748|journal=The Journal of Allergy and Clinical Immunology|volume=112|issue=2|pages=397–403|issn=0091-6749|pmid=12897748}}</ref> C4a is generated from the cleavage of the native complement protein C4 via the classical and lectin pathways. A follow up study, published in 2009, found that other elements of the lectin pathway also responded differently to an exercise challenge in ME/CFS patients compared to controls. Both C4 and mannan-binding lectin serine protease 2 (MASP2) were observed at higher levels in ME/CFS subjects 1 hour post-exercise.<ref>{{Cite journal|last=Sorensen|first=Bristol|author-link=|last2=Jones|first2=James F|author-link2=|last3=Vernon|first3=Suzanne D|author-link3=Suzanne Vernon|last4=Rajeevan|first4=Mangalathu S|author-link4=Mangalathu Rajeevan|author-link5=|date=Jan 2009|title=Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/|journal=Molecular Medicine|volume=15|issue=1-2|pages=34–42|doi=10.2119/molmed.2008.00098|pmc=2583111|pmid=19015737|quote=|via=}}</ref> The authors speculated this to contribute to the increased C4a split product 6 hours after the exercise challenge. In a 2010 study by Nijs et al. there was no increase in C4a after exercise in ME/CFS patients, though a significant correlation with post-exertional pain and fatigue was found.<ref>{{Cite journal|last=Nijs|first=J.|last2=Van Oosterwijck|first2=J.|last3=Meeus|first3=M.|last4=Lambrecht|first4=L.|last5=Metzger|first5=K.|last6=Frémont|first6=M.|last7=Paul|first7=L.|date=Apr 2010|title=Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1β|url=https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2009.02178.x|journal=Journal of Internal Medicine|volume=267|issue=4|pages=418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=0954-6820}}</ref>
==== Cytokines ====
The expression of cytokines after physical exercise has been researched in ME/CFS patients since the mid-1990s. Most of these studies have found negative results (see table below).

{| class="wikitable"
|Study
|Number of participants
|Exercise challenge
|Cytokines tested:
|Results:
|-
|[[Daniel Peterson|Peterson]] et al. (1994)<ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=Mar 1994|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7496949|journal=Clinical and Diagnostic Laboratory Immunology|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>
|10 ([[Holmes criteria]], all cases were post-infectious)
|Walking 1 mile per hour for 30 min
|[[Interleukin 1 beta|IL-1 β]], [[Interleukin 6|IL-6]], and [[TNF-alpha|TNF-α]], [[TGF beta|TGF-β]]
|Negative results
|-
|[[Andrew Lloyd|Lloyd]] et al. (1994)<ref>{{Cite journal|last=Lloyd|first=A.|last2=Gandevia|first2=S.|last3=Brockman|first3=A.|last4=Hales|first4=J.|last5=Wakefield|first5=D.|date=Jan 1994|title=Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/8148442|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S142–146|issn=1058-4838|pmid=8148442}}</ref>
|12 ([[Australian criteria]])
|30 min hand grip exercises
|[[Interferon gamma|IFN-γ]], [[Interferon alpha |IFN-α]], [[Interleukin 1 beta|IL-1 β]], [[TNF-alpha|TNF-α]]
|Negative results
|-
|[[La Manca]] et al. (1999)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=Zhou|first3=X. D.|last4=Ottenweller|first4=J. E.|last5=Cook|first5=S.|last6=Peckerman|first6=A.|last7=Zhang|first7=Q.|last8=Denny|first8=T. N.|last9=Gause|first9=W. C.|date=Mar 1999|title=Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion|url=https://www.ncbi.nlm.nih.gov/pubmed/10226888|journal=Journal of Clinical Immunology|volume=19|issue=2|pages=135–142|issn=0271-9142|pmid=10226888}}</ref>
|20 ([[Fukuda criteria]]) "only patients with an illness duration of less than 6 years, who reported at least substantial intensity on symptom severity scales in the month prior to recruitment and who had no major psychiatric diagnosis in the 5 years prior to illness onset" were included
|An exhaustive treadmill exercise test
|[[Interleukin 2|IL-2]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]]<nowiki>, [[Interferon gamma|IFN-γ, </nowiki>[[TNF-alpha|TNF-α]]
|Negative results
|-
|Cannon et al. (1997)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Abad|first3=L. W.|last4=Vannier|first4=E.|last5=Mileno|first5=M. D.|last6=Fagioli|first6=L.|last7=Wolff|first7=S. M.|last8=Komaroff|first8=A. L.|date=May 1997|title=Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9168406|journal=Journal of Clinical Immunology|volume=17|issue=3|pages=253–261|issn=0271-9142|pmid=9168406}}</ref>
|8 (Holmes criteria) “their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]], [[interleukin-1 receptor antagonist]] (IL-1Ra), and [[soluble interleukin-1 receptor type II]] (IL-lsRII).
|Negative results
|-
|Gupta et al. (1998)<ref>{{Cite journal|last=Gupta|first=S.|last2=Aggarwal|first2=S.|last3=Starr|first3=A.|date=Feb 1999|title=Increased production of interleukin-6 by adherent and non-adherent mononuclear cells during 'natural fatigue' but not following 'experimental fatigue' in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9917531|journal=International Journal of Molecular Medicine|volume=3|issue=2|pages=209–213|issn=1107-3756|pmid=9917531}}</ref>
|5 (Holmes criteria)
|30 min hand grip exercises
|[[Interleukin 6|IL-6]]
|Negative results
|-
|Cannon et al. (1999)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Ball|first3=R. W.|last4=Abad|first4=L. W.|last5=Fagioli|first5=L.|last6=Komaroff|first6=A. L.|date=Nov 1999|title=Acute phase responses and cytokine secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10634215|journal=Journal of Clinical Immunology|volume=19|issue=6|pages=414–421|issn=0271-9142|pmid=10634215}}</ref>
|10 (Holmes criteria) their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]],[[IL-6]]
|Negative results
|-
|Yammes et al. (2009)<ref name=":25" />
|9 ([[Fukuda criteria]]) 6/9 had practiced sport at high levelxxxxxxxx, for more than 4 years before the symptoms occurred.
|Cycling test until maximal work load
|[[IL-6]], [[TNF-a]]
|Negative results
|-
|Robinson et al (2010)<ref>{{Cite journal|last=Robinson|first=M.|last2=Gray|first2=S. R.|last3=Watson|first3=M. S.|last4=Kennedy|first4=G.|last5=Hill|first5=A.|last6=Belch|first6=J. J. F.|last7=Nimmo|first7=M. A.|date=Apr 2010|title=Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19422646|journal=Scandinavian Journal of Medicine & Science in Sports|volume=20|issue=2|pages=282–290|doi=10.1111/j.1600-0838.2009.00895.x|issn=1600-0838|pmid=19422646}}</ref>
|6 (Fukuda criteria)
|Incremental exercise test to exhaustion
|IL-6, [[sIL-6R]] and [[sgp130]]
|Negative results
|-
|[[Andrea White]] et al. (2010)<ref name=":26">{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010-07-01|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20230500|journal=Psychophysiology|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1540-5958|pmc=4378647|pmid=20230500}}</ref>
|19 (Fukuda criteria)
|The authors used "a moderate whole-body exercise task (working both arms and legs) for 25 min that was mild enough that all CFS patients were able to complete it successfully but did induce a flare of fatigue and pain symptoms that remained above pre-exercise levels for 48 h post-exercise in the majority of patients."
|[[Interleukin 1 beta |IL-1β]], [[Interleukin 2 |IL-2]], [[Interleukin 12|IL-12]], [[TNF-alpha |TNFα]], soluble [[CD40L]], [[Interferon gamma |IFN-γ]], [[Interleukin 4|IL-4]], [[Interleukin 10 |IL-10]], [[Interleukin 13|IL-13]], [[Interleukin 6|IL-6]] and [[Interleukin 8|IL-8]]

 
|Positive results for a subgroup (11/19) of patients with high PEM

 
|-
|Andrew Lloyd et al. (2018)<ref name=":27">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=En|volume=8|issue=1|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|24 ([[Fukuda criteria]]) “we used the 1994 Centers for Disease Control (CDC)/Fukuda international diagnostic criteria for ME/CFS, but required participants to have post exertional malaise. Terefore, in labeling our patients this refers to the revised [[International Consensus Criteria|international consensus criteria]] from 2011”
|Symptom limited exercise on an ergocycle.
|Growth factors: [[FGF beta|FGF-β]], [[HGF]], [[NGF]], [[PDGF-BB]], [[TGF alpha|TGFα]], [[TGF-β1]], [[Vascular endothelial growth factor|VEGF]]

 

[[Colony stimulating factors]] and [[stem cell factors]]: [[G-CSF]], [[GM-CSF]], [[M-CSF]], [[SCF]]

 

Interleukins: [[Interleukin 1alpha|IL-1α]], [[Interleukin 1beta|IL-1β]], [[Interleukin 1RA|IL-1RA]], [[Interleukin 2|IL-2]], [[IL-4]], [[IL-5]], [[IL-6]], [[Interleukin 7|IL-7]], [[Interleukin |IL-8]], [[Interleukin 10|IL-10]], [[Interleukin 12p40|IL12p40]], [[Interleukin 12p70|IL12p70]], [[Interleukin 13|IL-13]], [[Interleukin 15|IL-15]], [[Interleukin 17|IL-17]], [[Interleukin 17f|IL-17F]], [[Interleukin 18|IL-18]] and [[LIF]]

 

[[Chemokine|Chemokines]]: [[CCL2]] ([[MCP-1]]), [[CCL3]] ([[MIP-1α]]), [[CCL4]] ([[MIP-1β]]), [[CCL5]] ([[RANTES]]) [[CCL7]] ([[MCP-3]]), [[CXCL1]] ([[Gro alpha|Gro-α]]), [[CXCL5]] ([[ENA78]]), [[CXCL9]] ([[MIG]]), [[CXCL10]] ([[IP-10]]), [[CCL11]] ([[Eotaxin]])

 

[[Interferon|Interferons]]: [[Interferon alpha |INF-α]], [[Interferon beta |INF-β]], [[Interferon gamma|INF-γ]]

 

[[Adhesion Molecule|Adhesion Molecules]] : [[ICAM-1]], [[VCAM-1]]

 

Other factors: [[CD40L]], [[FASL]], [[Leptin]], [[PAI-1]], [[Resistin]], [[TNF-α]], [[TNF-β]], [[TRAIL]]
|Positive results: ME/CFS had a distinct [[cytokine profile]] post-exercise.
|}
Moneghetti et al. took a different approach and looked at the cytokine profiling after exercise, as this may differentiate patients with ME/CFS from sedentary controls. Of the 51 [[cytokine]]s and growth factors tested, 10 significantly changed after exercise in both groups, a further 7 only changed in controls and five only changed in ME/CFS (namely, [[CXCL10]], [[IL-8]], [[CCL4]], [[TNF-β]] and [[ICAM-1]]). This suggests a distinct [[cytokine inflammatory signature]] in ME/CFS.<ref name=":27" /> White et al. (2010) differentiated their 19 ME/CFS patients with a high or low post-exertional malaise (called symptom flare SF, in the study). While the cytokine expression after exercise of patients with low PEM was similar to those of healthy controls, patients with high PEM showed opposite results. As the authors noted:<blockquote>"In sum, low SF patients and controls showed a pattern of post-exercise decreases in both pro and anti-inflammatory cytokines (with the exception of increases in IL-8), whereas the high SF patients showed a pattern of increases in both cytokine types at 8 h and no decreases at any time."<ref name=":26" /></blockquote>

=== Autonomic response ===
Several research teams have noted post-exertional abnormalities in the [[Autonomic nervous system|autonomic]] function of ME/CFS patients, though the exact meaning of these results is not yet clear.

A Canadian team under the guidance of [[Terrence Montague]] noted that during a maximal exercise test, ME/CFS patients have a lower maximal heart rate than controls. The authors noted that: <blockquote>“...patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.”<ref>{{Cite journal|last=Montague|first=T.J.|last2=Marrie|first2=T.J.|last3=Klassen|first3=G.A.|last4=Bewick|first4=D.J.|last5=Horacek|first5=B.M.|date=Apr 1989|title=Cardiac function at rest and with exercise in the chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/2924607|journal=Chest|volume=95|issue=4|pages=779–784|issn=0012-3692|pmid=2924607}}</ref> </blockquote>A significantly lower peak heart rate has been repeatedly observed in CPET-studies with ME/CFS patients.<ref>{{Cite journal|last=Gibson|first=H|last2=Carroll|first2=N|last3=Clague|first3=J E|last4=Edwards|first4=R H|date=Sep 1993|title=Exercise performance and fatiguability in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC489735/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=56|issue=9|pages=993–998|issn=0022-3050|pmid=8410041}}</ref><ref>{{Cite journal|last=Sisto|first=Sue Ann|last2=LaManca|first2=John|last3=Cordero|first3=Douglas L.|last4=Bergen|first4=Michael T.|last5=Ellis|first5=Steven P.|last6=Drastal|first6=Susan|last7=Boda|first7=Wanda L.|last8=Tapp|first8=Walter N.|last9=Natelson|first9=Benjamin H.|date=Jun 1996|title=Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome|url=https://www.amjmed.com/article/S0002-9343(96)00041-1/pdf|journal=The American Journal of Medicine|language=English|volume=100|issue=6|pages=634–640|doi=10.1016/S0002-9343(96)00041-1|issn=0002-9343}}</ref><ref>{{Cite journal|last=Rowbottom|first=David|last2=Keast|first2=David|last3=Pervan|first3=Zhukov|last4=Morton|first4=Alan|date=Jan 1998|title=The Physiological Response to Exercise in Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v04n02_04|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=4|issue=2|pages=33–49|doi=10.1300/j092v04n02_04|issn=1057-3321}}</ref> In one of the largest of these into exercise performance, the authors noted the same phenomenon as Montague et al. <blockquote>“The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects.”<ref>{{Cite journal|last=De Becker|first=P.|last2=Roeykens|first2=J.|last3=Reynders|first3=M.|last4=McGregor|first4=N.|last5=De Meirleir|first5=K.|date=2000-11-27|title=Exercise capacity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11088089|journal=Archives of Internal Medicine|volume=160|issue=21|pages=3270–3277|issn=0003-9926|pmid=11088089}}</ref></blockquote>The Belgium team Van Oosterwijck et al. reported an impaired heart rate recovery in 20 female ME/CFS patients following exercise.<ref>{{Cite journal|last=Van Oosterwijck|first=J.|last2=Marusic|first2=U.|last3=De Wandele|first3=I.|last4=Meeus|first4=M.|last5=Paul|first5=L.|last6=Lambrecht|first6=L.|last7=Moorkens|first7=G.|last8=Nijs|first8=J.|date=May 2015|title=Reduced parasympathetic reactivation during recovery from exercise in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)|url=https://www.physiotherapyjournal.com/article/S0031-9406(15)02014-3/fulltext|journal=Physiotherapy|language=English|volume=101|pages=e1091–e1092|doi=10.1016/j.physio.2015.03.1984|issn=0031-9406|issue=|quote=|author-link=Jessica Van Oosterwijck|author-link2=|author-link3=|author-link4=|author-link5=|via=|author-link8=Jo Nijs}}</ref> In other disease groups this is associated with risk for cardiac events and sudden death. Cordero et al. did not find a significant difference in mean heart rate between 11 ME/CFS patients and six healthy controls after walking on a treadmill, but they did find patients to have significantly less ‘vagal power’, a measure for respiratory-related parasympathetic contributions to heart rate.<ref>{{Cite journal|last=Cordero|first=D. L.|last2=Sisto|first2=S. A.|last3=Tapp|first3=W. N.|last4=LaManca|first4=J. J.|last5=Pareja|first5=J. G.|last6=Natelson|first6=B. H.|date=Dec 1996|title=Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8985621|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=6|issue=6|pages=329–333|issn=0959-9851|pmid=8985621}}</ref> Soetekouw et al. noted that during a handgrip exercise, the hemodynamics response was lower in the ME/CFS group than in the control group, although this could be attributed to the lower level of muscle exertion in the ME/CFS group.<ref>{{Cite journal|last=Soetekouw|first=P. M.|last2=Lenders|first2=J. W.|last3=Bleijenberg|first3=G.|last4=Thien|first4=T.|last5=van der Meer|first5=J. W.|date=Dec 1999|title=Autonomic function in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10638807|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=9|issue=6|pages=334–340|issn=0959-9851|pmid=10638807}}</ref> LaManca et al. studied 19 ME/CFS (Holmes criteria) and found that they had a diminished heart rate and blood pressure in response to a cognitive test compared to healthy controls, though exercise did not magnify this effect.<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Peckerman|first2=A.|last3=Sisto|first3=S. A.|last4=DeLuca|first4=J.|last5=Cook|first5=S.|last6=Natelson|first6=B. H.|date=Sep 2001|title=Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/11573024|journal=Psychosomatic Medicine|volume=63|issue=5|pages=756–764|issn=0033-3174|pmid=11573024}}</ref> Similar results were found by a Norwegian research team. They studied 13 adolescents with ME/CFS and 53 age-matched controls after a mental stress test (arithmetic questions). Though heart rate was significantly higher in patients at baseline, there were no meaningful differences during the arithmetic challenge.<ref>{{Cite journal|last=Egge|first=Caroline|last2=Wyller|first2=Vegard Bruun|date=2010-12-14|title=No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/21156045|journal=BioPsychoSocial Medicine|volume=4|pages=22|doi=10.1186/1751-0759-4-22|issn=1751-0759|pmc=3012010|pmid=21156045}}</ref> Finally, Ocon et al. (2012) studied 16 patients with both the diagnosis of ME/CFS and POTS after increased orthostatic stress and a cognitive challenge. An impairment of the neurocognitive abilities was noted, that was not seen in healthy controls.<ref>{{Cite journal|last=Ocon|first=Anthony J.|last2=Messer|first2=Zachary R.|last3=Medow|first3=Marvin S.|last4=Stewart|first4=Julian M.|date=Mar 2012|title=Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/21919887|journal=Clinical Science (London, England: 1979)|volume=122|issue=5|pages=227–238|doi=10.1042/CS20110241|issn=1470-8736|pmc=3368269|pmid=21919887}}</ref>

=== Sleep ===
A first study into the effects of exercise on sleep in ME/CFS found a beneficial effect: approximately half the patients slept better after exercise.<ref>{{Cite journal|last=Togo|first=Fumiharu|last2=Natelson|first2=Benjamin H.|last3=Cherniack|first3=Neil S.|last4=Klapholz|first4=Marc|last5=Rapoport|first5=David M.|last6=Cook|first6=Dane B.|date=Jan 2010|title=Sleep is not disrupted by exercise in patients with chronic fatigue syndromes|url=https://www.ncbi.nlm.nih.gov/pubmed/20010134|journal=Medicine and Science in Sports and Exercise|volume=42|issue=1|pages=16–22|doi=10.1249/MSS.0b013e3181b11bc7|issn=1530-0315|pmc=2796587|pmid=20010134}}</ref> A follow-up study by the same research team (under the guidance of Benjamin Natelson) found more post-exercise improvement (transitions to deeper [[sleep stages]]) of sleep in ME/CFS patients than in controls. The patients, however, reported more fatigue in the morning after exercise while healthy controls showed significant improvement in sleepiness and fatigue. The authors speculated this to be due to a disruption of the [[REM]] sleep: ME/CFS showed, both at baseline and post-exercise, an increased rate of transition from REM to wake compared to controls and this correlated with symptoms of fatigue, pain and sleepiness.<ref>{{Cite journal|last=Kishi|first=Akifumi|last2=Togo|first2=Fumiharu|last3=Cook|first3=Dane B|last4=Klapholz|first4=Marc|last5=Yamamoto|first5=Yoshiharu|last6=Rapoport|first6=David M|last7=Natelson|first7=Benjamin H|date=Nov 2013|title=The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871467/|journal=Physiological Reports|volume=1|issue=6|doi=10.1002/phy2.152|issn=2051-817X|pmc=3871467|pmid=24400154}}</ref> An Australian study followed up on 35 ME/CFS patients after performing a physical (stationary cycling) or cognitive (stimulated driving) challenge. While patients spent a greater proportion of wakeful hours lying down, they did not report significant changes in sleep quality or sleep duration. The authors did however note that the expected increase in [[heart rate variability]] (HRV) between wake and sleep, was significantly reduced in ME/CFS patients after completing the challenges. These changes in HRV have been associated with the falling asleep, and might be related to the unfreshed sleep of ME/CFS patients.<ref>{{Cite journal|last=Cvejic|first=Erin|last2=Sandler|first2=Carolina X.|last3=Keech|first3=Andrew|last4=Barry|first4=Benjamin K.|last5=Lloyd|first5=Andrew R.|last6=Vollmer-Conna|first6=Uté|date=Dec 2017|title=Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29167053|journal=Journal of Psychosomatic Research|volume=103|pages=91–94|doi=10.1016/j.jpsychores.2017.10.010|issn=1879-1360|pmid=29167053}}</ref> Finally, Ohashi et al. recorded physical activity for 6-days in 10 patients with ME/CFS and 6 controls before and after performing a maximal treadmill test. Their results indicate an increase in [[circadian]] rest-activity in ME/CFS patients after exercise as the activity pattern of patients shifted toward later hours in the day.<ref>{{Cite journal|last=Ohashi|first=Kyoko|last2=Yamamoto|first2=Yoshiharu|last3=Natelson|first3=Benjamin H.|date=Sep 2002|title=Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12213500|journal=Physiology & Behavior|volume=77|issue=1|pages=39–44|issn=0031-9384|pmid=12213500}}</ref>
=== Cognitive performance ===
While some studies have found a decreased cognitive performance after exercise in ME/CFS, others have not (see table below).<ref name=":0" /> This difference may be due to heterogeneity of the patient sample and methods used.

{| class="wikitable"
|Study
|Number of ME/CFS subjects
|Neurocognitive tests
|Results
|-
|[[Marshall]] et al. (1997)<ref>{{Cite journal|last=Marshall|first=P. S.|last2=Forstot|first2=M.|last3=Callies|first3=A.|last4=Peterson|first4=P. K.|last5=Schenck|first5=C. H.|date=Jan 1997|title=Cognitive slowing and working memory difficulties in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9021867|journal=Psychosomatic Medicine|volume=59|issue=1|pages=58–66|issn=0033-3174|pmid=9021867}}</ref>
|8
|Buschke Selective Reminding Test, Continuous-Performance Test-Identical Pairs Version (CPTIP), Paced Auditory Serial Addition Task (PASAT), Stroop Color Word Test, Reaction-Time Tests, Salthouse Reading Span Task (SRST), Verbal Scholastic Aptitude Test (SAT).
|Negative
|-
|[[Blackwood]] et al. (1998)<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=Oct 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781}}</ref>
|10
|"The following aspects of cognitive function were examined (in order): working memory/auditory attention (digit span, from WAIS-R); psychomotor speed (digit symbol, also from WAIS-R); word fluency (FAS test, using the letters F and S only); and selective attention and sustained attention (telephone search and lottery tasks respectively, both from the test of everyday attention)”
|Positive
|-
|[[La Manca]] et al. (1998)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=DeLuca|first3=J.|last4=Johnson|first4=S. K.|last5=Lange|first5=G.|last6=Pareja|first6=J.|last7=Cook|first7=S.|last8=Natelson|first8=B. H.|date=1998-09-28|title=Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9790484|journal=The American Journal of Medicine|volume=105|issue=3A|pages=59S–65S|issn=0002-9343|pmid=9790484}}</ref>
|19
|The Stroop Color and Word Test, the Symbol Digit Modalities Test (SDMT), an oral version of the Trail Making Test (TMT) and the Serial 13s Test (STT)
|Positive
|-
|[[Claypoole]] et al. (2001)<ref>{{Cite journal|last=Claypoole|first=Keith|last2=Mahurin|first2=Roderick|last3=Fischer|first3=Mary E.|last4=Goldberg|first4=Jack|last5=Schmaling|first5=Karen B.|last6=Schoene|first6=Robert B.|last7=Ashton|first7=Suzanne|last8=Buchwald|first8=Dedra|date=Mar 2001|title=Cognitive Compromise Following Exercise in Monozygotic Twins Discordant for Chronic Fatigue Syndrome: Fact or Artifact?|url=http://dx.doi.org/10.1207/s15324826an0801_5|journal=Applied Neuropsychology|volume=8|issue=1|pages=31–40|doi=10.1207/s15324826an0801_5|issn=0908-4282}}</ref>
|21
|The Wechsler Adult Intelligence Scale–Revised, Digit Span Forward and Backward subtests, The Hopkins Verbal Learning Test, . The Digit Vigilance Test, the Lafayette Clinic Repeatable Neuropsychological Test Battery, Controlled Oral Word Association Test (COWAT)
|Negative
|-
|[[Dane Cook|Cook]] et al. (2005)<ref>{{Cite journal|last=Cook|first=Dane B.|last2=Nagelkirk|first2=Paul R.|last3=Peckerman|first3=Arnold|last4=Poluri|first4=Ashok|last5=Mores|first5=John|last6=Natelson|first6=Benjamin H.|date=Sep 2005|title=Exercise and cognitive performance in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16177595|journal=Medicine and Science in Sports and Exercise|volume=37|issue=9|pages=1460–1467|issn=0195-9131|pmid=16177595}}</ref>
|20 ME/CFS only and 19 ME/CFS with comorbid fibromyalgia
|Participants completed cognitive testing using the automated neuropsychological assessment matrices (ANAM)
|Negative
|-
|[[Yoshiuchi]] et al. (2007)<ref>{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref>
|9
|A one-back memory task
|Negative
|-
|Cook et al. (2017)<ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref>
|15
|The Paced Auditory Serial Addition Task (PASAT) and a simple number recognition task
|Positive
|}

=== Pain modulation ===
Another post-exertional abnormality reported in ME/CFS is pain modulation. When healthy people exercise, their brain produces [[endorphins]] that increase pain thresholds. In some chronic pain patients like [[fibromyalgia]] and whiplash associated disorders, this endogenous pain inhibition response is defect and pain thresholds decrease shortly after exercise (i.e. they experience more pain while they should be feeling less). In 2004 Whiteside et al. first showed this defect in ME/CFS patients.<ref name=":22" /> These results were confirmed by two studies by the Belgium pain in motion team: while pain thresholds increased in normal controls they decreased in the ME/CFS patient group.<ref name=":23" /><ref name=":24" /> As a caveat, one must note that these studies only included ME/CFS patients that were suffering from chronic pain, while comorbid FM was not assessed. So it remains unclear if these results will also show up in ME/CFS patients that do not have comorbid FM.<ref>{{Cite journal|last=Yunus|first=Muhammad|date=2015-07-02|title=Editorial Review (Thematic Issue: An Update on Central Sensitivity Syndromes and the Issues of Nosology and Psychobiology)|url=http://dx.doi.org/10.2174/157339711102150702112236|journal=Current Rheumatology Reviews|language=en|volume=11|issue=2|pages=70–85|doi=10.2174/157339711102150702112236|issn=1573-3971}}</ref>

=== Other ===

==== The gut microbiome ====
Shukla et al. (2015) found post-exertional changes in the gut microbiome in ME/CFS patients that were not seen in healthy controls. Increased clearance of bacteria in the blood was also noted, which made the authors speculate that exercise induced a bacterial translocation in ME/CFS patients.<ref>{{Cite journal|last=Shukla|first=Sanjay K.|last2=Cook|first2=Dane|last3=Meyer|first3=Jacob|last4=Vernon|first4=Suzanne D.|last5=Le|first5=Thao|last6=Clevidence|first6=Derek|last7=Robertson|first7=Charles E.|last8=Schrodi|first8=Steven J.|last9=Yale|first9=Steven|date=2015-12-18|title=Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=http://dx.doi.org/10.1371/journal.pone.0145453|journal=PLOS ONE|volume=10|issue=12|pages=e0145453|doi=10.1371/journal.pone.0145453|issn=1932-6203}}</ref>

==== Catecholaminergic hyporeactivity ====
Strahler et al. found that ME/CFS patients showed an attenuated response (lower increases) of epinephrine to an exercise challenge, compared to heathy controls. This ‘catecholaminergic hyporeactivity’ was however subtle and short-lived.<ref>{{Cite journal|last=Strahler|first=Jana|last2=Fischer|first2=Susanne|last3=Nater|first3=Urs M.|last4=Ehlert|first4=Ulrike|last5=Gaab|first5=Jens|date=Sep 2013|title=Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23770415|journal=Biological Psychology|volume=94|issue=1|pages=160–166|doi=10.1016/j.biopsycho.2013.06.002|issn=1873-6246|pmid=23770415}}</ref>

==== Nitric oxide metabolites ====
A [[Spain|Spanish]] research team found much higher increases of nitric oxide metabolites (nitrates) after a maximal exercise test in 44 ME/CFS patients compared to 25 healthy controls while there were no differences between the groups at baseline.<ref>{{Cite journal|last=Suárez|first=Andrea|last2=Guillamó|first2=Elisabet|last3=Roig|first3=Teresa|last4=Blázquez|first4=Alicia|last5=Alegre|first5=José|last6=Bermúdez|first6=Jordi|last7=Ventura|first7=José Luis|last8=García-Quintana|first8=Ana María|last9=Comella|first9=Agustí|date=Jun 2010|title=Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study|url=http://dx.doi.org/10.1089/jwh.2008.1255|journal=Journal of Women's Health|volume=19|issue=6|pages=1073–1077|doi=10.1089/jwh.2008.1255|issn=1540-9996}}</ref>

== Problems in defining PEM ==

=== Asking the right questions ===
[[Leonard Jason|Jason]] et al. (1999) reported that in a group of ME/CFS patients, the percentage endorsing PEM ranged from 40,6 to 93,8% depending on how the question assessed this symptom.<ref>{{Cite web|url=https://www.meassociation.org.uk/2012/04/to-pem-or-not-to-pem-that-is-the-question-for-case-definition-research-1st-website-27-april-2012/|title=To PEM or not to PEM? That is the question for case definition {{!}} Research 1st website|date=27 April 2012|website=www.meassociation.org.uk|language=en-US|access-date=2018-10-10}}</ref> The report of the National Academy of Medicine noted that “the prevalence of PEM among ME/CFS patients as diagnosed by existing criteria varies from 69 to 100 percent.”<ref name=":0" />

Some patients try to reduce post-exertional relapses by pacing themselves and reducing exertion that exceeds their energy limits. Questionnaires assessing PEM by frequency instead of propensity, might erroneously label these patients as not having PEM. In a 2015 study, Jason et al. measured ME/CFS patients’ responses to the PEM-criterion in the [[Keiji Fukida|Fukuda]] et al. (1994) definition: ‘Do you feel generally worse than usual or fatigued for 24 hours or more after you have exercised?’ Although the majority (75%) endorsed this item, a notable percentage (25%) did not. Yet when the question was framed differently, leaving out the 24 hours’ time period and substituting exercise with normal daily activity, these participants also agreed they experienced high levels of fatigue after normal daily activity.<ref name=":19" /> This clearly shows that patients who have already modified their activities to avoid or reduce PEM may potentially show up as false negatives.

Another issue is the definition of PEM in the Fukuda-criteria. While the wording used here is vague, the time criterion is rather strict requiring PEM to last more than 24 hours. Some patients do not endorse this item because they only have post-exertional malaise for less than 24 hours.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=King|first2=Caroline P.|last3=Richman|first3=Judith A.|last4=Taylor|first4=Renee R.|last5=Torres|first5=Susan R.|last6=Song|first6=Sharon|date=Jan 1999|title=U.S. Case Definition of Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v05n03_02?journalCode=icfs20|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=5|issue=3-4|pages=3–33|doi=10.1300/j092v05n03_02|issn=1057-3321}}</ref> A 2018 study concluded that setting the criterion at 24 hours would exclude almost 30% of ME/CFS patients. It advises that this definition might be useful in research settings but that in a clinical context, a 14-23 hour time period might be more appropriate.<ref>{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref>

These observations point to the need of a more precise definition of PEM and several attempts to this end have been made.
=== More than just fatigue ===
Few instruments have assessed PEM adequately. The [[CDC 2005 Symptom Inventory for CFS|CDC symptom inventory]] for example, only asks about fatigue after exertion, while PEM entails much more than that. An [[Australia|Australian]] group at the University of New South Wales tried to better define PEM, using 19 ME/CFS patients after exposure to different stressors.<ref>{{Cite journal|last=Keech|first=Andrew|last2=Sandler|first2=Carolina X.|last3=Vollmer-Conna|first3=Ute|last4=Cvejic|first4=Erin|last5=Lloyd|first5=Andrew R.|last6=Barry|first6=Benjamin K.|date=Dec 2015|title=Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26359713|journal=Journal of Psychosomatic Research|volume=79|issue=6|pages=537–549|doi=10.1016/j.jpsychores.2015.08.008|issn=1879-1360|pmid=26359713}}</ref> Participants indicated that the term fatigue did not adequately describe the sensation they experienced on a daily basis. A word frequency analysis of descriptors nominated by these patients indicated 5 themes:
# Exhausted or tired.
# Heaviness in the limbs or whole-body.
# Fogginess in the head.
# Weakness in the muscles.
# Drained of energy.
===The DePaul Symptom Questionnaire (DSQ) subscale ===
The instrument most commonly used to assess PEM is a subscale from the [[DePaul Symptom Questionnaire]] (DSQ). The DSQ is a 54-item questionnaire was developed in 2010 to operationalize the Canadian Consensus Criteria, providing concrete directives to assess ME/CFS-symptoms with their frequency and severity.<ref>{{Cite web|url=https://www.semanticscholar.org/paper/The-Development-of-a-Revised-Canadian-Myalgic-Case-Jason-Evans/b2a2564f55daa57721d24502df6bd6c161238ff0|title=The Development of a Revised Canadian Myalgic Encephalomyelitis Chronic Fatigue Syndrome Case Definition|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth Anne|date=2010|language=en|access-date=2018-10-10|last3=Porter|first3=Nicole|last4=Brown|first4=Molly|last5=Brown|first5=Abigail A.|last6=Hunnell|first6=Jessica|last7=Anderson|first7=Valerie C.|last8=Lerch|first8=Athena|last9=Meirleir|first9=Kenny de}}</ref> In a Norwegian comparison with physician assessments, The DSQ scored a sensitivity of 92% and a specificity of 75%.<ref>{{Cite journal|last=Strand|first=Elin B.|last2=Lillestøl|first2=Kristine|last3=Jason|first3=Leonard A.|last4=Tveito|first4=Kari|last5=Diep|first5=Lien My|last6=Valla|first6=Simen Strand|last7=Sunnquist|first7=Madison|last8=Helland|first8=Ingrid B.|last9=Herder|first9=Ingrid|date=2016-01-02|title=Comparing the DePaul Symptom Questionnaire with physician assessments: a preliminary study|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1126026|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=4|issue=1|pages=52–62|doi=10.1080/21641846.2015.1126026|issn=2164-1846}}</ref> This indicated that the DSQ is a useful tool in detecting and screening symptoms, but that a follow-up medical examination is necessarily to confirm the diagnosis and identify possible exclusionary medical and psychiatric disorders.

The post-exertional malaise subscale on the DSQ particularly demonstrated excellent clinical utility as it was able to differentiate between ME/CFS patients and controls.<ref>{{Cite journal|last=Murdock|first=Kyle W.|last2=Wang|first2=Xin Shelley|last3=Shi|first3=Qiuling|last4=Cleeland|first4=Charles S.|last5=Fagundes|first5=Christopher P.|last6=Vernon|first6=Suzanne D.|date=Apr 2017|title=The utility of patient-reported outcome measures among patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/27600520|journal=Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation|volume=26|issue=4|pages=913–921|doi=10.1007/s11136-016-1406-3|issn=1573-2649|pmc=5336422|pmid=27600520}}</ref> In early 2018 the Common Data Elements working group on PEM formed by [[National Institute of Neurological Disorders and Stroke|NINDS]] and the CDC, recommended the use of 5 items from the DSQ to measure PEM.<ref name=":4">https://www.commondataelements.ninds.nih.gov/Doc/MECFS/PEM_Subgroup_Summary.pdf</ref>
# Dead, heavy feeling after starting to exercise.
# Next day soreness after non-strenuous, everyday activities.
# Mentally tired after the slightest effort.
# Minimum exercise makes physically tired.
# Physically drained or sick after mild activity.
To meet criteria for post-exertional malaise, one of these items need to be endorsed at sufficient frequency and severity (2 or greater on a scale of 0-4).

Although the DSQ has good test-retest reliability and is regarded as a useful tool in making the diagnosis of ME/CFS, its ability to capture PEM accurately has been questioned. Originally these five items formed one of the five subdomains of the ME/CFS Fatigue Types Questionnaire (MFTQ)<ref>{{Cite journal|last=Jason|first=Leonard|last2=Jessen|first2=Tricia|last3=Porter|first3=Nicole|last4=Boulton|first4=Aaron|last5=Gloria-Njoku|first5=Mary|date=2009-07-16|title=Examining Types of Fatigue Among Individuals with ME/CFS|url=http://dsq-sds.org/article/view/938|journal=Disability Studies Quarterly|language=en|volume=29|issue=3|doi=10.18061/dsq.v29i3.938|issn=2159-8371}}</ref><ref>{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> and critics argue that these items are focused too much on fatigue/tiredness to be an adequate measure of PEM. A document formulated by the Science for ME PEM working group to address these issues, explained:<blockquote>"The DSQ PEM items focus largely on feeling fatigue or tiredness, and, apart from one item, do not mention that post-exertional symptoms may be delayed. There is no mention of prolonged recovery or the loss of functional capacity."<ref name=":5" /></blockquote>The NINDS/CDC common data elements PEM subgroup also noted about the DSQ: <blockquote>"...the instrument does not assess the full range of symptoms that could be exacerbated by PEM and only one item addresses the sometimes delayed onset/ prolonged duration of PEM.<ref>https://www.commondataelements.ninds.nih.gov/Doc/MECFS/F2771_Guidance_for_Core_PEM_Assessment.pdf</ref> </blockquote>In an online poll to which 783 people responded, 68% answered that the DSQ PEM did not reflect their experience of post-exertional malaise<ref name=":5" />, though questions have been raised about the neutrality of the wording used.<ref name=":6">{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> In response Jason et al. noted that the DSQ PEM items were developed and selected to screen for the presence of PEM, rather than to comprehensively measure all aspects and variations of PEM. A 2018 analysis, using a large patient sample (n = 704), showed that screening items from the DSQ PEM subscale, were able to identify 97% of patients, which was higher than any other item to describe PEM.<ref name=":6" />

Furthermore, the authors have recently revised the DSQ PEM subscale to include new items, some based on Ramsay’s writings.<ref name=":7" /> An extra 5 questions can be used after the initial screening with the DSQ PEM subscale, to better differentiate ME/CFS from other, comparable conditions:
# Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?
# Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?
# If you feel worse after activities, how long does this last?
# If you were to become exhausted after actively participating in extracurricular activities, sports, or outings with friends, would you recover within an hour or two after the activity ended?
# If you do not exercise, is it because exercise makes your symptoms worse?
An analysis showed that these questions (the duration of PEM in particular) helped to differentiate ME/CFS patients from controls with [[Multiple sclerosis|MS]] or [[post-polio syndrome]].<ref name=":7" />

=== The DePaul Post-Exertional Malaise Questionnaire (DPEMQ) ===
The DPEMQ is a [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf questionnaire] based on input from hundreds of patients.<ref name=":29">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref><blockquote>Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.<ref name=":29" /></blockquote>

=== PENE ===
Of all case definitions, the 2011 International Consensus Criteria (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> offered the most precise and elaborated definition of the post-exertional relapses that characterize ME. To differentiate it with post-exertional malaise, the term used in the Fukuda-criteria, the authors introduced a new name: Post-Exertional Neuroimmune Exhaustion (PENE). PENE is described as “a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions”<ref name=":2" /> and has the following characteristics:
# Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
# Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
# Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
# Recovery period is prolonged, usually taking 24 hours or longer. A relapse can last days, weeks or longer.
# Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.
The definition fails however to make clear how many of these characteristics are necessary to diagnose PENE.
=== Muscle weakness ===
A more prominent criticism of PENE came from a 2016 factor analysis of PEM, using a large sample of 704 participants. Results suggested that “PEM is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue.”<ref name=":8" /> The latter refers to the description of ME by Ramsay, where post-exertional muscle weakness was highlighted. This element of PEM was confirmed in a study by the [[Workwell Foundation]] where the symptoms of 25 ME/CFS patients and 23 age-matched controls were followed up. As the report noted: <blockquote>"The two groups also differed with respect to the experience of physical weakness or instability immediately after testing. This was reported by 16 patients (64%) as opposed to 5 controls (22%). Weakness persisted into the next day in 10 patients (40%) but in only 1 control (4%). However, distinct differences can be observed in the severity of the weakness between groups when analyzing their reports. The sole report of weakness from a control stated: '[I had] tired legs when going up stairs—fine overall.' In contrast, statements from CFS patients included: 'Unable to walk without assistance.' '[I experienced] falling from muscle weakness.'<ref name=":13" /></blockquote>A Norwegian in depth-report of ME/CFS-patients relationship to exercise also highlighted muscle weakness: <blockquote>"Some related how they would struggle to get home after exercise – one had to stop her car on her way from the fitness centre. Another was walking in the woods and suddenly felt it would be impossible to make his way back home. They described feeling that something completely wrong had happened to their bodies, without understanding what was going on. Thought processes did not work as usual, motor abilities were reduced, or the legs would not move them as they would usually expect. Some participants described a paralyzed feeling subsequent to activity, where a lot of energy would be needed to be able to move."<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>While many descriptions of PEM like the DSQ subscale assess this element indirectly by asking patients about a dead heavy feeling after exercise or next day soreness, it is fully lacking in the ICC definition of PENE.<ref name=":8" />
=== Common data elements PEM working group ===
The NINDS/CDC Common Data Elements (CDE) PEM working group emphasized the need of a better definition of PEM. Its draft recommendations highlighted that <blockquote>"The definition of PEM is based primarily on clinician experience, patient reports and a few formal studies. There is a dearth of studies asking participants about their experiences of PEM in an openended manner, which is needed."<ref name=":4" /> </blockquote>A 2018 analysis showed that patients' preferences to describe PEM are generally not well-represented within present case definition criteria or descriptions.<ref>{{Cite journal|last=Jason|first=Leonard|last2=McManimen|first2=Stephanie|last3=Sunnquist|first3=Madison|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.researchgate.net/publication/323916016_Patient_perceptions_of_post_exertional_malaise|journal=Fatigue: Biomedicine, Health & Behavior|doi=10.1080/21641846.2018.1453265}}</ref> Although the CDE working group acknowledged the need to device a better instrument to assess PEM, it currently promotes the use of the DSQ PEM subscale as a screening tool, after which a clinician’s assessment is advised to diagnose PEM. The CDE PEM working group also provided a description of PEM, based on the 2015 literature review by the National Academy of Medicine: <blockquote>"PEM is defined as an abnormal response to minimal amounts of physical or cognitive exertion that is characterized by:</blockquote>
# Exacerbation of some or all of an individual study participant's ME/CFS symptoms. Symptoms exacerbated can include physical fatigue, cognitive fatigue, problems thinking (e.g. slowed information processing speed, memory, concentration), [[unrefreshing sleep]], [[Myalgia|muscle pain]], [[Arthralgia|joint pain]], [[Headache|headaches]], weakness/instability, light-headedness, flu-like symptoms, sore throat, [[nausea]], and other symptoms. Study participants can experience new or non-typical symptoms as well as exacerbation of their more typical symptoms.
# Loss of stamina and/or functional capacity.
# An onset that can be immediate or delayed after the exertional stimulus by hours, days or even longer.
# A prolonged, unpredictable recovery period that may last days, weeks, or even months.
# Severity and duration of symptoms that is often out-of-proportion to the type, intensity, frequency, and/or duration of the exertion. For some study participants, even basic activities of daily living like toileting, bathing, dressing, communicating, and reading can trigger PEM."<ref name=":4" />

==Notable studies==
* 1999, Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome<ref>{{Cite journal|last=Paul|first=L.|last2=Wood|first2=L.|last3=Behan|first3=W. M.|last4=Maclaren|first4=W. M.|date=1999|title=Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10209352|journal=European Journal of Neurology|volume=6|issue=1|pages=63–69|issn=1351-5101|pmid=10209352|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/10209352 (Abstract)]
* 2010, Postexertional Malaise in Women with Chronic Fatigue Syndrome<ref name="VanNess2010" /> [https://www.liebertpub.com/doi/10.1089/jwh.2009.1507 (Abstract)]

[[File:2010 VanNess Post exertional worsening of symptoms chart.png|center|frame|Post-exertional worsening of symptoms<ref name="VanNess2010" />]]
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Top 10 Things You Should Know About Post-Exertional Relapse'' (2012) By University of the Pacific/Solve CFS - 2010 study, ''PEM in Women w/ CFS'' is discussed in this video">https://www.youtube.com/watch?v=B20H1u1LjCE</embedvideo>

* 2013, Post-exertion malaise in chronic fatigue syndrome: symptoms and [[gene expression]]<ref name="MeyerJ2013" /> [http://www.tandfonline.com/doi/abs/10.1080/21641846.2013.838444 (Abstract)]
* 2015, Myalgic Encephalomyelitis: Symptoms and [[Biomarker]]s<ref name="JasonL2015bio" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/#!po=2.51799 (Full Text)]
*2015, Changes in Gut and Plasma [[Microbiome]] following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="ShuklaS2015" /> [http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0145453 (Full Text)]
*2016, Deconstructing post-exertional malaise: An exploratory factor analysis<ref name="McManimen, 2016" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/ (Full Text)]

*2018, Comparing Post-Exertional Symptoms Following Serial Exercise Tests<ref>{{Cite journal|last=Mateo|first=Lariel J.|date=2018|title=Comparing Post-Exertional Symptoms Following Serial Exercise Tests|url=https://scholarlycommons.pacific.edu/purcc/2018/events/87/|journal=PURCC|language=en|volume=|pages=|via=Scholarly Commons}}</ref> [https://scholarlycommons.pacific.edu/purcc/2018/events/87/ (Abstract)]

* 2018, The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome<ref name=":31" /><ref name=":30" /> [http://journals.sagepub.com/doi/abs/10.1177/1359105318805819?journalCode=hpqa& (Abstract)] [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf (Questionnaire)]

==Notable articles==
* Dec 30, 2015 [http://me-cfs.se/blogg/suggestion-to-replace-pem-by-par/ Suggestion to replace PEM (Post Exertional Malaise) with PAR (Post Activity Relapse)]<ref name="MEBlogg2015" />

*Nov 4, 2016 [http://www.medscape.com/viewarticle/871482#vp_1 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome]<ref>{{Cite web|url=http://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|last=Tucker|first=Miriam|date=|website=www.medscape.com|type=Login Required|archive-url=|archive-date=|dead-url=|access-date=2018-09-06}}</ref>

==Talks & interviews==
* 2013, [https://www.youtube.com/watch?v=zZ8aPYihkpQ CFS gene expression after exercise (part 1)]<ref>{{Cite web|url=https://www.youtube.com/watch?v=zZ8aPYihkpQ|title=CFS gene expression after exercise (part 1)|last=|first=|date=May 26, 2013|website=YouTube|publisher=Jw N|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

==See also==

*[[Exercise]]
*[[Exertion]]
*[[Flu-like symptoms]]
*[[Malaise]]
==Learn more==

*[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html International CFS/ME Awareness Day - What Health]<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-08-17}}</ref> (PEM Definition Included)
*[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf Post-Exertional Malaise in Chronic Fatigue Syndrome]<ref name="SpotilaJ2010" />
*[http://solvecfs.org/post-exertional-malaise-cause-and-effect/ Post-Exertional Malaise: Cause and Effect]<ref name="SpotilaJ20120523" />
*[https://www.verywellhealth.com/what-is-post-exertional-malaise-716023 What is Post-Exertional Malaise]<ref name="AboutHealthPEM" />
*[http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/ The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained?]<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/|title=The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained? - Health Rising|last=Johnson|first=Cort|date=2016-07-04|work=Health Rising|access-date=2018-08-17|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== References ==
<references>
<ref name="AboutHealthPEM">{{Cite news|url=https://www.verywellhealth.com/what-is-post-exertional-malaise-716023|title=What is Post-Exertional Malaise? Learn About a Key ME/CFS Symptom|last=Dellwo|first=Adrienne|date=|work=Verywell Health|access-date=2018-08-17|archive-url=|archive-date=|dead-url=}}</ref>
<ref name="JasonL2015bio">{{Citation
| last1 = Jason | first1 = LA | authorlink1 = Leonard Jason
| last2 = Zinn | first2 = ML | authorlink2 = Marcie Zinn
| last3 = Zinn | first3 = MA | authorlink3 = Mark Zinn
| display-authors =
| title = Myalgic Encephalomyelitis: Symptoms and Biomarkers
| journal = Current Neuropharmacology | volume = 13(5) | page = 701-734
| date = September 2015
| doi = 10.2174/1570159X13666150928105725
| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/#!po=2.51799
}}</ref>
<ref name="McManimen, 2016">{{Citation
| last1 = McManimen | first1 = SL | authorlink1 =
| last2 = Sunnquist | first2 = ML | authorlink2 = Madison Sunnquist
| last3 = Jason | first3 = LA | authorlink3 = Leonard Jason
| title = Deconstructing post-exertional malaise: An exploratory factor analysis
| journal = Journal of Health Psychology | volume = | issue = | page =
| date = 2016
| pmid = 27557649
| doi = 10.1177/1359105316664139
}}
</ref>
<ref name="MEBlogg2015">{{citation
| author = ME Blogg
| title = Suggestion to replace PEM by PAR
| date = 30 Dec 2015
| url = http://me-cfs.se/blogg/suggestion-to-replace-pem-by-par/
}}</ref>
<ref name="MeyerJ2013">{{citation
| last1 = Meyer | first1 = JD | authorlink1 = Jacob Meyer
| last2 = Light | first2 = AR | authorlink2 = Alan Light
| last3 = Shukla | first3 = SK | authorlink3 = Sanjay Shukla
| last4 = Clevidence | first4 = D | authorlink4 = Derek Clevidence
| last5 = Yale | first5 = S | authorlink5 = Steven Yale
| last6 = Stegner | first6 = AJ | authorlink6 = Aaron Stegner
| last7 = Cook | first7 = DB | authorlink7 = Dane Cook
| display-authors =
| title = Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 1 | issue = 4 | page = 190-209
| date = 2 Oct 2013
| doi = 10.1080/21641846.2013.838444
| url = http://www.tandfonline.com/doi/abs/10.1080/21641846.2013.838444
}}</ref>
<ref name="ShuklaS2015">{{Citation
| last1 = Shukla | first1 = SK | authorlink1 = Sanjay Shukla
| last2 = Cook | first2 = D | authorlink2 = Dane Cook
| last3 = Meyer | first3 = JD | authorlink3 = Jacob Meyer
| last4 = Vernon | first4 = SD | authorlink4 = Suzanne Vernon
| last5 = Lee | first5 = T | authorlink5 = Thao Lee
| last6 = Clevidence | first6 = D | authorlink6 = Derek Clevidence
| last7 = Robertson | first7 = CE | authorlink7 = Charles Robertson
| last8 = Schrodi | first8 = SJ | authorlink8 = Steven Schrodi
| last9 = Yale | first9 = S | authorlink9 = Steven Yale
| last10 = Frank | first10= DN | authorlink10= Daniel Frank
| display-authors = 3
| title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
| journal = Plos One | volume = 10(12) | page =
| date = 18 December 2015
| pmid =
| doi = 10.1371/journal.pone.0145453
| url = http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0145453
}}</ref>
<ref name="SpotilaJ2010">{{citation
| last1 = Spotila | first1 = JM | authorlink1 = Jennie Spotila
| title = Post-Exertional Malaise in Chronic Fatigue Syndrome
| journal = Solve ME/CFS
| date = 2010
| url = http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf
}}</ref>
<ref name="SpotilaJ20120523">{{citation
| last1 = Spotila | first1 = JM | authorlink1 = Jennie Spotila
| title = Post-Exertional Malaise: Cause and Effect
| journal = Solve ME/CFS
| date = 23 May 2012
| url = http://solvecfs.org/post-exertional-malaise-cause-and-effect/
}}</ref>
<ref name="VanNess2010">{{Citation
| last1 = VanNess | first1 = M | authorlink1 = Mark VanNess
| last2 = Stevens | first2 = S | authorlink2 = Staci Stevens
| last3 = Bateman | first3 = L | authorlink3 = Lucinda Bateman
| last4 = Stiles | first4 = TL | authorlink4 = TL Stiles
| last5 = Snell | first5 = CR | authorlink5 = Christopher Snell
| display-authors =
| title = Postexertional malaise in women with chronic fatigue syndrome
| journal = Journal of Women's Health | volume = | issue = | page =
| date = February 2010
| pmid = 20095909
| doi = 10.1089/jwh.2009.1507
}}
</ref>
</references>

[[Category:Signs and symptoms]]

Canadian Consensus Criteria

2019-04-19T13:28:10Z

MEandCFS:/* Definition */ x

The [[Canadian Consensus Criteria|Canadian consensus criteria]] (CCC) are a proposed clinical criteria for [[ME/CFS]], published in 2003, and frequently used as a case definition in research.<ref name="Carruthers, 2003" /> It is a stricter criteria than the [[Fukuda criteria]] and according to [[Leonard Jason]] represents a more severely impaired population.<ref>http://www.meaction.net/2015/12/10/norwegian-researchers-ask-what-exactly-is-m-e/</ref> Adults are diagnosed at six months and pediatric cases at three months.

==Definition==

{| class="wikitable"
|+'''Canadian Consensus Criteria''' for Myalgic Encephalomyelitis
| colspan="3" |A patient with [[ME/CFS]] will meet the criteria for fatigue, [[Post-exertional malaise]] and/or [[Chronic fatigue|fatigue]], [[sleep dysfunction]], and [[pain]]; have two or more [[Nervous system|neurological]]/[[Cognitive dysfunction|cognitive]] manifestations and one or more symptoms from two of the categories of (a) [[Autonomic nervous system|autonomic]], (b) [[neuroendocrine]], and (c) [[Immune system|immune]] manifestations; and adhere to item 7.
|-
|1
|'''[[Chronic fatigue|Fatigue]]'''
|The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental [[fatigue]] that substantially reduces activity level.
|-
|2
|'''[[Post-exertional malaise|Post-Exertional Malaise]] and/or Post-Exertional Fatigue'''
|There is an inappropriate [[loss of physical and mental stamina]], rapid [[Muscle fatigability|muscular]] and [[cognitive fatigability]], [[Post-exertional malaise|post-exertional malaise]] and/or post-exertional fatigue<ref name=":0">{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|date=|access-date=|website=investinme.org|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|archive-url=|archive-date=|dead-url=|type=|page=4|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref> and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period – usually 24 hours or longer.
|-
|3
|[[Sleep dysfunction|'''Sleep Dysfunction''']]*
|There is [[unrefreshed sleep]] or sleep quantity or rhythm disturbances such as [[reversed or chaotic diurnal sleep rhythms]].
|-
|4
|[[Pain|'''Pain''']]*
|There is a significant degree of [[myalgia]]. Pain can be experienced in the [[Myalgia|muscles]], and/or [[Arthralgia|joints]], and is often widespread and migratory in nature. Often there are significant [[headache]]s of new type, pattern or severity.
|-
|5
|'''[[Nervous system|Neurological]]/[[Cognitive dysfunction|Cognitive]] Manifestations'''
|'''Two or more''' of the following difficulties should be present: [[confusion]], [[Attention deficit|impairment of concentration]]<nowiki/>and [[Memory problems|short-term memory consolidation]], [[disorientation]], difficulty with [[information processing]], categorizing and word retrieval ([[Word-finding problems]]), and perceptual and sensory disturbances – e.g. [[spatial instability and disorientation]]<nowiki/>and [[inability to focus vision]].

[[Ataxia]], [[muscle weakness]] <nowiki/>and [[fasciculations]] <nowiki/>are common. There may be [[overload]]1 phenomena: cognitive, sensory – e.g. [[photophobia]] and [[Hyperacusis|hypersensitivity to noise]] – and/or [[emotional overload]], which may lead to "crash"2 periods and/or [[anxiety]].
|-
|6
|'''At Least One Symptom From Two of the Following Categories'''
|(a) '''Autonomic Manifestations''': [[Orthostatic intolerance]] – [[Neurally mediated hypotension]] (NMH), [[Postural orthostatic tachycardia]] syndrome (POTS), [[delayed postural hypotension]]; [[light-headedness]]; [[extreme pallor]]; [[nausea]] and [[irritable bowel syndrome]]; [[urinary frequency]] and [[bladder dysfunction]]; [[palpitations]] with or without [[cardiac arrhythmia]]s; [[exertional dyspnea]].

(b) '''Neuroendocrine Manifestations''': loss of thermostatic stability – [[subnormal body temperature]] and [[marked diurnal fluctuation]], [[excessive sweating|sweating episodes]], recurrent feelings of [[low-grade fever|feverishness]] and [[cold extremities]]; [[temperature sensitivity|intolerance of extremes of heat and cold]]; marked [[weight change]] – [[Anorexia, eating disorders and ME/CFS|anorexia]] or [[abnormal appetite]]; [[loss of adaptability]] and [[worsening of symptoms with stress]].

(c) '''Immune Manifestations''': [[tender lymph nodes]], recurrent [[sore throat]], recurrent [[flu-like symptoms]], [[Malaise|general malaise]], new [[food sensitivities]], medications and/or [[chemical sensitivities]].
|-
|7
|'''The Illness Persists for at Least Six Months'''
|It usually has a distinct onset,** although it may be gradual. Preliminary diagnosis may be possible earlier. Three months is appropriate for [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|children]].
|}
To be included, the symptoms must have begun or have been significantly altered after the onset of this illness. It is unlikely that a patient will suffer from all symptoms in criteria 5 & 6. The disturbances tend to form symptom clusters that may fluctuate and change over time. [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|Children]] often have numerous prominent symptoms but their order of severity tends to vary from day to day.

<nowiki>*</nowiki> There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset.

<nowiki>**</nowiki> Some patients have been unhealthy for other reasons prior to the onset of ME/ CFS and lack detectable triggers at onset or have more gradual or insidious onset.

1 “Overload” refers to hypersensitivities to stimuli that have changed from pre-illness status.

2 "Crash" refers to a temporary period of immobilizing physical and /or cognitive fatigue.

==Authors==
[[Bruce Carruthers]], [[Anil Kumar Jain]], [[Kenny de Meirleir]], [[Daniel Peterson]], [[Nancy Klimas]], [[A Martin Lerner]], [[Alison Bested]], [[Pierre Flor-Henry]], [[Pradip Joshi]], [[A C Peter Powles]], [[Jeffrey Sherkey]], [[Marjorie van de Sande]]<ref>http://sacfs.asn.au/download/consensus_overview_me_cfs.pdf</ref>

==See also==
*[[Case Definition Comparison - Graph 1]]
*[[Definitions of ME and CFS]]

=== Generally accepted criteria for diagnosis ===
*Canadian consensus criteria (CCC).<ref name="Carruthers, 2003" /> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using these criteria. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria|International consensus criteria]] (ICC).<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> These criteria will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease|Systemic exertion intolerance disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegria|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A. Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*[http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview of the Canadian Consensus Document]<ref name=":0" /> (the above 7 criteria are listed on page 2 of this document).
*[http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf Canadian Consensus Report - ''Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols'']<ref name="Carruthers, 2003" /> (full version of the Canadian consensus criteria).
*An Overview of the Canadian Consensus Document in French - [http://iacfsme.org/Portals/0/pdf/Abrege%20du%20C.c.%20sur%20EM-SFC.PDF Encéphalomyélite myalgique/syndrome de fatigue chronique: Définition clinique et lignes directrices à l’intention des médecins, Abrégé du Consensus canadien]<ref>{{Cite web|url=http://iacfsme.org/Portals/0/pdf/Abrege%20du%20C.c.%20sur%20EM-SFC.PDF|title=Encéphalomyélite myalgique /syndrome de fatigue chronique: Définition cliniqueet lignes directricesà l’intention des médecins - Abrégé duConsensus canadien|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|date=|website=iacfsme.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
==References==
<references>
<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf
}}</ref>
</references>

[[Category:Definitions]]

Canadian Consensus Criteria

2019-04-19T13:27:33Z

MEandCFS:x

The [[Canadian Consensus Criteria|Canadian consensus criteria]] (CCC) are a proposed clinical criteria for [[ME/CFS]], published in 2003, and frequently used as a case definition in research.<ref name="Carruthers, 2003" /> It is a stricter criteria than the [[Fukuda criteria]] and according to [[Leonard Jason]] represents a more severely impaired population.<ref>http://www.meaction.net/2015/12/10/norwegian-researchers-ask-what-exactly-is-m-e/</ref> Adults are diagnosed at six months and pediatric cases at three months.

==Definition==

{| class="wikitable"
|+'''Canadian Consensus Criteria''' for Myalgic Encephalomyelitis
| colspan="3" |A patient with [[ME/CFS]] will meet the criteria for fatigue, [[Post-exertional malaise]] and/or [[Chronic fatigue|fatigue]], [[sleep dysfunction]], and [[pain]]; have two or more [[Nervous system|neurological]]/[[Cognitive dysfunction|cognitive]] manifestations and one or more symptoms from two of the categories of (a) [[Autonomic nervous system|autonomic]], (b) [[neuroendocrine]], and (c) [[Immune system|immune]] manifestations; and adhere to item 7.
|-
|1
|'''[[Chronic fatigue|Fatigue]]'''
|The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental [[fatigue]] that substantially reduces activity level.
|-
|2
|'''[[Post-exertional malaise|Post-Exertional Malaise]] and/or Fatigue'''
|There is an inappropriate [[loss of physical and mental stamina]], rapid [[Muscle fatigability|muscular]] and [[cognitive fatigability]], [[Post-exertional malaise|post-exertional malaise]] and/or post-exertional fatigue<ref name=":0">{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|date=|access-date=|website=investinme.org|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|archive-url=|archive-date=|dead-url=|type=|page=4|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref> and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period – usually 24 hours or longer.
|-
|3
|[[Sleep dysfunction|'''Sleep Dysfunction''']]*
|There is [[unrefreshed sleep]] or sleep quantity or rhythm disturbances such as [[reversed or chaotic diurnal sleep rhythms]].
|-
|4
|[[Pain|'''Pain''']]*
|There is a significant degree of [[myalgia]]. Pain can be experienced in the [[Myalgia|muscles]], and/or [[Arthralgia|joints]], and is often widespread and migratory in nature. Often there are significant [[headache]]s of new type, pattern or severity.
|-
|5
|'''[[Nervous system|Neurological]]/[[Cognitive dysfunction|Cognitive]] Manifestations'''
|'''Two or more''' of the following difficulties should be present: [[confusion]], [[Attention deficit|impairment of concentration]]<nowiki/>and [[Memory problems|short-term memory consolidation]], [[disorientation]], difficulty with [[information processing]], categorizing and word retrieval ([[Word-finding problems]]), and perceptual and sensory disturbances – e.g. [[spatial instability and disorientation]]<nowiki/>and [[inability to focus vision]].

[[Ataxia]], [[muscle weakness]] <nowiki/>and [[fasciculations]] <nowiki/>are common. There may be [[overload]]1 phenomena: cognitive, sensory – e.g. [[photophobia]] and [[Hyperacusis|hypersensitivity to noise]] – and/or [[emotional overload]], which may lead to "crash"2 periods and/or [[anxiety]].
|-
|6
|'''At Least One Symptom From Two of the Following Categories'''
|(a) '''Autonomic Manifestations''': [[Orthostatic intolerance]] – [[Neurally mediated hypotension]] (NMH), [[Postural orthostatic tachycardia]] syndrome (POTS), [[delayed postural hypotension]]; [[light-headedness]]; [[extreme pallor]]; [[nausea]] and [[irritable bowel syndrome]]; [[urinary frequency]] and [[bladder dysfunction]]; [[palpitations]] with or without [[cardiac arrhythmia]]s; [[exertional dyspnea]].

(b) '''Neuroendocrine Manifestations''': loss of thermostatic stability – [[subnormal body temperature]] and [[marked diurnal fluctuation]], [[excessive sweating|sweating episodes]], recurrent feelings of [[low-grade fever|feverishness]] and [[cold extremities]]; [[temperature sensitivity|intolerance of extremes of heat and cold]]; marked [[weight change]] – [[Anorexia, eating disorders and ME/CFS|anorexia]] or [[abnormal appetite]]; [[loss of adaptability]] and [[worsening of symptoms with stress]].

(c) '''Immune Manifestations''': [[tender lymph nodes]], recurrent [[sore throat]], recurrent [[flu-like symptoms]], [[Malaise|general malaise]], new [[food sensitivities]], medications and/or [[chemical sensitivities]].
|-
|7
|'''The Illness Persists for at Least Six Months'''
|It usually has a distinct onset,** although it may be gradual. Preliminary diagnosis may be possible earlier. Three months is appropriate for [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|children]].
|}
To be included, the symptoms must have begun or have been significantly altered after the onset of this illness. It is unlikely that a patient will suffer from all symptoms in criteria 5 & 6. The disturbances tend to form symptom clusters that may fluctuate and change over time. [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|Children]] often have numerous prominent symptoms but their order of severity tends to vary from day to day.

<nowiki>*</nowiki> There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset.

<nowiki>**</nowiki> Some patients have been unhealthy for other reasons prior to the onset of ME/ CFS and lack detectable triggers at onset or have more gradual or insidious onset.

1 “Overload” refers to hypersensitivities to stimuli that have changed from pre-illness status.

2 "Crash" refers to a temporary period of immobilizing physical and /or cognitive fatigue.

==Authors==
[[Bruce Carruthers]], [[Anil Kumar Jain]], [[Kenny de Meirleir]], [[Daniel Peterson]], [[Nancy Klimas]], [[A Martin Lerner]], [[Alison Bested]], [[Pierre Flor-Henry]], [[Pradip Joshi]], [[A C Peter Powles]], [[Jeffrey Sherkey]], [[Marjorie van de Sande]]<ref>http://sacfs.asn.au/download/consensus_overview_me_cfs.pdf</ref>

==See also==
*[[Case Definition Comparison - Graph 1]]
*[[Definitions of ME and CFS]]

=== Generally accepted criteria for diagnosis ===
*Canadian consensus criteria (CCC).<ref name="Carruthers, 2003" /> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using these criteria. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria|International consensus criteria]] (ICC).<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> These criteria will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease|Systemic exertion intolerance disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegria|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A. Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*[http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview of the Canadian Consensus Document]<ref name=":0" /> (the above 7 criteria are listed on page 2 of this document).
*[http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf Canadian Consensus Report - ''Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols'']<ref name="Carruthers, 2003" /> (full version of the Canadian consensus criteria).
*An Overview of the Canadian Consensus Document in French - [http://iacfsme.org/Portals/0/pdf/Abrege%20du%20C.c.%20sur%20EM-SFC.PDF Encéphalomyélite myalgique/syndrome de fatigue chronique: Définition clinique et lignes directrices à l’intention des médecins, Abrégé du Consensus canadien]<ref>{{Cite web|url=http://iacfsme.org/Portals/0/pdf/Abrege%20du%20C.c.%20sur%20EM-SFC.PDF|title=Encéphalomyélite myalgique /syndrome de fatigue chronique: Définition cliniqueet lignes directricesà l’intention des médecins - Abrégé duConsensus canadien|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|date=|website=iacfsme.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
==References==
<references>
<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf
}}</ref>
</references>

[[Category:Definitions]]

Canadian Consensus Criteria

2019-04-19T13:26:39Z

MEandCFS:citations, c/e

The [[Canadian Consensus Criteria|Canadian consensus criteria]] (CCC) are a proposed clinical criteria for [[ME/CFS]], published in 2003, and frequently used as a case definition in research.<ref name="Carruthers, 2003" /> It is a stricter criteria than the [[Fukuda criteria]] and according to [[Leonard Jason]] represents a more severely impaired population.<ref>http://www.meaction.net/2015/12/10/norwegian-researchers-ask-what-exactly-is-m-e/</ref> Adults are diagnosed at six months and pediatric cases at three months.

==Definition==

{| class="wikitable"
|+'''Canadian Consensus Criteria''' for Myalgic Encephalomyelitis
| colspan="3" |A patient with [[ME/CFS]] will meet the criteria for fatigue, [[Post-exertional malaise]] and/or [[Chronic fatigue|fatigue]], [[sleep dysfunction]], and [[pain]]; have two or more [[Nervous system|neurological]]/[[Cognitive dysfunction|cognitive]] manifestations and one or more symptoms from two of the categories of (a) [[Autonomic nervous system|autonomic]], (b) [[neuroendocrine]], and (c) [[Immune system|immune]] manifestations; and adhere to item 7.
|-
|1
|'''[[Chronic fatigue|Fatigue]]'''
|The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental [[fatigue]] that substantially reduces activity level.
|-
|2
|'''[[Post-exertional malaise|Post-Exertional Malaise]] and/or Fatigue'''
|There is an inappropriate [[loss of physical and mental stamina]], rapid [[Muscle fatigability|muscular]] and [[cognitive fatigability]], [[Post-exertional malaise|post-exertional malaise]] and/or post-exertional fatigue and/or post-exertional pain<ref name=":0">{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|date=|access-date=|website=investinme.org|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|archive-url=|archive-date=|dead-url=|type=|page=4|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref> and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period – usually 24 hours or longer.
|-
|3
|[[Sleep dysfunction|'''Sleep Dysfunction''']]*
|There is [[unrefreshed sleep]] or sleep quantity or rhythm disturbances such as [[reversed or chaotic diurnal sleep rhythms]].
|-
|4
|[[Pain|'''Pain''']]*
|There is a significant degree of [[myalgia]]. Pain can be experienced in the [[Myalgia|muscles]], and/or [[Arthralgia|joints]], and is often widespread and migratory in nature. Often there are significant [[headache]]s of new type, pattern or severity.
|-
|5
|'''[[Nervous system|Neurological]]/[[Cognitive dysfunction|Cognitive]] Manifestations'''
|'''Two or more''' of the following difficulties should be present: [[confusion]], [[Attention deficit|impairment of concentration]]<nowiki/>and [[Memory problems|short-term memory consolidation]], [[disorientation]], difficulty with [[information processing]], categorizing and word retrieval ([[Word-finding problems]]), and perceptual and sensory disturbances – e.g. [[spatial instability and disorientation]]<nowiki/>and [[inability to focus vision]].

[[Ataxia]], [[muscle weakness]] <nowiki/>and [[fasciculations]] <nowiki/>are common. There may be [[overload]]1 phenomena: cognitive, sensory – e.g. [[photophobia]] and [[Hyperacusis|hypersensitivity to noise]] – and/or [[emotional overload]], which may lead to "crash"2 periods and/or [[anxiety]].
|-
|6
|'''At Least One Symptom From Two of the Following Categories'''
|(a) '''Autonomic Manifestations''': [[Orthostatic intolerance]] – [[Neurally mediated hypotension]] (NMH), [[Postural orthostatic tachycardia]] syndrome (POTS), [[delayed postural hypotension]]; [[light-headedness]]; [[extreme pallor]]; [[nausea]] and [[irritable bowel syndrome]]; [[urinary frequency]] and [[bladder dysfunction]]; [[palpitations]] with or without [[cardiac arrhythmia]]s; [[exertional dyspnea]].

(b) '''Neuroendocrine Manifestations''': loss of thermostatic stability – [[subnormal body temperature]] and [[marked diurnal fluctuation]], [[excessive sweating|sweating episodes]], recurrent feelings of [[low-grade fever|feverishness]] and [[cold extremities]]; [[temperature sensitivity|intolerance of extremes of heat and cold]]; marked [[weight change]] – [[Anorexia, eating disorders and ME/CFS|anorexia]] or [[abnormal appetite]]; [[loss of adaptability]] and [[worsening of symptoms with stress]].

(c) '''Immune Manifestations''': [[tender lymph nodes]], recurrent [[sore throat]], recurrent [[flu-like symptoms]], [[Malaise|general malaise]], new [[food sensitivities]], medications and/or [[chemical sensitivities]].
|-
|7
|'''The Illness Persists for at Least Six Months'''
|It usually has a distinct onset,** although it may be gradual. Preliminary diagnosis may be possible earlier. Three months is appropriate for [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|children]].
|}
To be included, the symptoms must have begun or have been significantly altered after the onset of this illness. It is unlikely that a patient will suffer from all symptoms in criteria 5 & 6. The disturbances tend to form symptom clusters that may fluctuate and change over time. [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|Children]] often have numerous prominent symptoms but their order of severity tends to vary from day to day.

<nowiki>*</nowiki> There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset.

<nowiki>**</nowiki> Some patients have been unhealthy for other reasons prior to the onset of ME/ CFS and lack detectable triggers at onset or have more gradual or insidious onset.

1 “Overload” refers to hypersensitivities to stimuli that have changed from pre-illness status.

2 "Crash" refers to a temporary period of immobilizing physical and /or cognitive fatigue.

==Authors==
[[Bruce Carruthers]], [[Anil Kumar Jain]], [[Kenny de Meirleir]], [[Daniel Peterson]], [[Nancy Klimas]], [[A Martin Lerner]], [[Alison Bested]], [[Pierre Flor-Henry]], [[Pradip Joshi]], [[A C Peter Powles]], [[Jeffrey Sherkey]], [[Marjorie van de Sande]]<ref>http://sacfs.asn.au/download/consensus_overview_me_cfs.pdf</ref>

==See also==
*[[Case Definition Comparison - Graph 1]]
*[[Definitions of ME and CFS]]

=== Generally accepted criteria for diagnosis ===
*Canadian consensus criteria (CCC).<ref name="Carruthers, 2003" /> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using these criteria. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria|International consensus criteria]] (ICC).<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> These criteria will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease|Systemic exertion intolerance disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegria|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A. Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*[http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview of the Canadian Consensus Document]<ref name=":0" /> (the above 7 criteria are listed on page 2 of this document).
*[http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf Canadian Consensus Report - ''Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols'']<ref name="Carruthers, 2003" /> (full version of the Canadian consensus criteria).
*An Overview of the Canadian Consensus Document in French - [http://iacfsme.org/Portals/0/pdf/Abrege%20du%20C.c.%20sur%20EM-SFC.PDF Encéphalomyélite myalgique/syndrome de fatigue chronique: Définition clinique et lignes directrices à l’intention des médecins, Abrégé du Consensus canadien]<ref>{{Cite web|url=http://iacfsme.org/Portals/0/pdf/Abrege%20du%20C.c.%20sur%20EM-SFC.PDF|title=Encéphalomyélite myalgique /syndrome de fatigue chronique: Définition cliniqueet lignes directricesà l’intention des médecins - Abrégé duConsensus canadien|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|date=|website=iacfsme.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
==References==
<references>
<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf
}}</ref>
</references>

[[Category:Definitions]]

Post-exertional malaise

2019-04-19T13:19:37Z

MEandCFS:/* History */ citation

'''Post-exertional malaise (PEM)''' refers to a ''worsening'' of [[List of symptoms in ME CFS|ME/CFS symptoms]] after minimal ''physical'' or ''mental'' [[exertion]],<ref name=":14" /><ref name=":32" /> which can be delayed 24-72 hours or more.<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15" /><ref name=":28">{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=137|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=2018-10-16|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.}}</ref><ref name=":30">{{Cite journal|last=|first=|date=2018|title=SAGE Journals: Your gateway to world-class journal research|url=http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf|journal=Sage Pub|language=en|volume=|pages=4-5|doi=10.1177/1359105318805819/suppl_file/appendix.__the_development_of_a_comprehensive_measure_of_post-exertional_malaise.8.20.2018.pdf|via=}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref> PEM is considered to be the hallmark symptom of [[ME/CFS]].<ref name=":0">{{Cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK274235/|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness|last=Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last2=Board on the Health of Select Populations|last3=Institute of Medicine|date=2015|publisher=National Academies Press (US)|isbn=9780309316897|series=The National Academies Collection: Reports funded by National Institutes of Health|location=Washington (DC)|pmid=25695122}}</ref><ref>{{Cite web|url=https://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|website=www.medscape.com|access-date=2018-10-10}}</ref><ref>{{Cite web|url=https://ammes.org/2018/06/04/deconstructing-post-exertional-malaise-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-a-patient-centered-cross-sectional-survey/|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-10-16}}</ref> While in most diseases patients experience symptom relief after [[exercise|exercise,]]<ref>{{Cite journal|last=Loy|first=Bryan D.|last2=O'Connor|first2=Patrick J.|last3=Dishman|first3=Rodney K.|date=Oct 2013|title=The effect of a single bout of exercise on energy and fatigue states: a systematic review and meta-analysis|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2013.843266?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=1|issue=4|pages=223–242|doi=10.1080/21641846.2013.843266|issn=2164-1846}}</ref><ref>{{Cite journal|last=Robb-Nicholson|first=L. C.|last2=Daltroy|first2=L.|last3=Eaton|first3=H.|last4=Gall|first4=V.|last5=Wright|first5=E.|last6=Hartley|first6=L. H.|last7=Schur|first7=P. H.|last8=Liang|first8=M. H.|date=Dec 1989|title=Effects of aerobic conditioning in lupus fatigue: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/2590802|journal=British Journal of Rheumatology|volume=28|issue=6|pages=500–505|issn=0263-7103|pmid=2590802}}</ref><ref>{{Cite journal|last=Mostert|first=S.|last2=Kesselring|first2=J.|date=Apr 2002|title=Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis|url=https://www.ncbi.nlm.nih.gov/pubmed/11990874|journal=Multiple Sclerosis (Houndmills, Basingstoke, England)|volume=8|issue=2|pages=161–168|doi=10.1191/1352458502ms779oa|issn=1352-4585|pmid=11990874}}</ref><ref>{{Cite news|url=https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise-and-chronic-disease/art-20046049|title=What you need to know about exercise and chronic disease|work=Mayo Clinic|access-date=2018-10-10|language=en}}</ref><ref>{{Cite journal|last=Dunn|first=A. L.|last2=Trivedi|first2=M. H.|last3=O'Neal|first3=H. A.|date=June 2001|title=Physical activity dose-response effects on outcomes of depression and anxiety|url=https://www.ncbi.nlm.nih.gov/pubmed/11427783|journal=Medicine and Science in Sports and Exercise|volume=33|issue=6 Suppl|pages=S587–597; discussion 609–610|issn=0195-9131|pmid=11427783}}</ref> the opposite is true for ME/CFS patients for whom even minimal exertion can cause a symptom flare-up.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Almond|first2=Freya|last3=De Becker|first3=Pascale|last4=Truijen|first4=Steven|last5=Paul|first5=Lorna|date=May 2008|title=Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial|url=https://www.ncbi.nlm.nih.gov/pubmed/18441039|journal=Clinical Rehabilitation|volume=22|issue=5|pages=426–435|doi=10.1177/0269215507084410|issn=0269-2155|pmid=18441039}}</ref> Because recovery is often prolonged,<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> lasting days or sometimes weeks to months,<ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> patients refer to these post-exertional setbacks as ‘crashes’.<ref>{{Cite news|url=https://www.healthrising.org/the-community-reports-best-practices-on-managing-thriving-with-or-just-surviving-chronic-fatigue-syndrome-mecfs/how-to-best-recover-from-a-crash-the-mecfs-community-reports/|title=How to Best Recover From a Crash: the ME/CFS Community Reports|work=Health Rising|access-date=2018-10-10|language=en-US}}</ref><ref name=":28" /> Depending on the criteria a patient meets ([[Systemic Exertion Intolerance Disease]] (SEID) for ME/CFS's [[Systemic Exertion Intolerance Disease#Diagnostic criteria| minimum core symptoms]], the [[Canadian Consensus Criteria]] (CCC) for [[Canadian Consensus Criteria#Definition| this criterion's ME/CFS symptoms]], or the [[International Consensus Criteria]] (ICC) for [[myalgic encephalomyelitis]] (ME) and [[International Consensus Criteria#Criteria|its ME symptoms]]) will correlate with the patient's symptoms that will worsen.

PEM can be caused by [[Exertion#Exertion in ME.2FCFS|physical as well as mental exertion]]<ref name=":14" /> and the symptom complex it invokes does not necessarily relate to the initial trigger.<ref name=":3" /> ME/CFS patients suffer from a post-exertional [[Flu-like symptoms|flu-like feeling,]]<ref name=":1" /> with [[brain fog|brain fog,]]<ref name=":13" /> [[photophobia]] and other symptoms not usually reported after exertion.<ref name=":3" /> In contrast to most forms of exercise intolerance, the onset of PEM is frequently delayed<ref name=":15" /> with many patients reporting the height of their symptom flare-up, two<ref name=":13" /> or several days after the initial trigger.

It is important to understand that in [[pediatric]] cases of ME/CFS, children do not describe having PEM. They can experience a relapse from exertion, perhaps from just taking the school bus, having to spend prolonged periods in bed.<ref>[https://www.me-pedia.org/wiki/Pediatric_myalgic_encephalomyelitis_and_chronic_fatigue_syndrome ME/CFS in Children - by David S. Bell - David Bell - Open Medicine Foundation - June 25, 2016]</ref>

[[File:Cfs woman sketch.jpg|435x435px|thumb|Post-exertional malaise (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]
The distinctive characteristics of post-exertional malaise are confirmed by scientific research. Exertion induces abnormalities in [[Cognitive dysfunction|cognitive functioning,]]<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=October 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781|via=}}</ref><ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref> [[immune activation|immune activation,]]<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723|issue=|quote=|author-link=Jo Nijs|author-link2=Andrea Nees|author-link3=Lorna Paul|author-link4=Margot De Kooning|author-link5=Kelly Ickmans|via=|author-link6=Mira Meeus|author-link7=Jessica Van Oosterwijck}}</ref> [[gene expression]]<ref name=":20">{{Cite journal|last=Light|first=Alan R.|last2=White|first2=Andrea T.|last3=Hughen|first3=Ronald W.|last4=Light|first4=Kathleen C.|date=Oct 2009|title=Moderate Exercise Increases Expression for Sensory, Adrenergic, and Immune Genes in Chronic Fatigue Syndrome Patients But Not in Normal Subjects|url=http://dx.doi.org/10.1016/j.jpain.2009.06.003|journal=The Journal of Pain|volume=10|issue=10|pages=1099–1112|doi=10.1016/j.jpain.2009.06.003|issn=1526-5900}}</ref><ref name=":21">{{Cite journal|last=Light|first=A. 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C.|date=2011-07-13|title=Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome|url=http://dx.doi.org/10.1111/j.1365-2796.2011.02405.x|journal=Journal of Internal Medicine|volume=271|issue=1|pages=64–81|doi=10.1111/j.1365-2796.2011.02405.x|issn=0954-6820}}</ref><ref>{{Cite journal|last=Meyer|first=Jacob D.|last2=Light|first2=Alan R.|last3=Shukla|first3=Sanjay K.|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron J.|last7=Cook|first7=Dane B.|date=Oct 2013|title=Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression|url=http://dx.doi.org/10.1080/21641846.2013.838444|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|issue=4|pages=190–209|doi=10.1080/21641846.2013.838444|issn=2164-1846}}</ref><ref>{{Cite journal|last=White|first=A. T.|last2=Light|first2=A. R.|last3=Hughen|first3=R. W.|last4=VanHaitsma|first4=T. A.|last5=Light|first5=K. C.|date=2011-12-30|title=Differences in Metabolite-Detecting, Adrenergic, and Immune Gene Expression After Moderate Exercise in Patients With Chronic Fatigue Syndrome, Patients With Multiple Sclerosis, and Healthy Controls|url=http://dx.doi.org/10.1097/psy.0b013e31824152ed|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/psy.0b013e31824152ed|issn=0033-3174}}</ref> and [[endogenous pain inhibition]]<ref name=":22">{{Cite journal|last=Whiteside|first=Alan|last2=Hansen|first2=Stig|last3=Chaudhuri|first3=Abhijit|date=Jun 2004|title=Exercise lowers pain threshold in chronic fatigue syndrome|url=http://dx.doi.org/10.1016/j.pain.2004.02.029|journal=Pain|volume=109|issue=3|pages=497–499|doi=10.1016/j.pain.2004.02.029|issn=0304-3959}}</ref><ref name=":23">{{Cite journal|last=Meeus|first=M|last2=Roussel|first2=NA|last3=Truijen|first3=S|date=2010|title=Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: An experimental study|url=http://dx.doi.org/10.2340/16501977-0595|journal=Journal of Rehabilitation Medicine|volume=42|issue=9|pages=884–890|doi=10.2340/16501977-0595|issn=1650-1977}}</ref><ref name=":24">{{Cite journal|last=Van Oosterwijck|first=J.|last2=Nijs|first2=J.|last3=Meeus|first3=M.|last4=Lefever|first4=I.|last5=Huybrechts|first5=L.|last6=Lambrecht|first6=L.|last7=Paul|first7=L.|date=2010-03-03|title=Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: An experimental study|url=http://dx.doi.org/10.1111/j.1365-2796.2010.02228.x|journal=Journal of Internal Medicine|volume=268|issue=3|pages=265–278|doi=10.1111/j.1365-2796.2010.02228.x|issn=0954-6820|quote=|author-link=Jessica Van Oosterwijck|author-link2=Jo Nijs|author-link3=Mira Meeus|author-link4=|author-link5=|via=|author-link7=Lorna Paul}}</ref> in ME/CFS patients that were not seen before exertion or in healthy controls. Most importantly PEM can be demonstrated by a [[Two-day cardiopulmonary exercise test|2-day cardiopulmonary exercise test]] (CPET) procedure.<ref name=":16" /><ref name=":28" /> On the second day [[Two-day cardiopulmonary exercise test|CPET]], ME/CFS patients display a significant drop in [[VO2 max]] and [[maximal workload]], that is not seen in healthy controls or other diseases.<ref>{{Cite journal|last=Snell|first=C. R.|last2=Stevens|first2=S. R.|last3=Davenport|first3=T. E.|last4=Van Ness|first4=J. M.|date=2013-06-27|title=Discriminative Validity of Metabolic and Workload Measurements for Identifying People With Chronic Fatigue Syndrome|url=http://dx.doi.org/10.2522/ptj.20110368|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=0031-9023}}</ref><ref>{{Cite journal|last=Vermeulen|first=Ruud CW|last2=Kurk|first2=Ruud M|last3=Visser|first3=Frans C|last4=Sluiter|first4=Wim|last5=Scholte|first5=Hans R|date=2010|title=Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity|url=http://dx.doi.org/10.1186/1479-5876-8-93|journal=Journal of Translational Medicine|volume=8|issue=1|pages=93|doi=10.1186/1479-5876-8-93|issn=1479-5876}}</ref><ref name=":17" /><ref>{{Cite journal|last=Vanness|first=J. Mark|last2=Snell|first2=Christopher R.|last3=Stevens|first3=Staci R.|date=Jan 2007|title=Diminished Cardiopulmonary Capacity During Post-Exertional Malaise|url=http://dx.doi.org/10.1300/j092v14n02_07|journal=Journal of Chronic Fatigue Syndrome|volume=14|issue=2|pages=77–85|doi=10.1300/j092v14n02_07|issn=1057-3321}}</ref><ref name=":18" /> These objective measures track strongly with the presence, severity and duration of PEM.<ref name=":0" /> [[Brian Vastag]] won a groundbreaking long term disability (LTD) claim using CPET to prove his PEM was a severe disabling symptom.<ref>[US District Court of NJ: Brian Vastag v. Prudential Insurance Company of America, Civ.15-6197 (KSH), (CLW) https://t.co/Vq9GXo4VEI]</ref><ref>{{Cite web|url=https://www.meaction.net/2018/06/04/victory-for-me-disability-claim-court-upholds-plaintiffs-lawsuit-after-being-denied-disability/|title=Victory for ME Disability Claim - U.S. Court Upholds Plaintiff's Lawsuit After Being Denied Disability|last=Tillman|first=Adriane|authorlink=|last2=|first2=|authorlink2=|date=2018-06-04|website=#MEAction|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-02}}</ref>

A 2015 review of the literature by the [[National Academy of Medicine]] (NAM) concluded there to be “sufficient evidence that PEM is a primary feature that helps distinguish ME/CFS from other conditions.”<ref name=":0" /> Disagreement exists however on the precise nature of PEM and how it should be defined,<ref name=":19">{{Cite journal|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth|last3=So|first3=Suzanna|last4=Scott|first4=Jilian|last5=Brown|first5=Abigail|date=2015|title=Problems in Defining Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295644/|journal=Journal of prevention & intervention in the community|volume=43|issue=1|pages=20–31|doi=10.1080/10852352.2014.973239|issn=1085-2352|pmc=4295644|pmid=25584525}}</ref> with some diagnostic criteria emphasizing [[Paresis|muscle weakness]] and others a more a general form of [[fatigue]] and exhaustion.<ref name=":8">{{Cite journal|last=McManimen|first=Stephanie L.|last2=Sunnquist|first2=Madison L.|last3=Jason|first3=Leonard A.|date=2016-08-24|title=Deconstructing post-exertional malaise: An exploratory factor analysis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/|journal=Journal of health psychology|doi=10.1177/1359105316664139|issn=1359-1053|pmc=5325824|pmid=27557649}}</ref>

The [[Centers for Disease Control and Prevention]] (CDC) outline different types of exertion that may trigger PEM and how it impacts patients noting some may be house-bound or completely bed-bound during a crash. "People with ME/CFS may not be able to predict what will cause a crash or how long it will last."<ref name=":32">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-11-21}}</ref> Examples of PEM given by the CDC are: attending a child’s school event may leave a patient house-bound for a couple of days unable to do needed tasks, like laundry; grocery shopping may cause a crash that requires a nap in the car before driving home or a call for a ride home; a shower may leave a patient bed-bound and unable to do anything for days; keeping up with work may lead to spending evenings and weekends recovering.<ref name=":32" />

== PEM described by Dr. David Kaufman ==
{{#ev:youtube|https://www.youtube.com/watch?v=RC9TjgE_PlU|400|right|'''PEM described by Dr. David Kaufman''' (2018) Kaufman/''Unrest'' Video begins @2:16 and PEM is described until @3:35|frame|start=136&rel=0&autoplay=0}}

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

(Video begins @2:16 and PEM is described until @3:35. View entire 11:47 for a full description of ME/CFS)

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Patients' description==
[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]
[[File:PEM.JPG|300px|thumb|right|#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with [[Neurally mediated hypotension|high pulse and very low energy]]. Even though you sometimes can see the exhaustion in someone's face, most [[List of symptoms in ME CFS|ME symptoms]] are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaise<ref>{{Cite web|url=https://twitter.com/ezchili/status/1085927134248488965|title=#TwoFacesofME First picture: Happy to be outside and feeling ok. Second picture: A crash with high pulse and very low energy. Even though you sometimes can see the exhaustion in someone's face, most ME symptoms are invisible. #pwME #MEcfs #millionsmissing #PostExertionalMalaisepic.twitter.com/FKSTo8W0hH|last=ez 📎|date=2019-01-17|website=@ezchili|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM2.JPG|300px|thumb|right|#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.<ref>{{Cite web|url=https://twitter.com/kaisecam/status/1085886323276349440|title=#twofacesofME #MEcfs - It's not always easy to predict when you'll take a turn for the worst. It's not even easy to tell how you'll feel when you crash. You just know that at some point in the future, it's going to happen.pic.twitter.com/nTJVG63jRm|last=Kaise 🥄|first=Mx|date=2019-01-17|website=@kaisecam|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM3.JPG|300px|thumb|right|#TwoFacesofME Workday me v’s weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.<ref>{{Cite web|url=https://twitter.com/RachelFrancis/status/1085940724774912000|title=#TwoFacesofME Workday me vs weekend me. I’m so grateful that most of the time I can work, but losing out on family time on a weekend to recover is hard.pic.twitter.com/qZNiQaVHyD|last=Francis|first=Rachel|date=2019-01-17|website=@RachelFrancis|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

[[File:PEM6.JPG|300px|thumb|right|What the [world] don’t [see] two faces of M.E.<ref>{{Cite web|url=https://twitter.com/SharonTiday/status/1085122891220430848|title=What the don’t two faces of M.E.pic.twitter.com/DYZVhtyrG5|last=Awareness|first=CFDA #|date=2019-01-15|website=@SharonTiday|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM7.JPG|300px|thumb|right|Joining #pwME sharing #TwoFacesofME for #MEAwareness 1: a fall day when I got outside (but ended up in bed a week) 2: what no one sees (constant [[Chronic pain|pain]], post exertional malaise & [[Sleep dysfunction|sleep deprivation]]) Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)<ref>{{Cite web|url=https://twitter.com/ceibakoru/status/1085894325832040448|title=Joining #pwME sharing #TwoFacesofME for #MEAwareness, 1: a fall day when I got outside (but ended up in bed a week), 2: what no one sees (constant pain, post exertional malaise & sleep deprivation). Bonus for comparison: snowboarding shortly after cancer treatment (but before ME)pic.twitter.com/EpsMLT8E11|last=Ceiba 🌳Koru 🌀|date=2019-01-17|website=@ceibakoru|language=en|access-date=2019-01-17}}</ref>]]

=== An illness within an illness ===

PEM refers to a worsening of many ME/CFS symptoms as a result of physical or mental exertion. It consists of more than post-exertional fatigue and can cause severe debility. As one patient described it: <blockquote>“When I do any activity that goes beyond what I can do—I literally collapse—my body is in major pain, it hurts to lay in bed, it hurts to think, I can’t hardly talk—I can’t find the words, I feel my insides are at war.”<ref name=":0" /></blockquote> Another patient emphasized that the feeling of PEM is very different from what one experiences as a healthy person: <blockquote>"PEM is like nothing else you will experience in healthy life; a combination of a hangover, the flu, finishing a 10k run, all at the same time at varying levels of severity."<ref>{{Cite news|url=https://twitter.com/Fatigo_MECFS/status/1050305665565102080|title=Fatigo_MECFS on Twitter|work=Twitter|access-date=2018-10-11|language=en}}</ref></blockquote>Considering the serious but fluctuating debility PEM causes, ME/CFS expert Dr. [[Anthony Komaroff]] described it as “an illness within an illness”.<ref>{{Cite news|url=https://phoenixrising.me/archives/11884|title=Post-Exertional Malaise II: Perception and Reality By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref>

=== Energy conservation and pacing ===
Patients often report the feeling of a red line, an energy level that if exceeded, will result in a relapse. As one [[Norway|Norwegian]] patient described: <blockquote>“....And suddenly it is just too much. The body turns itself off, as if it has gone on strike. You have pushed too much for too long, it repeats itself, and the body stops functioning.”<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>Energy conservation strategies such as [[pacing]] and the [[Energy Envelope Theory|envelope theory]] have been developed to minimize PEM while allowing patients to stay as active as possible.<ref>{{Cite journal|last=Goudsmit|first=Ellen M.|last2=Nijs|first2=Jo|last3=Jason|first3=Leonard A.|last4=Wallman|first4=Karen E.|date=2012|title=Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document|url=https://www.ncbi.nlm.nih.gov/pubmed/22181560|journal=Disability and Rehabilitation|volume=34|issue=13|pages=1140–1147|doi=10.3109/09638288.2011.635746|issn=1464-5165|pmid=22181560}}</ref> These techniques advise patients to balance energy availability and expenditure and to recognize early signs of PEM so they can reduce activity levels before a relapse occurs.

== History ==

=== Case definitions ===
Early descriptions of symptom exacerbation in [[Myalgic encephalomyelitis|ME]] focused on post-exertional muscle weakness. Renowned ME-expert [[Melvin Ramsay]] for example wrote: <blockquote>"[[Muscle fatigability]] whereby, even after a minor degree of physical effort, three, four or five days or longer elapse before full [[muscle]] power is restored is unique and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME."<ref name=":10">Ramsay M. (1988). Myalgic Encephalomyelitis and Postviral Fatigue States: The Saga of Royal Free Disease. Gower Medical Publishing. Second edition.</ref> </blockquote>In a 1985 study [[Peter Behan|Behan]] et al. noted that all of their patients “had the same primary symptom that of gross fatigue made worse by exercise".<ref>{{Cite journal|last=Behan|first=P. O.|last2=Behan|first2=W. M.|last3=Bell|first3=E. J.|date=May 1985|title=The postviral fatigue syndrome - an analysis of the findings in 50 cases|url=https://www.ncbi.nlm.nih.gov/pubmed/2993423|journal=The Journal of Infection|volume=10|issue=3|pages=211–222|issn=0163-4453|pmid=2993423}}</ref>

'''Formerly used to define Chronic fatigue syndrome'''

In the 1988 [[Holmes criteria|Holmes definition]] of [[Chronic fatigue syndrome|CFS]], unexplained generalized muscle weakness was one of the 11 minor symptoms, yet it was fatigue that set the tone. Another minor symptom referred to “prolonged (24 hours or greater) generalized fatigue after levels of [[exercise]] that would have been easily tolerated in the patient’s premorbid state”.<ref>{{Cite journal|last=Holmes|first=G. P.|last2=Kaplan|first2=J. E.|last3=Gantz|first3=N. M.|last4=Komaroff|first4=A. L.|last5=Schonberger|first5=L. B.|last6=Straus|first6=S. E.|last7=Jones|first7=J. F.|last8=Dubois|first8=R. E.|last9=Cunningham-Rundles|first9=C.|date=Mar 1988|title=Chronic fatigue syndrome: a working case definition|url=https://www.ncbi.nlm.nih.gov/pubmed/2829679|journal=Annals of Internal Medicine|volume=108|issue=3|pages=387–389|issn=0003-4819|pmid=2829679}}</ref> PEM is not a mandatory symptom under the Holmes definition.

The wording post-exertional malaise was first used in one of the 8 minor symptoms in the 1994 [[Fukuda criteria]], but without further clarification of the term, except that it lasts more than 24 hours. PEM is not a mandatory symptom under the Fukuda criterion.

'''Currently disputed to define Chronic fatigue syndrome'''

The [[Oxford criteria]] is flawed as it does not list PEM as a symptom. Patients with the symptom of [[fatigue]], which many illnesses and diseases have, are swept into the diagnosis and research studies. ''The Argus Report'' article ''US NIH Report Calls for UK Definition of ME/CFS to be Scrapped'' wrote the following:<blockquote> The [[United States]] [[National Institutes of Health]] (NIH) has issued a draft report that highlights the dire need for scientific research that will help find a cure for the millions of people suffering from [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS) worldwide. The report also highlights the fact that the decades-old UK Royal Society of Medicine’s Oxford criteria for ME/CFS are severely “flawed,” and that continuing to use these criteria may “cause harm.” Further, the NIH report says that the Royal Society definition should “be retired” and replaced with a single case definition agreed to by the ME/CFS community.<ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref></blockquote>There are further criticisms [https://www.me-pedia.org/wiki/Oxford_criteria#Criticisms here].

'''Currently used to define ME/CFS'''

In 2003, [[Canadian Consensus Criteria]] (CCC) PEM became a recognized symptom for the diagnosis of ME/CFS. The CCC were the first criteria to stress that the onset of PEM could be delayed and to describe its debility as a flu-like distress.<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|last2=Jain|first2=Anil Kumar|last3=De Meirleir|first3=Kenny L.|last4=Peterson|first4=Daniel L.|last5=Klimas|first5=Nancy G.|last6=Lerner|first6=A. Martin|last7=Bested|first7=Alison C.|last8=Flor-Henry|first8=Pierre|last9=Joshi|first9=Pradip|date=Jan 2003|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v11n01_02|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=11|issue=1|pages=7–115|doi=10.1300/j092v11n01_02|issn=1057-3321}}</ref> [[Canadian Consensus Criteria#Definition|PEM and/or post-exertional fatigue and/or post-exertional pain]] is used for the CCC criterion.<ref>{{Cite web|url=http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners - An Overview fo the Canadian Consensus Document|last=|first=|authorlink=Bruce Carruthers|last2=|first2=|authorlink2=Marjorie van de Sande|date=|website=investinme.org|page=4|type=|archive-url=|archive-date=|dead-url=|access-date=|quote=Physical or mental exertion often causes debilitating malaise and/or fatigue, generalized pain, deterioration of cognitive functions, and worsening of other symptoms that may occur
immediately after activity or be delayed. Patients experience rapid muscle fatigue and lack endurance.}}</ref>

The 2015 report of the [[National Academy of Medicine]] (NAM) describes PEM more generally as “an exacerbation of some or all of an individual’s ME/CFS symptoms that occurs after physical or cognitive exertion and leads to a reduction in functional ability.” The report confirmed PEM as the hallmark symptom of ME/CFS and advised to rename the disease accordingly to [[Systemic Exertion Intolerance Disease]] (SEID).<ref name=":0" /> PEM is a mandatory symptom under the SEID criterion.

'''Currently used to define Myalgic encephalomyelitis'''

In 2011, the [[International Consensus Criteria]] (ICC) introduced the new term '''Post-Exertional Neuro-immune Exhaustion (PENE)''' to refer to the characteristic exercise and exertion intolerance of [[myalgic encephalomyelitis]] (ME) patients. It notes a delayed onset and prolonged recovery, and uses acute [[flu-like symptoms]] to describe PENE. By definition PENE results in a substantial reduction in functioning, as even simple activities of daily living can cause a relapse.<ref name=":2">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> PENE is a mandatory symptom under the ICC criterion.

===Dismissed as disturbed effort perceptions or kinesiophobia ===
[[File:Brian vastag.png|thumb|right|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]
The existence of PEM as a distinctive and complex symptom of ME/CFS has been dismissed in early research into the disease. Some interpreted it as just fatigue after exercise<ref>https://www.cdc.gov/me-cfs/pdfs/symptom-inventory-questionnaire-508.pdf</ref>, while others saw it as an artifact of disturbed effort perceptions<ref>{{Cite journal|last=Lawrie|first=S. M.|last2=Machale|first2=S. M.|last3=Power|first3=M. J.|last4=Goodwin|first4=G. M.|date=Sep 1997|title=Is the chronic fatigue syndrome best understood as a primary disturbance of the sense of effort?|url=https://www.cambridge.org/core/journals/psychological-medicine/article/editorial-is-the-chronic-fatigue-syndrome-best-understood-as-a-primary-disturbance-of-the-sense-of-effort/434A5EB2C5B4F971A4A36C1DC3400A7E|journal=Psychological Medicine|language=en|volume=27|issue=5|pages=995–999|issn=1469-8978}}</ref><ref>{{Cite journal|last=Rosen|first=S D|last2=King|first2=J C|last3=Wilkinson|first3=J B|last4=Nixon|first4=P G|date=Dec 1990|title=Is chronic fatigue syndrome synonymous with effort syndrome?|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292947/|journal=Journal of the Royal Society of Medicine|volume=83|issue=12|pages=761–764|issn=0141-0768|pmc=1292947|pmid=2125315}}</ref><ref>{{Cite journal|last=Wallman|first=Karen E.|last2=Sacco|first2=Paul|date=Jan 2007|title=Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17365951|journal=Research in Sports Medicine|volume=15|issue=1|pages=47–59|doi=10.1080/15438620601184331|issn=1543-8627|pmid=17365951}}</ref> or an irrational fear of movement<ref>{{Cite journal|last=Silver|first=A.|last2=Haeney|first2=M.|last3=Vijayadurai|first3=P.|last4=Wilks|first4=D.|last5=Pattrick|first5=M.|last6=Main|first6=C. J.|date=Jun 2002|title=The role of fear of physical movement and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12069873|journal=Journal of Psychosomatic Research|volume=52|issue=6|pages=485–493|issn=0022-3999|pmid=12069873}}</ref><ref>{{Cite journal|last=Fischler|first=B.|last2=Dendale|first2=P.|last3=Michiels|first3=V.|last4=Cluydts|first4=R.|last5=Kaufman|first5=L.|last6=De Meirleir|first6=K.|date=Apr 1997|title=Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology|url=https://www.ncbi.nlm.nih.gov/pubmed/9160276|journal=Journal of Psychosomatic Research|volume=42|issue=4|pages=369–378|issn=0022-3999|pmid=9160276}}</ref>. One example of this is the [http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf Tampa scale kinesiophobia], adapted for [[chronic fatigue syndrome]]. Some of the questions in this scale ask about the experience of PEM such as: “If I were to try to overcome it, my symptoms would increase” or “my symptoms let me know when to stop exercising so that I do not harm myself”. Yet these symptoms are classified as an indicator of irrational fear of movement and exercise, instead of PEM.<ref>{{Cite web|url=http://www.paininmotion.be/EN/sem-TSK-CFSEnglish.pdf|title=Tampa Scale Kinesiophobia - Version Chronic Fatigue Syndrome|last=Nijs|first=J|last2=De Meirleir|first2=K|date=2004|website=painmotion.be|publisher=Archives of Physical Medicine and Rehabilitation|archive-url=|archive-date=|dead-url=|access-date=|last3=Duquet|first3=W}}</ref>

=== Critique of the term ===
The name post-exertional malaise was introduced by the 1994 Fukuda criteria and had no prior medical meaning attached to it.<ref name=":3">{{Cite journal|last=Chu|first=Lily|last2=Valencia|first2=Ian J.|last3=Garvert|first3=Donn W.|last4=Montoya|first4=Jose G.|date=2018|title=Deconstructing post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: A patient-centered, cross-sectional survey|url=https://www.ncbi.nlm.nih.gov/pubmed/29856774|journal=PloS One|volume=13|issue=6|pages=e0197811|doi=10.1371/journal.pone.0197811|issn=1932-6203|pmc=5983853|pmid=29856774|quote=|author-link=Lily Chu|author-link2=Ian Valencia|author-link3=Donn Gavert|author-link4=Jose Montoya|author-link5=|via=}}</ref> While in the scientific literature, the term has become the standard to describe the relapses ME/CFS patients suffer after exertion, patients argue that it trivializes their experience. The term malaise after all refers to “a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify”<ref>{{Cite web|url=https://en.oxforddictionaries.com/definition/malaise|title=Definition of malaise in English by Oxford Dictionaries|website=Oxford Dictionaries {{!}} English|access-date=2018-10-13}}</ref>. Doctor of [http://sph.berkeley.edu/ Public Health at Berkely], [[David Tuller]], calls post-exertional malaise a “complete misnomer” arguing what ME/CFS patients experience "is much closer to a serious crash or relapse than a Victorian fainting spell.”<ref>{{Cite web|url=http://www.virology.ws/2011/11/23/chronic-fatigue-syndrome-and-the-cdc-a-long-tangled-tale/|title=Chronic Fatigue Syndrome and the CDC: A Long, Tangled Tale|website=www.virology.ws|language=en-US|access-date=2018-10-10}}</ref> ME/CFS patients usually use the abbreviation PEM or the term ‘crash’ to describe their relapses.

== The distinctive characteristics of PEM ==
Four aspects differentiate the post-exertional malaise of ME/CFS patients from the exercise intolerance commonly reported in patients suffering from [[deconditioning]] or other conditions.

=== Timing ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertional Malaise: History, Characteristics, Evidence'' (2015) By Dr. Lily Chu/Solve CFS">https://www.youtube.com/watch?v=hxJPrkWHcBo</embedvideo>
First of all, there is the time lapse. While physical complaints are usually reported during or shortly after exercise, PEM often has a delayed onset, hours or sometimes even days after the original trigger. Yoshiuchi et al. for example wrote that: “after a briefer maximal exercise task, reports of worsening CFS symptoms were inconsistent or absent until 5 days after the challenge, a pattern not typically observed in real life.”<ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> The authors noted that this delay could be used to distinguish ME/CFS from other fatiguing illness. Another study from Stanford University showed that in up to 37% of the 150 ME/CFS patients studied, PEM may not begin until a day or more after an [[Exertion|exertional]] trigger.<ref name=":3" />

[[File:Rosa SEID.JPG|400px|thumb|Rosa age 25 in 1986. In 2015 the [[SEID]] criteria were released. Rosa read about PEM and how it is delayed and makes [[ME/CFS]] symptoms including [[chronic fatigue]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her [[List of symptoms in ME CFS|worsening symptoms]] with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled]]

Patients may not be familiar with this characteristic of their relapses, since it is very counter-intuitive. As one patient noted:<blockquote>"It's really counter-intuitive to feel bad after a delay of 24 hours after exertion. It may take quite some time before people even make that connection, if ever. I only noticed it about three years in, and I hesitated to mention to others because I thought it might make me sound nuts."<ref name=":5">{{Cite news|url=https://www.s4me.info/threads/s4me-submission-to-the-public-review-on-common-data-elements-for-me-cfs-concerns-with-the-proposed-measure-of-post-exertional-malaise.2220/|title=S4ME: Submission to the public review on Common Data Elements for ME/CFS: Concerns with the proposed measure of post-exertional malaise|work=Science for ME|access-date=2018-10-10|language=en-US}}</ref></blockquote>Another time-related characteristic of PEM is a prolonged recovery period. In a 2010 study 25 M/CFS patients and 23 matched controls were followed up for seven days after performing a maximal cardiopulmonary exercise test. After two days, all controls subjects were recovered while only one ME/CFS patient was. Most (60%) of the ME/CFS participants reported that it took more than five days to fully recover from the test and many reported feeling at their worst 24 to 48 hours after the test.<ref name=":9">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health |volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref> Other studies have found the same prolonged recovery period in ME/CFS patients after exertion. A Dutch study for example noted: <blockquote>"For CFS patients, daily observed fatigue was increased up to 2 days after the exercise test. For controls, self-observed fatigue returned to baseline after 2 h."<ref>{{Cite journal|last=Bazelmans|first=Ellen|last2=Bleijenberg|first2=Gijs|last3=Voeten|first3=Marinus J. M.|last4=van der Meer|first4=Jos W. M.|last5=Folgering|first5=Hans|date=Oct 2005|title=Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16223622|journal=Journal of Psychosomatic Research|volume=59|issue=4|pages=201–208|doi=10.1016/j.jpsychores.2005.04.003|issn=0022-3999|pmid=16223622|quote=|author-link=Ellen Bazelmans|author-link2=Gijs Bleijenberg|author-link3=Marinus Voeten|author-link4=Jos van der Meer|author-link5=Hans Folgering|via=}}</ref></blockquote>[[Charles Lapp|Lapp]] et al. followed 31 ME/CFS patients for 12 days after performing a maximal exercise test of 8-10 minutes. The average relapse lasted 8,82 days, although 22% of patients were still in relapse when the study ended at 12 days.<ref>{{Cite journal|last=Lapp|first=C. W.|date=Jul 1997|title=Exercise limits in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9236491|journal=The American Journal of Medicine|volume=103|issue=1|pages=83–84|issn=0002-9343|pmid=9236491}}</ref> In the Stanford study by [[Lily Chu|Chu]] et al. 87% of respondents indicated that they endure PEM for 24 hours or more. The authors concluded: <blockquote>"In many medical conditions, exertion-exacerbated symptoms usually start during exertion or immediately after and usually resolve immediately or shortly after exertion stops. In contrast, PEM may not start until hours or even days after the trigger starts or has been removed, may peak after the first day, and may not stop until hours to months later. This characteristic of PEM often leads patients and clinicians to believe that symptom exacerbations are random rather than associated with a trigger; most people will not intuit that symptoms are caused by a trigger that occurred hours to days prior unless specifically asked by their clinicians to pay attention."<ref name=":3" /> </blockquote>

=== Type of symptoms ===
The second characteristic of PEM is the [[List of symptoms in ME CFS|type of symptoms reported]]. The [[Canadian Consensus Criteria]], a 2003 clinical guideline formed by experts in the field, underlines that many PEM symptoms are [[Immune system|immune-related]]: <blockquote>"The [[malaise]] that follows exertion is difficult to describe but is often reported to be similar to the generalized [[pain]], discomfort and fatigue associated with the acute phase of [[influenza]]. Delayed malaise and fatigue may be associated with signs of immune activation: [[sore throat]], lymph glandular tenderness and/or [[Swollen lymph nodes|swelling]], general malaise, increased pain or [[Brain fog|cognitive fog]]."<ref name=":1" /> </blockquote>[[Mark VanNess|Van Ness]] et al. noted how [[Cognitive dysfunction|cognitive difficulties]] after exertion differentiate ME/CFS patients from healthy controls: <blockquote>"Another interesting difference between groups was the reported symptom of [[cognitive dysfunction]], for example, ‘‘[[Brain fog|brain-fog]]’’ or ‘‘difficulty concentrating.’’ Problems of this nature were not reported by any of the control subjects, whereas 12 patients (48%) experienced these problems: “Carrying on conversations was hard.” “Can’t think straight.” “My mind was not clear.”<ref name=":9" /></blockquote>This was elaborated by [[Lily Chu|Chu]] et al., the research team who conducted the first in-depth investigation on how ME/CFS patients describe their PEM: <blockquote>"There exists no medical condition the authors are familiar with where exertion or emotional distress causes immune/ [[Inflammation|inflammatory]]-related symptoms like sore throat, tender lymph nodes, or flu-like feelings, yet 60% and 36% of our subjects, respectively, reported these symptoms with either stimuli and about a quarter experienced all 3 with exertion. Conversely, symptoms typically associated with physical exertion in other conditions, like [[Dyspnea|shortness of breath]] or [[chest pain]] in [[chronic lung]] or [[heart disease]], are rarely reported in ME/CFS. Furthermore, it is well-established that physical activity improves [[Mood swings|mood]], [[Sleep dysfunction|sleep]], and pain in both healthy people as well those with chronic illnesses like depression or anxiety yet our subjects report worsened sleep, mood, and pain with physical activity."<ref name=":3" /></blockquote>

=== Triggers ===
A third characteristic of PEM is that it can be elicited by multiple triggers. Research has shown that ME/CFS patients experience PEM after both [[Exertion#Exertion in ME.2FCFS|physical and cognitive exertion]]. A 2014 study for example followed up on 32 ME/CFS patients after completing a battery of neurocognitive tests. As the authors concluded: “following a challenging cognitive demand, fatigue significantly increased two days after testing”, which was “suggestive of post-exertional symptom exacerbation following mental effort.”<ref name=":14">{{Cite journal|last=Arroll|first=Megan A.|last2=Attree|first2=Elizabeth A.|last3=O'Leary|first3=John M.|last4=Dancey|first4=Christine P.|date=2014-04-03|title=The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2014.892755|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=2|issue=2|pages=57–63|doi=10.1080/21641846.2014.892755|issn=2164-1846}}</ref> Commenting on the [https://www.me-pedia.org/wiki/1980-81_Ayrshire_outbreak outbreak in West Kilbride, Ayrshire], Ramsay remarked: <blockquote>“Once the disease was established the most characteristic symptom was extreme exhaustion, particularly after exercise. The exhaustion also occurred after emotional or mental strain.”<ref name=":10" /> </blockquote>Some other precipitants of PEM that have been reported include positional changes and exposure to excessive light or sounds<ref>{{Cite web|url=http://anilvanderzee.com/dance-hermit-16-vs-sumo-baby-part-1/|title=Dance hermit ’16 vs. Sumo Baby (part 1) {{!}} Anil van der Zee|website=anilvanderzee.com|language=en-GB|access-date=2018-10-13}}</ref>. While PEM was often thought of as symptom exacerbation after exercise, it is clear that for some ME/CFS patients even basic activities of daily living such as toileting, bathing, dressing, communicating, and reading can trigger relapses.<ref name=":11" /> As long time ME/CFS expert [[Jennie Spotila|Jennifer Spotila]] explained in a four-piece exploration of the phenomenon post-exertional malaise:<blockquote>“The use of the word ‘exertion’ may create the impression that PEM is triggered by strenuous or intense activity, but this is not the case […] Some patients need only attempt to make a simple meal or get dressed before PEM descends.”<ref>{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|work=Phoenix Rising|access-date=2018-10-10|language=en-US}}</ref></blockquote>This was confirmed by Chu et al. <blockquote>"[…] our results provide formal evidence supporting patient narratives, clinician experiences, and current case definitions which assert that even tasks like walking, cooking, or reading can provoke PEM."<ref name=":3" /> </blockquote>In some instances, the specific trigger of PEM cannot be identified.<ref name=":11">NINDS/CDC Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Post-Exertional Malaise Subgroup Draft Recommendations Public Review Comments Due January 31, 2018</ref>

=== Loss of functional capacity ===
A fourth distinctive element of PEM is often described as a loss of stamina and/or functional capacity. This refers to the results of the 2-day cardiopulmonary exercise test (CPET) procedure. A CPET is usually reproducible and normally has a test-retest difference of 7-12%<ref name=":16">{{Cite journal|last=Stevens|first=Staci|last2=Snell|first2=Chris|last3=Stevens|first3=Jared|last4=Keller|first4=Betsy|last5=VanNess|first5=J. Mark|date=2018|title=Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2018.00242/full|journal=Frontiers in Pediatrics|language=English|volume=6|doi=10.3389/fped.2018.00242|issn=2296-2360}}</ref>. ME/CFS patients however show strikingly lower results on several measures at the second CPET compared to the first, despite meeting objective markers of maximal effort. These results have been replicated by several research teams, though there is inconsistency on which measure ([[VO2]] or maximal workload, at peak or ventilatory threshold), the decline in functional capacity is best represented.

{| class="wikitable"
! colspan="8" |Physiological changes between first and second exercise test during 2-day CPET procedure in patients with ME/CFS
|-
|
|Number of ME/CFS patients
|VO2 peak
|VO2 at VT
|Workload peak
|Workload at VT
|HR peak
|O2pulse at VT
|-
|[[Mark VanNess|VanNess]] et al. 2007.
|6
| -22%
| -26%
|?
|?
|?
|?
|-
|[[Vemeulen]] et al. 2010.
|15
| -6.3%
| -7.0%
| -5.3%
| -7.0%
| -1.9%
| -8.8%
|-
|[[Christopher Snell|Snell]] et al. 2013.
|51
| -5%
| -10.8%
| -7.2%
| -55.2%
|?
|?
|-
|[[Betsy Keller|Keller]] et al. 2014.
|22
| -13.8%
| -15.8%
| -12.5%
| -21.3%
| -5.9%
| -12.6%
|-
|[[Hodges]] et al. 2018.
|10
| +5.3%
| +6.1%
| -6.7%
| -11.4%
| -0.6%
|?
|}
The drop in functional capacity on the second CPET is usually not seen in other diseases. According to [[Betsy Keller|Keller]] et al. "ME/CFS patients currently represent a unique class of ill patients who do not reproduce maximal CPET measures, unlike individuals with cardiovascular disease, lung disease, end-stage renal disease pulmonary arterial hypertension and cystic fibrosis".<ref name=":17">{{Cite journal|last=Keller|first=Betsy A.|last2=Pryor|first2=John Luke|last3=Giloteaux|first3=Ludovic|date=2014-04-23|title=Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment|url=https://www.ncbi.nlm.nih.gov/pubmed/24755065|journal=Journal of Translational Medicine|volume=12|pages=104|doi=10.1186/1479-5876-12-104|issn=1479-5876|pmc=4004422|pmid=24755065}}</ref> A preliminary study from [[New Zealand]] suggests that patients with MS do not display the same decline on the second day of exercise testing, as do patients with ME/CFS.<ref name=":18">{{Cite journal|last=Hodges|first=L. D.|last2=Nielsen|first2=T.|last3=Baken|first3=D.|date=Jul 2018|title=Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study|url=https://www.ncbi.nlm.nih.gov/pubmed/28782878|journal=Clinical Physiology and Functional Imaging|volume=38|issue=4|pages=639–644|doi=10.1111/cpf.12460|issn=1475-097X|pmid=28782878}}</ref>

Questions have however been raised about the clinical use of the 2-day CPET procedure. [[Christopher Snell|Snell]] et al. suggested it might be unethical to use this method since many ME/CFS patients might suffer a serious relapse as a result of exercise performance.<ref>{{Cite journal|last=Snell|first=Christopher R.|last2=Stevens|first2=Staci R.|last3=Davenport|first3=Todd E.|last4=Van Ness|first4=J. Mark|date=Nov 2013|title=Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23813081|journal=Physical Therapy|volume=93|issue=11|pages=1484–1492|doi=10.2522/ptj.20110368|issn=1538-6724|pmid=23813081}}</ref> Others have noted that the CPET- procedure is not practical either. It cannot be used in patients with severe ME/CFS (thus excluding these patients from study) and because of cost and expertise, may not be available to most clinicians.<ref name=":11" /> CPET for ME/CFS is usually not covered by insurance and can cost hundreds of dollars.<ref name=":7">{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref> For these reasons PEM is usually assessed using self-reporting questionnaires.

== Differentiation ==
Several studies have shown that PEM is the symptom of ME/CFS that best differentiates it from other diseases.

=== Healthy controls and idiopathic chronic fatigue ===
PEM was one of the symptoms in the CDC symptom inventory list that differentiated subjects with ME/CFS from those without the disease.<ref>{{Cite journal|last=Wagner|first=Dieter|last2=Nisenbaum|first2=Rosane|last3=Heim|first3=Christine|last4=Jones|first4=James F.|last5=Unger|first5=Elizabeth R.|last6=Reeves|first6=William C.|date=2005-07-22|title=Psychometric properties of the CDC Symptom Inventory for assessment of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16042777|journal=Population Health Metrics|volume=3|pages=8|doi=10.1186/1478-7954-3-8|issn=1478-7954|pmc=1183246|pmid=16042777}}</ref> It was also the highest loading factor among a data set of 38 measurements used for a principal component analysis of unexplained chronic fatigue.<ref>{{Cite journal|last=Vollmer-Conna|first=Uté|last2=Aslakson|first2=Eric|last3=White|first3=Peter D|date=Apr 2006|title=An empirical delineation of the heterogeneity of chronic unexplained fatigue in women|url=https://www.futuremedicine.com/doi/abs/10.2217/14622416.7.3.355|journal=Pharmacogenomics|language=en|volume=7|issue=3|pages=355–364|doi=10.2217/14622416.7.3.355|issn=1462-2416}}</ref> Data for this study came from the epidemiological study in Wichita, Kansas.

The other major epidemiological study, carried out in Chicago, also identified PEM as the hallmark symptom of ME/CFS. In a 10 year follow-up study on the 32 patients originally identified as having ME/CFS, all of the contacted patients reported post-exertional malaise at some point in time. This symptom was able to differentiate ME/CFS patients with those with [[idiopathic chronic fatigue]], those with exclusionary illnesses and healthy controls. According to the author: <blockquote>"Among all the variables in this study, only for post-exertional malaise did the CFS group significantly differ from the other three conditions. This reaffirms the importance of this being a cardinal and critical symptom for CFS."<ref>{{Cite journal|last=Jason|first=Leonard A.|date=Feb 2011|title=Natural History of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171164/|journal=Rehabilitation psychology|volume=56|issue=1|pages=32–42|doi=10.1037/a0022595|issn=0090-5550|pmc=3171164|pmid=21401284}}</ref> </blockquote>Using a large sample of ME/CFS patients from Newcastle, [[Norway]] and the [https://www.me-pedia.org/wiki/Solve_ME/CFS_Initiative#Biobank Solve ME/CFS Biobank], Jason et al. conducted an analysis of different case definitions and symptoms. The domain of post-exertional malaise was found to be most adequate at differentiating ME/CFS patients from controls. As the authors noted: <blockquote>Using the latent variables from the empiric criteria, only one factor (PEM) was needed to reach a sensitivity of 90.8%, specificity of 92.5% and accuracy of 91.6%, and this was the only data mining where all percentages were over 90%. […] the fact that PEM came out in all analyses supports the importance of this domain in the case definition.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Reed|first5=Jordan|last6=Furst|first6=Jacob|last7=Newton|first7=Julia L.|last8=Strand|first8=Elin Bolle|last9=Vernon|first9=Suzanne D.|date=2014-04-01|title=Comparing and Contrasting Consensus versus Empirical Domains|url=https://www.ncbi.nlm.nih.gov/pubmed/26977374|journal=Fatigue: Biomedicine, Health & Behavior|volume=3|issue=2|pages=63–74|doi=10.1080/21641846.2015.1017344|issn=2164-1846|pmc=4788637|pmid=26977374}}</ref> </blockquote>A 2014 examination, using 236 patients and 86 controls, showed that three symptoms accurately classified 95.4% of participants as patient or control: fatigue/extreme tiredness, inability to focus on multiple things simultaneously, and experiencing a dead/heavy feeling after starting to exercise.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Sunnquist|first2=Madison|last3=Brown|first3=Abigail|last4=Evans|first4=Meredyth|last5=Vernon|first5=Suzanne D.|last6=Furst|first6=Jacob|last7=Simonis|first7=Valerie|date=2014-01-01|title=Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/24511456|journal=Fatigue: Biomedicine, Health & Behavior|volume=2|issue=1|pages=40–56|doi=10.1080/21641846.2013.862993|issn=2164-1846|pmc=3912876|pmid=24511456}}</ref> Another data mining study by the same research group, suggested the selection of four symptoms: next to extreme tiredness, unrefreshing sleep and [[Word-finding problems|difficulty finding the right word to say]] or [[Aphasia|expressing thoughts]], PEM was once again represented with the item “physically drained/sick after mild activity.”<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=Kot|first2=Bobby|last3=Sunnquist|first3=Madison|last4=Brown|first4=Abigail|last5=Evans|first5=Meredyth|last6=Jantke|first6=Rachel|last7=Williams|first7=Yolonda|last8=Furst|first8=Jacob|last9=Vernon|first9=Suzanne D.|date=2015|title=Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: Toward An Empirical Case Definition|url=https://www.ncbi.nlm.nih.gov/pubmed/26029488|journal=Health Psychology and Behavioral Medicine|volume=3|issue=1|pages=82–93|doi=10.1080/21642850.2015.1014489|issn=2164-2850|pmc=4443921|pmid=26029488}}</ref>

[[Michael Maes|Maes]] et al. divided ME/CFS patients into two groups: those with or without PEM lasting for more than 24 hours. Analysis showed this to be a meaningful division as the former group (45% of the sample) not only had higher symptom scores on concentration difficulties and a subjective experience of infection, but also higher markers of immune-activation such as [[Interleukin 1|IL-1]], [[TNFa]], [[lysozyme]] and [[neopterin]], than the CFS group without PEM. According to the authors their findings, "underscore the relevance of post-exertional malaise to identify a subgroup of CFS patients that should be diagnosed as ME".<ref>{{Cite journal|last=Maes|first=Michael|last2=Twisk|first2=Frank N. M.|last3=Johnson|first3=Cort|date=2012-12-30|title=Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data|url=https://www.ncbi.nlm.nih.gov/pubmed/22521895|journal=Psychiatry Research|volume=200|issue=2-3|pages=754–760|doi=10.1016/j.psychres.2012.03.031|issn=1872-7123|pmid=22521895}}</ref>

=== Multiple sclerosis ===
According to a 2015 report by the National Academy of Medicine, the prevalence of PEM among ME/CFS patients varies from 69 to 100%, which is much higher than in other disease groups.<ref name=":0" /> In a 1996 study by Komaroff et al. 13 of 25 MS-patients (52%) reported PEM<ref name=":12">{{Cite journal|last=Komaroff|first=A. L.|last2=Fagioli|first2=L. R.|last3=Geiger|first3=A. M.|last4=Doolittle|first4=T. H.|last5=Lee|first5=J.|last6=Kornish|first6=R. J.|last7=Gleit|first7=M. A.|last8=Guerriero|first8=R. T.|date=Jan 1996|title=An examination of the working case definition of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8579088|journal=The American Journal of Medicine|volume=100|issue=1|pages=56–64|issn=0002-9343|pmid=8579088}}</ref>, a figure similar to what Jason et al. found with the DSQ PEM subscale in a cohort of 106 MS-patients.<ref>{{Cite journal|last=Jason|first=L. A.|last2=Ohanian|first2=D.|last3=Brown|first3=A.|last4=Sunnquist|first4=M.|last5=McManimen|first5=S.|last6=Klebek|first6=L.|last7=Fox|first7=P.|last8=Sorenson|first8=M.|date=2017|title=Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29430570|journal=Insights in Biomedicine|volume=2|issue=2|doi=10.21767/2572-5610.10027|issn=2572-5610|pmc=5800741|pmid=29430570}}</ref> Both studies used a broad definition of PEM which focused on fatigue after exercise. Preliminary research suggests that adding more specific questions, for example about the prolonged recovery and various type of triggers, PEM might be able to differentiate ME/CFS from [[multiple sclerosis]]. A 2018 study for example showed that ME/CFS patients reported to experience PEM more often through mental exertion and to recover more slowly from PEM compared to multiple sclerosis patients.<ref name=":7" />
=== Major Depressive disorder ===
In the 1996 study by Komaroff et al., only 19% of patients with major [[depression]] reported PEM.<ref name=":12" /> A similar figure was found by Hawk et al., who found PEM in 3 patients in their sample of 15 with major depressive disorder.<ref>{{Cite journal|last=Hawk|first=Caroline|last2=Jason|first2=Leonard A.|last3=Torres-Harding|first3=Susan|date=2006|title=Differential diagnosis of chronic fatigue syndrome and major depressive disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/17078775|journal=International Journal of Behavioral Medicine|volume=13|issue=3|pages=244–251|doi=10.1207/s15327558ijbm1303_8|issn=1070-5503|pmid=17078775}}</ref> In contrast all of the 15 studied ME/CFS patients reported PEM, making it the largest discriminant function for all investigated symptoms. White et al. studied patients with persistent symptoms of fatigue and poor concentration after glandular fever. According to the authors "the complaint of post-exertional physical fatigue may help to differentiate post-viral fatigue states from psychiatric disorders."<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmed/8588010|title=The validity and reliability of the fatigue syndrome that follows glandular fever. - PubMed - NCBI|last=White|first=PD|website=www.ncbi.nlm.nih.gov|language=en|access-date=2018-10-24}}</ref>

=== Gulf war illness ===
[[James Baraniuk|Baraniuk]] and Shivapurkar (2017) looked at [[MicroRNA]]<nowiki/>s (miRNA) in the [[cerebrospinal fluid]] of ME/CFS patients, healthy controls and patients with [[Gulf War Illness]] before and after an exercise challenge (a submaximal bicycle exercise). While there were no differences in miRNA between the groups at baseline, a distinct signature appeared after exercise. According to the authors, "exercise caused distinct patterns of [[miRNA]] changes in CFS and […] [[Gulf War Illness|GWI]] indicating significant pathophysiological differences between conditions."<ref>{{Cite journal|last=Baraniuk|first=James N.|last2=Shivapurkar|first2=Narayan|date=2017-11-10|title=Exercise – induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects|url=https://www.nature.com/articles/s41598-017-15383-9|journal=Scientific Reports|language=En|volume=7|issue=1|doi=10.1038/s41598-017-15383-9|issn=2045-2322}}</ref> A 2013 study under the guidance of [[Nancy Klimas]] compared the immune signature in 30 Gulf war patients, 22 ME/CFS patients and 30 controls, after an graded exercise test. Results indicated the importance of physical exercise for differentiating these different groups: <blockquote>"Common to both GWI and CFS illness signatures were the direct or indirect contributions of IL-10 and IL-23 expression though these occurred at very different times. While levels measured at rest supported an illness signature in GWI, their impact in CFS was only observable during and after exercise, again emphasizing the importance of a challenge and response timeline in distinguishing these illnesses."<ref>{{Cite journal|last=Smylie|first=Anne Liese|last2=Broderick|first2=Gordon|last3=Fernandes|first3=Henrique|last4=Razdan|first4=Shirin|last5=Barnes|first5=Zachary|last6=Collado|first6=Fanny|last7=Sol|first7=Connie|last8=Fletcher|first8=Mary Ann|last9=Klimas|first9=Nancy|date=2013-06-25|title=A comparison of sex-specific immune signatures in Gulf War illness and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23800166|journal=BMC immunology|volume=14|pages=29|doi=10.1186/1471-2172-14-29|issn=1471-2172|pmc=3698072|pmid=23800166}}</ref></blockquote>

== Objective findings after exertion: ==
In the 1980s Melvin A. Ramsay stressed the use of assessing ME-patients after exertion. Regarding muscle weakness – what he regarded as the hallmark symptom of the disease –he noted: <blockquote>"If muscle power is found to be satisfactory, a re-examination should be made after exercise; a walk of half a mile is sufficient, as very few ME case can manage more. […] It is most important to stress the fact that cases of ME of mild or even moderate severity may have normal muscle power in a remission. In such cases, test for muscle power should be repeated after exercise."<ref name=":10" /> </blockquote>Though the definition of PEM has been expended far beyond muscle weakness, modern day research has confirmed the utility of testing ME/CFS after exertion. Many markers that are normal in resting state in ME/CFS patients turn out to be abnormal after a physical or cognitive stressor.<ref name=":0" />

=== Gene expression ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''72. Gene-expression and exercise / Gen-expressie en inspanning – dr. Lucinda Bateman'' (2015) By Dr. Lucinda Bateman/Wetenschap voor Patienten - ME/cvs Vereniging">https://https://www.youtube.com/watch?v=F1PP21TmUPs</embedvideo>

One example is gene expression. In a 2009 study Light et al. showed that after a moderate exercise test, the [[Leucocyte|leukocytes]] of ME/CFS patients showed an increase in expression of [[Adrenergic receptor|adrenergic]], [[metabolite]] detecting and [[immune-related genes]] that was not seen in healthy controls. Before the exercise test there were no abnormalities in the expression of these genes of ME/CFS patients. The authors speculated this to be evidence for sensitization of fatigue pathways in ME/CFS.<ref name=":20" /> The research team was able to confirm their results in a subsequent study using a larger sample of 48 patients.<ref name=":21" /> In a 2012 comparison MS patients also displayed an increase in post-exercise gene expression, but only ME/CFS patients showed increases in metabolite-detecting sensory receptors. According to the authors:<blockquote>"Because only the CFS patients showed increases in these metabolite-detecting receptors, the sensory receptor elements of this gene profile seem particularly specific to CFS and may reflect dysregulated pathways that directly contribute to increased effort sense during exercise and postexertional malaise."<ref>{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=VanHaitsma|first4=Timothy A.|last5=Light|first5=Kathleen C.|date=Jan 2012|title=Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/PSY.0b013e31824152ed|issn=0033-3174|pmc=3256093|pmid=22210239}}</ref></blockquote>Attempts at replication by other research teams have produced contradictory results. Meyer et al. were unable to confirm most of the post-exertional increases in gene expression, except for some in the adrenergic and glucocorticoid pathway.<ref>{{Cite journal|last=Meyer|first=Jacob|last2=R. Light|first2=Alan|last3=Shukla|first3=Sanjay|last4=Clevidence|first4=Derek|last5=Yale|first5=Steven|last6=Stegner|first6=Aaron|last7=Cook|first7=Dane|date=2013-10-01|title=Post-exertion malaise in chronic fatigue syndrome: Symptoms and gene expression|url=https://www.researchgate.net/publication/258165434_Post-exertion_malaise_in_chronic_fatigue_syndrome_Symptoms_and_gene_expression|journal=Fatigue: Biomedicine, Health & Behavior|volume=1|pages=190–209|doi=10.1080/21641846.2013.838444}}</ref> An [[Australia|Australian]] team under the guidance of [[Andrew Lloyd]] failed to find any significant exercise-induced changes in leucocyte gene expression, though the patient sample used (n = 10) was rather small and did not include any patients with severe [[functional disability]].<ref>{{Cite journal|last=Keech|first=Andrew|last2=Vollmer-Conna|first2=Ute|last3=Barry|first3=Benjamin K.|last4=Lloyd|first4=Andrew R.|date=2016|title=Gene Expression in Response to Exercise in Patients with Chronic Fatigue Syndrome: A Pilot Study|url=https://www.ncbi.nlm.nih.gov/pubmed/27713703|journal=Frontiers in Physiology|volume=7|pages=421|doi=10.3389/fphys.2016.00421|issn=1664-042X|pmc=5031769|pmid=27713703}}</ref>

=== Immune activation ===
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Inducing Post-Exertional Malaise in ME/CFS: A Look at the Research Evidence'' (2015) By Dr. Peter Rowe/Solve CFS">https://www.youtube.com/watch?v=ux93w7yGQ5g</embedvideo>
There are many studies demonstrating exercise-induced immunological abnormalities in ME/CFS patients.<ref>{{Cite journal|last=Nijs|first=Jo|last2=Nees|first2=Andrea|last3=Paul|first3=Lorna|last4=De Kooning|first4=Margot|last5=Ickmans|first5=Kelly|last6=Meeus|first6=Mira|last7=Van Oosterwijck|first7=Jessica|date=2014|title=Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review|url=https://www.ncbi.nlm.nih.gov/pubmed/24974723|journal=Exercise Immunology Review|volume=20|pages=94–116|issn=1077-5552|pmid=24974723}}</ref> Most findings however still have to be replicated by other research groups, using larger samples.

==== Oxidative stress ====
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Post-Exertion Malaise: The Intersection of Biology and Behavior'' (2015) By Dr. Dane B. Cook/Solve CFS">https://www.youtube.com/watch?v=vfmrPd4-rIE</embedvideo>
In 2005 the French team Yammes et al. found a lengthened and accentuated oxidative stress response in ME/CFS patients after a cycling exercise until exhaustion. At baseline markers of [[oxidative stress]] (thiobarbituric acidreactiv substances and ascorbic acid) did not differ significantly from healthy controls. After the exercise challenge however, the oxidative stress response occurred sooner and lasted longer in the ME/CFS group. This was associated with alterations in muscle excitability (lengthened [[M-wave]] duration) in ME/CFS-patients, which were not seen in controls.<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Mambrini|first3=O.|last4=Brégeon|first4=F.|last5=Delliaux|first5=S.|date=Mar 2005|title=Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/15715687|journal=Journal of Internal Medicine|volume=257|issue=3|pages=299–310|doi=10.1111/j.1365-2796.2005.01452.x|issn=0954-6820|pmid=15715687}}</ref> A small 2009 follow-up study confirmed these results and associated it with a post-exertional reduction of [[Heat shock protein|heat shock proteins]] HSP 27 and HSP 70 after exercise.<ref name=":25">{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|last4=Brégeon|first4=F.|date=Aug 2009|title=Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses|url=https://www.ncbi.nlm.nih.gov/pubmed/19457057|journal=Journal of Internal Medicine|volume=266|issue=2|pages=196–206|doi=10.1111/j.1365-2796.2009.02079.x|issn=1365-2796|pmid=19457057}}</ref> According to the authors, this is another indication of an impaired redox status in ME/CFS patients. A 2011 study confirmed most of these results in a larger cohort of 43 ME/CFS patients and 23 healthy controls. Again the data indicated an increased exercise-induced oxidative stress and a reduced Hsp response. Though it is know that deconditioning can increase oxidative stress, the authors argued this to be unlikely in their study population, for several reasons: <blockquote>“…deconditioning can be ruled out in our study because (i) it induces carbohydrate and lipid disorders that were not observed during routine biochemical check-up in these CFS patients, (ii) CFS patients did not have reduced maximal exercise performance or an accentuated lactic acid response and (iii) we found no correlation between the duration of CFS symptoms […] and the resting levels of oxidant–antioxidant status and HSPs.”<ref>{{Cite journal|last=Jammes|first=Y.|last2=Steinberg|first2=J. G.|last3=Delliaux|first3=S.|date=Jul 2012|title=Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins|url=https://www.ncbi.nlm.nih.gov/pubmed/22112145|journal=Journal of Internal Medicine|volume=272|issue=1|pages=74–84|doi=10.1111/j.1365-2796.2011.02488.x|issn=1365-2796|pmid=22112145}}</ref></blockquote>A [[Canada|Canadian]] research team had already reported a marked decline of HSP 27 during the post-exercise period of six ME/CFS patients in 2002.<ref>{{Cite journal|last=Thambirajah|first=Anita A.|last2=Sleigh|first2=Kenna|last3=Stiver|first3=H. Grant|last4=Chow|first4=Anthony W.|date=2008-12-01|title=Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/19032901|journal=Clinical and Investigative Medicine. Medecine Clinique Et Experimentale|volume=31|issue=6|pages=E319–327|issn=1488-2353|pmid=19032901}}</ref>

==== Complement C4a ====
In 2003 Sorensen et al. found that the [[Complement C4a|complement split product C4a]] was increased after exercise in the 20 ME/CFS patients, but not in controls. Furthermore a significant correlation was found between the increase in C4a and total symptom score.<ref>{{Cite journal|last=Sorensen|first=Bristol|last2=Streib|first2=Joanne E.|last3=Strand|first3=Matthew|last4=Make|first4=Barry|last5=Giclas|first5=Patricia C.|last6=Fleshner|first6=Monika|last7=Jones|first7=James F.|date=Aug 2003|title=Complement activation in a model of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12897748|journal=The Journal of Allergy and Clinical Immunology|volume=112|issue=2|pages=397–403|issn=0091-6749|pmid=12897748}}</ref> C4a is generated from the cleavage of the native complement protein C4 via the classical and lectin pathways. A follow up study, published in 2009, found that other elements of the lectin pathway also responded differently to an exercise challenge in ME/CFS patients compared to controls. Both C4 and mannan-binding lectin serine protease 2 (MASP2) were observed at higher levels in ME/CFS subjects 1 hour post-exercise.<ref>{{Cite journal|last=Sorensen|first=Bristol|author-link=|last2=Jones|first2=James F|author-link2=|last3=Vernon|first3=Suzanne D|author-link3=Suzanne Vernon|last4=Rajeevan|first4=Mangalathu S|author-link4=Mangalathu Rajeevan|author-link5=|date=Jan 2009|title=Transcriptional Control of Complement Activation in an Exercise Model of Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/|journal=Molecular Medicine|volume=15|issue=1-2|pages=34–42|doi=10.2119/molmed.2008.00098|pmc=2583111|pmid=19015737|quote=|via=}}</ref> The authors speculated this to contribute to the increased C4a split product 6 hours after the exercise challenge. In a 2010 study by Nijs et al. there was no increase in C4a after exercise in ME/CFS patients, though a significant correlation with post-exertional pain and fatigue was found.<ref>{{Cite journal|last=Nijs|first=J.|last2=Van Oosterwijck|first2=J.|last3=Meeus|first3=M.|last4=Lambrecht|first4=L.|last5=Metzger|first5=K.|last6=Frémont|first6=M.|last7=Paul|first7=L.|date=Apr 2010|title=Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1β|url=https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2009.02178.x|journal=Journal of Internal Medicine|volume=267|issue=4|pages=418–435|doi=10.1111/j.1365-2796.2009.02178.x|issn=0954-6820}}</ref>
==== Cytokines ====
The expression of cytokines after physical exercise has been researched in ME/CFS patients since the mid-1990s. Most of these studies have found negative results (see table below).

{| class="wikitable"
|Study
|Number of participants
|Exercise challenge
|Cytokines tested:
|Results:
|-
|[[Daniel Peterson|Peterson]] et al. (1994)<ref>{{Cite journal|last=Peterson|first=P. K.|last2=Sirr|first2=S. A.|last3=Grammith|first3=F. C.|last4=Schenck|first4=C. H.|last5=Pheley|first5=A. M.|last6=Hu|first6=S.|last7=Chao|first7=C. C.|date=Mar 1994|title=Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients|url=https://www.ncbi.nlm.nih.gov/pubmed/7496949|journal=Clinical and Diagnostic Laboratory Immunology|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref>
|10 ([[Holmes criteria]], all cases were post-infectious)
|Walking 1 mile per hour for 30 min
|[[Interleukin 1 beta|IL-1 β]], [[Interleukin 6|IL-6]], and [[TNF-alpha|TNF-α]], [[TGF beta|TGF-β]]
|Negative results
|-
|[[Andrew Lloyd|Lloyd]] et al. (1994)<ref>{{Cite journal|last=Lloyd|first=A.|last2=Gandevia|first2=S.|last3=Brockman|first3=A.|last4=Hales|first4=J.|last5=Wakefield|first5=D.|date=Jan 1994|title=Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/8148442|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=18 Suppl 1|pages=S142–146|issn=1058-4838|pmid=8148442}}</ref>
|12 ([[Australian criteria]])
|30 min hand grip exercises
|[[Interferon gamma|IFN-γ]], [[Interferon alpha |IFN-α]], [[Interleukin 1 beta|IL-1 β]], [[TNF-alpha|TNF-α]]
|Negative results
|-
|[[La Manca]] et al. (1999)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=Zhou|first3=X. D.|last4=Ottenweller|first4=J. E.|last5=Cook|first5=S.|last6=Peckerman|first6=A.|last7=Zhang|first7=Q.|last8=Denny|first8=T. N.|last9=Gause|first9=W. C.|date=Mar 1999|title=Immunological response in chronic fatigue syndrome following a graded exercise test to exhaustion|url=https://www.ncbi.nlm.nih.gov/pubmed/10226888|journal=Journal of Clinical Immunology|volume=19|issue=2|pages=135–142|issn=0271-9142|pmid=10226888}}</ref>
|20 ([[Fukuda criteria]]) "only patients with an illness duration of less than 6 years, who reported at least substantial intensity on symptom severity scales in the month prior to recruitment and who had no major psychiatric diagnosis in the 5 years prior to illness onset" were included
|An exhaustive treadmill exercise test
|[[Interleukin 2|IL-2]], [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]]<nowiki>, [[Interferon gamma|IFN-γ, </nowiki>[[TNF-alpha|TNF-α]]
|Negative results
|-
|Cannon et al. (1997)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Abad|first3=L. W.|last4=Vannier|first4=E.|last5=Mileno|first5=M. D.|last6=Fagioli|first6=L.|last7=Wolff|first7=S. M.|last8=Komaroff|first8=A. L.|date=May 1997|title=Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9168406|journal=Journal of Clinical Immunology|volume=17|issue=3|pages=253–261|issn=0271-9142|pmid=9168406}}</ref>
|8 (Holmes criteria) “their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]], [[interleukin-1 receptor antagonist]] (IL-1Ra), and [[soluble interleukin-1 receptor type II]] (IL-lsRII).
|Negative results
|-
|Gupta et al. (1998)<ref>{{Cite journal|last=Gupta|first=S.|last2=Aggarwal|first2=S.|last3=Starr|first3=A.|date=Feb 1999|title=Increased production of interleukin-6 by adherent and non-adherent mononuclear cells during 'natural fatigue' but not following 'experimental fatigue' in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9917531|journal=International Journal of Molecular Medicine|volume=3|issue=2|pages=209–213|issn=1107-3756|pmid=9917531}}</ref>
|5 (Holmes criteria)
|30 min hand grip exercises
|[[Interleukin 6|IL-6]]
|Negative results
|-
|Cannon et al. (1999)<ref>{{Cite journal|last=Cannon|first=J. G.|last2=Angel|first2=J. B.|last3=Ball|first3=R. W.|last4=Abad|first4=L. W.|last5=Fagioli|first5=L.|last6=Komaroff|first6=A. L.|date=Nov 1999|title=Acute phase responses and cytokine secretion in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10634215|journal=Journal of Clinical Immunology|volume=19|issue=6|pages=414–421|issn=0271-9142|pmid=10634215}}</ref>
|10 (Holmes criteria) their chronic illness began abruptly with a "flu-like" condition, (c) they had been ill for less than 3 years, and (d) they regularly experienced postexertional malaise”
|Stepping up and down on a platform for 15 min
|[[Interleukin 1 beta |IL-1 β]],[[IL-6]]
|Negative results
|-
|Yammes et al. (2009)<ref name=":25" />
|9 ([[Fukuda criteria]]) 6/9 had practiced sport at high levelxxxxxxxx, for more than 4 years before the symptoms occurred.
|Cycling test until maximal work load
|[[IL-6]], [[TNF-a]]
|Negative results
|-
|Robinson et al (2010)<ref>{{Cite journal|last=Robinson|first=M.|last2=Gray|first2=S. R.|last3=Watson|first3=M. S.|last4=Kennedy|first4=G.|last5=Hill|first5=A.|last6=Belch|first6=J. J. F.|last7=Nimmo|first7=M. A.|date=Apr 2010|title=Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/19422646|journal=Scandinavian Journal of Medicine & Science in Sports|volume=20|issue=2|pages=282–290|doi=10.1111/j.1600-0838.2009.00895.x|issn=1600-0838|pmid=19422646}}</ref>
|6 (Fukuda criteria)
|Incremental exercise test to exhaustion
|IL-6, [[sIL-6R]] and [[sgp130]]
|Negative results
|-
|[[Andrea White]] et al. (2010)<ref name=":26">{{Cite journal|last=White|first=Andrea T.|last2=Light|first2=Alan R.|last3=Hughen|first3=Ronald W.|last4=Bateman|first4=Lucinda|last5=Martins|first5=Thomas B.|last6=Hill|first6=Harry R.|last7=Light|first7=Kathleen C.|date=2010-07-01|title=Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20230500|journal=Psychophysiology|volume=47|issue=4|pages=615–624|doi=10.1111/j.1469-8986.2010.00978.x|issn=1540-5958|pmc=4378647|pmid=20230500}}</ref>
|19 (Fukuda criteria)
|The authors used "a moderate whole-body exercise task (working both arms and legs) for 25 min that was mild enough that all CFS patients were able to complete it successfully but did induce a flare of fatigue and pain symptoms that remained above pre-exercise levels for 48 h post-exercise in the majority of patients."
|[[Interleukin 1 beta |IL-1β]], [[Interleukin 2 |IL-2]], [[Interleukin 12|IL-12]], [[TNF-alpha |TNFα]], soluble [[CD40L]], [[Interferon gamma |IFN-γ]], [[Interleukin 4|IL-4]], [[Interleukin 10 |IL-10]], [[Interleukin 13|IL-13]], [[Interleukin 6|IL-6]] and [[Interleukin 8|IL-8]]

 
|Positive results for a subgroup (11/19) of patients with high PEM

 
|-
|Andrew Lloyd et al. (2018)<ref name=":27">{{Cite journal|last=Moneghetti|first=Kegan J.|last2=Skhiri|first2=Mehdi|last3=Contrepois|first3=Kévin|last4=Kobayashi|first4=Yukari|last5=Maecker|first5=Holden|last6=Davis|first6=Mark|last7=Snyder|first7=Michael|last8=Haddad|first8=Francois|last9=Montoya|first9=Jose G.|date=2018-02-09|title=Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nature.com/articles/s41598-018-20941-w|journal=Scientific Reports|language=En|volume=8|issue=1|doi=10.1038/s41598-018-20941-w|issn=2045-2322}}</ref>
|24 ([[Fukuda criteria]]) “we used the 1994 Centers for Disease Control (CDC)/Fukuda international diagnostic criteria for ME/CFS, but required participants to have post exertional malaise. Terefore, in labeling our patients this refers to the revised [[International Consensus Criteria|international consensus criteria]] from 2011”
|Symptom limited exercise on an ergocycle.
|Growth factors: [[FGF beta|FGF-β]], [[HGF]], [[NGF]], [[PDGF-BB]], [[TGF alpha|TGFα]], [[TGF-β1]], [[Vascular endothelial growth factor|VEGF]]

 

[[Colony stimulating factors]] and [[stem cell factors]]: [[G-CSF]], [[GM-CSF]], [[M-CSF]], [[SCF]]

 

Interleukins: [[Interleukin 1alpha|IL-1α]], [[Interleukin 1beta|IL-1β]], [[Interleukin 1RA|IL-1RA]], [[Interleukin 2|IL-2]], [[IL-4]], [[IL-5]], [[IL-6]], [[Interleukin 7|IL-7]], [[Interleukin |IL-8]], [[Interleukin 10|IL-10]], [[Interleukin 12p40|IL12p40]], [[Interleukin 12p70|IL12p70]], [[Interleukin 13|IL-13]], [[Interleukin 15|IL-15]], [[Interleukin 17|IL-17]], [[Interleukin 17f|IL-17F]], [[Interleukin 18|IL-18]] and [[LIF]]

 

[[Chemokine|Chemokines]]: [[CCL2]] ([[MCP-1]]), [[CCL3]] ([[MIP-1α]]), [[CCL4]] ([[MIP-1β]]), [[CCL5]] ([[RANTES]]) [[CCL7]] ([[MCP-3]]), [[CXCL1]] ([[Gro alpha|Gro-α]]), [[CXCL5]] ([[ENA78]]), [[CXCL9]] ([[MIG]]), [[CXCL10]] ([[IP-10]]), [[CCL11]] ([[Eotaxin]])

 

[[Interferon|Interferons]]: [[Interferon alpha |INF-α]], [[Interferon beta |INF-β]], [[Interferon gamma|INF-γ]]

 

[[Adhesion Molecule|Adhesion Molecules]] : [[ICAM-1]], [[VCAM-1]]

 

Other factors: [[CD40L]], [[FASL]], [[Leptin]], [[PAI-1]], [[Resistin]], [[TNF-α]], [[TNF-β]], [[TRAIL]]
|Positive results: ME/CFS had a distinct [[cytokine profile]] post-exercise.
|}
Moneghetti et al. took a different approach and looked at the cytokine profiling after exercise, as this may differentiate patients with ME/CFS from sedentary controls. Of the 51 [[cytokine]]s and growth factors tested, 10 significantly changed after exercise in both groups, a further 7 only changed in controls and five only changed in ME/CFS (namely, [[CXCL10]], [[IL-8]], [[CCL4]], [[TNF-β]] and [[ICAM-1]]). This suggests a distinct [[cytokine inflammatory signature]] in ME/CFS.<ref name=":27" /> White et al. (2010) differentiated their 19 ME/CFS patients with a high or low post-exertional malaise (called symptom flare SF, in the study). While the cytokine expression after exercise of patients with low PEM was similar to those of healthy controls, patients with high PEM showed opposite results. As the authors noted:<blockquote>"In sum, low SF patients and controls showed a pattern of post-exercise decreases in both pro and anti-inflammatory cytokines (with the exception of increases in IL-8), whereas the high SF patients showed a pattern of increases in both cytokine types at 8 h and no decreases at any time."<ref name=":26" /></blockquote>

=== Autonomic response ===
Several research teams have noted post-exertional abnormalities in the [[Autonomic nervous system|autonomic]] function of ME/CFS patients, though the exact meaning of these results is not yet clear.

A Canadian team under the guidance of [[Terrence Montague]] noted that during a maximal exercise test, ME/CFS patients have a lower maximal heart rate than controls. The authors noted that: <blockquote>“...patients with chronic fatigue syndrome have normal resting cardiac function but a markedly abbreviated exercise capacity characterized by slow acceleration of heart rate and fatigue of exercising muscles long before peak heart rate is achieved.”<ref>{{Cite journal|last=Montague|first=T.J.|last2=Marrie|first2=T.J.|last3=Klassen|first3=G.A.|last4=Bewick|first4=D.J.|last5=Horacek|first5=B.M.|date=Apr 1989|title=Cardiac function at rest and with exercise in the chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/2924607|journal=Chest|volume=95|issue=4|pages=779–784|issn=0012-3692|pmid=2924607}}</ref> </blockquote>A significantly lower peak heart rate has been repeatedly observed in CPET-studies with ME/CFS patients.<ref>{{Cite journal|last=Gibson|first=H|last2=Carroll|first2=N|last3=Clague|first3=J E|last4=Edwards|first4=R H|date=Sep 1993|title=Exercise performance and fatiguability in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC489735/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=56|issue=9|pages=993–998|issn=0022-3050|pmid=8410041}}</ref><ref>{{Cite journal|last=Sisto|first=Sue Ann|last2=LaManca|first2=John|last3=Cordero|first3=Douglas L.|last4=Bergen|first4=Michael T.|last5=Ellis|first5=Steven P.|last6=Drastal|first6=Susan|last7=Boda|first7=Wanda L.|last8=Tapp|first8=Walter N.|last9=Natelson|first9=Benjamin H.|date=Jun 1996|title=Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome|url=https://www.amjmed.com/article/S0002-9343(96)00041-1/pdf|journal=The American Journal of Medicine|language=English|volume=100|issue=6|pages=634–640|doi=10.1016/S0002-9343(96)00041-1|issn=0002-9343}}</ref><ref>{{Cite journal|last=Rowbottom|first=David|last2=Keast|first2=David|last3=Pervan|first3=Zhukov|last4=Morton|first4=Alan|date=Jan 1998|title=The Physiological Response to Exercise in Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v04n02_04|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=4|issue=2|pages=33–49|doi=10.1300/j092v04n02_04|issn=1057-3321}}</ref> In one of the largest of these into exercise performance, the authors noted the same phenomenon as Montague et al. <blockquote>“The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects.”<ref>{{Cite journal|last=De Becker|first=P.|last2=Roeykens|first2=J.|last3=Reynders|first3=M.|last4=McGregor|first4=N.|last5=De Meirleir|first5=K.|date=2000-11-27|title=Exercise capacity in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11088089|journal=Archives of Internal Medicine|volume=160|issue=21|pages=3270–3277|issn=0003-9926|pmid=11088089}}</ref></blockquote>The Belgium team Van Oosterwijck et al. reported an impaired heart rate recovery in 20 female ME/CFS patients following exercise.<ref>{{Cite journal|last=Van Oosterwijck|first=J.|last2=Marusic|first2=U.|last3=De Wandele|first3=I.|last4=Meeus|first4=M.|last5=Paul|first5=L.|last6=Lambrecht|first6=L.|last7=Moorkens|first7=G.|last8=Nijs|first8=J.|date=May 2015|title=Reduced parasympathetic reactivation during recovery from exercise in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)|url=https://www.physiotherapyjournal.com/article/S0031-9406(15)02014-3/fulltext|journal=Physiotherapy|language=English|volume=101|pages=e1091–e1092|doi=10.1016/j.physio.2015.03.1984|issn=0031-9406|issue=|quote=|author-link=Jessica Van Oosterwijck|author-link2=|author-link3=|author-link4=|author-link5=|via=|author-link8=Jo Nijs}}</ref> In other disease groups this is associated with risk for cardiac events and sudden death. Cordero et al. did not find a significant difference in mean heart rate between 11 ME/CFS patients and six healthy controls after walking on a treadmill, but they did find patients to have significantly less ‘vagal power’, a measure for respiratory-related parasympathetic contributions to heart rate.<ref>{{Cite journal|last=Cordero|first=D. L.|last2=Sisto|first2=S. A.|last3=Tapp|first3=W. N.|last4=LaManca|first4=J. J.|last5=Pareja|first5=J. G.|last6=Natelson|first6=B. H.|date=Dec 1996|title=Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8985621|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=6|issue=6|pages=329–333|issn=0959-9851|pmid=8985621}}</ref> Soetekouw et al. noted that during a handgrip exercise, the hemodynamics response was lower in the ME/CFS group than in the control group, although this could be attributed to the lower level of muscle exertion in the ME/CFS group.<ref>{{Cite journal|last=Soetekouw|first=P. M.|last2=Lenders|first2=J. W.|last3=Bleijenberg|first3=G.|last4=Thien|first4=T.|last5=van der Meer|first5=J. W.|date=Dec 1999|title=Autonomic function in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10638807|journal=Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society|volume=9|issue=6|pages=334–340|issn=0959-9851|pmid=10638807}}</ref> LaManca et al. studied 19 ME/CFS (Holmes criteria) and found that they had a diminished heart rate and blood pressure in response to a cognitive test compared to healthy controls, though exercise did not magnify this effect.<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Peckerman|first2=A.|last3=Sisto|first3=S. A.|last4=DeLuca|first4=J.|last5=Cook|first5=S.|last6=Natelson|first6=B. H.|date=Sep 2001|title=Cardiovascular responses of women with chronic fatigue syndrome to stressful cognitive testing before and after strenuous exercise|url=https://www.ncbi.nlm.nih.gov/pubmed/11573024|journal=Psychosomatic Medicine|volume=63|issue=5|pages=756–764|issn=0033-3174|pmid=11573024}}</ref> Similar results were found by a Norwegian research team. They studied 13 adolescents with ME/CFS and 53 age-matched controls after a mental stress test (arithmetic questions). Though heart rate was significantly higher in patients at baseline, there were no meaningful differences during the arithmetic challenge.<ref>{{Cite journal|last=Egge|first=Caroline|last2=Wyller|first2=Vegard Bruun|date=2010-12-14|title=No differences in cardiovascular autonomic responses to mental stress in chronic fatigue syndrome adolescents as compared to healthy controls|url=https://www.ncbi.nlm.nih.gov/pubmed/21156045|journal=BioPsychoSocial Medicine|volume=4|pages=22|doi=10.1186/1751-0759-4-22|issn=1751-0759|pmc=3012010|pmid=21156045}}</ref> Finally, Ocon et al. (2012) studied 16 patients with both the diagnosis of ME/CFS and POTS after increased orthostatic stress and a cognitive challenge. An impairment of the neurocognitive abilities was noted, that was not seen in healthy controls.<ref>{{Cite journal|last=Ocon|first=Anthony J.|last2=Messer|first2=Zachary R.|last3=Medow|first3=Marvin S.|last4=Stewart|first4=Julian M.|date=Mar 2012|title=Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/21919887|journal=Clinical Science (London, England: 1979)|volume=122|issue=5|pages=227–238|doi=10.1042/CS20110241|issn=1470-8736|pmc=3368269|pmid=21919887}}</ref>

=== Sleep ===
A first study into the effects of exercise on sleep in ME/CFS found a beneficial effect: approximately half the patients slept better after exercise.<ref>{{Cite journal|last=Togo|first=Fumiharu|last2=Natelson|first2=Benjamin H.|last3=Cherniack|first3=Neil S.|last4=Klapholz|first4=Marc|last5=Rapoport|first5=David M.|last6=Cook|first6=Dane B.|date=Jan 2010|title=Sleep is not disrupted by exercise in patients with chronic fatigue syndromes|url=https://www.ncbi.nlm.nih.gov/pubmed/20010134|journal=Medicine and Science in Sports and Exercise|volume=42|issue=1|pages=16–22|doi=10.1249/MSS.0b013e3181b11bc7|issn=1530-0315|pmc=2796587|pmid=20010134}}</ref> A follow-up study by the same research team (under the guidance of Benjamin Natelson) found more post-exercise improvement (transitions to deeper [[sleep stages]]) of sleep in ME/CFS patients than in controls. The patients, however, reported more fatigue in the morning after exercise while healthy controls showed significant improvement in sleepiness and fatigue. The authors speculated this to be due to a disruption of the [[REM]] sleep: ME/CFS showed, both at baseline and post-exercise, an increased rate of transition from REM to wake compared to controls and this correlated with symptoms of fatigue, pain and sleepiness.<ref>{{Cite journal|last=Kishi|first=Akifumi|last2=Togo|first2=Fumiharu|last3=Cook|first3=Dane B|last4=Klapholz|first4=Marc|last5=Yamamoto|first5=Yoshiharu|last6=Rapoport|first6=David M|last7=Natelson|first7=Benjamin H|date=Nov 2013|title=The effects of exercise on dynamic sleep morphology in healthy controls and patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871467/|journal=Physiological Reports|volume=1|issue=6|doi=10.1002/phy2.152|issn=2051-817X|pmc=3871467|pmid=24400154}}</ref> An Australian study followed up on 35 ME/CFS patients after performing a physical (stationary cycling) or cognitive (stimulated driving) challenge. While patients spent a greater proportion of wakeful hours lying down, they did not report significant changes in sleep quality or sleep duration. The authors did however note that the expected increase in [[heart rate variability]] (HRV) between wake and sleep, was significantly reduced in ME/CFS patients after completing the challenges. These changes in HRV have been associated with the falling asleep, and might be related to the unfreshed sleep of ME/CFS patients.<ref>{{Cite journal|last=Cvejic|first=Erin|last2=Sandler|first2=Carolina X.|last3=Keech|first3=Andrew|last4=Barry|first4=Benjamin K.|last5=Lloyd|first5=Andrew R.|last6=Vollmer-Conna|first6=Uté|date=Dec 2017|title=Autonomic nervous system function, activity patterns, and sleep after physical or cognitive challenge in people with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/29167053|journal=Journal of Psychosomatic Research|volume=103|pages=91–94|doi=10.1016/j.jpsychores.2017.10.010|issn=1879-1360|pmid=29167053}}</ref> Finally, Ohashi et al. recorded physical activity for 6-days in 10 patients with ME/CFS and 6 controls before and after performing a maximal treadmill test. Their results indicate an increase in [[circadian]] rest-activity in ME/CFS patients after exercise as the activity pattern of patients shifted toward later hours in the day.<ref>{{Cite journal|last=Ohashi|first=Kyoko|last2=Yamamoto|first2=Yoshiharu|last3=Natelson|first3=Benjamin H.|date=Sep 2002|title=Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12213500|journal=Physiology & Behavior|volume=77|issue=1|pages=39–44|issn=0031-9384|pmid=12213500}}</ref>
=== Cognitive performance ===
While some studies have found a decreased cognitive performance after exercise in ME/CFS, others have not (see table below).<ref name=":0" /> This difference may be due to heterogeneity of the patient sample and methods used.

{| class="wikitable"
|Study
|Number of ME/CFS subjects
|Neurocognitive tests
|Results
|-
|[[Marshall]] et al. (1997)<ref>{{Cite journal|last=Marshall|first=P. S.|last2=Forstot|first2=M.|last3=Callies|first3=A.|last4=Peterson|first4=P. K.|last5=Schenck|first5=C. H.|date=Jan 1997|title=Cognitive slowing and working memory difficulties in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9021867|journal=Psychosomatic Medicine|volume=59|issue=1|pages=58–66|issn=0033-3174|pmid=9021867}}</ref>
|8
|Buschke Selective Reminding Test, Continuous-Performance Test-Identical Pairs Version (CPTIP), Paced Auditory Serial Addition Task (PASAT), Stroop Color Word Test, Reaction-Time Tests, Salthouse Reading Span Task (SRST), Verbal Scholastic Aptitude Test (SAT).
|Negative
|-
|[[Blackwood]] et al. (1998)<ref>{{Cite journal|last=Blackwood|first=S.|last2=MacHale|first2=S.|last3=Power|first3=M.|last4=Goodwin|first4=G.|last5=Lawrie|first5=S.|date=Oct 1998|title=Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170292/|journal=Journal of Neurology, Neurosurgery, and Psychiatry|volume=65|issue=4|pages=541–546|issn=0022-3050|pmc=2170292|pmid=9771781}}</ref>
|10
|"The following aspects of cognitive function were examined (in order): working memory/auditory attention (digit span, from WAIS-R); psychomotor speed (digit symbol, also from WAIS-R); word fluency (FAS test, using the letters F and S only); and selective attention and sustained attention (telephone search and lottery tasks respectively, both from the test of everyday attention)”
|Positive
|-
|[[La Manca]] et al. (1998)<ref>{{Cite journal|last=LaManca|first=J. J.|last2=Sisto|first2=S. A.|last3=DeLuca|first3=J.|last4=Johnson|first4=S. K.|last5=Lange|first5=G.|last6=Pareja|first6=J.|last7=Cook|first7=S.|last8=Natelson|first8=B. H.|date=1998-09-28|title=Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/9790484|journal=The American Journal of Medicine|volume=105|issue=3A|pages=59S–65S|issn=0002-9343|pmid=9790484}}</ref>
|19
|The Stroop Color and Word Test, the Symbol Digit Modalities Test (SDMT), an oral version of the Trail Making Test (TMT) and the Serial 13s Test (STT)
|Positive
|-
|[[Claypoole]] et al. (2001)<ref>{{Cite journal|last=Claypoole|first=Keith|last2=Mahurin|first2=Roderick|last3=Fischer|first3=Mary E.|last4=Goldberg|first4=Jack|last5=Schmaling|first5=Karen B.|last6=Schoene|first6=Robert B.|last7=Ashton|first7=Suzanne|last8=Buchwald|first8=Dedra|date=Mar 2001|title=Cognitive Compromise Following Exercise in Monozygotic Twins Discordant for Chronic Fatigue Syndrome: Fact or Artifact?|url=http://dx.doi.org/10.1207/s15324826an0801_5|journal=Applied Neuropsychology|volume=8|issue=1|pages=31–40|doi=10.1207/s15324826an0801_5|issn=0908-4282}}</ref>
|21
|The Wechsler Adult Intelligence Scale–Revised, Digit Span Forward and Backward subtests, The Hopkins Verbal Learning Test, . The Digit Vigilance Test, the Lafayette Clinic Repeatable Neuropsychological Test Battery, Controlled Oral Word Association Test (COWAT)
|Negative
|-
|[[Dane Cook|Cook]] et al. (2005)<ref>{{Cite journal|last=Cook|first=Dane B.|last2=Nagelkirk|first2=Paul R.|last3=Peckerman|first3=Arnold|last4=Poluri|first4=Ashok|last5=Mores|first5=John|last6=Natelson|first6=Benjamin H.|date=Sep 2005|title=Exercise and cognitive performance in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/16177595|journal=Medicine and Science in Sports and Exercise|volume=37|issue=9|pages=1460–1467|issn=0195-9131|pmid=16177595}}</ref>
|20 ME/CFS only and 19 ME/CFS with comorbid fibromyalgia
|Participants completed cognitive testing using the automated neuropsychological assessment matrices (ANAM)
|Negative
|-
|[[Yoshiuchi]] et al. (2007)<ref>{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref>
|9
|A one-back memory task
|Negative
|-
|Cook et al. (2017)<ref>{{Cite journal|date=2017-05-01|title=Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.sciencedirect.com/science/article/pii/S088915911730051X|journal=Brain, Behavior, and Immunity|language=en|volume=62|pages=87–99|doi=10.1016/j.bbi.2017.02.009|issn=0889-1591}}</ref>
|15
|The Paced Auditory Serial Addition Task (PASAT) and a simple number recognition task
|Positive
|}

=== Pain modulation ===
Another post-exertional abnormality reported in ME/CFS is pain modulation. When healthy people exercise, their brain produces [[endorphins]] that increase pain thresholds. In some chronic pain patients like [[fibromyalgia]] and whiplash associated disorders, this endogenous pain inhibition response is defect and pain thresholds decrease shortly after exercise (i.e. they experience more pain while they should be feeling less). In 2004 Whiteside et al. first showed this defect in ME/CFS patients.<ref name=":22" /> These results were confirmed by two studies by the Belgium pain in motion team: while pain thresholds increased in normal controls they decreased in the ME/CFS patient group.<ref name=":23" /><ref name=":24" /> As a caveat, one must note that these studies only included ME/CFS patients that were suffering from chronic pain, while comorbid FM was not assessed. So it remains unclear if these results will also show up in ME/CFS patients that do not have comorbid FM.<ref>{{Cite journal|last=Yunus|first=Muhammad|date=2015-07-02|title=Editorial Review (Thematic Issue: An Update on Central Sensitivity Syndromes and the Issues of Nosology and Psychobiology)|url=http://dx.doi.org/10.2174/157339711102150702112236|journal=Current Rheumatology Reviews|language=en|volume=11|issue=2|pages=70–85|doi=10.2174/157339711102150702112236|issn=1573-3971}}</ref>

=== Other ===

==== The gut microbiome ====
Shukla et al. (2015) found post-exertional changes in the gut microbiome in ME/CFS patients that were not seen in healthy controls. Increased clearance of bacteria in the blood was also noted, which made the authors speculate that exercise induced a bacterial translocation in ME/CFS patients.<ref>{{Cite journal|last=Shukla|first=Sanjay K.|last2=Cook|first2=Dane|last3=Meyer|first3=Jacob|last4=Vernon|first4=Suzanne D.|last5=Le|first5=Thao|last6=Clevidence|first6=Derek|last7=Robertson|first7=Charles E.|last8=Schrodi|first8=Steven J.|last9=Yale|first9=Steven|date=2015-12-18|title=Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|url=http://dx.doi.org/10.1371/journal.pone.0145453|journal=PLOS ONE|volume=10|issue=12|pages=e0145453|doi=10.1371/journal.pone.0145453|issn=1932-6203}}</ref>

==== Catecholaminergic hyporeactivity ====
Strahler et al. found that ME/CFS patients showed an attenuated response (lower increases) of epinephrine to an exercise challenge, compared to heathy controls. This ‘catecholaminergic hyporeactivity’ was however subtle and short-lived.<ref>{{Cite journal|last=Strahler|first=Jana|last2=Fischer|first2=Susanne|last3=Nater|first3=Urs M.|last4=Ehlert|first4=Ulrike|last5=Gaab|first5=Jens|date=Sep 2013|title=Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23770415|journal=Biological Psychology|volume=94|issue=1|pages=160–166|doi=10.1016/j.biopsycho.2013.06.002|issn=1873-6246|pmid=23770415}}</ref>

==== Nitric oxide metabolites ====
A [[Spain|Spanish]] research team found much higher increases of nitric oxide metabolites (nitrates) after a maximal exercise test in 44 ME/CFS patients compared to 25 healthy controls while there were no differences between the groups at baseline.<ref>{{Cite journal|last=Suárez|first=Andrea|last2=Guillamó|first2=Elisabet|last3=Roig|first3=Teresa|last4=Blázquez|first4=Alicia|last5=Alegre|first5=José|last6=Bermúdez|first6=Jordi|last7=Ventura|first7=José Luis|last8=García-Quintana|first8=Ana María|last9=Comella|first9=Agustí|date=Jun 2010|title=Nitric Oxide Metabolite Production During Exercise in Chronic Fatigue Syndrome: A Case-Control Study|url=http://dx.doi.org/10.1089/jwh.2008.1255|journal=Journal of Women's Health|volume=19|issue=6|pages=1073–1077|doi=10.1089/jwh.2008.1255|issn=1540-9996}}</ref>

== Problems in defining PEM ==

=== Asking the right questions ===
[[Leonard Jason|Jason]] et al. (1999) reported that in a group of ME/CFS patients, the percentage endorsing PEM ranged from 40,6 to 93,8% depending on how the question assessed this symptom.<ref>{{Cite web|url=https://www.meassociation.org.uk/2012/04/to-pem-or-not-to-pem-that-is-the-question-for-case-definition-research-1st-website-27-april-2012/|title=To PEM or not to PEM? That is the question for case definition {{!}} Research 1st website|date=27 April 2012|website=www.meassociation.org.uk|language=en-US|access-date=2018-10-10}}</ref> The report of the National Academy of Medicine noted that “the prevalence of PEM among ME/CFS patients as diagnosed by existing criteria varies from 69 to 100 percent.”<ref name=":0" />

Some patients try to reduce post-exertional relapses by pacing themselves and reducing exertion that exceeds their energy limits. Questionnaires assessing PEM by frequency instead of propensity, might erroneously label these patients as not having PEM. In a 2015 study, Jason et al. measured ME/CFS patients’ responses to the PEM-criterion in the [[Keiji Fukida|Fukuda]] et al. (1994) definition: ‘Do you feel generally worse than usual or fatigued for 24 hours or more after you have exercised?’ Although the majority (75%) endorsed this item, a notable percentage (25%) did not. Yet when the question was framed differently, leaving out the 24 hours’ time period and substituting exercise with normal daily activity, these participants also agreed they experienced high levels of fatigue after normal daily activity.<ref name=":19" /> This clearly shows that patients who have already modified their activities to avoid or reduce PEM may potentially show up as false negatives.

Another issue is the definition of PEM in the Fukuda-criteria. While the wording used here is vague, the time criterion is rather strict requiring PEM to last more than 24 hours. Some patients do not endorse this item because they only have post-exertional malaise for less than 24 hours.<ref>{{Cite journal|last=Jason|first=Leonard A.|last2=King|first2=Caroline P.|last3=Richman|first3=Judith A.|last4=Taylor|first4=Renee R.|last5=Torres|first5=Susan R.|last6=Song|first6=Sharon|date=Jan 1999|title=U.S. Case Definition of Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v05n03_02?journalCode=icfs20|journal=Journal of Chronic Fatigue Syndrome|language=en|volume=5|issue=3-4|pages=3–33|doi=10.1300/j092v05n03_02|issn=1057-3321}}</ref> A 2018 study concluded that setting the criterion at 24 hours would exclude almost 30% of ME/CFS patients. It advises that this definition might be useful in research settings but that in a clinical context, a 14-23 hour time period might be more appropriate.<ref>{{Cite journal|last=Cotler|first=Joseph|last2=Holtzman|first2=Carly|last3=Dudun|first3=Catherine|last4=Jason|first4=Leonard A.|date=2018-09-11|title=A Brief Questionnaire to Assess Post-Exertional Malaise|url=https://www.ncbi.nlm.nih.gov/pubmed/30208578|journal=Diagnostics (Basel, Switzerland)|volume=8|issue=3|doi=10.3390/diagnostics8030066|issn=2075-4418|pmid=30208578}}</ref>

These observations point to the need of a more precise definition of PEM and several attempts to this end have been made.
=== More than just fatigue ===
Few instruments have assessed PEM adequately. The [[CDC 2005 Symptom Inventory for CFS|CDC symptom inventory]] for example, only asks about fatigue after exertion, while PEM entails much more than that. An [[Australia|Australian]] group at the University of New South Wales tried to better define PEM, using 19 ME/CFS patients after exposure to different stressors.<ref>{{Cite journal|last=Keech|first=Andrew|last2=Sandler|first2=Carolina X.|last3=Vollmer-Conna|first3=Ute|last4=Cvejic|first4=Erin|last5=Lloyd|first5=Andrew R.|last6=Barry|first6=Benjamin K.|date=Dec 2015|title=Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26359713|journal=Journal of Psychosomatic Research|volume=79|issue=6|pages=537–549|doi=10.1016/j.jpsychores.2015.08.008|issn=1879-1360|pmid=26359713}}</ref> Participants indicated that the term fatigue did not adequately describe the sensation they experienced on a daily basis. A word frequency analysis of descriptors nominated by these patients indicated 5 themes:
# Exhausted or tired.
# Heaviness in the limbs or whole-body.
# Fogginess in the head.
# Weakness in the muscles.
# Drained of energy.
===The DePaul Symptom Questionnaire (DSQ) subscale ===
The instrument most commonly used to assess PEM is a subscale from the [[DePaul Symptom Questionnaire]] (DSQ). The DSQ is a 54-item questionnaire was developed in 2010 to operationalize the Canadian Consensus Criteria, providing concrete directives to assess ME/CFS-symptoms with their frequency and severity.<ref>{{Cite web|url=https://www.semanticscholar.org/paper/The-Development-of-a-Revised-Canadian-Myalgic-Case-Jason-Evans/b2a2564f55daa57721d24502df6bd6c161238ff0|title=The Development of a Revised Canadian Myalgic Encephalomyelitis Chronic Fatigue Syndrome Case Definition|last=Jason|first=Leonard A.|last2=Evans|first2=Meredyth Anne|date=2010|language=en|access-date=2018-10-10|last3=Porter|first3=Nicole|last4=Brown|first4=Molly|last5=Brown|first5=Abigail A.|last6=Hunnell|first6=Jessica|last7=Anderson|first7=Valerie C.|last8=Lerch|first8=Athena|last9=Meirleir|first9=Kenny de}}</ref> In a Norwegian comparison with physician assessments, The DSQ scored a sensitivity of 92% and a specificity of 75%.<ref>{{Cite journal|last=Strand|first=Elin B.|last2=Lillestøl|first2=Kristine|last3=Jason|first3=Leonard A.|last4=Tveito|first4=Kari|last5=Diep|first5=Lien My|last6=Valla|first6=Simen Strand|last7=Sunnquist|first7=Madison|last8=Helland|first8=Ingrid B.|last9=Herder|first9=Ingrid|date=2016-01-02|title=Comparing the DePaul Symptom Questionnaire with physician assessments: a preliminary study|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2015.1126026|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=4|issue=1|pages=52–62|doi=10.1080/21641846.2015.1126026|issn=2164-1846}}</ref> This indicated that the DSQ is a useful tool in detecting and screening symptoms, but that a follow-up medical examination is necessarily to confirm the diagnosis and identify possible exclusionary medical and psychiatric disorders.

The post-exertional malaise subscale on the DSQ particularly demonstrated excellent clinical utility as it was able to differentiate between ME/CFS patients and controls.<ref>{{Cite journal|last=Murdock|first=Kyle W.|last2=Wang|first2=Xin Shelley|last3=Shi|first3=Qiuling|last4=Cleeland|first4=Charles S.|last5=Fagundes|first5=Christopher P.|last6=Vernon|first6=Suzanne D.|date=Apr 2017|title=The utility of patient-reported outcome measures among patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/27600520|journal=Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation|volume=26|issue=4|pages=913–921|doi=10.1007/s11136-016-1406-3|issn=1573-2649|pmc=5336422|pmid=27600520}}</ref> In early 2018 the Common Data Elements working group on PEM formed by [[National Institute of Neurological Disorders and Stroke|NINDS]] and the CDC, recommended the use of 5 items from the DSQ to measure PEM.<ref name=":4">https://www.commondataelements.ninds.nih.gov/Doc/MECFS/PEM_Subgroup_Summary.pdf</ref>
# Dead, heavy feeling after starting to exercise.
# Next day soreness after non-strenuous, everyday activities.
# Mentally tired after the slightest effort.
# Minimum exercise makes physically tired.
# Physically drained or sick after mild activity.
To meet criteria for post-exertional malaise, one of these items need to be endorsed at sufficient frequency and severity (2 or greater on a scale of 0-4).

Although the DSQ has good test-retest reliability and is regarded as a useful tool in making the diagnosis of ME/CFS, its ability to capture PEM accurately has been questioned. Originally these five items formed one of the five subdomains of the ME/CFS Fatigue Types Questionnaire (MFTQ)<ref>{{Cite journal|last=Jason|first=Leonard|last2=Jessen|first2=Tricia|last3=Porter|first3=Nicole|last4=Boulton|first4=Aaron|last5=Gloria-Njoku|first5=Mary|date=2009-07-16|title=Examining Types of Fatigue Among Individuals with ME/CFS|url=http://dsq-sds.org/article/view/938|journal=Disability Studies Quarterly|language=en|volume=29|issue=3|doi=10.18061/dsq.v29i3.938|issn=2159-8371}}</ref><ref>{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> and critics argue that these items are focused too much on fatigue/tiredness to be an adequate measure of PEM. A document formulated by the Science for ME PEM working group to address these issues, explained:<blockquote>"The DSQ PEM items focus largely on feeling fatigue or tiredness, and, apart from one item, do not mention that post-exertional symptoms may be delayed. There is no mention of prolonged recovery or the loss of functional capacity."<ref name=":5" /></blockquote>The NINDS/CDC common data elements PEM subgroup also noted about the DSQ: <blockquote>"...the instrument does not assess the full range of symptoms that could be exacerbated by PEM and only one item addresses the sometimes delayed onset/ prolonged duration of PEM.<ref>https://www.commondataelements.ninds.nih.gov/Doc/MECFS/F2771_Guidance_for_Core_PEM_Assessment.pdf</ref> </blockquote>In an online poll to which 783 people responded, 68% answered that the DSQ PEM did not reflect their experience of post-exertional malaise<ref name=":5" />, though questions have been raised about the neutrality of the wording used.<ref name=":6">{{Cite journal|last=Jason|first=L. A.|last2=McManimen|first2=S. L.|last3=Sunnquist|first3=M.|last4=Holtzman|first4=C. S.|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1453265|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=6|issue=2|pages=92–105|doi=10.1080/21641846.2018.1453265|issn=2164-1846}}</ref> In response Jason et al. noted that the DSQ PEM items were developed and selected to screen for the presence of PEM, rather than to comprehensively measure all aspects and variations of PEM. A 2018 analysis, using a large patient sample (n = 704), showed that screening items from the DSQ PEM subscale, were able to identify 97% of patients, which was higher than any other item to describe PEM.<ref name=":6" />

Furthermore, the authors have recently revised the DSQ PEM subscale to include new items, some based on Ramsay’s writings.<ref name=":7" /> An extra 5 questions can be used after the initial screening with the DSQ PEM subscale, to better differentiate ME/CFS from other, comparable conditions:
# Do you experience a worsening of your fatigue/energy related illness after engaging in minimal physical effort?
# Do you experience a worsening of your fatigue/energy related illness after engaging in mental effort?
# If you feel worse after activities, how long does this last?
# If you were to become exhausted after actively participating in extracurricular activities, sports, or outings with friends, would you recover within an hour or two after the activity ended?
# If you do not exercise, is it because exercise makes your symptoms worse?
An analysis showed that these questions (the duration of PEM in particular) helped to differentiate ME/CFS patients from controls with [[Multiple sclerosis|MS]] or [[post-polio syndrome]].<ref name=":7" />

=== The DePaul Post-Exertional Malaise Questionnaire (DPEMQ) ===
The DPEMQ is a [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf questionnaire] based on input from hundreds of patients.<ref name=":29">{{Cite journal|last=Jason|first=Leonard A|last2=Holtzman|first2=Carly S|last3=Sunnquist|first3=Madison|last4=Cotler|first4=Joseph|date=2018-10-24|title=The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome|url=https://doi.org/10.1177/1359105318805819|journal=Journal of Health Psychology|language=en|pages=1359105318805819|doi=10.1177/1359105318805819|issn=1359-1053}}</ref><blockquote>Post-exertional malaise, or a variation of this term, is a key symptom of myalgic encephalomyelitis and chronic fatigue syndrome, as this symptom is mentioned in almost all myalgic encephalomyelitis and chronic fatigue syndrome case definitions. Until now there has not been a comprehensive questionnaire to assess post-exertional malaise. To rectify this situation, in this article we describe the development of a new questionnaire, called the DePaul Post-Exertional Malaise Questionnaire, which was based on input from hundreds of patients. Preliminary validation was provided by the findings of significant and predictable relationships between different domains of this post-exertional malaise questionnaire and physical functioning.<ref name=":29" /></blockquote>

=== PENE ===
Of all case definitions, the 2011 International Consensus Criteria (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> offered the most precise and elaborated definition of the post-exertional relapses that characterize ME. To differentiate it with post-exertional malaise, the term used in the Fukuda-criteria, the authors introduced a new name: Post-Exertional Neuroimmune Exhaustion (PENE). PENE is described as “a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions”<ref name=":2" /> and has the following characteristics:
# Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
# Postexertional symptom exacerbation: e.g. acute flu-like symptoms, pain and worsening of other symptoms.
# Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
# Recovery period is prolonged, usually taking 24 hours or longer. A relapse can last days, weeks or longer.
# Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.
The definition fails however to make clear how many of these characteristics are necessary to diagnose PENE.
=== Muscle weakness ===
A more prominent criticism of PENE came from a 2016 factor analysis of PEM, using a large sample of 704 participants. Results suggested that “PEM is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue.”<ref name=":8" /> The latter refers to the description of ME by Ramsay, where post-exertional muscle weakness was highlighted. This element of PEM was confirmed in a study by the [[Workwell Foundation]] where the symptoms of 25 ME/CFS patients and 23 age-matched controls were followed up. As the report noted: <blockquote>"The two groups also differed with respect to the experience of physical weakness or instability immediately after testing. This was reported by 16 patients (64%) as opposed to 5 controls (22%). Weakness persisted into the next day in 10 patients (40%) but in only 1 control (4%). However, distinct differences can be observed in the severity of the weakness between groups when analyzing their reports. The sole report of weakness from a control stated: '[I had] tired legs when going up stairs—fine overall.' In contrast, statements from CFS patients included: 'Unable to walk without assistance.' '[I experienced] falling from muscle weakness.'<ref name=":13" /></blockquote>A Norwegian in depth-report of ME/CFS-patients relationship to exercise also highlighted muscle weakness: <blockquote>"Some related how they would struggle to get home after exercise – one had to stop her car on her way from the fitness centre. Another was walking in the woods and suddenly felt it would be impossible to make his way back home. They described feeling that something completely wrong had happened to their bodies, without understanding what was going on. Thought processes did not work as usual, motor abilities were reduced, or the legs would not move them as they would usually expect. Some participants described a paralyzed feeling subsequent to activity, where a lot of energy would be needed to be able to move."<ref>{{Cite journal|last=Larun|first=Lillebeth|last2=Malterud|first2=Kirsti|date=May 2011|title=Finding the right balance of physical activity: a focus group study about experiences among patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20580520|journal=Patient Education and Counseling|volume=83|issue=2|pages=222–226|doi=10.1016/j.pec.2010.05.027|issn=1873-5134|pmid=20580520}}</ref></blockquote>While many descriptions of PEM like the DSQ subscale assess this element indirectly by asking patients about a dead heavy feeling after exercise or next day soreness, it is fully lacking in the ICC definition of PENE.<ref name=":8" />
=== Common data elements PEM working group ===
The NINDS/CDC Common Data Elements (CDE) PEM working group emphasized the need of a better definition of PEM. Its draft recommendations highlighted that <blockquote>"The definition of PEM is based primarily on clinician experience, patient reports and a few formal studies. There is a dearth of studies asking participants about their experiences of PEM in an openended manner, which is needed."<ref name=":4" /> </blockquote>A 2018 analysis showed that patients' preferences to describe PEM are generally not well-represented within present case definition criteria or descriptions.<ref>{{Cite journal|last=Jason|first=Leonard|last2=McManimen|first2=Stephanie|last3=Sunnquist|first3=Madison|date=2018-03-21|title=Patient perceptions of post exertional malaise|url=https://www.researchgate.net/publication/323916016_Patient_perceptions_of_post_exertional_malaise|journal=Fatigue: Biomedicine, Health & Behavior|doi=10.1080/21641846.2018.1453265}}</ref> Although the CDE working group acknowledged the need to device a better instrument to assess PEM, it currently promotes the use of the DSQ PEM subscale as a screening tool, after which a clinician’s assessment is advised to diagnose PEM. The CDE PEM working group also provided a description of PEM, based on the 2015 literature review by the National Academy of Medicine: <blockquote>"PEM is defined as an abnormal response to minimal amounts of physical or cognitive exertion that is characterized by:</blockquote>
# Exacerbation of some or all of an individual study participant's ME/CFS symptoms. Symptoms exacerbated can include physical fatigue, cognitive fatigue, problems thinking (e.g. slowed information processing speed, memory, concentration), [[unrefreshing sleep]], [[Myalgia|muscle pain]], [[Arthralgia|joint pain]], [[Headache|headaches]], weakness/instability, light-headedness, flu-like symptoms, sore throat, [[nausea]], and other symptoms. Study participants can experience new or non-typical symptoms as well as exacerbation of their more typical symptoms.
# Loss of stamina and/or functional capacity.
# An onset that can be immediate or delayed after the exertional stimulus by hours, days or even longer.
# A prolonged, unpredictable recovery period that may last days, weeks, or even months.
# Severity and duration of symptoms that is often out-of-proportion to the type, intensity, frequency, and/or duration of the exertion. For some study participants, even basic activities of daily living like toileting, bathing, dressing, communicating, and reading can trigger PEM."<ref name=":4" />

==Notable studies==
* 1999, Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome<ref>{{Cite journal|last=Paul|first=L.|last2=Wood|first2=L.|last3=Behan|first3=W. M.|last4=Maclaren|first4=W. M.|date=1999|title=Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/10209352|journal=European Journal of Neurology|volume=6|issue=1|pages=63–69|issn=1351-5101|pmid=10209352|via=}}</ref> [https://www.ncbi.nlm.nih.gov/pubmed/10209352 (Abstract)]
* 2010, Postexertional Malaise in Women with Chronic Fatigue Syndrome<ref name="VanNess2010" /> [https://www.liebertpub.com/doi/10.1089/jwh.2009.1507 (Abstract)]

[[File:2010 VanNess Post exertional worsening of symptoms chart.png|center|frame|Post-exertional worsening of symptoms<ref name="VanNess2010" />]]
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''Top 10 Things You Should Know About Post-Exertional Relapse'' (2012) By University of the Pacific/Solve CFS - 2010 study, ''PEM in Women w/ CFS'' is discussed in this video">https://www.youtube.com/watch?v=B20H1u1LjCE</embedvideo>

* 2013, Post-exertion malaise in chronic fatigue syndrome: symptoms and [[gene expression]]<ref name="MeyerJ2013" /> [http://www.tandfonline.com/doi/abs/10.1080/21641846.2013.838444 (Abstract)]
* 2015, Myalgic Encephalomyelitis: Symptoms and [[Biomarker]]s<ref name="JasonL2015bio" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/#!po=2.51799 (Full Text)]
*2015, Changes in Gut and Plasma [[Microbiome]] following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)<ref name="ShuklaS2015" /> [http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0145453 (Full Text)]
*2016, Deconstructing post-exertional malaise: An exploratory factor analysis<ref name="McManimen, 2016" /> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325824/ (Full Text)]

*2018, Comparing Post-Exertional Symptoms Following Serial Exercise Tests<ref>{{Cite journal|last=Mateo|first=Lariel J.|date=2018|title=Comparing Post-Exertional Symptoms Following Serial Exercise Tests|url=https://scholarlycommons.pacific.edu/purcc/2018/events/87/|journal=PURCC|language=en|volume=|pages=|via=Scholarly Commons}}</ref> [https://scholarlycommons.pacific.edu/purcc/2018/events/87/ (Abstract)]

* 2018, The development of an instrument to assess post-exertional malaise in patients with myalgic encephalomyelitis and chronic fatigue syndrome<ref name=":31" /><ref name=":30" /> [http://journals.sagepub.com/doi/abs/10.1177/1359105318805819?journalCode=hpqa& (Abstract)] [http://journals.sagepub.com/doi/suppl/10.1177/1359105318805819/suppl_file/Appendix.__The_Development_of_a_Comprehensive_Measure_of_Post-Exertional_Malaise.8.20.2018.pdf (Questionnaire)]

==Notable articles==
* Dec 30, 2015 [http://me-cfs.se/blogg/suggestion-to-replace-pem-by-par/ Suggestion to replace PEM (Post Exertional Malaise) with PAR (Post Activity Relapse)]<ref name="MEBlogg2015" />

*Nov 4, 2016 [http://www.medscape.com/viewarticle/871482#vp_1 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome]<ref>{{Cite web|url=http://www.medscape.com/viewarticle/871482#vp_1|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|last=Tucker|first=Miriam|date=|website=www.medscape.com|type=Login Required|archive-url=|archive-date=|dead-url=|access-date=2018-09-06}}</ref>

==Talks & interviews==
* 2013, [https://www.youtube.com/watch?v=zZ8aPYihkpQ CFS gene expression after exercise (part 1)]<ref>{{Cite web|url=https://www.youtube.com/watch?v=zZ8aPYihkpQ|title=CFS gene expression after exercise (part 1)|last=|first=|date=May 26, 2013|website=YouTube|publisher=Jw N|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

==See also==

*[[Exercise]]
*[[Exertion]]
*[[Flu-like symptoms]]
*[[Malaise]]
==Learn more==

*[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html International CFS/ME Awareness Day - What Health]<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-08-17}}</ref> (PEM Definition Included)
*[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf Post-Exertional Malaise in Chronic Fatigue Syndrome]<ref name="SpotilaJ2010" />
*[http://solvecfs.org/post-exertional-malaise-cause-and-effect/ Post-Exertional Malaise: Cause and Effect]<ref name="SpotilaJ20120523" />
*[https://www.verywellhealth.com/what-is-post-exertional-malaise-716023 What is Post-Exertional Malaise]<ref name="AboutHealthPEM" />
*[http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/ The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained?]<ref>{{Cite news|url=http://www.healthrising.org/blog/2016/07/04/exercise-intolerance-fibromyalgia-chronic-fatigue-pots-explained/|title=The Exercise Intolerance in POTS, ME/CFS and Fibromyalgia Explained? - Health Rising|last=Johnson|first=Cort|date=2016-07-04|work=Health Rising|access-date=2018-08-17|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== References ==
<references>
<ref name="AboutHealthPEM">{{Cite news|url=https://www.verywellhealth.com/what-is-post-exertional-malaise-716023|title=What is Post-Exertional Malaise? Learn About a Key ME/CFS Symptom|last=Dellwo|first=Adrienne|date=|work=Verywell Health|access-date=2018-08-17|archive-url=|archive-date=|dead-url=}}</ref>
<ref name="JasonL2015bio">{{Citation
| last1 = Jason | first1 = LA | authorlink1 = Leonard Jason
| last2 = Zinn | first2 = ML | authorlink2 = Marcie Zinn
| last3 = Zinn | first3 = MA | authorlink3 = Mark Zinn
| display-authors =
| title = Myalgic Encephalomyelitis: Symptoms and Biomarkers
| journal = Current Neuropharmacology | volume = 13(5) | page = 701-734
| date = September 2015
| doi = 10.2174/1570159X13666150928105725
| url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/#!po=2.51799
}}</ref>
<ref name="McManimen, 2016">{{Citation
| last1 = McManimen | first1 = SL | authorlink1 =
| last2 = Sunnquist | first2 = ML | authorlink2 = Madison Sunnquist
| last3 = Jason | first3 = LA | authorlink3 = Leonard Jason
| title = Deconstructing post-exertional malaise: An exploratory factor analysis
| journal = Journal of Health Psychology | volume = | issue = | page =
| date = 2016
| pmid = 27557649
| doi = 10.1177/1359105316664139
}}
</ref>
<ref name="MEBlogg2015">{{citation
| author = ME Blogg
| title = Suggestion to replace PEM by PAR
| date = 30 Dec 2015
| url = http://me-cfs.se/blogg/suggestion-to-replace-pem-by-par/
}}</ref>
<ref name="MeyerJ2013">{{citation
| last1 = Meyer | first1 = JD | authorlink1 = Jacob Meyer
| last2 = Light | first2 = AR | authorlink2 = Alan Light
| last3 = Shukla | first3 = SK | authorlink3 = Sanjay Shukla
| last4 = Clevidence | first4 = D | authorlink4 = Derek Clevidence
| last5 = Yale | first5 = S | authorlink5 = Steven Yale
| last6 = Stegner | first6 = AJ | authorlink6 = Aaron Stegner
| last7 = Cook | first7 = DB | authorlink7 = Dane Cook
| display-authors =
| title = Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 1 | issue = 4 | page = 190-209
| date = 2 Oct 2013
| doi = 10.1080/21641846.2013.838444
| url = http://www.tandfonline.com/doi/abs/10.1080/21641846.2013.838444
}}</ref>
<ref name="ShuklaS2015">{{Citation
| last1 = Shukla | first1 = SK | authorlink1 = Sanjay Shukla
| last2 = Cook | first2 = D | authorlink2 = Dane Cook
| last3 = Meyer | first3 = JD | authorlink3 = Jacob Meyer
| last4 = Vernon | first4 = SD | authorlink4 = Suzanne Vernon
| last5 = Lee | first5 = T | authorlink5 = Thao Lee
| last6 = Clevidence | first6 = D | authorlink6 = Derek Clevidence
| last7 = Robertson | first7 = CE | authorlink7 = Charles Robertson
| last8 = Schrodi | first8 = SJ | authorlink8 = Steven Schrodi
| last9 = Yale | first9 = S | authorlink9 = Steven Yale
| last10 = Frank | first10= DN | authorlink10= Daniel Frank
| display-authors = 3
| title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
| journal = Plos One | volume = 10(12) | page =
| date = 18 December 2015
| pmid =
| doi = 10.1371/journal.pone.0145453
| url = http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0145453
}}</ref>
<ref name="SpotilaJ2010">{{citation
| last1 = Spotila | first1 = JM | authorlink1 = Jennie Spotila
| title = Post-Exertional Malaise in Chronic Fatigue Syndrome
| journal = Solve ME/CFS
| date = 2010
| url = http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf
}}</ref>
<ref name="SpotilaJ20120523">{{citation
| last1 = Spotila | first1 = JM | authorlink1 = Jennie Spotila
| title = Post-Exertional Malaise: Cause and Effect
| journal = Solve ME/CFS
| date = 23 May 2012
| url = http://solvecfs.org/post-exertional-malaise-cause-and-effect/
}}</ref>
<ref name="VanNess2010">{{Citation
| last1 = VanNess | first1 = M | authorlink1 = Mark VanNess
| last2 = Stevens | first2 = S | authorlink2 = Staci Stevens
| last3 = Bateman | first3 = L | authorlink3 = Lucinda Bateman
| last4 = Stiles | first4 = TL | authorlink4 = TL Stiles
| last5 = Snell | first5 = CR | authorlink5 = Christopher Snell
| display-authors =
| title = Postexertional malaise in women with chronic fatigue syndrome
| journal = Journal of Women's Health | volume = | issue = | page =
| date = February 2010
| pmid = 20095909
| doi = 10.1089/jwh.2009.1507
}}
</ref>
</references>

[[Category:Signs and symptoms]]

Canadian Consensus Criteria

2019-04-19T13:08:07Z

MEandCFS:/* Definition */ post-exertional fatigue

The [[Canadian Consensus Criteria|Canadian consensus criteria]] (CCC) are a proposed clinical criteria for [[ME/CFS]], published in 2003, and frequently used as a case definition in research.<ref name="Carruthers, 2003" /> It is a stricter criteria than the [[Fukuda criteria]] and according to [[Leonard Jason]] represents a more severely impaired population.<ref>http://www.meaction.net/2015/12/10/norwegian-researchers-ask-what-exactly-is-m-e/</ref> Adults are diagnosed at six months and pediatric cases at three months.

==Definition==

{| class="wikitable"
|+'''Canadian Consensus Criteria''' for Myalgic Encephalomyelitis
| colspan="3" |A patient with [[ME/CFS]] will meet the criteria for fatigue, [[Post-exertional malaise]] and/or [[Chronic fatigue|fatigue]], [[sleep dysfunction]], and [[pain]]; have two or more [[Nervous system|neurological]]/[[Cognitive dysfunction|cognitive]] manifestations and one or more symptoms from two of the categories of (a) [[Autonomic nervous system|autonomic]], (b) [[neuroendocrine]], and (c) [[Immune system|immune]] manifestations; and adhere to item 7.
|-
|1
|'''[[Chronic fatigue|Fatigue]]'''
|The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental [[fatigue]] that substantially reduces activity level.
|-
|2
|'''[[Post-exertional malaise|Post-Exertional Malaise]] and/or Fatigue'''
|There is an inappropriate [[loss of physical and mental stamina]], rapid [[Muscle fatigability|muscular]] and [[cognitive fatigability]], [[Post-exertional malaise|post exertional malaise]] and/or post-exertional fatigue and/or post-exertional pain and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period – usually 24 hours or longer.
|-
|3
|[[Sleep dysfunction|'''Sleep Dysfunction''']]*
|There is [[unrefreshed sleep]] or sleep quantity or rhythm disturbances such as [[reversed or chaotic diurnal sleep rhythms]].
|-
|4
|[[Pain|'''Pain''']]*
|There is a significant degree of [[myalgia]]. Pain can be experienced in the [[Myalgia|muscles]], and/or [[Arthralgia|joints]], and is often widespread and migratory in nature. Often there are significant [[headache]]s of new type, pattern or severity.
|-
|5
|'''[[Nervous system|Neurological]]/[[Cognitive dysfunction|Cognitive]] Manifestations'''
|'''Two or more''' of the following difficulties should be present: [[confusion]], [[Attention deficit|impairment of concentration]]<nowiki/>and [[Memory problems|short-term memory consolidation]], [[disorientation]], difficulty with [[information processing]], categorizing and word retrieval ([[Word-finding problems]]), and perceptual and sensory disturbances – e.g. [[spatial instability and disorientation]]<nowiki/>and [[inability to focus vision]].

[[Ataxia]], [[muscle weakness]] <nowiki/>and [[fasciculations]] <nowiki/>are common. There may be [[overload]]1 phenomena: cognitive, sensory – e.g. [[photophobia]] and [[Hyperacusis|hypersensitivity to noise]] – and/or [[emotional overload]], which may lead to "crash"2 periods and/or [[anxiety]].
|-
|6
|'''At Least One Symptom From Two of the Following Categories'''
|(a) '''Autonomic Manifestations''': [[Orthostatic intolerance]] – [[Neurally mediated hypotension]] (NMH), [[Postural orthostatic tachycardia]] syndrome (POTS), [[delayed postural hypotension]]; [[light-headedness]]; [[extreme pallor]]; [[nausea]] and [[irritable bowel syndrome]]; [[urinary frequency]] and [[bladder dysfunction]]; [[palpitations]] with or without [[cardiac arrhythmia]]s; [[exertional dyspnea]].

(b) '''Neuroendocrine Manifestations''': loss of thermostatic stability – [[subnormal body temperature]] and [[marked diurnal fluctuation]], [[excessive sweating|sweating episodes]], recurrent feelings of [[low-grade fever|feverishness]] and [[cold extremities]]; [[temperature sensitivity|intolerance of extremes of heat and cold]]; marked [[weight change]] – [[Anorexia, eating disorders and ME/CFS|anorexia]] or [[abnormal appetite]]; [[loss of adaptability]] and [[worsening of symptoms with stress]].

(c) '''Immune Manifestations''': [[tender lymph nodes]], recurrent [[sore throat]], recurrent [[flu-like symptoms]], [[Malaise|general malaise]], new [[food sensitivities]], medications and/or [[chemical sensitivities]].
|-
|7
|'''The Illness Persists for at Least Six Months'''
|It usually has a distinct onset,** although it may be gradual. Preliminary diagnosis may be possible earlier. Three months is appropriate for [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|children]].
|}
To be included, the symptoms must have begun or have been significantly altered after the onset of this illness. It is unlikely that a patient will suffer from all symptoms in criteria 5 & 6. The disturbances tend to form symptom clusters that may fluctuate and change over time. [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|Children]] often have numerous prominent symptoms but their order of severity tends to vary from day to day.

<nowiki>*</nowiki> There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset.

<nowiki>**</nowiki> Some patients have been unhealthy for other reasons prior to the onset of ME/ CFS and lack detectable triggers at onset or have more gradual or insidious onset.

1 “Overload” refers to hypersensitivities to stimuli that have changed from pre-illness status.

2 "Crash" refers to a temporary period of immobilizing physical and /or cognitive fatigue.

==Authors==
[[Bruce Carruthers]], [[Anil Kumar Jain]], [[Kenny de Meirleir]], [[Daniel Peterson]], [[Nancy Klimas]], [[A Martin Lerner]], [[Alison Bested]], [[Pierre Flor-Henry]], [[Pradip Joshi]], [[A C Peter Powles]], [[Jeffrey Sherkey]], [[Marjorie van de Sande]]<ref>http://sacfs.asn.au/download/consensus_overview_me_cfs.pdf</ref>

==See also==
*[[Case Definition Comparison - Graph 1]]
*[[Definitions of ME and CFS]]

=== Generally accepted criteria for diagnosis ===
*Canadian consensus criteria (CCC).<ref name="Carruthers, 2003" /> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using these criteria. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria|International consensus criteria]] (ICC).<ref name=":1">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> These criteria will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease|Systemic exertion intolerance disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegria|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A. Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*[http://www.investinme.org/Documents/PDFdocuments/Canadian_ME_Overview_A4.pdf An Overview of the Canadian Consensus Document] (the above 7 criteria are listed on page 2 of this document).
*[http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf Canadian Consensus Report - ''Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols'']<ref name="Carruthers, 2003" />(full version of the Canadian consensus criteria).
*An Overview of the Canadian Consensus Document in French - [http://iacfsme.org/Portals/0/pdf/Abrege%20du%20C.c.%20sur%20EM-SFC.PDF Encéphalomyélite myalgique/syndrome de fatigue chronique: Définition clinique et lignes directrices à l’intention des médecins, Abrégé du Consensus canadien]
==References==
<references>
<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://www.meresearch.org.uk/wp-content/uploads/2012/11/2003-Carruthers-Canadian-Definition-JCFS.pdf
}}</ref>
</references>

[[Category:Definitions]]

List of symptoms in ME CFS

2019-04-19T13:04:01Z

MEandCFS:/* Systemic Exertion Intolerance Disease (SEID) symptom list */ post-exertional fatigue under CCC

{{Cleanup|date=January 2019|reason= International Consensus Criteria Pediatric symptoms missing}}
{{stub}}

{{mbox|text= Except for introduction information and SEID criteria symptoms, this page draws symptoms from subpages.}}

The '''list of symptoms in ME CFS''' can be extensive and most patients will not have every symptom possible

A minimum list of core symptoms of [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]; [[Cognitive dysfunction|cognitive impairment]]; and/or [[orthostatic intolerance]] (OI) can [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnose]] a person with [[Systemic Exertion Intolerance Disease]] (SEID), an [[ME/CFS]] definition. Other symptoms can be present but a diagnosis of the SEID criterion for ME/CFS requires less symptoms than the [[Canadian Consensus Criteria]] (CCC) or the [[International Consensus Criteria]] (ICC). The CCC is another ME/CFS definition which includes the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet its [[Canadian Consensus Criteria#Definition|diagnostic criteria]]. The ICC is for [[International Consensus Criteria#Criteria|diagnosing]] the [[Nervous system|neurological]] disease [[myalgic encephalomyelitis]] (ME) which was defined by the [[World Health Organization]] (WHO) in 1969.<ref name=":3">{{Cite book|url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y|title=International Classification of Diseases|last=World Health Organization|first=|publisher=WHO|year=1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic), (myalgic, benign) 323|editor-last2=|editor-link2=}}</ref>

It includes the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment.
== Systemic Exertion Intolerance Disease (SEID) symptom list ==
These are the minimum of core symptoms necessary to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with SEID]], an ME/CFS criteria. Patients can have more symptoms<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/7|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academy of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=141|language=en|chapter=5|quote=|editor-last2=|editor-link2=}}</ref> and they are outlined in the [[Institute of Medicine report]].

These core symptoms are also part of the [[Canadian Consensus Criteria|CCC]] and [[International Consensus Criteria|ICC]] criteria below. However, the CCC lists PEM as optional with Post-exertional fatigue. ICC refers to PEM as [[Post-exertional malaise|Postexertional neuroimmune exhaustion]] (PENE) and instead of CF the term "[[lack of stamina]]" is used. ME/CFS and ME patients will always have the core symptoms and the SEID diagnostic criteria can be used to diagnose these patients also. However, the SEID diagnostic criteria cannot speak to the number of symptoms and their severity all ME/CFS and ME patients experience. The IOM report authors who created the SEID diagnostic criteria did include some other symptoms in chapters 4 and 5.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/6|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academy of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=|language=en|chapter=4 and 5|quote=|editor-last2=|editor-link2=}}</ref>

=== Core symptoms ===
* [[chronic fatigue]] and

* [[post-exertional malaise]] (PEM) and

* [[unrefreshing sleep]]
and at least one of the following:
* [[Cognitive dysfunction|cognitive impairment]]
or
* [[orthostatic intolerance]] (OI)
<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

=== Pediatric ===
[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]] cases have the same symptoms.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/8|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=nap.edu|pages=181|language=en|chapter=6|quote=|editor-last2=|editor-link2=}}</ref> However, the CDC notes some differences: OI ([[dizziness]] and lightheadedness) is experienced more often making their other ME/CFS symptoms worse. [[Sleep dysfunction|Sleep problems]] may be harder to detect; they will experience [[insomnia]], daytime sleepiness, and intense and vidid dreaming. Children and adolescents do not usually have [[muscle]] and [[Arthralgia|joint pain]] but [[Headache|headaches]] and stomach pain are more common.<ref name=":5">{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/children-symptoms-diagnosis.html|title=Symptoms and Diagnosis of ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref> Dr. [[David Bell]] agrees the symptoms for children can be different noting abdominal pain is more common and in teens there can be facial flushing. Although children do not describe having PEM, a hallmark symptom used in diagnosing ME/CFS, they can experience a relapse from exertion, perhaps from just taking the school bus, having to spend prolonged periods in bed.<ref name=":6">{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref>

Children, particularly adolescents, will more likely have an acute illness like the [[Influenza|flu]] or [[mononucleosis]] as their onset.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/children-symptoms-diagnosis.html|title=Symptoms and Diagnosis of ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref>

==Canadian consensus criteria (CCC) symptom list ==

The [[Canadian Consensus Criteria]] (CCC), an ME/CFS criteria, includes a list of recognized signs and symptoms in the appendix. Only some of these symptoms within the categories below are needed to be diagnosed under the [[Canadian Consensus Criteria#Definition|Canadian Consensus Criteria diagnostic criteria]]. PEM is not required and post-exertional fatigue can be selected as an OR option. Pediatric cases have the same symptoms; please note the information for the "Pediatric" heading under "Systemic Exertion Intolerance Disease (SEID) symptom list" above.
=== Cognitive ===
{{:List of symptoms in ME CFS/Canadian/Cognitive}}<div style="clear: both"></div><hr />
=== Motor (movement) and balance ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Motor_and_balance}} <div style="clear: both"></div><hr />
=== Sleep disruption ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Sleep}} <div style="clear: both"></div><hr />
=== Visual and auditory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Visual_and_auditory}} <div style="clear: both"></div><hr />
=== Neuropsychological ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neuropsychological}} <div style="clear: both"></div><hr />
=== Immune system ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Immune_system}} <div style="clear: both"></div><hr />
=== Reproductive ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Reproductive}} <div style="clear: both"></div><hr/>
=== Respiratory (breathing)===
{{:List_of_symptoms_in_ME_CFS/Canadian/Respiratory}} <div style="clear: both"></div><hr />
=== Urinary ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Urinary}} <div style="clear: both"></div><hr />
=== Circulatory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Circulatory}} <div style="clear: both"></div><hr />
=== Digestive ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Digestive}} <div style="clear: both"></div><hr />
=== Neuroendocrine ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neuroendocrine}} <div style="clear: both"></div><hr />
=== Musculoskeletal ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Musculoskeletal}} <div style="clear: both"></div><hr />
=== Neurological (nervous system) ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Neurological}} <div style="clear: both"></div><hr />
===Sensory ===
{{:List_of_symptoms_in_ME_CFS/Canadian/Sensory}}<div style="clear: both"></div><ref name="canadianconsensus" /> 

==International consensus criteria (ICC) symptom list ==
The [[International Consensus Criteria]] (ICC) will diagnose [[myalgic encephalomyelitis]] (ME). See the [[International Consensus Criteria#Criteria|International Consensus Criteria diagnostic criteria]] for diagnostic guidance. Not every symptom listed is necessary to diagnose ME but having symptoms within categories is necessary. The ICC refers to "[[lack of stamina]]" instead of CF.

=== Post-exertional Neuroimmune Exhaustion (PENE) ===

''Previously known as [[Post-exertional malaise]].''
{{:List_of_symptoms_in_ME_CFS/ICC/PENE}} <div style="clear: both"></div><hr />

=== Neurological ===
'''Neurocognitive Impairments'''
{{:List of symptoms in ME CFS/ICC/Neurological/Neurocognitive}}
'''Pain'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Pain}}
'''Sleep disturbances'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Sleep}} <div style="clear: both"></div>
'''Neurosensory, Perceptual and Motor Disturbances'''
{{:List_of_symptoms_in_ME_CFS/ICC/Neurological/Neurosensory_and_perceptual}} <div style="clear: both"></div>
{{:List of symptoms in ME CFS/ICC/Neurological/Motor}} <div style="clear: both"><hr />

=== Immune, Gastro-intestinal and Genitourinary ===
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Immune}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Gastro}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/Urinary}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Immune_Gastro/MCS}} <div style="clear: both"><hr />

=== Energy Metabolism/Ion Transportation ===
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Cardiovascular}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Respiratory}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Metabolism}} <div style="clear: both"></div>
* {{:List_of_symptoms_in_ME_CFS/ICC/Energy_Ion/Extreme_Temperature}} <div style="clear: both">
<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref><hr />

===Children's symptoms===
* {{:List_of_symptoms_in_ME_CFS/ICC/Pediatric}} <div style="clear: both"></div>
<div style="clear: both"></div><ref name="ICC2011primer" /><hr />

==See also==

* [[Common symptoms in ME/CFS|Common symptoms]]
* [[Rare and uncommon symptoms]]
* [[Canadian Consensus Criteria]]

* [[International Consensus Criteria]]

* [[Institute of Medicine report]]

==Learn more==

* [http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf International Consensus Primer for medical practitioners]<ref name="ICC2011primer" />

* [http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx IOM report] - Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

* [http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf Canadian Consensus Criteria]

==References==
<references>
<ref name="ICC2011primer"><cite id="CITEREFCarruthersvan_de_SandeDe_MeirleirKlimas2012" class="citation">[[Bruce Carruthers|Carruthers, BM]]; [[Marjorie van de Sande|van de Sande, MI]]; [[Kenny de Meirleir|De Meirleir, KL]]; [[Nancy Klimas|Klimas, NG]]; [[Gordon Broderick|Broderick, G]]; [[Terry Mitchell|Mitchell, T]]; [[Donald Staines|Staines, D]]; [[A C Peter Powles|Powles, ACP]]; [[Nigel Speight|Speight, N]]; [[Rosamund Vallings|Vallings, R]]; [[Lucinda Bateman|Bateman, L]]; [[David Bell|Bell, DS]]; [[Nicoletta Carlo-Stella|Carlo-Stella, N]]; [[John Chia|Chia, J]]; [[Austin Darragh|Darragh, A]]; [[Anne Gerken|Gerken, A]]; [[Daehyun Jo|Jo, D]]; [[Donald Lewis|Lewis, DP]]; [[Alan Light|Light, AR]]; [[Kathleen Light|Light, KC]]; [[Sonya Marshall-Gradisnik|Marshall-Gradisnik, S]]; [[John McLaren-Howard|McLaren-Howard, J]]; [[Ismael Mena|Mena, I]]; [[Kunihisa Miwa|Miwa, K]]; [[Modra Murovska|Murovska, M]]; [[Staci Stevens|Stevens, SR]] (2012), [http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf ''Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners''] (PDF), [[International Standard Book Number|ISBN]] [[Special:BookSources/978-0-9739335-3-6|978-0-9739335-3-6]]</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Myalgic+encephalomyelitis%3A+Adult+%26+Paediatric%3A+International+Consensus+Primer+for+Medical+Practitioners&rft.date=2012&rft.isbn=978-0-9739335-3-6&rft.aulast=Carruthers&rft.aufirst=BM&rft.au=van+de+Sande%2C+MI&rft.au=De+Meirleir%2C+KL&rft.au=Klimas%2C+NG&rft.au=Broderick%2C+G&rft.au=Mitchell%2C+T&rft.au=Staines%2C+D&rft.au=Powles%2C+ACP&rft.au=Speight%2C+N&rft.au=Vallings%2C+R&rft.au=Bateman%2C+L&rft.au=Bell%2C+DS&rft.au=Carlo-Stella%2C+N&rft.au=Chia%2C+J&rft.au=Darragh%2C+A&rft.au=Gerken%2C+A&rft.au=Jo%2C+D&rft.au=Lewis%2C+DP&rft.au=Light%2C+AR&rft.au=Light%2C+KC&rft.au=Marshall-Gradisnik%2C+S&rft.au=McLaren-Howard%2C+J&rft.au=Mena%2C+I&rft.au=Miwa%2C+K&rft.au=Murovska%2C+M&rft.au=Stevens%2C+SR&rft_id=http%3A%2F%2Fwww.investinme.org%2FDocuments%2FGuidelines%2FMyalgic%2520Encephalomyelitis%2520International%2520Consensus%2520Primer%2520-2012-11-26.pdf&rfr_id=info%3Asid%2Fwww.me-pedia.org%3AList+of+symptoms+in+ME+CFS" class="Z3988"> </ref>
<ref name="canadianconsensus"><cite id="CITEREFCarruthersJainDe_MeirleirPeterson2003" class="citation">[[Bruce Carruthers|Carruthers, Bruce M.]]; [[Anil Kumar Jain|Jain, Anil Kumar]]; [[Kenny De Meirleir|De Meirleir, Kenny L.]]; [[Daniel Peterson|Peterson, Daniel L.]]; [[Nancy Klimas|Klimas, Nancy G.]]; [[Martin Lerner|Lerner, A. Martin]]; [[Alison Bested|Bested, Alison C.]]; [[Pierre Flor-Henry|Flor-Henry, Pierre]]; [[Pradip Joshi|Joshi, Pradip]]; [[A C Peter Powles|Powles, A C Peter]]; [[Jeffrey Sherkey|Sherkey, Jeffrey A.]]; [[Marjorie van de Sande|van de Sande, Marjorie I.]] (2003), [http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols"] (PDF), ''Journal of Chronic Fatigue Syndrome'', 11 (2): 7-115, [[Digital object identifier|doi]]:[//doi.org/10.1300%2FJ092v11n01_02 10.1300/J092v11n01_02]</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Journal+of+Chronic+Fatigue+Syndrome&rft.atitle=Myalgic+Encephalomyelitis%2FChronic+Fatigue+Syndrome%3A+Clinical+Working+Case+Definition%2C+Diagnostic+and+Treatment+Protocols&rft.volume=11&rft.issue=2&rft.pages=7-115&rft.date=2003&rft_id=info%3Adoi%2F10.1300%2FJ092v11n01_02&rft.aulast=Carruthers&rft.aufirst=Bruce+M.&rft.au=Jain%2C+Anil+Kumar&rft.au=De+Meirleir%2C+Kenny+L.&rft.au=Peterson%2C+Daniel+L.&rft.au=Klimas%2C+Nancy+G.&rft.au=Lerner%2C+A.+Martin&rft.au=Bested%2C+Alison+C.&rft.au=Flor-Henry%2C+Pierre&rft.au=Joshi%2C+Pradip&rft.au=Powles%2C+A+C+Peter&rft.au=Sherkey%2C+Jeffrey+A.&rft.au=van+de+Sande%2C+Marjorie+I.&rft_id=http%3A%2F%2Fwww.investinme.org%2FDocuments%2FPDFdocuments%2FCanadianDefinitionME-CFS.pdf&rfr_id=info%3Asid%2Fwww.me-pedia.org%3AList+of+symptoms+in+ME+CFS" class="Z3988"> </ref>
</references>

Primer for the public

2019-04-14T14:39:34Z

MEandCFS:/* Symptoms */ x

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
'''Primer for the public''' offers a broad audience detailed information on [[myalgic encephalomyelitis]] (ME) and [[chronic fatigue syndrome]] (CFS), complex, chronic, and poorly understood medical conditions. ME was first categorized as a [[Nervous system|neurological]] disease by the [[World Health Organization]] (WHO) in 1969.<ref name=":32">{{Cite book|url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y|title=International Classification of Diseases|last=World Health Organization|first=|publisher=WHO|year=1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic), (myalgic, benign) 323|editor-last2=|editor-link2=}}</ref> [[Chronic fatigue syndrome|CFS]] was first formally defined by the United States [[Centers for Disease Control|Centers for Disease Control and Prevention]] (CDC) in 1988 as a framework for researching unexplained [[chronic fatigue]] (CF) associated with a [[mononucleosis]]-like syndrome. There remains a lack of consensus among members of the medical and research communities regarding the equivalence of [[Myalgic encephalomyelitis|ME]] and CFS. Some believe that CFS is intended to describe the same disease entity as ME, while others believe that they are distinct conditions but with overlapping symptom profiles. In deference to this lack of consensus, the combined term [[ME/CFS]] is often used.

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]]<ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":4">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] symptoms to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda19942">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":0232">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref> There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref>{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref> CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The CDC website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":03">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]
== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":043">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />
===Not a mental health disorder===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

===ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":0322">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":4" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":22">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-28}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":4" /><ref name="Carruthers, 20032" /><ref name=":5" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":12">{{Cite journal|last=Cairns|first=R.|last2=Hotopf|first2=M.|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":12" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

== Symptoms ==
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":023">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":0">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref name=":2">[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":023" /><ref name=":0" /><ref name=":1" /><ref name=":2" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
* [[chronic fatigue]]

*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]]<ref name=":6" /><ref name=":4" />
==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[https://me-pedia.org/wiki/Category:Neurological_signs_and_symptoms?title= neurological signs and symptoms] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ)<ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Drugs, treatments, and therapies ==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [https://me-pedia.org/wiki/Category:Potential_treatments potential treatments], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.

===Drugs===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the [[United States]] have failed so it is unavailable to many.<ref>{{Cite web|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|title=Ampligen for Chronic Fatigue Syndrome|last=|first=|authorlink=Adrienne Dellwo|last2=Grant|first2=Hughes|authorlink2=|date=Sep 16, 2018|website=Verywell Health|archive-url=|archive-date=|dead-url=|access-date=2019-02-09}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the United States, known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] ([[LDN]]) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Controversy===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Psychiatry has taken an inappropriate lead and treatment path for a biological disease. In the [[United Kingdom|UK]], [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are employed by ME Clinics. [[Exercise]] exacerbates symptoms and can further injure patients.<ref>[http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS - Slightly Alive - By: Mary Schweitzer]</ref><ref>[https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients GET and CBT are dangerous treatments for ME patients - Petition - 38 Degrees - By Michael Evison]</ref> [[Depression]] and [[anxiety]] drugs are utilized usually with poor and even damaging results.<ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

Treating a biological disease as a mental illness is seen as cost-effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance, having clauses excluding a mental health illness/disease, stop any payment or shorten the payout time-frame.<ref>[http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/ Trial by error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really? - By: David Tuller Virology Blog]</ref><ref>[https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders Physical Illnesses May Soon Be Labeled “Mental Disorders” - Psychology Today - Toni Bernhard, J.D.]</ref><ref>[http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth People with mental illness face widespread discrimination - The Guardian - David Batty]</ref><ref>[http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/ Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits - Thoughts About ME]</ref>

====Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
[[Graded exercise therapy|GET]] and [[Cognitive behavioral therapy|CBT]] are usually employed in the UK, [[Ireland]] and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

===Claims of curative treatments===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":7" /><ref name=":8" /><ref name=":9" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>
=== Working with government to move forward ===

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[National Institutes of Health]] (NIH), the [[Centers for Disease Control and Prevention]] (CDC) reinstating and increasing funding and education based on [[Institute of Medicine report]] recommendations and the [[U.S. Department of Health and Human Services|Health and Human Services]] (HHS) funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> #[[MEAction]] reports on this ongoing process.

====CDC Website updates====
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #MEAction report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

== Recommended viewing ==

==== Documentary ====
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

==== Short film ====
*[[The Last Great Medical Cover Up]] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)

==== News media ====
*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)

==== Talks and interviews ====
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Canary in a Coal Mine]] (now called Unrest) at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20.] (2016)

== Recommended reading ==
====Government health organizations====
:'''US'''

:[[Centers for Disease Control]] (CDC)
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html ME/CFS in Children Fact Sheets] (2017) Fact Sheets for Healthcare Professionals, Parents/Guardians, Education Professionals

:[[National Institutes of Health]] (NIH)
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]

:[[Institute of Medicine]] (IOM)
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts] From the [[Institute of Medicine report]]. (2015)

:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness] Report Brief on the Institute of Medicine report. (2015)

==== ME/CFS research foundations ====
:'''UK'''

:[[Invest in ME]]
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]

:'''US'''

:[[Open Medicine Foundation]] (OMF)
:*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]

==== ME/CFS organizations ====
:'''Australia'''

:[[Emerge Australia]]
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]

:'''UK'''

:[[ME Association]]
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]

:[[Tymes Trust]] (Pediatric)
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs] (2016)

:'''US'''
:[[Massachusetts CFIDS/ME & FM Association]]
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]

:[[Solve ME/CFS]]
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?] (2017)

:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS] (2016)

:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?] (2013)

:'''International'''
:[[MEAction]]
:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)] (2015)

:*[http://www.meaction.net/reports-and-fact-sheets/?utm_content=bufferc2125&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Reports and Fact Sheets] (2015)

==== Other organizations ====
:*[https://rarediseases.org/ National Organization for Rare Disorders] (NORD) has a section for [https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]

==== Other reading====
:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?] By Suzan Jackson

==History==
=== 1980's to present day ===
*''[[Osler's Web]] i''s a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref>

=== Disease names and acronyms around the world ===
The [[United States]] and [[Australia]] usually refer to the disease as CFS, (chronic fatigue syndrome). Many European countries, the [[United Kingdom]] and [[Ireland]] mostly use the name ME, (Myalgic Encephalomyelitis). Most countries, as well as doctors and researchers worldwide, will also use the acronym ME/CFS and a few CFS/ME. ''See:'' [http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Definitions of ME and CFS].

The symptom [[chronic fatigue]] (CF) should not be used in place of the name [[chronic fatigue syndrome]] (CFS); this has been a source of confusion of CF the symptom and CFS the disease. CFS is a grossly misnamed disease whereas CF is a symptom of many diseases, illnesses and drug therapies.<ref>[http://chronicfatigue.about.com/od/whatischronicfatigue/a/cf_vs_cfs.htm?utm_content=bufferda812&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Chronic Fatigue vs. Chronic Fatigue Syndrome - One's a Symptom, One's a Disease - About.com Health FMS/ME/CFS By Adrienne Dellwo]</ref><ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome What's the Difference? - About.com Health FMS/ME/CFS - By Carol Eustice]</ref> Dr. [[Jarred Younger]] explains chronic fatigue and begins by stating "Fatigue is not a disease and it is not even a symptom. So fatigue is a alarm system and the most general alarm system the body has." [https://www.youtube.com/watch?v=wJB95m4FLa0 Webinar with Jarred Younger, Ph.D. (@6:04-7:54)]

==== Myalgic Encephalomyelitis (ME) ====
Although many similar diseases have occurred for centuries, in the 1920s - 1940s there were sporadic outbreaks around the world<ref>[[List of outbreaks]]</ref>, of both poliomyelitis, and what Dr. [[Melvin Ramsay]] called 'Benign Myalgic Encephalomyelitis' ('benign because it is disabling but not usually fatal). In 1969, the World Health Organisation included "Myalgic Encephalitis' in its 'International Classification of Diseases' (ICD), under the category 'Diseases of the Nervous System', code G93.3.<ref>[http://www.hfme.org/thewhoandme.htm The WHO and M.E. (in brief) - The Hummingbirds' Foundation for M.E.]</ref><ref>[http://www.meactionuk.org.uk/ME_CFS_TERMINOLOGY.pdf ME/CFS Terminology - By: Margaret Williams - April - 2009]</ref>

==== From ME to CFS ====
[[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]], Lake Tahoe, NV, USA experienced an outbreak during 1984-1985. The CDC were sent to investigate. Dr. [[Anthony Komaroff]] studied cases from the outbreak and eventually he and a body of clinicians settled on the name "Chronic Fatigue Syndrome".<ref>[https://www.masscfids.org/diagnosis Diagnosis of ME/CFS - What is a Syndrome]</ref> Dr. Komaroff discusses the name emerging in the documentary film Forgotten Plague.

==== From CFS to 'any unexplained fatigue' ====
Various groups invented new definitions, that required only 'medically unexplained fatigue' such as [[Reeves criteria]] and [[Oxford criteria]]. Fatigue is a common symptom in any population, with many different causes. These new definitions allowed some psychiatrists to claim that CFS could be 'cured' through exercise and positive thinking which has been promoted through the [[PACE trial]] and that this 'cure' also applied to people who are severely ill with Myalgic Encephalomyelitis.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/19855350/ A review on cognitive behavioral therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based but also potentially harmful for many patients with ME/CFS.]</ref><ref>[http://www.meassociation.org.uk/2009/12/statements-of-concern-about-cbtget-provided-for-the-high-court-judicial-review/ Statements of concern about CBT/GET provided for the High Court judicial review - ME Association]</ref> [[Postviral fatigue syndrome]] (PVFS) is the next frontier of the psychological paradigm keeping control of an organic disease and have been laying groundwork to do so.<ref>[http://forums.phoenixrising.me/index.php?threads/elle-anecdotes-used-to-promote-osullivan-complain-shes-being-trolled.46176/ Mind Games - ELLE Magazine September 2016 - Phoenix Rising - '''ELLE''' Anecdotes used to promote O'Sullivan, complain she's being trolled]</ref>

==== SEID name and diagnostic criteria ====
[[Systemic Exertion Intolerance Disease]] (SEID) is a diagnostic criteria proposed by the [[Institute of Medicine]] (IOM) in the [[Institute of Medicine report]]. This clinical criteria was developed for doctors in the United States to diagnose at 6 months instead of years or even decades. Doctors are encouraged to perform tests prior to six months, such as a [[Tilt table test]] or sleep study if symptoms require further investigation. Treating symptoms such as [[orthostatic intolerance]] or a sleep disorder can begin prior to the six months needed to diagnose.<ref name="IOM2015MECFS" />

=== Different diagnostic criteria used worldwide ===
==== Currently used ====
<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[Canadian Consensus Criteria]] (CCC)
*[[Fukuda criteria]] (Sometimes referred to as CDC Criteria)
*[[International Consensus Criteria]] (ICC)
*[[Oxford criteria]]
*[[Reeves criteria]] (Sometimes called [[Empirical definition]])
*[[SEID]] or IOM 2015 (Used by CDC on their [https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html ME/CFS Diagnostic Criteria for Healthcare providers] page.)
</div>

==== Currently not in use ====

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[Holmes criteria]]
*[[London criteria]]
*[[Nightingale definition]]
*[[NIOF]]
*[[Ramsay definition]]
</div>

The different criteria used from one doctor to another and researcher to researcher results in confusion for doctors trying to diagnose, poor research and discord between patients, medical professionals, and charitable organizations. Adding to the confusion is a clinical criteria will at times be used in research and a research criteria used by a clinician to diagnose. Many US researchers will use Fukuda (using the PEM "option") and CCC in a single research project.<ref>[http://www.meaction.net/2016/03/18/study-says-scientists-must-agree-on-classifying-patients/ Study says scientists must agree on classifying patients - By: Sasha Nimmo - #MEAction]</ref> The [[NIH Post-Infectious ME/CFS Study]] will be using four: SEID, Fukuda, CCC and Reeves.<ref>[http://www.meaction.net/2016/02/09/positive-answers-to-initial-questions-re-nih-clinical-center-protocol/#comment-2067 Positive Answers to Initial Questions re NIH Clinical Center Protocol - #MEAction - Comments Section - "Polly"]</ref> The ME/CFS community wanted to participate in this study's design.<ref>[https://my.meaction.net/petitions/nih-put-me-cfs-patients-at-heart-of-research-design-process NIH: Put ME/CFS patients at heart of research design process - Petition - #MEAction]</ref><ref>[https://my.meaction.net/petitions/keep-psychiatry-out-of-nih-study-on-me-cfs PETITION - Keep Psychiatry Out of NIH Study on ME/CFS - #MEAction - By: Mary Schweitzer]</ref>

==Notable studies==
*2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*[https://me-pedia.org/wiki/List_of_enterovirus_infection_studies List of enterovirus infection studies]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|dead-url=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref>
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)

<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

== See also ==
<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[25 Percent ME Group]]
*[[Blood donation]]
*[[Fibromyalgia]]
*[[Primer for family, friends and care providers]]
*[[Primer for patients]]
</div>
== Learn more ==
'''Potential treatments and research'''
* [[Ampligen]] Used in [[Argentina]] for the treatment of [[Severe and very severe ME|severe ME/CFS]].
* [[Brain imaging]]
* [[Natural killer cell]]
* [[Vagus nerve infection hypothesis]]
'''Guides and reports'''
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers
*"[[In the Expectation of Recovery]]" by [[Centre for Welfare Reform]] UK

'''[[Patient mental health]]'''

:Patients that had been deemed as suffering from mental health and not a biological illness.
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.
* ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref><ref>[http://www.sleepydust.net/CHRONIC-FATIGUE-SYNDROME-AND-DEPRESSION.html Are ME/CFS & Depression The Same Thing? - Sleepy Dust]</ref><ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>
'''Outbreaks'''
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]

* [[List of outbreaks]]

== Other resources ==
*[[Verywell FMS/CFS]] Well written articles on ME/CFS and Fibromyalgia.

== References ==
<references>
<ref name="IOM2015MECFS">{{citation
| last1 = Institute of Medicine (USA)
| last2 = Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| display-authors =
| title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness
| date = 10 February 2015
| url = http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx
}}</ref>
</references>

[[Category:Primers]]

Primer for patients

2019-04-14T14:37:32Z

MEandCFS:/* Symptoms */ x

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
This '''Primer for patients''' will provide the information you need to better understand your personal diagnosis of [[chronic fatigue syndrome]] (CFS), [[myalgic encephalomyelitis]] (ME), or [[ME/CFS]], which can be very different with severity and symptoms from patient to patient.

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":2">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda19942">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":0232">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref> There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref>{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref>

CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":4">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-22}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":3">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-22}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

Take time when you are able to review this Primer. Because you are not well, this can be overwhelming at times, so only do what you are mentally and physically able.

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu2">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":04">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":14">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":4" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":4" />
===Not a mental health disorder===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":4" />

===ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":0322">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":2" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":0">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":2" /><ref name="Carruthers, 20032" /> <ref name=":5" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":1">{{Cite journal|last=Cairns|first=R.|author-link=|last2=Hotopf|first2=M.|author-link2=|author-link3=|author-link4=|author-link5=|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087|quote=|via=}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":1" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

== Symptoms ==
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-01}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":02">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":03">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1" /> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":152">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":132">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":02" /><ref name=":03" /><ref name=":0" /><ref name=":1" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]] <ref name=":6" /><ref name=":2" />
==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ)<ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]

== Tests to discuss with your doctor ==
* [[Natural killer cell]] (NKC) Blood Test

*[https://en.wikipedia.org/wiki/Sleep_study Sleep study] for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
*[[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Drugs and treatments==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [https://me-pedia.org/wiki/Category:Potential_treatments potential treatments], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.

===Drugs===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Controversy===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Psychiatry has taken an inappropriate lead and treatment path for a biological disease. In the UK, [[GET]] and [[CBT]] are employed by ME Clinics. [[Exercise]] exacerbates symptoms and can further injure patients.<ref>[http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS - Slightly Alive - By: Mary Schweitzer]</ref><ref>[https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients GET and CBT are dangerous treatments for ME patients - Petition - 38 Degrees - By Michael Evison]</ref> [[Depression]] and [[anxiety]] drugs are utilized usually with poor and even damaging results.<ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

Treating a biological disease as a mental illness is cost effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance having clauses excluding a mental health illness/disease kick in stopping any payment or shortening the payout time-frame.<ref>[http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/ Trial by error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really? - By: David Tuller Virology Blog]</ref><ref>[https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders Physical Illnesses May Soon Be Labeled “Mental Disorders” - Psychology Today - Toni Bernhard, J.D.]</ref><ref>[http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth People with mental illness face widespread discrimination - The Guardian - David Batty]</ref><ref>[http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/ Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits - Thoughts About ME]</ref>

==== Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
[[Graded exercise therapy]] (GET) and [[Cognitive behavioral therapy]] (CBT) are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

===Claims of curative treatments===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":7" /><ref name=":8" /><ref name=":9" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>
=== Working with government to move forward ===

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[National Institutes of Health]] (NIH), the [[Centers for Disease Control and Prevention]] (CDC) reinstating and increasing funding and education based on [[Institute of Medicine report]] recommendations and the [[U.S. Department of Health and Human Services|Health and Human Services]] (HHS) funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> #[[MEAction]] reports on this ongoing process.

===CDC Website updates===
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

== Recommended viewing ==

==== Documentary ====
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

==== Short film ====

*[[The Last Great Medical Cover Up]] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)

==== News media ====
*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)

==== Talks and interviews ====
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Canary in a Coal Mine]] (now titled [[Unrest]]) at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20.] (2016)

== Recommended reading ==
====Government health organizations====
:'''US'''

:[[Centers for Disease Control]] (CDC)
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html ME/CFS in Children Fact Sheets] (2017) Fact Sheets for Healthcare Professionals, Parents/Guardians, Education Professionals

:[[National Institutes of Health]] (NIH)
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]

:[[Institute of Medicine]] (IOM)
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts] From the [[Institute of Medicine report]]. (2015)

:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness] Report Brief on the Institute of Medicine report. (2015)

==== ME/CFS research foundations ====
:'''UK'''

:[[Invest in ME]]
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]

:'''US'''

:[[Open Medicine Foundation]] (OMF)
:*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]

==== ME/CFS organizations ====
:'''Australia'''

:[[Emerge Australia]]
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]

:'''UK'''

:[[ME Association]]
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]

:[[Tymes Trust]] (Pediatric)
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs] (2016)

:'''US'''
:[[Massachusetts CFIDS/ME & FM Association]]
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]

:[[Solve ME/CFS]]
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?] (2017)

:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS] (2016)

:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?] (2013)

:'''International'''
:[[MEAction]]
:*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers

:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)] (2015)

:*[http://www.meaction.net/reports-and-fact-sheets/?utm_content=bufferc2125&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Reports and Fact Sheets] (2015)

==== Other organizations ====
:[https://rarediseases.org/ National Organization for Rare Disorders] (NORD)
:*[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]

==== Other reading====
:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?] By: Suzan Jackson

==History==
*''[[Osler's Web]] i''s a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref>

==Notable studies==
*2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*[https://me-pedia.org/wiki/List_of_enterovirus_infection_studies List of enterovirus infection studies]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|dead-url=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref>
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

== Connect with organizations and other persons with ME/CFS ==
*For information and support, you may want to review materials offered by a patient group in your area.

:''See:'' [http://me-pedia.org/wiki/Category:Patient_groups_by_country Patient groups by country]

:[[Science for ME]], [[Phoenix Rising]], r/cfs, and [[Health Rising]] are forums where you can ask questions, get support, and read about the latest research.

*There are many research initiatives around the world working on ME/CFS.

:''See'': [http://me-pedia.org/wiki/Category:Research_initiatives_by_country Research initiatives by country]

:[[Solve ME/CFS]] produces printed, online and e-mail newsletters. Take their [http://solvecfs.org/do-i-have-mecfs-quiz/ Do I have ME/CFS? QUIZ]

== See also ==
*[[Primer for family, friends and care providers]]
==Learn more==
'''[[Patient mental health]]'''

:Patients that had been deemed as suffering from mental health and not a biological illness.
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.

*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref><ref>[http://www.sleepydust.net/CHRONIC-FATIGUE-SYNDROME-AND-DEPRESSION.html Are ME/CFS & Depression The Same Thing? - Sleepy Dust]</ref><ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

'''Outbreaks'''
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]

* [[List of outbreaks]]

===Other resources===
*[[Phoenix Rising]] Citizen Scientists debate the latest ME/CFS science.
*[[Science for ME]] Friendly forum on ME/CFS, FMS, and comorbid illnesses.
*[https://twitter.com/search?f=tweets&vertical=default&q=%23mecfs&src=tyah Twitter #mecfs] Connect with patients, caregivers, and ME/CFS organizations for support, articles, and research.
*[[Verywell FMS/CFS]] Well written articles with simply stated facts about ME/CFS and Fibromyalgia.

== References ==

[[Category:Primers]]
<references />

Primer for journalists

2019-04-14T14:35:32Z

MEandCFS:/* Evidence of a disease */ x

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
[[Myalgic Encephalomyelitis|Myalgic encephalomyelitis]] (ME), [[chronic fatigue syndrome]] (CFS), and [[chronic fatigue]] (CF) are widely misunderstood. In this '''Primer for journalists''', we provide evidence-based statements (with links to further reading & sources) to support journalists writing about the disease. ''Chronic Fatigue Syndrome'' must never be shortened to ''Chronic Fatigue'' in the body of an article or its headline. This has caused much confusion for readers who do not understand CFS is a debilitating lifelong illness and it is not the same as CF which is a symptom. There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":6">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":7">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":8">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref name=":9">{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":043">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":5">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":2">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptomsand [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] symptoms to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptom and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":4">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda1994">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":02">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing CFS, they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having CFS when in fact they are suffering from the symptom CF.<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref>

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":04">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

==What do we know?==
ME is a debilitating illness that has been recognized as a neurological condition by the [[World Health Organization]] (WHO) since 1969.<ref name=":32">{{Cite book|url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y|title=International Classification of Diseases|last=World Health Organization|first=|publisher=WHO|year=1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic), (myalgic, benign) 323|editor-last2=|editor-link2=}}</ref>

It is a systemic [[Neuro-immune disease|neuroimmune]] condition characterized by [[post-exertional malaise]] (PEM) (a severe worsening of symptoms after even minimal [[exertion]]). It causes dysregulation of both the [[immune system]] and the [[nervous system]]. The effects of ME are devastating enough to leave [[Severe and very severe ME|25% of patients housebound or bedbound]]. For moderate to severe patients, the disability of living with ME is like living with late-stage cancer, advanced stage AIDS, or congestive heart failure for decades.

In many parts of the world, it is commonly called chronic fatigue syndrome.

[[ME/CFS]] costs the US economy up to $24 billion per year in direct medical costs, and lost production.<ref name="IOM2015MECFS" /> Despite this, funding for research is not commensurate with the level of disease burden. In the 2015 financial year, the [[National Institutes of Health]] (NIH) provided only $5 million in research funding for ME/CFS, which is less funding than hayfever. This is in stark contrast to funding levels for other similarly disabling illnesses, like [[multiple sclerosis]] ($105 million) and HIV/AIDS ($3 billion).<ref>reference needed for NIH funding levels</ref> The [[Institute of Medicine]], a special advisory committee of the [[U.S. Department of Health and Human Services]] (HHS) (ref: [[Chronic Fatigue Syndrome Advisory Committee|CFSAC]] recommendations) and [[NIH]] expert advisory panel agree that it is imperative to increase research funding into ME/CFS.<ref name="NIHP2PFIN" />

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":044">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmental illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />
===Not a mental health disorder===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

=== ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":0322">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":2" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":0">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":2" /><ref name="Carruthers, 20032" /><ref name=":4" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS is considered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":1">{{Cite journal|last=Cairns|first=R.|author-link=|last2=Hotopf|first2=M.|author-link2=|author-link3=|author-link4=|author-link5=|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087|quote=|via=}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":1" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

==ME vs CFS vs CF==

The name myalgic encephalomyelitis (ME) was coined following an [[outbreak]] of an illness at the [[1955 Royal Free Hospital outbreak|Royal Free Hospital]] in the UK, in 1955. The name chronic fatigue syndrome (CFS) was coined by the [[Centers for Disease Control and Prevention]] (CDC) following an [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreak]] of a [[flu-like illness]] at [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]], at Lake Tahoe, in the 1980s. There is disagreement as to whether ME and CFS are the same condition, entirely separate conditions, or whether ME constitutes a more severe subset of CFS. Adding to the confusion, the diagnostic name given to patients is more often dependent on the country in which they live, than differing characteristics of their condition, as some countries use CFS (eg: US, [[Australia]]), and other countries (particularly in Europe) use ME. At this point in time, there is no clear biological evidence to resolve whether the conditions are the same or different, and there is unlikely to be a resolution until firm [[biomarkers]] have been identified. As such, many patients and researchers use the term ME/CFS.<ref name="Klimas20140621video" /> ''See:'' [http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Definitions of ME and CFS].

The name Chronic Fatigue Syndrome is itself controversial, as many consider it stigmatizing. In February 2016, Dr [[Anthony Komaroff]], who was part of the CDC group of clinicians who coined the name Chronic Fatigue Syndrome, said of it:
<blockquote>"I think that was a big mistake because the name, in my opinion, and the opinion of a lot of people, it both trivializes and stigmatizes the illness. It makes it seem unimportant, maybe not even real"<ref name="Komaroff20160217video" /></blockquote>

It is important to distinguish between ME/CFS and chronic fatigue (CF), which is a symptom of many different medical conditions (eg: [[anemia]], [[hepatitis]], [[multiple sclerosis]], [[Thyroid disease|hypothyroidism]], [[depression]], ME/CFS). "Chronic fatigue" is not a condition in its own right and it is incorrect and misleading to refer to ME/CFS as "chronic fatigue". While [[fatigue]] is a component of ME/CFS, many consider [[post-exertional malaise]] (PEM) to be the cardinal feature of ME/CFS.<ref>reference needed CCC</ref><ref name="IOM2015MECFS" />

==Evidence of a disease==

=== Symptoms ===
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":022">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":032">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref> <ref name=":1" /> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":152">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":132">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":0" /><ref name=":022" /><ref name=":032" /><ref name=":1" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]] <ref name=":5" /><ref name=":2" />
==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ) <ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]] (IOM)
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]

===Biological abnormalities===
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the condition. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. Whilst it is true that the condition is poorly understood, many biological abnormalities have been found in a range of different body systems that have been found in ME/CFS, particularly in the [[central nervous system]] (CNS), [[autonomic nervous system]], [[immune system]] and [[Metabolic|energy metabolism]].<ref name="IOM2015MECFS" /> Unfortunately, none have yet proved to be specific or practical enough to ME/CFS as to be useful as a [[biomarker]] of the condition, and many were identified in small studies, which are in need of replication. Whilst there have been abnormalities which have been identified to be associated with the condition, it cannot yet be determined whether these are a cause or consequence of the condition.
* [[Gastrointestinal system]]
* [[Natural killer cell]]

==== Notable studies ====
* [[Cytokine#Notable Studies|Cytokine ("Notable studies")]]
*Immune findings by [[Mady Hornig]] & [[Ian Lipkin]]<ref name="Hornig20150201immune" />
*[[List of enterovirus infection studies]]

*2014/15, [[Neuroinflammation]] Japanese Neuroinflammation study<ref name="NakatomiY2014" />, Younger's Leptin study <ref name="JohnsonC20150126younger" />
*2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

===Causes & triggers===

*Outbreaks - see [[List of outbreaks]]
*Possible infectious triggers: [[Enterovirus]]es, [[Epstein-Barr virus]]<ref name="Hickie2006" />, [[Q fever]]<ref name="Hickie2006" />, [[Ross River virus]]<ref name="Hickie2006" />, [[mononucleosis]]<ref name="Jason, Katz, 2017" />, ([[Ebola virus disease|Ebola]]?)<ref name="Hickie2006" />
*Non-viral triggers - [[trauma]], [[Environmental trigger|chemical]]

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Treatments==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.<ref name="IACFSME2014primer" /> There are many [http://me-pedia.org/wiki/Welcome_to_MEpedia#Potential_treatments potential treatments], though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.

=== Drugs ===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />
===Exercise as treatment===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Previously, two common treatment recommendations for ME/CFS were [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT). These treatments are based on the hypothesis that the condition might have begun with a viral infection but has been perpetuated by [[deconditioning]] from lack of activity, and fear and avoidance of activity. GET & CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that result in avoidance of activity and reconditioning through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which suggests that exercise may actually be harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,<ref name="MEASSUK20150529survey" /> which is consistent with other patient surveys.<ref name="Phoenix20160222Norway2012" />

The [[PACE trial]], published in 2011, is the largest GET ever conducted. It has received much publicity as a result of its claims of recovery rates, though it has come under strong criticism from within both the scientific and patient community, for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.<ref>http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00551-9/fulltext</ref> From 2015 to present day, the study was the subject of a series of investigative pieces that were highly critical of the trial by journalist Dr. [[David Tuller]]<ref name="viroblogMECFS" />, science writer [[Julie Rehmeyer]], patient advocate [[Tom Kindlon]], Dr. [[Keith Geraghty]]<ref name="Geraghty, 2017" />, psychologist Dr. [[Carolyn Wilshire]]<ref name="Wilshire C, et al, 2017" /> and others. A petition signed by almost 12,000 ME/CFS patients and allies,<ref name="MEACTIONpacepetition" /> and an open letter signed by 42 ME/CFS experts from around the world,<ref name="openletrLANCET2" /> were sent to The Lancet, both calling for the data to be reanalysed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.<ref name="MEACTION20160313openletr" /> To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the PACE trial continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.

One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of PEM, which is an exacerbation of symptoms following physical, mental or even emotional exertion. Studies have revealed immunological, muscular, neurological, autonomic and cardiovascular abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary controls, the adverse effects of exercise cannot be said to be due to [[deconditioning]].<ref name="TwiskF2015" /><ref>reference needed - Workwell Foundation studies</ref><ref>reference needed - the Lights epigenetic changes post-exercise</ref>

People with ME/CFS should approach exercise with caution, as there is much potential for harm.

[[Anaerobic]] threshold, use of heart rate monitors for activity and [[pacing]]. Analeptic, not [[aerobic]].
[[Energy Envelope Theory|Energy envelope]]/pacing - people do better if stay within their envelope, than push to increase activity

====Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
GET and CBT are usually employed in the [[United Kingdom|UK]], [[Ireland]] and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

==== Claims of recovery and cures ====
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":6" /><ref name=":7" /><ref name=":8" /><ref name=":9" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

==Severely ill patients==
Considerable variation exists in the severity of the condition. The [[International Consensus Criteria]] lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):

*Mild = 50% reduction in pre-illness activity levels
*Moderate = mostly housebound
*Severe = mostly bedridden
*Very Severe = totally bedridden, and needing help with basic functions.

At least [[Severe and very severe ME|25% of people with ME/CFS are bedbound or housebound]], often for years or even decades, so are largely an invisible population.<ref name="IOM2015MECFS" /><ref name="DerekPrisk2009" /><ref>[http://iacfsme.org/PDFS/2017JanNewsletter/8-Japan-2014-Patient-Survey.aspx ME/CFS Patient Survey Report: Ministry of Health Survey Reveals Harsh Reality of ME/CFS Patients in Japan - IACFSME - By Mieko Shinohara]</ref> So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The [[Open Medicine Foundation]]'s [[ME/CFS Severely Ill, Big Data Study]] will be the first in-depth study of people with a severe form of ME/CFS. This study has so far produced the groundbreaking paper [[Metabolic features of chronic fatigue syndrome]].
It is estimated that 25% of ME/CFS patients are severely ill and are housebound or bedbound.

Notable patients with severe or very severe ME/CFS include [[Whitney Dafoe]], [[Karina Hansen]], [[Lynn Gilderdale]], [[Laura Hillenbrand]], [[Tom Kindlon]], [[Vanessa Li]], [[Doctor Speedy]], [[Naomi Whittingham]], [[Jamison Hill]] and [[Jessica Taylor-Bearman]].

Though uncommon, there have been instances of deaths which have been attributed to the condition (see [[Sophia Mirza]], [[Merryn Crofts]]).

==Patients & psychiatry/psychology==

*Objections & scope
*Mind-body dualism
*The [[PACE trial]]. See [http://www.meaction.net/wp-content/uploads/2015/05/MEAction%E2%80%93patient-view-of-the-PACE-Trial-Controversy.pdf Patient view of the PACE Trial controversy]
*[[Patient mental health]]

===Stigmatization===

*Pretty young women slumped on desk
*[[Yuppie Flu]]
*Accusations of laziness/lethargy
*Epidemiological evidence - age, gender, demographic, racial/cultural

===Accusations of harassment===

*No arrests or convictions<ref>{{Cite web|url=http://www.virology.ws/2016/02/01/trial-by-error-continued-a-few-words-about-harassment/|title=Trial By Error, Continued: A Few Words About “Harassment”|last=|first=|authorlink=David Tuller|last2=|first2=|authorlink2=|date=Feb 1, 2016|website=www.virology.ws|archive-url=|archive-date=|dead-url=|access-date=2019-01-21}}</ref>
*Poor treatment of patients not mentioned. [[Ean Proctor]] and "The Mental Health Movement: Persecution of Patients?"<ref>[http://www.theoneclickgroup.co.uk/documents/ME-CFS_docs/The%20Mental%20Health%20Movement%20-%20Persecution%20of%20Patients.pdf The Mental Health Movement: Persecution of Patients?]</ref>

== Working with government to move forward ==

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[NIH]], the [[CDC]] reinstating and increasing funding and education based on [[IOM]] recommendations and the [[HHS]] funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> [[MEAction]] reports on this ongoing process.

====CDC Website updates====
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and GET and CBT recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref>

* Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>
'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

==Expert opinions==

===Quotes from ME/CFS experts and patients===
*[http://thoughtsaboutme.com/quotes/ Thoughts About ME - List of Quotes]
*[[Individual Quotes]]

===Doctors===
'''UK'''
*[[Jonathan Edwards]]
*[[Charles Shepherd]]

'''US'''
<div style="column-count:4;-moz-column-count:4;-webkit-column-count:4">

*[[Lucinda Bateman]]
*[[Lily Chu]]
*[[David Kaufman]]
*[[Nancy Klimas]]
*[[Anthony Komaroff]]
*[[Susan Levine]]
*[[Jose Montoya]]
*[[Benjamin Natelson]]
*[[Daniel Peterson]]
*[[Alan Pocinki]]
*[[Peter Rowe]]
*[[Ronald Tompkins]]
*[[David Tuller]]

</div>

===Researchers===
'''Australia'''
*[[Neil McGregor]]

'''UK'''
*[[Keith Geraghty]]

'''US'''
<div style="column-count:4;-moz-column-count:4;-webkit-column-count:4">
*[[Ron Davis]]
*[[Gunnar Gottschalk]]
*[[Maureen Hanson]]
*[[Mady Hornig]]
*[[Leonard Jason]]
*[[Betsy Keller]]
*[[Ian Lipkin]]
*[[Staci Stevens]]
*[[Suzanne Vernon]]
*[[Jarred Younger]]

</div>

===Patients===
====Australia====

===== Canada =====
*[[Scott Simpson]]

====Scotland====
*[[Emma Shorter]]

====US====
<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[Jennifer Brea]]
*[[Carol Head]]
*[[Ryan Prior]]
*[[Julie Rehmeyer]]
*[[Jaime Seltzer]]
</div>

====UK====
*[[Adam Lowe]]
*[[Graham McPhee]]
*[[Jessica Taylor-Bearman]]

====Ireland====
*[[Tom Kindlon]]

===Patient groups & charities===

'''[[:Category:Patient groups|Patient groups]]'''
<div style="column-count:3;-moz-column-count:3;-webkit-column-count:3">
*[[:Category:American patient groups|American patient groups]]
*[[:Category:Australian patient groups|Australian patient groups]]
*[[:Category:Belgian patient groups|Belgian patient groups]]
*[[:Category:British patient groups|British patient groups]]
*[[:Category:Canadian patient groups|Canadian patient groups]]
*[[:Category:Dutch patient groups|Dutch patient groups]]
*[[:Category:Irish patient groups|Irish patient groups]]
*[[:Category:Italian patient groups|Italian patient groups]]
*[[:Category:New Zealand patient groups|New Zealand patient groups]]
*[[:Category:Norwegian patient groups|Norwegian patient groups]]
*[[:Category:Scottish patient groups|Scottish patient groups]]
*[[:Category:Swedish patient groups|Swedish patient groups]]
</div>

==History==
*[[Osler's Web|''Osler's Web'']] is a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref>

==Other tips==

*Always interview a patient
*Interview more than one researcher (not just from the psychological etiology view)
*Avoid using derogatory, outdated & incorrect term "[[Yuppie Flu]]"
*Never shorten the disease name [[chronic fatigue syndrome]] (CFS) to the symptom [[chronic fatigue]] (CF). [[CFS]], [[ME]] or [[ME/CFS]] can be used to save print space.
*Use photographic imagery that represents the reality for patients - serious illness & disability - not well-groomed & slightly tired office workers at their computer or students with a pile of books sleeping at their desk. [[Solve ME/CFS Initiative]]'s [https://www.youtube.com/watch?v=cF2OuYFDriY Times Square Public Awareness Ad] shows the reality of the disease ME/CFS. Using photos of patients whether chronically ill yet functioning or a severely ill patient or stock photos that reflect life with this disease is necessary.

==Learn more==
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

'''ME/CFS organization and researchers material'''
*[https://www.youtube.com/watch?v=hRdn4A2SGic Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education] (The CDC's Dr. [[John Iskander]] interviews Dr. [[Anthony Komaroff]]. Video, 2016)
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers
*[http://youtu.be/c2vIQ92wU9Y ME/CFS Diagnosis and Name with Dr Nancy Klimas (video)]
*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?] By the [[Open Medicine Foundation]]

'''[[Patient mental health]]'''

:Patients
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end of a pool to make him swim and another time put him on a scary theme park ride to scare him into moving.

'''More mental health information'''
*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref><ref>[http://www.sleepydust.net/CHRONIC-FATIGUE-SYNDROME-AND-DEPRESSION.html Are ME/CFS & Depression The Same Thing? - Sleepy Dust]</ref><ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

'''Research'''
*[[Institute of Medicine report]] (2015) The CDC based its updated [https://www.cdc.gov/me-cfs/index.html ME/CFS page] on information in this report.
*[[Notable studies]]

==See also==
*[[Primer for the public#Disease_names_and_acronyms_around_the_world|Primer for the public (''Disease names and acronyms around the world'' section)]]

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[[Category:Primers]]

Primer for family, friends and care providers

2019-04-14T14:33:32Z

MEandCFS:/* Symptoms */ x

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
'''Primer for family, friends and care providers''' is for those who know or care for someone with [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS), a complicated and life-altering systemic, biological, [[neuro-immune disease]].<ref name=":0">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|website=Open Medicine Foundation|language=en-US|access-date=2019-01-24}}</ref> Patient care and severity of the disease is poorly understood due to decades of research neglect and a lack of clinical care worldwide.<ref>{{Cite web|url=http://healthaffairs.org/blog/2016/02/04/reexamining-chronic-fatigue-syndrome-research-and-treatment-policy/|title=Reexamining Chronic Fatigue Syndrome Research And Treatment Policy|last=Tuller|first=David|date=Feb 4, 2016|website=healthaffairs.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite news|url=http://www.meaction.net/2017/01/22/funding-for-me-research-centers-announced-falls-way-short/|title=Funding for U.S. research centers falls way short - #MEAction|date=2017-01-22|work=#MEAction|access-date=2018-09-07|language=en-US}}</ref>

Diagnosing [[ME/CFS]] is difficult as there is no clinically accepted [[biomarker]] and there are numerous [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|definitions and criteria]] that have been developed and utilized over the decades.
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref name=":5">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":8">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":7">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
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| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":6">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda1994">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":023">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref> There have been media reports of athletes diagnosed with [[myalgic encephalomyelitis]] (ME) or [[chronic fatigue syndrome]] (CFS) who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":9">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":10">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":11">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref>{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref> CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":02">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

== Recommended reading for care providers ==
* [https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref name=":14">{{Cite web|url=https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view?usp=embed_facebook|title=Caregivers Guide to ME.pdf|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=Google Docs|publisher=MEAction|archive-url=|archive-date=|dead-url=|access-date=2019-03-31}}</ref> by #[[MEAction]]
<blockquote>Myalgic Encephalomyelitis (also known as Chronic Fatigue Syndrome or ME/CFS) is a complex, challenging disease for everyone involved - not least the caregiver. Caring for someone with ME will require adaptability, steadfast patience and commitment over many years, if not a lifetime.<ref name=":14" /></blockquote>

:Table of Contents:
::1) Educate Yourself
::2) Take Care of Yourself
::3) Family Dynamic
::4) Relationship with the Patient
::5) Resources
::6) Advocate
::7) Power of Attorney
::8) Get Organized
::9) Join the Community
::10) Read more<ref name=":14" />

[[Greg Crowhurst]] has cared for his wife [[Linda Crowhurst|Linda]] for decades as she is [[Severe and very severe ME|very severely ill with ME]]. Greg has written several books on caring for someone with ME.

*[[Severe ME - Featuring: "Justice for Karina Hansen"]]
*[[Severe ME: Notes for Carers]]
*[[Caring for ME]]

'''Other books/guides'''
*[[A Beginner's Guide to ME/CFS]]
*[[Caring For The M.E. Patient]]
*[[Chronic Fatigue Syndrome/ME: Support for Family and Friends]]
*[[Understanding M.E. - A Guide For Friends, Family & Carers]]
*[[What Is M.E.? A Guide For Children]]

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":043">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />

=== Not a mental health disorder ===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

=== ME/CFS is not contagious ===
There is no evidence that ME/CFS patients are contagious.<ref name=":032">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":7" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and many rely on SSDI/SSI.<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
*:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
*:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>

*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":22">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-28}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":7" /><ref name="Carruthers, 20032" /><ref name=":6" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":12">{{Cite journal|last=Cairns|first=R.|last2=Hotopf|first2=M.|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":12" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

== Symptoms ==
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":0" /><ref name=":03">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":2">[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref><ref name=":4">{{Cite web|url=https://www.webmd.com/chronic-fatigue-syndrome/symptoms-chronic-fatigue|title=What Are the Symptoms of Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=WebMD|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-01-24}}</ref> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months..<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":0" /><ref name=":03" /><ref name=":2" /><ref name=":4" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]
*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]] <ref name=":8" /><ref name=":7" />

=== Other possible symptoms ===
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ) <ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness - Report Guide for Clinicians|last=|first=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> from the [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]<ref>{{Cite web|url=http://linkis.com/org/tUheh|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Toward Optimized Practice (TOP) - CPGs|website=linkis.com|access-date=2018-09-07}}</ref>

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Drugs, treatments, and therapies==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [https://me-pedia.org/wiki/Category:Potential_treatments potential treatments], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.

=== Drugs ===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]

Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in early 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>{{Cite news|url=https://www.healthrising.org/blog/2016/02/04/low-dose-naltrexone-combo-chronic-fatigue/|title=Low Dose Naltrexone Drug Combination Proposed for Chronic Fatigue Syndrome (ME/CFS)|last=Johnson|first=Cort|date=2016-02-04|work=Health Rising|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=https://cas.uab.edu/younger/2017/02/ldn-chronic-fatigue-syndrome-clinical-trial/|title=LDN Chronic Fatigue Syndrome Clinical Trial - Neuroinflammation, Pain and Fatigue Laboratory|date=2017-02-23|work=Neuroinflammation, Pain and Fatigue Laboratory|access-date=2018-09-07|language=en-US}}</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Controversy===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Psychiatry has taken an inappropriate lead and treatment path for an organic biological disease. In the UK, [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are employed by ME Clinics. Exercise exacerbates symptoms and can further injure patients.<ref>{{Cite web|url=http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html|title=Slightly Alive: Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS|last=Schweitzer|first=Mary|date=2016-03-17|website=Slightly Alive|access-date=2018-09-07}}</ref><ref>{{Cite news|url=https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients|title=GET and CBT are dangerous treatments for ME patients|last=Evison|first=Michael|date=|work=Campaigns by You|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-GB}}</ref> Depression and anxiety drugs are utilized usually with poor and even damaging results.<ref>{{Cite web|url=http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title=CFS or depression - what are the differences - DoctorMyhill|last=Myhill|first=Sarah|date=|website=drmyhill.co.uk|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>

Treating a biological disease as a mental illness is cost effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance having clauses excluding a mental health illness/disease kick in stopping any payment or shortening the payout time-frame.<ref>{{Cite web|url=http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/|title=Trial by Error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really?|last=Tuller|first=David|date=Nov 17, 2015|website=www.virology.ws|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders|title=Physical Illnesses May Soon Be Labeled “Mental Disorders”|last=Bernhard|first=Toni|date=Dec 27, 2012|website=Psychology Today|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite web|url=http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=People with mental illness face widespread discrimination|last=Batty|first=David|date=2004-04-28|website=the Guardian|language=en|access-date=2018-09-07}}</ref><ref>{{Cite news|url=http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/|title=Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits|date=2016-03-21|work=Thoughts About M.E.|access-date=2018-09-07|language=en-US}}</ref>

==== Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
GET and CBT are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

===Claims of curative treatments===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":9" /><ref name=":10" /><ref name=":11" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

=== Working with government to move forward ===

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[NIH]], the [[CDC]] reinstating and increasing funding and education based on [[IOM]] recommendations and the [[HHS]] funding to develop Centers of Excellence.<ref>{{Cite news|url=http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/|title=#MEAction meets with Senate staffers - #MEAction|date=2016-03-16|work=#MEAction|access-date=2018-09-07|language=en-US}}</ref> #[[MEAction]] reports on this ongoing process.

====CDC Website updates====
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>{{Cite web|url=http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/|title=Trial By Error: The CDC Drops CBT/GET|last=Tuller|first=David|date=Jul 10, 2017|website=www.virology.ws|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/treatment/index.html|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html|title=Information for Healthcare Providers {{!}} ME/CFS {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html|title=New ME/CFS Web Content for Healthcare Providers {{!}} CDC Online Newsroom {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME]<ref>{{Cite news|url=https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/|title=CDC Revises Its Information on ME - #MEAction|last=Seltzer|first=Jaime|date=2018-07-29|work=#MEAction|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref> #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

== Recommended viewing ==

==== Documentary ====
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

==== Short film ====
*[[The Last Great Medical Cover Up|''The Last Great Medical Cover Up'']] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)

==== News media ====

*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)

==== Talks and interviews ====
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Unrest]] at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20 - Youtube] (2016)

== Recommended reading ==
====Government health organizations====

:'''US'''

:[[Centers for Disease Control]] (CDC)
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html Factsheets - Pediatric]<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html|title=ME/CFS in Children Fact Sheets {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-07-14|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref> Fact sheets for Healthcare Professionals, Parents/Guardians, and Education Professionals. (2017)

:[[National Institutes of Health]] (NIH)
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]

:[[Institute of Medicine]] (IOM)
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - Key Facts|last=|first=|date=Feb 2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> From the [[Institute of Medicine report]]. (2015)

:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=Feb 2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Report Brief on the Institute of Medicine report. (2015)

==== ME/CFS research foundations ====

:'''UK'''

:[[Invest in ME]]
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]<ref>{{Cite web|url=http://www.investinme.org/faqs.shtml|title=Invest in ME Research - UK Charity for Myalgic Encephalomyelitis FAQs|last=Research|first=Invest in ME|website=www.investinme.org|access-date=2018-09-07}}</ref>

:'''US'''

:[[Open Medicine Foundation]] (OMF)
:*[https://www.omf.ngo/what-is-mecfs/ What is ME/CFS?]<ref name=":0" />

==== ME/CFS organizations ====

:'''Australia'''

:[[Emerge Australia]]
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]<ref>{{Cite news|url=https://emerge.org.au/mecfs/|title=What is ME/CFS? - Emerge Australia|work=Emerge Australia|access-date=2018-09-07|language=en-US}}</ref>

:'''UK'''

:[[ME Association]]
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]<ref>{{Cite web|url=https://www.meassociation.org.uk/about/what-is-mecfs/|title=What is ME/CFS?|website=www.meassociation.org.uk|language=en-US|access-date=2018-09-07}}</ref>

:[[Tymes Trust]] (Pediatric)
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs]<ref>{{Cite web|url=https://www.tymestrust.org/pdfs/mecfsseid.pdf|title=Paediatric ME, CFS, SEID for Families and their GPs|last=|first=|date=|website=tymestrust.org|publisher=The Young ME Sufferers Trust|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2016)

:'''US'''
:[[Massachusetts CFIDS/ME & FM Association]]
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]<ref>{{Cite web|url=https://www.massmecfs.org/cfids-me-cfs|title=ME/CFS|website=www.massmecfs.org|access-date=2019-01-24}}</ref>

:[[Solve ME/CFS]]
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?]<ref>{{Cite web|url=https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view|title=What, Exactly, Is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?|last=|first=|date=|website=drive.google.com|publisher=Solve ME/CFS Initiative|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=}}</ref>

:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS]<ref>{{Cite news|url=https://solvecfs.org/what-is-mecfs/|title=Get the Facts about ME/CFS - Solve ME/CFS Initiative|work=Solve ME/CFS Initiative|access-date=2018-09-07|language=en-US}}</ref> (2016)

:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?]<ref>{{Cite web|url=http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf|title=What is ME/CFS?|last=|first=|date=2013|website=solvecfs.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2013)

:'''International'''
:[[MEAction]]
:*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref name=":14" /> (2018) Guide for Caretakers

:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)]<ref>{{Cite web|url=http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf|title=Facts about Myalgic Encephalomyelitis (ME) - (Also called chronic fatigue syndrome or CFS)|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2015)

:*[http://www.meaction.net/reports-and-fact-sheets/?utm_content=bufferc2125&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Reports and Fact Sheets]<ref>{{Cite web|url=https://www.meaction.net/resources/reports-and-fact-sheets/|title=Learn about ME. Find educational tools for your advocacy.|last=|first=|date=|website=meaction.net|archive-url=|archive-date=|dead-url=|access-date=}}</ref> (2015)

==== Other organizations ====

:[https://rarediseases.org/ National Organization for Rare Disorders] (NORD)
:*[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]<ref>{{Cite news|url=https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/|title=Myalgic Encephalomyelitis - NORD (National Organization for Rare Disorders)|work=NORD (National Organization for Rare Disorders)|access-date=2018-09-07|language=en-US}}</ref>

==== Other reading====

:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?]<ref>{{Cite news|url=https://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/|title=What Do You Do When a Loved One Becomes Chronically Ill?|last=Jackson|first=Suzan|date=2016-10-28|work=thirdAGE|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== Research avenues ==

*Dr. [[Anthony Komaroff]] Webinar [https://www.youtube.com/watch?v=ENrdrGj0p-c Hot Areas in ME/CFS Research] (2016)
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]] CDC Video (2016)

==History==
*[[Osler's Web|''Osler's Web'']] is a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>{{Cite news|url=https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/|title=Not, sadly, the first|last=Senior|first=Richard|date=Jul 26, 2006|work=New Scientist|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref> See Editor's Note<ref>{{Cite news|url=https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/|title=First official UK death from chronic fatigue syndrome|last=Hooper|first=Rowan|date=Jun 16, 2006|work=New Scientist|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

== Notable studies ==
* 2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref name=":16">{{Cite web|url=https://pubs.rsna.org/doi/10.1148/radiol.14141079|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30|title=Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome|date=Oct 29, 2014|last=|first=|authorlink=Michael Zeineh|last2=|first2=|authorlink2=James Kang|archive-url=|archive-date=|dead-url=|last3=|authorlink3=Scott Atlas|last4=|authorlink4=Mira Raman|authorlink5=Allan Reiss|authorlink6=Jane Norris|authorlink7=Ian Valencia|authorlink8=Jose Montoya|publisher=Radiology}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.<ref name=":16" /></blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*[https://me-pedia.org/wiki/List_of_enterovirus_infection_studies List of enterovirus infection studies]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|dead-url=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref>
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

== See also ==
* [[Biopsychosocial model]] (BPS) An unproven psychiatric paradigm model applied to ME/CFS in the [[United Kingdom|UK]].
== Learn more ==
'''Potential treatments and research'''
*[[Ampligen]] Used in [[Argentina]] for the treatment of [[Severe and very severe ME|severe ME/CFS]].
*[[Brain imaging]]
*[[Natural killer cell]]
*[[Vagus nerve infection hypothesis]]

'''Guides and reports'''
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref name=":1" /> (2018) Guide for Caretakers
*"[[In the Expectation of Recovery]]" by [[Centre for Welfare Reform]] UK

'''[[Patient mental health]]'''

:Patients that had been deemed as suffering from mental health and not a biological illness.
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.
*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>{{Cite news|url=http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm|title=Depression in Fibromyalgia and Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Aug 2, 2018|work=Verywell Health|access-date=2018-09-07|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite web|url=http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title=CFS or depression - what are the differences - DoctorMyhill|website=drmyhill.co.uk|language=en|access-date=2018-09-07}}</ref>

'''Outbreaks'''
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]

*[[List of outbreaks]]

== References ==

[[Category:Primers]]
<references />

Primer for doctors and researchers

2019-04-14T14:31:47Z

MEandCFS:/* Evidence of a disease */ x

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
[[Chronic Fatigue Syndrome|Chronic fatigue syndrome]] (CFS) is also known as [[myalgic encephalomyelitis]] (ME) or [[ME/CFS]]. There are many [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome| clinical and research definitions]], which creates confusion for doctors, researchers, and patients.

It is worth noting that [[chronic fatigue]] (without the "syndrome") is a symptom of many diseases, illnesses, [[depression]], and drug therapies. This term is not interchangeable with the grossly misnamed disease [[CFS]].
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":04">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":022">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":4">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|page=9|archive-url=|archive-date=|dead-url=|access-date=}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] symptoms to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda1994">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":02">{{Cite journal|last=Sharpe|first=M C|last2=Archard|first2=L C|last3=Banatvala|first3=J E|last4=Borysiewicz|first4=L K|last5=Clare|first5=A W|last6=David|first6=A|last7=Edwards|first7=R H|last8=Hawton|first8=K E|last9=Lambert|first9=H P|date=Feb 1991|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|volume=84|issue=2|pages=118–121|issn=0141-0768|pmc=1293107|pmid=1999813}}</ref> are used for diagnosing CFS, they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having CFS when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|title=What Does a True ME Definition Look Like?|last=Feb 02|first=2015|last2=Reactions|first2=6|website=MEadvocacy.org|access-date=2019-01-25}}</ref><ref>{{Cite web|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|title=Fukuda Definition (1994)|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|date=2014-03-25|website=Shoutout about ME|archive-url=|archive-date=|dead-url=|access-date=2019-01-25}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|title=AHRQ Evidence Review Changes Its Conclusions|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|date= 2016-08-16|website=occupyme.net|archive-url=|archive-date=|dead-url=|access-date=2019-01-25}}</ref> There have been media reports of athletes diagnosed with [[myalgic encephalomyelitis]] (ME) or [[chronic fatigue syndrome]] (CFS) who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref name=":10">{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref>

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":04" /> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":042">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />
=== Not a mental health disorder ===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

===ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":032">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":4" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref><ref>{{Cite web|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|title=Pediatric ME/CFS Home Page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|last=Capelli|first=E.|last2=Zola|first2=R.|last3=Lorusso|first3=L.|last4=Venturini|first4=L.|last5=Sardi|first5=F.|last6=Ricevuti|first6=G.|date=Oct 2010|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|volume=23|issue=4|pages=981–989|doi=10.1177/039463201002300402|issn=0394-6320|pmid=21244747}}</ref> while the CDC states 4:1.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":22">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-28}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":4" /><ref name="Carruthers, 2003" /><ref name=":5" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS is considered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":12">{{Cite journal|last=Cairns|first=R.|last2=Hotopf|first2=M.|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":12" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

==Evidence of a disease==

=== Symptoms ===
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] like [[Chronic fatigue|CF]], [[Orthostatic intolerance|OI]], and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":022" /><ref name=":0">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=2010-08-06|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref name=":2">[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":022" /><ref name=":0" /><ref name=":1" /><ref name=":2" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[Unrefreshing sleep|unrefreshing]] sleep ''See also:'' [[sleep disturbance]] <ref name=":6" /><ref name=":4" />

==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ) <ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness - Report Guide for Clinicians|last=|first=|date=2015|website=nationalacademies.org|publisher=Institute of Medicine of the National Academies|archive-url=|archive-date=|dead-url=|access-date=}}</ref> via The [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Primary Symptoms]<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-08-23}}</ref>

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]<ref>{{Cite web|url=http://linkis.com/org/tUheh|title=Myalgic Encephalomyelitis/Chronic Fatigue Syn - Toward Optimized Practice (TOP) - CPGs - Linkis.com|last=|first=|date=Jan 2016|website=linkis.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-23}}</ref>

===Biological abnormalities===
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the condition. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. While it is true that the condition is poorly understood, many biological abnormalities have been found in a range of different body systems, particularly in the [[central nervous system]], [[autonomic nervous system]], [[immune system]], and [[Metabolic|energy metabolism]].<ref name="IOM2015MECFS" /> Unfortunately, none have yet proved to be specific enough to ME/CFS as to be useful as a [[Diagnostic biomarker|biomarker]] of the condition, and many were identified in small studies, which need replication. Whilst there have been abnormalities identified to be associated with the condition, it cannot yet be determined whether these are a cause or consequence of the condition.
* [[Gastrointestinal system]]
* [[Natural killer cell]] findings

==== Notable studies ====
* [[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*Immune findings by [[Mady Hornig]] & [[Ian Lipkin]]<ref name="Hornig20150201immune" />
*[[List of enterovirus infection studies]]

*2014/15, [[Neuroinflammation]] Japanese Neuroinflammation study<ref name="NakatomiY2014" />, Younger's Leptin study <ref name="JohnsonC20150126younger" />
* 2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=2018-12-14|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

===Causes & triggers===
*Outbreaks - see [[List of outbreaks]]
*Possible infectious triggers: [[Enterovirus]]es, [[Herpesvirus]]es including [[Epstein-Barr virus]]<ref name="Hickie2006" />, [[Q fever]]<ref name="Hickie2006" />, [[Ross River virus]]<ref name="Hickie2006" />, ([[Ebola]]?)<ref name="Hickie2006" />
*Non-viral triggers - [[trauma]], chemical

===Epidemiology===
Prevalence estimates for ME/CFS range between 0.2-2.5%, depending on the definition of the condition used.<ref name="ICC2011criteria" /> In the US, estimates range between 836,000 and 2.5 million people with the condition, though true numbers are under-reported. It is estimated that 84-91% of people with the condition remain undiagnosed.<ref name="IOM2015MECFS" />

*Level of disability (Norwegian study HRQoL)<ref name="Hvidberg2015" /> (suggests quality of life is LOWER than for many cancers, heart diseases, brain stroke, diabetes I & II, rheumatoid arthritis, chronic renal failure, sclerosis, schizophrenia, COPD, etc)

===Severely ill patients===
Considerable variation exists in the severity of the condition. The [[International Consensus Criteria]] lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):

*Mild = 50% reduction in pre-illness activity levels
*Moderate = mostly housebound
*Severe = mostly bedridden
*Very Severe = totally bedridden, and needing help with basic functions.

At least [[Severe and very severe ME|25% of people with ME/CFS are bed-bound or housebound]], often for years or even decades, so are largely an invisible population.<ref name="IOM2015MECFS" /> So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The [[Open Medicine Foundation]]'s [[ME/CFS Severely Ill, Big Data Study]] will be the first in-depth study of people with a severe form of ME/CFS.

Notable patients with severe ME/CFS include [[Whitney Dafoe]], [[Karina Hansen]] (had been sanctioned), [[Laura Hillenbrand]], [[Tom Kindlon]], [[Doctor Speedy]], [[Naomi Whittingham]], [[Jennifer Brea|Jen Brea]], and [[Emma Shorter]].

Though uncommon, there have been instances of deaths which have been attributed to the condition. See: [[Sophia Mirza]] (sanctioned and now diseased) and [[Merryn Crofts]]. Also, see [[Vanessa Li]] and [[Lynn Gilderdale]].

===Centers for Disease Control and Prevention (CDC) ===
*Jul 3, 2017, the [[CDC]]'s Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) recommendations have been removed.<ref>{{Cite web|url=http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/|title=Trial By Error: The CDC Drops CBT/GET|last=Tuller|first=David|date=2017-07-10|website=www.virology.ws|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-23}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/index.html|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-03|website=www.cdc.gov|language=en-us|access-date=2018-08-23}}</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC.gov]</ref><ref>{{Cite web|url=https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html|title=New ME/CFS Web Content for Healthcare Providers {{!}} CDC Online Newsroom {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-08-23}}</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] [[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's [[ME/CFS]] page have been created from patient feedback on the updates as well as asking for further patient input.

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Treatments==
There are currently no [[FDA]] approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.<ref name="IACFSME2014primer" /> There are many [http://me-pedia.org/wiki/Welcome_to_MEpedia#Potential_treatments potential treatments], though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.

=== Drugs ===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the [[United States]] have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the United States, known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced he will be undertaking a trial of [[low dose naltrexone]] ([[LDN]]) in ME/CFS.<ref>{{Cite web|url=https://www.youtube.com/watch?v=95OlnK-FEdk|title=2017 Study -- Low Dose Naltrexone for Chronic Fatigue Syndrome|last=Younger|first=Jared|date=2016-12-12|website=YouTube|publisher=Younger Lab|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Exercise as treatment===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Two common treatment recommendations for ME/CFS are [[GET]] and [[CBT]]. These treatments are based on the hypothesis that the condition might have begun with a viral infection but has been perpetuated by [[deconditioning]] from lack of activity, and fear and avoidance of activity. GET & CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that result in avoidance of activity and reconditioning through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which suggests that exercise may actually be harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,<ref name="MEASSUK20150529survey" /> which is consistent with other patient surveys.<ref name="Phoenix20160222Norway2012" />

The [[PACE trial]], published in 2011, is the largest GET trial ever conducted. It has received much publicity as a result of its recovery rate claims, though it has come under strong criticism from within both the scientific and patient community for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.<ref>{{Cite journal|last=Coyne|first=James Charles|last2=Laws|first2=Keith R|date=2016|title=Results of the PACE follow-up study are uninterpretable|url=http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00551-9/fulltext|journal=The Lancet Psychiatry|language=English|volume=3|issue=2|pages=e6–e7|doi=10.1016/S2215-0366(15)00551-9|issn=2215-0366|via=}}</ref> The study was the subject of a series of investigative pieces by journalist [[David Tuller]] in late 2015, that were highly critical of the trial.<ref name="viroblogMECFS" /> A petition signed by almost 12,000 ME/CFS patients and allies,<ref name="MEACTIONpacepetition" /> and an open letter signed by 42 ME/CFS experts from around the world,<ref name="openletrLANCET2" /> were sent to The Lancet, both calling for the data to be reanalyzed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.<ref name="MEACTION20160313openletr" /> To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the PACE trial continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.

One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of [[post-exertional malaise]] (PEM), which is an exacerbation of symptoms following physical, mental or even emotional [[exertion]]. Studies have revealed immunological, muscular, [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]] and [[Cardiovascular system|cardiovascular]] abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary controls, the adverse effects of exercise cannot be said to be due to deconditioning.<ref name="TwiskF2015" /><ref>reference needed - Workwell Foundation studies</ref><ref>reference needed - the Lights epigenetic changes post-exercise</ref>

People with ME/CFS should approach exercise with caution, as there is much potential for harm.

[[Anaerobic]] threshold, use of HR monitors for activity and pacing. Analeptic, not aerobic.
[[Energy Envelope Theory|Energy envelope]]/[[pacing]] - people do better if stay within their envelope than to push to increase activity

===Graded exercise therapy & Cognitive behavioral therapy ===
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]

[[Graded exercise therapy|GET]] and [[Cognitive behavioral therapy|CBT]] are usually employed in the [[United Kingdom|UK]], [[Ireland]] and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the disproven [[biopsychosocial model]] of ME/CFS, backed up by the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Maik Speedy|Dr Maik Speedy]] was also seriously injured by GET and has been bedbound since.
*British MP [[Brynmor John]] collapsed outside the House of Commons gym in 1998 and died, as a result of following his doctor's advice to exercise back to health.

=== Claims of recovery and cures ===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF) which is not the result of the neurological illness CFS. Some people misdiagnosed and "recovered" from CFS most likely had CF which can be caused by many illnesses, diseases, and drug therapies or a bad year or two perhaps with [[mononucleosis]] followed by a bout or two of [[influenza]]. These individuals were experiencing a proper immune response whereas ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":7" /><ref name=":8" /><ref name=":9" /><ref name=":10" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

== Notable studies ==
*[[Pathways to prevention report]] (P2P)
*[[Institute of Medicine report]]
*[[PACE trial]] is a highly criticized UK trial designed by psychiatrists to promote [[GET]] and [[CBT]] as therapy which is deemed harmful and useless for ME/CFS patients by many clinicians, researchers, patients, and advocates.

== Continuing education (CME and CE) ==
* [https://www.msms.org/Education/On-Demand-Webinars/Webinar/1059 Update on Chronic Fatigue Syndrome Part 1: Clinical Diagnostic Criteria for Chronic Fatigue Syndrome/CFS now called Myalgic Encephalomyelitis or ME/CFS]<ref>{{Cite web|url=https://www.msms.org/Education/On-Demand-Webinars/Webinar/1059|title=Update on Chronic Fatigue Syndrome Part 1: Clinical Diagnostic Criteria for Chronic Fatigue Syndrome/CFS now called Myalgic Encephalomyelitis or ME/CFS|last=|first=|authorlink=Lucinda Bateman|last2=|first2=|authorlink2=|date=|website=www.msms.org|publisher=Michigan State Medical Society|via=On-Demand Webinars|archive-url=|archive-date=|dead-url=|access-date=2019-02-25}}</ref> (CME)
* [https://www.msms.org/Education/On-Demand-Webinars/Webinar/1060 Update on Chronic Fatigue Syndrome Part 2: Uniting Compassion, Attention and Innovation to treat ME/CFS.]<ref>{{Cite web|url=https://www.msms.org/Education/On-Demand-Webinars/Webinar/1060|title=Update on Chronic Fatigue Syndrome Part 2: Uniting Compassion, Attention and Innovation to treat ME/CFS.|last=|first=|authorlink=Lucinda Bateman|last2=|first2=|authorlink2=|date=|website=www.msms.org|publisher=Michigan State Medical Society|via=On Demand Webinars|archive-url=|archive-date=|dead-url=|access-date=2019-02-25}}</ref> (CME)
* [https://www.medscape.org/viewarticle/907632?src=acdmpart_cdc Diagnosing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Experts Weigh In]<ref>{{Cite web|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUub3JnL3ZpZXdhcnRpY2xlLzkwNzYzMj9zcmM9YWNkbXBhcnRfY2Rj&ac=401|title=Diagnosing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Experts Weigh In|last=|first=|authorlink=Lucinda Bateman|last2=|first2=|authorlink2=Natalie Azar|date=|website=medscape.com|publisher=Medscape|archive-url=|archive-date=|dead-url=|access-date=2019-02-25|authorlink3=Nancy Klimas|authorlink4=Jose Montoya}}</ref> (CME/CE)
* [https://www.unrest.film/cme Watch ''Unrest'' and Receive Continuing Medical Education (CME /CE) Credit]<ref>{{Cite web|url=https://www.unrest.film/cme|title=Unrest Continuing Medical Education Program|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=UNREST|publisher=Unrest|language=en-US|others=Indiana University School of Medicine, American Medical Women’s Association|archive-url=|archive-date=|dead-url=|access-date=2019-02-25}}</ref>

==History==
*[[Osler's Web|''Osler's Web'']] is a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>{{Cite news|url=https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/|title=Not, sadly, the first|work=New Scientist|access-date=2018-08-23|language=en-US}}</ref> See Editor's Note<ref>{{Cite news|url=https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/|title=First official UK death from chronic fatigue syndrome|last=Hooper|first=Rowan|date=2006-06-16|work=New Scientist|access-date=2018-08-23|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

==See also==
*[[David Tuller]]
*[[Fibromyalgia]]
*[[PACE trial]]
*[[Primer for patients]]
*[[Primer for the public#Disease_names_and_acronyms_around_the_world|Primer for the public (''Disease names and acronyms around the world'' section)]]
==Learn more==
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

'''ME/CFS organization's and researcher's material'''
*[https://www.youtube.com/watch?v=hRdn4A2SGic Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]<ref>{{Cite web|url=https://www.youtube.com/watch?v=hRdn4A2SGic|title=Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education|last=Iskander|first=John|last2=Komaroff|first2=Anthony|date=2016-02-17|website=YouTube|publisher=Centers for Disease Control and Prevention (CDC)|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref>{{Cite news|url=https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view|title=Caregivers Guide to ME.pdf|last=|first=|date=2018|work=Google Docs|access-date=2018-08-23|archive-url=|archive-date=|dead-url=|publisher=#MEAction}}</ref>
*[http://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf IACFS/ME Primer for Clinical Practitioners - 2014 Edition]<ref name="IACFSME2014primer" />
*[http://www.meassociation.org.uk/2014/07/our-purple-booklet-clear-clinical-guidance-and-the-latest-research-all-wrapped-up-in-52-pages/ ME Association clinical guidance]<ref name="MEASSUKprimer2013" />
*[http://youtu.be/c2vIQ92wU9Y ME/CFS Diagnosis and Name with Dr Nancy Klimas (video)]<ref>{{Cite web|url=https://www.youtube.com/watch?v=c2vIQ92wU9Y&feature=youtu.be|title=ME/CFS Diagnosis and Name with Dr. Nancy Klimas|last=Klimas|first=Nancy|date=2014-06-21|website=YouTube|publisher=ME/CFS Community|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*[http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf ME/CFS Treatment Resource Guide for Practitioners by A Martin Lerner, MD]<ref name="LernerPrimer2011" />
*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf Myalgic Encephalomyelitis - Adult & Pediatric - International Consensus Criteria Primer for Medical Practitioners]<ref name="ICP2011primer" />
*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]<ref>{{Cite news|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS? {{!}} Open Medicine Foundation|work=Open Medicine Foundation|access-date=2018-08-23|language=en-US}}</ref>

'''[[Patient mental health]]'''

:Patients
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.

'''More mental health information'''
*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>{{Cite news|url=http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm|title=Depression in Fibromyalgia and Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Aug 2, 2018|work=Verywell Health|access-date=2018-08-23|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite web|url=http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title=CFS or depression - what are the differences - DoctorMyhill|website=drmyhill.co.uk|language=en|access-date=2018-08-23}}</ref>

'''Research'''
* 2015, [[Institute of Medicine report]] (IOM Report)

* 2016, [http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598 The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem]<ref name="Edwards2016" />
*2018, The CDC based its updated [https://www.cdc.gov/me-cfs/index.html ME/CFS page] based on the IOM Report.
*[[Notable studies]]
'''Articles and blogs'''
* Feb 21, 2019 ''[https://www.rcseng.ac.uk/news-and-events/blog/differential-diagnosis-me/ Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined?]''<ref>{{Cite web|url=https://www.rcseng.ac.uk/news-and-events/blog/differential-diagnosis-me/|title=Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined?|last=Muirhead|first=Nina|authorlink=|last2=|first2=|authorlink2=|date=Feb 21, 2019|website=Royal College of Surgeons|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-22}}</ref>

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[[Category:Primers]]

Primer for doctors and researchers

2019-04-14T14:29:50Z

MEandCFS:/* Evidence of a disease */ x

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
[[Chronic Fatigue Syndrome|Chronic fatigue syndrome]] (CFS) is also known as [[myalgic encephalomyelitis]] (ME) or [[ME/CFS]]. There are many [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome| clinical and research definitions]], which creates confusion for doctors, researchers, and patients.

It is worth noting that [[chronic fatigue]] (without the "syndrome") is a symptom of many diseases, illnesses, [[depression]], and drug therapies. This term is not interchangeable with the grossly misnamed disease [[CFS]].
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":04">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":022">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":4">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|page=9|archive-url=|archive-date=|dead-url=|access-date=}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] symptoms to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
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| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
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| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[Portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda1994">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":02">{{Cite journal|last=Sharpe|first=M C|last2=Archard|first2=L C|last3=Banatvala|first3=J E|last4=Borysiewicz|first4=L K|last5=Clare|first5=A W|last6=David|first6=A|last7=Edwards|first7=R H|last8=Hawton|first8=K E|last9=Lambert|first9=H P|date=Feb 1991|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|volume=84|issue=2|pages=118–121|issn=0141-0768|pmc=1293107|pmid=1999813}}</ref> are used for diagnosing CFS, they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having CFS when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|title=What Does a True ME Definition Look Like?|last=Feb 02|first=2015|last2=Reactions|first2=6|website=MEadvocacy.org|access-date=2019-01-25}}</ref><ref>{{Cite web|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|title=Fukuda Definition (1994)|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|date=2014-03-25|website=Shoutout about ME|archive-url=|archive-date=|dead-url=|access-date=2019-01-25}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|title=AHRQ Evidence Review Changes Its Conclusions|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|date= 2016-08-16|website=occupyme.net|archive-url=|archive-date=|dead-url=|access-date=2019-01-25}}</ref> There have been media reports of athletes diagnosed with [[myalgic encephalomyelitis]] (ME) or [[chronic fatigue syndrome]] (CFS) who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref name=":10">{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref>

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":04" /> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":042">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />
=== Not a mental health disorder ===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

===ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":032">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":4" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref><ref>{{Cite web|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|title=Pediatric ME/CFS Home Page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|last=Capelli|first=E.|last2=Zola|first2=R.|last3=Lorusso|first3=L.|last4=Venturini|first4=L.|last5=Sardi|first5=F.|last6=Ricevuti|first6=G.|date=Oct 2010|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|volume=23|issue=4|pages=981–989|doi=10.1177/039463201002300402|issn=0394-6320|pmid=21244747}}</ref> while the CDC states 4:1.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-29}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":22">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-28}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":4" /><ref name="Carruthers, 2003" /><ref name=":5" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS is considered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":12">{{Cite journal|last=Cairns|first=R.|last2=Hotopf|first2=M.|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":12" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

==Evidence of a disease==

=== Symptoms ===
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about [[Post-exertional malaise|PEM]] and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] of [[Chronic fatigue|CF]] and [[Cognitive dysfunction|cognition]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":022" /><ref name=":0">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=2010-08-06|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref name=":2">[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":022" /><ref name=":0" /><ref name=":1" /><ref name=":2" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[Unrefreshing sleep|unrefreshing]] sleep ''See also:'' [[sleep disturbance]] <ref name=":6" /><ref name=":4" />

==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ) <ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide]<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness - Report Guide for Clinicians|last=|first=|date=2015|website=nationalacademies.org|publisher=Institute of Medicine of the National Academies|archive-url=|archive-date=|dead-url=|access-date=}}</ref> via The [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Primary Symptoms]<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-05-18|website=www.cdc.gov|language=en-us|access-date=2018-08-23}}</ref>

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]<ref>{{Cite web|url=http://linkis.com/org/tUheh|title=Myalgic Encephalomyelitis/Chronic Fatigue Syn - Toward Optimized Practice (TOP) - CPGs - Linkis.com|last=|first=|date=Jan 2016|website=linkis.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-23}}</ref>

===Biological abnormalities===
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the condition. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. While it is true that the condition is poorly understood, many biological abnormalities have been found in a range of different body systems, particularly in the [[central nervous system]], [[autonomic nervous system]], [[immune system]], and [[Metabolic|energy metabolism]].<ref name="IOM2015MECFS" /> Unfortunately, none have yet proved to be specific enough to ME/CFS as to be useful as a [[Diagnostic biomarker|biomarker]] of the condition, and many were identified in small studies, which need replication. Whilst there have been abnormalities identified to be associated with the condition, it cannot yet be determined whether these are a cause or consequence of the condition.
* [[Gastrointestinal system]]
* [[Natural killer cell]] findings

==== Notable studies ====
* [[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*Immune findings by [[Mady Hornig]] & [[Ian Lipkin]]<ref name="Hornig20150201immune" />
*[[List of enterovirus infection studies]]

*2014/15, [[Neuroinflammation]] Japanese Neuroinflammation study<ref name="NakatomiY2014" />, Younger's Leptin study <ref name="JohnsonC20150126younger" />
* 2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=2018-12-14|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

===Causes & triggers===
*Outbreaks - see [[List of outbreaks]]
*Possible infectious triggers: [[Enterovirus]]es, [[Herpesvirus]]es including [[Epstein-Barr virus]]<ref name="Hickie2006" />, [[Q fever]]<ref name="Hickie2006" />, [[Ross River virus]]<ref name="Hickie2006" />, ([[Ebola]]?)<ref name="Hickie2006" />
*Non-viral triggers - [[trauma]], chemical

===Epidemiology===
Prevalence estimates for ME/CFS range between 0.2-2.5%, depending on the definition of the condition used.<ref name="ICC2011criteria" /> In the US, estimates range between 836,000 and 2.5 million people with the condition, though true numbers are under-reported. It is estimated that 84-91% of people with the condition remain undiagnosed.<ref name="IOM2015MECFS" />

*Level of disability (Norwegian study HRQoL)<ref name="Hvidberg2015" /> (suggests quality of life is LOWER than for many cancers, heart diseases, brain stroke, diabetes I & II, rheumatoid arthritis, chronic renal failure, sclerosis, schizophrenia, COPD, etc)

===Severely ill patients===
Considerable variation exists in the severity of the condition. The [[International Consensus Criteria]] lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):

*Mild = 50% reduction in pre-illness activity levels
*Moderate = mostly housebound
*Severe = mostly bedridden
*Very Severe = totally bedridden, and needing help with basic functions.

At least [[Severe and very severe ME|25% of people with ME/CFS are bed-bound or housebound]], often for years or even decades, so are largely an invisible population.<ref name="IOM2015MECFS" /> So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The [[Open Medicine Foundation]]'s [[ME/CFS Severely Ill, Big Data Study]] will be the first in-depth study of people with a severe form of ME/CFS.

Notable patients with severe ME/CFS include [[Whitney Dafoe]], [[Karina Hansen]] (had been sanctioned), [[Laura Hillenbrand]], [[Tom Kindlon]], [[Doctor Speedy]], [[Naomi Whittingham]], [[Jennifer Brea|Jen Brea]], and [[Emma Shorter]].

Though uncommon, there have been instances of deaths which have been attributed to the condition. See: [[Sophia Mirza]] (sanctioned and now diseased) and [[Merryn Crofts]]. Also, see [[Vanessa Li]] and [[Lynn Gilderdale]].

===Centers for Disease Control and Prevention (CDC) ===
*Jul 3, 2017, the [[CDC]]'s Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) recommendations have been removed.<ref>{{Cite web|url=http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/|title=Trial By Error: The CDC Drops CBT/GET|last=Tuller|first=David|date=2017-07-10|website=www.virology.ws|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-23}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/index.html|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-03|website=www.cdc.gov|language=en-us|access-date=2018-08-23}}</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC.gov]</ref><ref>{{Cite web|url=https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html|title=New ME/CFS Web Content for Healthcare Providers {{!}} CDC Online Newsroom {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-08-23}}</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] [[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's [[ME/CFS]] page have been created from patient feedback on the updates as well as asking for further patient input.

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Treatments==
There are currently no [[FDA]] approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.<ref name="IACFSME2014primer" /> There are many [http://me-pedia.org/wiki/Welcome_to_MEpedia#Potential_treatments potential treatments], though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.

=== Drugs ===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the [[United States]] have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the United States, known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced he will be undertaking a trial of [[low dose naltrexone]] ([[LDN]]) in ME/CFS.<ref>{{Cite web|url=https://www.youtube.com/watch?v=95OlnK-FEdk|title=2017 Study -- Low Dose Naltrexone for Chronic Fatigue Syndrome|last=Younger|first=Jared|date=2016-12-12|website=YouTube|publisher=Younger Lab|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Exercise as treatment===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Two common treatment recommendations for ME/CFS are [[GET]] and [[CBT]]. These treatments are based on the hypothesis that the condition might have begun with a viral infection but has been perpetuated by [[deconditioning]] from lack of activity, and fear and avoidance of activity. GET & CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that result in avoidance of activity and reconditioning through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which suggests that exercise may actually be harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,<ref name="MEASSUK20150529survey" /> which is consistent with other patient surveys.<ref name="Phoenix20160222Norway2012" />

The [[PACE trial]], published in 2011, is the largest GET trial ever conducted. It has received much publicity as a result of its recovery rate claims, though it has come under strong criticism from within both the scientific and patient community for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.<ref>{{Cite journal|last=Coyne|first=James Charles|last2=Laws|first2=Keith R|date=2016|title=Results of the PACE follow-up study are uninterpretable|url=http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00551-9/fulltext|journal=The Lancet Psychiatry|language=English|volume=3|issue=2|pages=e6–e7|doi=10.1016/S2215-0366(15)00551-9|issn=2215-0366|via=}}</ref> The study was the subject of a series of investigative pieces by journalist [[David Tuller]] in late 2015, that were highly critical of the trial.<ref name="viroblogMECFS" /> A petition signed by almost 12,000 ME/CFS patients and allies,<ref name="MEACTIONpacepetition" /> and an open letter signed by 42 ME/CFS experts from around the world,<ref name="openletrLANCET2" /> were sent to The Lancet, both calling for the data to be reanalyzed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.<ref name="MEACTION20160313openletr" /> To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the PACE trial continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.

One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of [[post-exertional malaise]] (PEM), which is an exacerbation of symptoms following physical, mental or even emotional [[exertion]]. Studies have revealed immunological, muscular, [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]] and [[Cardiovascular system|cardiovascular]] abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary controls, the adverse effects of exercise cannot be said to be due to deconditioning.<ref name="TwiskF2015" /><ref>reference needed - Workwell Foundation studies</ref><ref>reference needed - the Lights epigenetic changes post-exercise</ref>

People with ME/CFS should approach exercise with caution, as there is much potential for harm.

[[Anaerobic]] threshold, use of HR monitors for activity and pacing. Analeptic, not aerobic.
[[Energy Envelope Theory|Energy envelope]]/[[pacing]] - people do better if stay within their envelope than to push to increase activity

===Graded exercise therapy & Cognitive behavioral therapy ===
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]

[[Graded exercise therapy|GET]] and [[Cognitive behavioral therapy|CBT]] are usually employed in the [[United Kingdom|UK]], [[Ireland]] and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the disproven [[biopsychosocial model]] of ME/CFS, backed up by the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Maik Speedy|Dr Maik Speedy]] was also seriously injured by GET and has been bedbound since.
*British MP [[Brynmor John]] collapsed outside the House of Commons gym in 1998 and died, as a result of following his doctor's advice to exercise back to health.

=== Claims of recovery and cures ===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF) which is not the result of the neurological illness CFS. Some people misdiagnosed and "recovered" from CFS most likely had CF which can be caused by many illnesses, diseases, and drug therapies or a bad year or two perhaps with [[mononucleosis]] followed by a bout or two of [[influenza]]. These individuals were experiencing a proper immune response whereas ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":7" /><ref name=":8" /><ref name=":9" /><ref name=":10" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

== Notable studies ==
*[[Pathways to prevention report]] (P2P)
*[[Institute of Medicine report]]
*[[PACE trial]] is a highly criticized UK trial designed by psychiatrists to promote [[GET]] and [[CBT]] as therapy which is deemed harmful and useless for ME/CFS patients by many clinicians, researchers, patients, and advocates.

== Continuing education (CME and CE) ==
* [https://www.msms.org/Education/On-Demand-Webinars/Webinar/1059 Update on Chronic Fatigue Syndrome Part 1: Clinical Diagnostic Criteria for Chronic Fatigue Syndrome/CFS now called Myalgic Encephalomyelitis or ME/CFS]<ref>{{Cite web|url=https://www.msms.org/Education/On-Demand-Webinars/Webinar/1059|title=Update on Chronic Fatigue Syndrome Part 1: Clinical Diagnostic Criteria for Chronic Fatigue Syndrome/CFS now called Myalgic Encephalomyelitis or ME/CFS|last=|first=|authorlink=Lucinda Bateman|last2=|first2=|authorlink2=|date=|website=www.msms.org|publisher=Michigan State Medical Society|via=On-Demand Webinars|archive-url=|archive-date=|dead-url=|access-date=2019-02-25}}</ref> (CME)
* [https://www.msms.org/Education/On-Demand-Webinars/Webinar/1060 Update on Chronic Fatigue Syndrome Part 2: Uniting Compassion, Attention and Innovation to treat ME/CFS.]<ref>{{Cite web|url=https://www.msms.org/Education/On-Demand-Webinars/Webinar/1060|title=Update on Chronic Fatigue Syndrome Part 2: Uniting Compassion, Attention and Innovation to treat ME/CFS.|last=|first=|authorlink=Lucinda Bateman|last2=|first2=|authorlink2=|date=|website=www.msms.org|publisher=Michigan State Medical Society|via=On Demand Webinars|archive-url=|archive-date=|dead-url=|access-date=2019-02-25}}</ref> (CME)
* [https://www.medscape.org/viewarticle/907632?src=acdmpart_cdc Diagnosing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Experts Weigh In]<ref>{{Cite web|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUub3JnL3ZpZXdhcnRpY2xlLzkwNzYzMj9zcmM9YWNkbXBhcnRfY2Rj&ac=401|title=Diagnosing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Experts Weigh In|last=|first=|authorlink=Lucinda Bateman|last2=|first2=|authorlink2=Natalie Azar|date=|website=medscape.com|publisher=Medscape|archive-url=|archive-date=|dead-url=|access-date=2019-02-25|authorlink3=Nancy Klimas|authorlink4=Jose Montoya}}</ref> (CME/CE)
* [https://www.unrest.film/cme Watch ''Unrest'' and Receive Continuing Medical Education (CME /CE) Credit]<ref>{{Cite web|url=https://www.unrest.film/cme|title=Unrest Continuing Medical Education Program|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=UNREST|publisher=Unrest|language=en-US|others=Indiana University School of Medicine, American Medical Women’s Association|archive-url=|archive-date=|dead-url=|access-date=2019-02-25}}</ref>

==History==
*[[Osler's Web|''Osler's Web'']] is a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>{{Cite news|url=https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/|title=Not, sadly, the first|work=New Scientist|access-date=2018-08-23|language=en-US}}</ref> See Editor's Note<ref>{{Cite news|url=https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/|title=First official UK death from chronic fatigue syndrome|last=Hooper|first=Rowan|date=2006-06-16|work=New Scientist|access-date=2018-08-23|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

==See also==
*[[David Tuller]]
*[[Fibromyalgia]]
*[[PACE trial]]
*[[Primer for patients]]
*[[Primer for the public#Disease_names_and_acronyms_around_the_world|Primer for the public (''Disease names and acronyms around the world'' section)]]
==Learn more==
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

'''ME/CFS organization's and researcher's material'''
*[https://www.youtube.com/watch?v=hRdn4A2SGic Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]<ref>{{Cite web|url=https://www.youtube.com/watch?v=hRdn4A2SGic|title=Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education|last=Iskander|first=John|last2=Komaroff|first2=Anthony|date=2016-02-17|website=YouTube|publisher=Centers for Disease Control and Prevention (CDC)|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis]<ref>{{Cite news|url=https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view|title=Caregivers Guide to ME.pdf|last=|first=|date=2018|work=Google Docs|access-date=2018-08-23|archive-url=|archive-date=|dead-url=|publisher=#MEAction}}</ref>
*[http://iacfsme.org/portals/0/pdf/Primer_Post_2014_conference.pdf IACFS/ME Primer for Clinical Practitioners - 2014 Edition]<ref name="IACFSME2014primer" />
*[http://www.meassociation.org.uk/2014/07/our-purple-booklet-clear-clinical-guidance-and-the-latest-research-all-wrapped-up-in-52-pages/ ME Association clinical guidance]<ref name="MEASSUKprimer2013" />
*[http://youtu.be/c2vIQ92wU9Y ME/CFS Diagnosis and Name with Dr Nancy Klimas (video)]<ref>{{Cite web|url=https://www.youtube.com/watch?v=c2vIQ92wU9Y&feature=youtu.be|title=ME/CFS Diagnosis and Name with Dr. Nancy Klimas|last=Klimas|first=Nancy|date=2014-06-21|website=YouTube|publisher=ME/CFS Community|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
*[http://treatmentcenterforcfs.com/documents/MECFSTreatmentResourceGuideforPractitioners.pdf ME/CFS Treatment Resource Guide for Practitioners by A Martin Lerner, MD]<ref name="LernerPrimer2011" />
*[http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf Myalgic Encephalomyelitis - Adult & Pediatric - International Consensus Criteria Primer for Medical Practitioners]<ref name="ICP2011primer" />
*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]<ref>{{Cite news|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS? {{!}} Open Medicine Foundation|work=Open Medicine Foundation|access-date=2018-08-23|language=en-US}}</ref>

'''[[Patient mental health]]'''

:Patients
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.

'''More mental health information'''
*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>{{Cite news|url=http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm|title=Depression in Fibromyalgia and Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Aug 2, 2018|work=Verywell Health|access-date=2018-08-23|archive-url=|archive-date=|dead-url=}}</ref><ref>{{Cite web|url=http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences|title=CFS or depression - what are the differences - DoctorMyhill|website=drmyhill.co.uk|language=en|access-date=2018-08-23}}</ref>

'''Research'''
* 2015, [[Institute of Medicine report]] (IOM Report)

* 2016, [http://www.tandfonline.com/doi/full/10.1080/21641846.2016.1160598 The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem]<ref name="Edwards2016" />
*2018, The CDC based its updated [https://www.cdc.gov/me-cfs/index.html ME/CFS page] based on the IOM Report.
*[[Notable studies]]
'''Articles and blogs'''
* Feb 21, 2019 ''[https://www.rcseng.ac.uk/news-and-events/blog/differential-diagnosis-me/ Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined?]''<ref>{{Cite web|url=https://www.rcseng.ac.uk/news-and-events/blog/differential-diagnosis-me/|title=Are surgeons missing the major differential diagnosis that is more common than multiple sclerosis and HIV combined?|last=Muirhead|first=Nina|authorlink=|last2=|first2=|authorlink2=|date=Feb 21, 2019|website=Royal College of Surgeons|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-22}}</ref>

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[[Category:Primers]]

Systemic Exertion Intolerance Disease

2019-04-14T14:21:06Z

MEandCFS:/* Development */ x

'''Systemic Exertion Intolerance Disease''' (SEID) was the new name proposed at the same time as the diagnostic criteria developed by the [[National Academy of Medicine]] (NAM) (formerly the Institute of Medicine, IOM) published on February 10, 2015. The report was titled ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', and is also referred to as the [[Institute of Medicine report]].

The IOM diagnostic criteria requires [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]; and [[Cognitive dysfunction|cognitive impairment]] and/or [[orthostatic intolerance]] (OI).<ref name=":2">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Diagnostic Algorithm for ME/CFS|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> It is also useful for a more severe presentation of the disease; symptom severity and other symptoms are outlined in the Institute of Medicine report.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/7|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=141-162|language=en|chapter=5|quote=|editor-last2=|editor-link2=}}</ref>

Adults can be diagnosed at six months of illness and [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|pediatric]] cases are diagnosed at three months.
[[File:Morgan Fairchild.png |300px|thumb|right|[[Morgan Fairchild]] is an [[United States|American]] actress of film and television. She was diagnosed with [[chronic fatigue syndrome]] (CFS) in 1989. On March 25, 2015, she gave a [https://www.youtube.com/watch?v=lWTF80daWtw speech] during the [[IOM]] briefing of the rollout of SEID where she says compared to others suffering with [[ME/CFS]] she has a mild case]]

==Authors==
[[File:Rosa SEID.JPG|400px|thumb|Rosa age 25 in 1986 and mildly ill with [[ME/CFS]]. Rosa believes she then met the SEID criteria developed in 2015 and this is when she first read about [[Post-exertional malaise|PEM]]. She became worse over the years and in 2003 was diagnosed and disabled with [[chronic fatigue syndrome]] (CFS) which was the name for ME/CFS at the time. Rosa now meets the [[CCC]] criteria with PEM "[[Canadian Consensus Criteria#Definition|option]]". ME/CFS onset was [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|age 17]] and [[fibromyalgia]] since puberty]]
The committee on the Diagnostic Criteria for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) consisted of [[Ellen Wright Clayton]], [[Margarita Alegría]], [[Lucinda Bateman]], [[Lily Chu]], [[Charles Cleeland]], [[Ronald Davis]], [[Betty Diamond]], [[Theodore Ganiats]], [[Betsy Keller]], [[Nancy Klimas]], [[A Martin Lerner]], [[Cynthia Mulrow]], [[Benjamin Natelson]], [[Peter Rowe]], and [[Michael Shelanski]].

==Development==
In 2014, the [[U.S. Department of Health and Human Services]] (HHS), the [[National Institutes of Health]] (NIH), the [[Agency for Healthcare Research and Quality]] (AHRQ), the [[Centers for Disease Control & Prevention]] (CDC), the [[Food and Drug Administration]] (FDA), and the [[Social Security Administration]] (SSA) asked the [[Institute of Medicine]] (IOM) to convene an expert committee to examine the evidence base for [[ME/CFS]]. In ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', the committee proposes new diagnostic criteria that will facilitate timely diagnosis and care and enhance understanding among health care providers and the public. These criteria, based on expert analysis and the most up-to-date scientific literature, are streamlined for practical use in the clinical setting. The IOM committee also recommends that the name of the disease be changed—from ME/CFS to systemic exertion intolerance disease (SEID)—to more accurately capture the central characteristics of the illness.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=|website=nationalacademies.org|page=5|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

'''The proposed name and acronym SEID is meant to hone in on key aspects of''' ME/CFS'''.''' '''''S'''ystemic'' would give credence to the disease being body wide. '''''E'''xertion '''I'''ntolerance'' would key doctors into understanding that the patient CAN NOT tolerate exertion of any kind; physical, cognitive or emotional.<ref>{{Cite news|url=http://www.shoutoutaboutme.com/about-mecfs/seid-diagnostic-criteria-proposed/|title=NIH/IOM 2015 Definition (SEID)|last=Logan|first=Russell|date=Jan 3, 2015|work=Shoutout about ME|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-us}}</ref> (Intolerance is well understood in the medical field in that there is a medical problem. Other diseases, such as gluten intolerance, is a serious medical condition; gluten CAN NOT be consumed.) '''''D'''isease'' gave the self-explanatory label of being an organic biological disease.

==Diagnostic criteria==
[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm<ref name=":2" />]]
'''Diagnosis requires that the patient have the following three symptoms:'''

1. A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied
by [[Chronic fatigue|fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest]], and

2. [[Post-exertional malaise]],* and

3. [[Unrefreshing sleep]]*

'''At least one of the two following manifestations is also required:'''

1. [[Cognitive impairment]]* or

2. [[Orthostatic intolerance]]

: * Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS (SEID) should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

===Centers for Disease Control and Prevention (CDC) website===

:Note: The name "Systemic Exertion Intolerance Disease" (SEID) has not been adopted but the new diagnostic criteria have been incorporated into the [[Centers for Disease Control and Prevention]] (CDC) ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html IOM 2015 Diagnostic Criteria].<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== SEID vs Other criteria ==
The SEID criteria are the most symptom liberal of the valid ''disease'' definition criteria. The [[Canadian Consensus Criteria]] (CCC) are for ME/CFS, and [[International Consensus Criteria]] (ICC) are for ME.<ref>{{Cite journal|last=Chu|first=Lily|last2=Norris|first2=Jane L.|last3=Valencia|first3=Ian J.|last4=Montoya|first4=Jose G.|date=2017-03-13|title=Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria|url=http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=114–128|doi=10.1080/21641846.2017.1299079|issn=2164-1846}}</ref>

The IOM report calls for the "retirement" of the [[Oxford criteria]] for [[chronic fatigue syndrome]] (CFS).<ref>{{Cite web|url=http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/|title=US NIH Report Calls for UK Definition of ME/CFS to be Scrapped|last=Swift|first=Penny|date=|website=theargusreport.com|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-03}}</ref> The [[Fukuda criteria]] are also for CFS.

Comparison chart of the [[International Consensus Criteria|ICC]] and SEID: [https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663 ICC compared to IOM (SEID)].<ref>{{Cite web|url=https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663|title=International Consensus Criteria (ICC) vs Systemic Exertion Intolerance Disease (SEID)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cloudfront.net|publisher=MEadvocacy.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

== Criticism ==
The main criticism is the missing of [[immune system]] and [[nervous system]] symptoms, and the unclear and wide criterion of the main symptom (PEM) and missing of important symptoms like pain, lab tests, and missing exclusions.

ME was the original name for CFS; the names are often used interchangeably or with the acronym ME/CFS.<ref name=":0">{{Cite news|url=https://www.verywellhealth.com/myalgic-encephalomyelitis-me-715663|title=Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Nov 24, 2018|work=Verywell Health|access-date=2018-11-28|archive-url=|archive-date=|dead-url=|quote=|author-link=}}</ref> The name SEID, although giving credence to the fact that patients are intolerant to [[exertion]], does not capture the debilitating [[central nervous system]] (CNS) symptoms patients experience as the name ME does.

[[Frank Twisk|Twisk]] (2017) stated that ME and CFS are different illnesses, with ME being a neuromuscular disease and CFS being a partially overlapping fatigue-based illness, and that it was not possible to replace both ME and CFS with a single diagnostic entity. Twisk also stated that SEID included some patients that did not meet either ME or CFS diagnostic criteria.<ref name=":1">{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|author-link2=|author-link3=|author-link4=|author-link5=|date=Jun 27, 2017|title=An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods|url=https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf|journal=Journal of Medical Diagnostic Methods|volume=6|issue=3|pages=|doi=10.4172/2168-9784.1000249|quote=|via=l}}</ref>

== Clinicians guide ==
The [http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Report Guide for Clinicians] explains the core symptoms, additional symptoms, diagnostic criteria and more. (Feb 10, 2015)

===Centers for Disease Control and Prevention (CDC) website===

: Note: This clinicians guide has been incorporated into the CDC's ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers] under the "Resources" heading with a page disclaimer: "The findings and conclusions in these documents are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC)."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html|title=Information for Healthcare Providers {{!}} ME/CFS {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== The Institute of Medicine report ==

'''''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'''''

===Read the report===
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Key facts] (two pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Report brief] (four pages)
*[http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx Download full report] (282 pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm Diagnostic Algorithm Chart]
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ProposedDiagnosticCriteria Proposed Diagnostic Criteria Chart]
*[http://www.nap.edu/read/19012/chapter/1 Read the full 282 page report online]
**[http://www.nap.edu/read/19012/chapter/1 Front matter]
**[http://www.nap.edu/read/19012/chapter/2 Summary]
**[http://www.nap.edu/read/19012/chapter/3 1. Introduction]
**[http://www.nap.edu/read/19012/chapter/4 2. Background]
**[http://www.nap.edu/read/19012/chapter/5 3. Current Case Definitions and Diagnostic Criteria, Terminology, and Symptom Constructs and Clusters]
**[http://www.nap.edu/read/19012/chapter/6 4. Review of the Evidence on Major ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/7 5. Review of the Evidence on Other ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/8 6. Pediatric ME/CFS]
**[http://www.nap.edu/read/19012/chapter/9 7. Recommendations]
**[http://www.nap.edu/read/19012/chapter/10 8. Dissemination Strategy]
**[http://www.nap.edu/read/19012/chapter/11 Public Session Agendas]
**[http://www.nap.edu/read/19012/chapter/12 GRADE Grid Template]
**[http://www.nap.edu/read/19012/chapter/13 Disability in ME/CFS]
**[http://www.nap.edu/read/19012/chapter/14 Questionnaires and Tools That May Be Useful for Assessing ME/CFS Symptoms]
**[http://www.nap.edu/read/19012/chapter/15 Biographical Sketches of Committee Members, Consultants, and Staff]

[http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" Official video presentation]

== Videos ==
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]]
:[[CDC]] Posted Video - Dr. [[John Iskander]] of CDC interviews Dr. [[Anthony Komaroff]] (Feb 17, 2016)

*[https://www.youtube.com/watch?v=ZW2Tcsp75a0 SMCI IOM Briefing in Washington, D.C. Full Coverage]<ref>{{Cite web|url=https://www.youtube.com/watch?v=ZW2Tcsp75a0|title=SMCI IOM Briefing in Washington, D.C. Full Coverage|last=|first=|date=Mar 25, 2015|website=YouTube|publisher=SolveCFS|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:[[Carol Head]] of [[Solve ME/CFS]], Dr. [[Ellen Wright Clayton]] and [https://en.wikipedia.org/wiki/Morgan_Fairchild Morgan Fairchild]

*[https://www.youtube.com/watch?v=X4Tnt2d-5S8 New Clinical Definitions for ME/CFS - Dr. Lucinda Bateman]<ref>{{Cite web|url=https://www.youtube.com/watch?v=X4Tnt2d-5S8|title="New Clinical Definitions for ME/CFS" Dr. Lucinda Bateman|last=Bateman|first=Lucinda|date=Mar 8, 2015|website=YouTube|publisher=Bateman Horne Center|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:Dr. [[Lucinda Bateman]] of [[Bateman Horne Center]] discusses. (Mar 8, 2015)

==Notable studies==
* 2015, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556426/pdf/nihms699325.pdf Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease]<ref name="Jason, Sunn, 2015" />
* 2015, Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease<ref>{{Cite journal|last=Jason|first=Leonard A.|author-link=Leonard Jason|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Kot|first3=Bobby|author-link3=Bobby Kot|last4=Brown|first4=Abigail|author-link4=Abigail Brown|last5=|last7=|last8=|date=Jun 23, 2015|title=Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease|url=https://www.mdpi.com/2075-4418/5/2/272|journal=Diagnostics|language=en|volume=5|issue=2|pages=272–286|doi=10.3390/diagnostics5020272|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/5/2/272/htm (Full text)]
* 2016, Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward<ref>{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|last2=|first2=|author-link2=|author-link3=|author-link4=|author-link5=|date=Feb 6, 2016|title=Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward|url=https://www.mdpi.com/2075-4418/6/1/10|journal=Diagnostics|language=en|volume=6|issue=1|pages=10|doi=10.3390/diagnostics6010010|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/6/1/10 (Full text)]
* 2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20& Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria]<ref name="Chu, 2017" />

==Letters and commentary==
*2017, An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods<ref name=":1" /> [https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf (Full text)]
*2017, [http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1362750 Article commentary - Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox]<ref name="Chu, Valencia, Montoya, 2017" />
*2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1362780 Article commentary - Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.]<ref name="Jason, Sunnquist, Gleason, Fox, 2017" />

==In popular culture==
A February 2016 comic strip referred to SEID and implied it is simply tiredness. ''See'': [[Blondie comic]]

==See also==
* [[Chronic fatigue syndrome]]
* [[ME/CFS]]
* [[Myalgic encephalomyelitis]]

*[[NIH Post-Infectious ME/CFS Study]] - [[SEID]] will be used in this study.<ref>{{Cite news|url=http://www.meaction.net/2016/02/09/positive-answers-to-initial-questions-re-nih-clinical-center-protocol/|title=Positive Answers to Initial Questions re NIH Clinical Center Protocol - #MEAction|last=Alexander Miller|first=Courtney|date=2016-02-09|work=#MEAction|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Severe and very severe ME]]

===Generally accepted criteria for diagnosing ME/CFS and ME ===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria]] (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> This criterion will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegría|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*2015, [https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/ Chronic fatigue syndrome gets yet another name]<ref>{{Cite news|url=https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/|title=Chronic fatigue syndrome gets yet another name|last=Coghlan|first=Andy|date=Feb 10, 2015|work=New Scientist|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*2015, [http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract Systemic Exercise Intolerance Disease: What’s in a name?]<ref>{{Cite journal|last=Sen|first=Mahadev Singh|last2=Sahoo|first2=Swapnajeet|last3=Aggarwal|first3=Shivali|last4=Singh|first4=Shubh Mohan|date=2016|title=Systemic exercise intolerance disease: What’s in a name?|url=http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract|journal=Asian Journal of Psychiatry|language=English|volume=22|pages=157–158|doi=10.1016/j.ajp.2016.06.003|issn=1876-2018|via=}}</ref>
*2018, [https://youtu.be/RC9TjgE_PlU?t=89 Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome]<ref>{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=89|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=Oct 16, 2018|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.|at=1:29}}</ref> (Notes the IOM report's diagnostic criteria.)

== References ==
<references>
<ref name="Chu, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Norris | first2 = Jane | authorlink2 = Jane Norris
| last3 = Valencia | first3 = Ian J. | authorlink3 =
| last4 = Montoya | first4 = Jose G. | authorlink4 = Jose Montoya
| title = Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 5 | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1299079
}}
</ref>
<ref name="Chu, Valencia, Montoya, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Valencia | first2 = Ian J. | authorlink2 =
| last3 = Montoya | first3 = Jose G. | authorlink3 = Jose Montoya
| title = Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1362750
}}
</ref>
<ref name="Jason, Sunn, 2015">{{Citation
| last1 = Jason | first1 = L.A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = M. | authorlink2 = Madison Sunnquist
| last3 = Brown | first3 = A. | authorlink3 =
| last4 = Newton | first4 = J.L. | authorlink4 = Julia Newton
| last5 = Strand | first5 = E.B. | authorlink5 = Elin Strand
| last6 = Vernon | first6 = S.D. | authorlink6 = Suzanne Vernon
| title = Chronic fatigue syndrome versus systemic exertion intolerance disease
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 3 | issue = 3 | page = 127-141
| date = 2015
| pmid =
| doi = 10.1080/21641846.2015.1051291
}}</ref>
<ref name="Jason, Sunnquist, Gleason, Fox, 2017">{{Citation
| last1 = Jason | first1 = Leonard A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = Madison | authorlink2 = Madison Sunnquist
| last3 = Gleason | first3 = Kristen | authorlink3 = Kristen Gleason
| last4 = Fox | first4 = Pamela | authorlink4 = Pamela Fox
| title = Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| pmid =
| doi = 10.1080/21641846.2017.1362780
}}
</ref>
</references>

[[Category:Definitions]]
[[Category:Diagnoses]]
[[Category:Disease names]]

Systemic Exertion Intolerance Disease

2019-04-14T14:16:21Z

MEandCFS:/* Authors */ x

'''Systemic Exertion Intolerance Disease''' (SEID) was the new name proposed at the same time as the diagnostic criteria developed by the [[National Academy of Medicine]] (NAM) (formerly the Institute of Medicine, IOM) published on February 10, 2015. The report was titled ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', and is also referred to as the [[Institute of Medicine report]].

The IOM diagnostic criteria requires [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]; and [[Cognitive dysfunction|cognitive impairment]] and/or [[orthostatic intolerance]] (OI).<ref name=":2">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Diagnostic Algorithm for ME/CFS|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> It is also useful for a more severe presentation of the disease; symptom severity and other symptoms are outlined in the Institute of Medicine report.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/7|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=141-162|language=en|chapter=5|quote=|editor-last2=|editor-link2=}}</ref>

Adults can be diagnosed at six months of illness and [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|pediatric]] cases are diagnosed at three months.
[[File:Morgan Fairchild.png |300px|thumb|right|[[Morgan Fairchild]] is an [[United States|American]] actress of film and television. She was diagnosed with [[chronic fatigue syndrome]] (CFS) in 1989. On March 25, 2015, she gave a [https://www.youtube.com/watch?v=lWTF80daWtw speech] during the [[IOM]] briefing of the rollout of SEID where she says compared to others suffering with [[ME/CFS]] she has a mild case]]

==Authors==
[[File:Rosa SEID.JPG|400px|thumb|Rosa age 25 in 1986 and mildly ill with [[ME/CFS]]. Rosa believes she then met the SEID criteria developed in 2015 and this is when she first read about [[Post-exertional malaise|PEM]]. She became worse over the years and in 2003 was diagnosed and disabled with [[chronic fatigue syndrome]] (CFS) which was the name for ME/CFS at the time. Rosa now meets the [[CCC]] criteria with PEM "[[Canadian Consensus Criteria#Definition|option]]". ME/CFS onset was [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|age 17]] and [[fibromyalgia]] since puberty]]
The committee on the Diagnostic Criteria for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) consisted of [[Ellen Wright Clayton]], [[Margarita Alegría]], [[Lucinda Bateman]], [[Lily Chu]], [[Charles Cleeland]], [[Ronald Davis]], [[Betty Diamond]], [[Theodore Ganiats]], [[Betsy Keller]], [[Nancy Klimas]], [[A Martin Lerner]], [[Cynthia Mulrow]], [[Benjamin Natelson]], [[Peter Rowe]], and [[Michael Shelanski]].

==Development==
In 2014, the [[U.S. Department of Health and Human Services]] (HHS), the [[National Institutes of Health]] (NIH), the [[Agency for Healthcare Research and Quality]] (AHRQ), the [[Centers for Disease Control & Prevention]] (CDC), the [[Food and Drug Administration]] (FDA), and the [[Social Security Administration]] (SSA) asked the [[Institute of Medicine]] (IOM) to convene an expert committee to examine the evidence base for [[ME/CFS]]. In ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', the committee proposes new diagnostic criteria that will facilitate timely diagnosis and care and enhance understanding among health care providers and the public. These criteria, based on expert analysis and the most up-to-date scientific literature, are streamlined for practical use in the clinical setting. The IOM committee also recommends that the name of the disease be changed—from ME/CFS to systemic exertion intolerance disease (SEID)—to more accurately capture the central characteristics of the illness.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=|website=nationalacademies.org|page=5|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

'''The proposed name and acronym SEID is meant to hone in on key aspects of''' ME/CFS'''.''' '''''S'''ystemic'' would give credence to the disease being body wide. '''''E'''xertion '''I'''ntolerance'' would key doctors into understanding that the patient CANNOT tolerate exertion of any kind; physical, cognitive or emotional.<ref>{{Cite news|url=http://www.shoutoutaboutme.com/about-mecfs/seid-diagnostic-criteria-proposed/|title=NIH/IOM 2015 Definition (SEID)|last=Logan|first=Russell|date=Jan 3, 2015|work=Shoutout about ME|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-us}}</ref> (Intolerance is well understood in the medical field in that there is a medical problem. Other diseases, such as gluten intolerance, is a serious medical condition; gluten CAN NOT be consumed.) '''''D'''isease'' gave the self-explanatory label of being an organic biological disease.

==Diagnostic criteria==
[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm<ref name=":2" />]]
'''Diagnosis requires that the patient have the following three symptoms:'''

1. A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied
by [[Chronic fatigue|fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest]], and

2. [[Post-exertional malaise]],* and

3. [[Unrefreshing sleep]]*

'''At least one of the two following manifestations is also required:'''

1. [[Cognitive impairment]]* or

2. [[Orthostatic intolerance]]

: * Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS (SEID) should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

===Centers for Disease Control and Prevention (CDC) website===

:Note: The name "Systemic Exertion Intolerance Disease" (SEID) has not been adopted but the new diagnostic criteria have been incorporated into the [[Centers for Disease Control and Prevention]] (CDC) ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html IOM 2015 Diagnostic Criteria].<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== SEID vs Other criteria ==
The SEID criteria are the most symptom liberal of the valid ''disease'' definition criteria. The [[Canadian Consensus Criteria]] (CCC) are for ME/CFS, and [[International Consensus Criteria]] (ICC) are for ME.<ref>{{Cite journal|last=Chu|first=Lily|last2=Norris|first2=Jane L.|last3=Valencia|first3=Ian J.|last4=Montoya|first4=Jose G.|date=2017-03-13|title=Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria|url=http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=114–128|doi=10.1080/21641846.2017.1299079|issn=2164-1846}}</ref>

The IOM report calls for the "retirement" of the [[Oxford criteria]] for [[chronic fatigue syndrome]] (CFS).<ref>{{Cite web|url=http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/|title=US NIH Report Calls for UK Definition of ME/CFS to be Scrapped|last=Swift|first=Penny|date=|website=theargusreport.com|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-03}}</ref> The [[Fukuda criteria]] are also for CFS.

Comparison chart of the [[International Consensus Criteria|ICC]] and SEID: [https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663 ICC compared to IOM (SEID)].<ref>{{Cite web|url=https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663|title=International Consensus Criteria (ICC) vs Systemic Exertion Intolerance Disease (SEID)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cloudfront.net|publisher=MEadvocacy.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

== Criticism ==
The main criticism is the missing of [[immune system]] and [[nervous system]] symptoms, and the unclear and wide criterion of the main symptom (PEM) and missing of important symptoms like pain, lab tests, and missing exclusions.

ME was the original name for CFS; the names are often used interchangeably or with the acronym ME/CFS.<ref name=":0">{{Cite news|url=https://www.verywellhealth.com/myalgic-encephalomyelitis-me-715663|title=Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Nov 24, 2018|work=Verywell Health|access-date=2018-11-28|archive-url=|archive-date=|dead-url=|quote=|author-link=}}</ref> The name SEID, although giving credence to the fact that patients are intolerant to [[exertion]], does not capture the debilitating [[central nervous system]] (CNS) symptoms patients experience as the name ME does.

[[Frank Twisk|Twisk]] (2017) stated that ME and CFS are different illnesses, with ME being a neuromuscular disease and CFS being a partially overlapping fatigue-based illness, and that it was not possible to replace both ME and CFS with a single diagnostic entity. Twisk also stated that SEID included some patients that did not meet either ME or CFS diagnostic criteria.<ref name=":1">{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|author-link2=|author-link3=|author-link4=|author-link5=|date=Jun 27, 2017|title=An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods|url=https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf|journal=Journal of Medical Diagnostic Methods|volume=6|issue=3|pages=|doi=10.4172/2168-9784.1000249|quote=|via=l}}</ref>

== Clinicians guide ==
The [http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Report Guide for Clinicians] explains the core symptoms, additional symptoms, diagnostic criteria and more. (Feb 10, 2015)

===Centers for Disease Control and Prevention (CDC) website===

: Note: This clinicians guide has been incorporated into the CDC's ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers] under the "Resources" heading with a page disclaimer: "The findings and conclusions in these documents are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC)."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html|title=Information for Healthcare Providers {{!}} ME/CFS {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== The Institute of Medicine report ==

'''''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'''''

===Read the report===
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Key facts] (two pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Report brief] (four pages)
*[http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx Download full report] (282 pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm Diagnostic Algorithm Chart]
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ProposedDiagnosticCriteria Proposed Diagnostic Criteria Chart]
*[http://www.nap.edu/read/19012/chapter/1 Read the full 282 page report online]
**[http://www.nap.edu/read/19012/chapter/1 Front matter]
**[http://www.nap.edu/read/19012/chapter/2 Summary]
**[http://www.nap.edu/read/19012/chapter/3 1. Introduction]
**[http://www.nap.edu/read/19012/chapter/4 2. Background]
**[http://www.nap.edu/read/19012/chapter/5 3. Current Case Definitions and Diagnostic Criteria, Terminology, and Symptom Constructs and Clusters]
**[http://www.nap.edu/read/19012/chapter/6 4. Review of the Evidence on Major ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/7 5. Review of the Evidence on Other ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/8 6. Pediatric ME/CFS]
**[http://www.nap.edu/read/19012/chapter/9 7. Recommendations]
**[http://www.nap.edu/read/19012/chapter/10 8. Dissemination Strategy]
**[http://www.nap.edu/read/19012/chapter/11 Public Session Agendas]
**[http://www.nap.edu/read/19012/chapter/12 GRADE Grid Template]
**[http://www.nap.edu/read/19012/chapter/13 Disability in ME/CFS]
**[http://www.nap.edu/read/19012/chapter/14 Questionnaires and Tools That May Be Useful for Assessing ME/CFS Symptoms]
**[http://www.nap.edu/read/19012/chapter/15 Biographical Sketches of Committee Members, Consultants, and Staff]

[http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" Official video presentation]

== Videos ==
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]]
:[[CDC]] Posted Video - Dr. [[John Iskander]] of CDC interviews Dr. [[Anthony Komaroff]] (Feb 17, 2016)

*[https://www.youtube.com/watch?v=ZW2Tcsp75a0 SMCI IOM Briefing in Washington, D.C. Full Coverage]<ref>{{Cite web|url=https://www.youtube.com/watch?v=ZW2Tcsp75a0|title=SMCI IOM Briefing in Washington, D.C. Full Coverage|last=|first=|date=Mar 25, 2015|website=YouTube|publisher=SolveCFS|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:[[Carol Head]] of [[Solve ME/CFS]], Dr. [[Ellen Wright Clayton]] and [https://en.wikipedia.org/wiki/Morgan_Fairchild Morgan Fairchild]

*[https://www.youtube.com/watch?v=X4Tnt2d-5S8 New Clinical Definitions for ME/CFS - Dr. Lucinda Bateman]<ref>{{Cite web|url=https://www.youtube.com/watch?v=X4Tnt2d-5S8|title="New Clinical Definitions for ME/CFS" Dr. Lucinda Bateman|last=Bateman|first=Lucinda|date=Mar 8, 2015|website=YouTube|publisher=Bateman Horne Center|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:Dr. [[Lucinda Bateman]] of [[Bateman Horne Center]] discusses. (Mar 8, 2015)

==Notable studies==
* 2015, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556426/pdf/nihms699325.pdf Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease]<ref name="Jason, Sunn, 2015" />
* 2015, Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease<ref>{{Cite journal|last=Jason|first=Leonard A.|author-link=Leonard Jason|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Kot|first3=Bobby|author-link3=Bobby Kot|last4=Brown|first4=Abigail|author-link4=Abigail Brown|last5=|last7=|last8=|date=Jun 23, 2015|title=Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease|url=https://www.mdpi.com/2075-4418/5/2/272|journal=Diagnostics|language=en|volume=5|issue=2|pages=272–286|doi=10.3390/diagnostics5020272|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/5/2/272/htm (Full text)]
* 2016, Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward<ref>{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|last2=|first2=|author-link2=|author-link3=|author-link4=|author-link5=|date=Feb 6, 2016|title=Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward|url=https://www.mdpi.com/2075-4418/6/1/10|journal=Diagnostics|language=en|volume=6|issue=1|pages=10|doi=10.3390/diagnostics6010010|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/6/1/10 (Full text)]
* 2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20& Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria]<ref name="Chu, 2017" />

==Letters and commentary==
*2017, An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods<ref name=":1" /> [https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf (Full text)]
*2017, [http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1362750 Article commentary - Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox]<ref name="Chu, Valencia, Montoya, 2017" />
*2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1362780 Article commentary - Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.]<ref name="Jason, Sunnquist, Gleason, Fox, 2017" />

==In popular culture==
A February 2016 comic strip referred to SEID and implied it is simply tiredness. ''See'': [[Blondie comic]]

==See also==
* [[Chronic fatigue syndrome]]
* [[ME/CFS]]
* [[Myalgic encephalomyelitis]]

*[[NIH Post-Infectious ME/CFS Study]] - [[SEID]] will be used in this study.<ref>{{Cite news|url=http://www.meaction.net/2016/02/09/positive-answers-to-initial-questions-re-nih-clinical-center-protocol/|title=Positive Answers to Initial Questions re NIH Clinical Center Protocol - #MEAction|last=Alexander Miller|first=Courtney|date=2016-02-09|work=#MEAction|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Severe and very severe ME]]

===Generally accepted criteria for diagnosing ME/CFS and ME ===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria]] (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> This criterion will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegría|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*2015, [https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/ Chronic fatigue syndrome gets yet another name]<ref>{{Cite news|url=https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/|title=Chronic fatigue syndrome gets yet another name|last=Coghlan|first=Andy|date=Feb 10, 2015|work=New Scientist|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*2015, [http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract Systemic Exercise Intolerance Disease: What’s in a name?]<ref>{{Cite journal|last=Sen|first=Mahadev Singh|last2=Sahoo|first2=Swapnajeet|last3=Aggarwal|first3=Shivali|last4=Singh|first4=Shubh Mohan|date=2016|title=Systemic exercise intolerance disease: What’s in a name?|url=http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract|journal=Asian Journal of Psychiatry|language=English|volume=22|pages=157–158|doi=10.1016/j.ajp.2016.06.003|issn=1876-2018|via=}}</ref>
*2018, [https://youtu.be/RC9TjgE_PlU?t=89 Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome]<ref>{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=89|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=Oct 16, 2018|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.|at=1:29}}</ref> (Notes the IOM report's diagnostic criteria.)

== References ==
<references>
<ref name="Chu, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Norris | first2 = Jane | authorlink2 = Jane Norris
| last3 = Valencia | first3 = Ian J. | authorlink3 =
| last4 = Montoya | first4 = Jose G. | authorlink4 = Jose Montoya
| title = Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 5 | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1299079
}}
</ref>
<ref name="Chu, Valencia, Montoya, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Valencia | first2 = Ian J. | authorlink2 =
| last3 = Montoya | first3 = Jose G. | authorlink3 = Jose Montoya
| title = Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1362750
}}
</ref>
<ref name="Jason, Sunn, 2015">{{Citation
| last1 = Jason | first1 = L.A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = M. | authorlink2 = Madison Sunnquist
| last3 = Brown | first3 = A. | authorlink3 =
| last4 = Newton | first4 = J.L. | authorlink4 = Julia Newton
| last5 = Strand | first5 = E.B. | authorlink5 = Elin Strand
| last6 = Vernon | first6 = S.D. | authorlink6 = Suzanne Vernon
| title = Chronic fatigue syndrome versus systemic exertion intolerance disease
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 3 | issue = 3 | page = 127-141
| date = 2015
| pmid =
| doi = 10.1080/21641846.2015.1051291
}}</ref>
<ref name="Jason, Sunnquist, Gleason, Fox, 2017">{{Citation
| last1 = Jason | first1 = Leonard A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = Madison | authorlink2 = Madison Sunnquist
| last3 = Gleason | first3 = Kristen | authorlink3 = Kristen Gleason
| last4 = Fox | first4 = Pamela | authorlink4 = Pamela Fox
| title = Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| pmid =
| doi = 10.1080/21641846.2017.1362780
}}
</ref>
</references>

[[Category:Definitions]]
[[Category:Diagnoses]]
[[Category:Disease names]]

Systemic Exertion Intolerance Disease

2019-04-14T14:04:39Z

MEandCFS:/* Authors */ x

'''Systemic Exertion Intolerance Disease''' (SEID) was the new name proposed at the same time as the diagnostic criteria developed by the [[National Academy of Medicine]] (NAM) (formerly the Institute of Medicine, IOM) published on February 10, 2015. The report was titled ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', and is also referred to as the [[Institute of Medicine report]].

The IOM diagnostic criteria requires [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]; and [[Cognitive dysfunction|cognitive impairment]] and/or [[orthostatic intolerance]] (OI).<ref name=":2">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Diagnostic Algorithm for ME/CFS|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> It is also useful for a more severe presentation of the disease; symptom severity and other symptoms are outlined in the Institute of Medicine report.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/7|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=141-162|language=en|chapter=5|quote=|editor-last2=|editor-link2=}}</ref>

Adults can be diagnosed at six months of illness and [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|pediatric]] cases are diagnosed at three months.
[[File:Morgan Fairchild.png |300px|thumb|right|[[Morgan Fairchild]] is an [[United States|American]] actress of film and television. She was diagnosed with [[chronic fatigue syndrome]] (CFS) in 1989. On March 25, 2015, she gave a [https://www.youtube.com/watch?v=lWTF80daWtw speech] during the [[IOM]] briefing of the rollout of SEID where she says compared to others suffering with [[ME/CFS]] she has a mild case]]

==Authors==
[[File:Rosa SEID.JPG|400px|thumb|Rosa age 25 in 1986 and mildly ill with [[ME/CFS]] when she believes she would have met the SEID criteria developed in 2015 and she first read about [[Post-exertional malaise|PEM]]. She became worse over the years and in 2003 was diagnosed and disabled with [[chronic fatigue syndrome]] (CFS) which was the name for ME/CFS at the time. Rosa now meets the [[CCC]] criteria with PEM "[[Canadian Consensus Criteria#Definition|option]]". ME/CFS onset was [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|age 17]] and [[fibromyalgia]] since puberty]]
The committee on the Diagnostic Criteria for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) consisted of [[Ellen Wright Clayton]], [[Margarita Alegría]], [[Lucinda Bateman]], [[Lily Chu]], [[Charles Cleeland]], [[Ronald Davis]], [[Betty Diamond]], [[Theodore Ganiats]], [[Betsy Keller]], [[Nancy Klimas]], [[A Martin Lerner]], [[Cynthia Mulrow]], [[Benjamin Natelson]], [[Peter Rowe]], and [[Michael Shelanski]].

==Development==
In 2014, the [[U.S. Department of Health and Human Services]] (HHS), the [[National Institutes of Health]] (NIH), the [[Agency for Healthcare Research and Quality]] (AHRQ), the [[Centers for Disease Control & Prevention]] (CDC), the [[Food and Drug Administration]] (FDA), and the [[Social Security Administration]] (SSA) asked the [[Institute of Medicine]] (IOM) to convene an expert committee to examine the evidence base for [[ME/CFS]]. In ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', the committee proposes new diagnostic criteria that will facilitate timely diagnosis and care and enhance understanding among health care providers and the public. These criteria, based on expert analysis and the most up-to-date scientific literature, are streamlined for practical use in the clinical setting. The IOM committee also recommends that the name of the disease be changed—from ME/CFS to systemic exertion intolerance disease (SEID)—to more accurately capture the central characteristics of the illness.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=|website=nationalacademies.org|page=5|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

'''The proposed name and acronym SEID is meant to hone in on key aspects of''' ME/CFS'''.''' '''''S'''ystemic'' would give credence to the disease being body wide. '''''E'''xertion '''I'''ntolerance'' would key doctors into understanding that the patient CANNOT tolerate exertion of any kind; physical, cognitive or emotional.<ref>{{Cite news|url=http://www.shoutoutaboutme.com/about-mecfs/seid-diagnostic-criteria-proposed/|title=NIH/IOM 2015 Definition (SEID)|last=Logan|first=Russell|date=Jan 3, 2015|work=Shoutout about ME|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-us}}</ref> (Intolerance is well understood in the medical field in that there is a medical problem. Other diseases, such as gluten intolerance, is a serious medical condition; gluten CAN NOT be consumed.) '''''D'''isease'' gave the self-explanatory label of being an organic biological disease.

==Diagnostic criteria==
[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm<ref name=":2" />]]
'''Diagnosis requires that the patient have the following three symptoms:'''

1. A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied
by [[Chronic fatigue|fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest]], and

2. [[Post-exertional malaise]],* and

3. [[Unrefreshing sleep]]*

'''At least one of the two following manifestations is also required:'''

1. [[Cognitive impairment]]* or

2. [[Orthostatic intolerance]]

: * Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS (SEID) should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

===Centers for Disease Control and Prevention (CDC) website===

:Note: The name "Systemic Exertion Intolerance Disease" (SEID) has not been adopted but the new diagnostic criteria have been incorporated into the [[Centers for Disease Control and Prevention]] (CDC) ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html IOM 2015 Diagnostic Criteria].<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== SEID vs Other criteria ==
The SEID criteria are the most symptom liberal of the valid ''disease'' definition criteria. The [[Canadian Consensus Criteria]] (CCC) are for ME/CFS, and [[International Consensus Criteria]] (ICC) are for ME.<ref>{{Cite journal|last=Chu|first=Lily|last2=Norris|first2=Jane L.|last3=Valencia|first3=Ian J.|last4=Montoya|first4=Jose G.|date=2017-03-13|title=Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria|url=http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=114–128|doi=10.1080/21641846.2017.1299079|issn=2164-1846}}</ref>

The IOM report calls for the "retirement" of the [[Oxford criteria]] for [[chronic fatigue syndrome]] (CFS).<ref>{{Cite web|url=http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/|title=US NIH Report Calls for UK Definition of ME/CFS to be Scrapped|last=Swift|first=Penny|date=|website=theargusreport.com|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-03}}</ref> The [[Fukuda criteria]] are also for CFS.

Comparison chart of the [[International Consensus Criteria|ICC]] and SEID: [https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663 ICC compared to IOM (SEID)].<ref>{{Cite web|url=https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663|title=International Consensus Criteria (ICC) vs Systemic Exertion Intolerance Disease (SEID)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cloudfront.net|publisher=MEadvocacy.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

== Criticism ==
The main criticism is the missing of [[immune system]] and [[nervous system]] symptoms, and the unclear and wide criterion of the main symptom (PEM) and missing of important symptoms like pain, lab tests, and missing exclusions.

ME was the original name for CFS; the names are often used interchangeably or with the acronym ME/CFS.<ref name=":0">{{Cite news|url=https://www.verywellhealth.com/myalgic-encephalomyelitis-me-715663|title=Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Nov 24, 2018|work=Verywell Health|access-date=2018-11-28|archive-url=|archive-date=|dead-url=|quote=|author-link=}}</ref> The name SEID, although giving credence to the fact that patients are intolerant to [[exertion]], does not capture the debilitating [[central nervous system]] (CNS) symptoms patients experience as the name ME does.

[[Frank Twisk|Twisk]] (2017) stated that ME and CFS are different illnesses, with ME being a neuromuscular disease and CFS being a partially overlapping fatigue-based illness, and that it was not possible to replace both ME and CFS with a single diagnostic entity. Twisk also stated that SEID included some patients that did not meet either ME or CFS diagnostic criteria.<ref name=":1">{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|author-link2=|author-link3=|author-link4=|author-link5=|date=Jun 27, 2017|title=An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods|url=https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf|journal=Journal of Medical Diagnostic Methods|volume=6|issue=3|pages=|doi=10.4172/2168-9784.1000249|quote=|via=l}}</ref>

== Clinicians guide ==
The [http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Report Guide for Clinicians] explains the core symptoms, additional symptoms, diagnostic criteria and more. (Feb 10, 2015)

===Centers for Disease Control and Prevention (CDC) website===

: Note: This clinicians guide has been incorporated into the CDC's ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers] under the "Resources" heading with a page disclaimer: "The findings and conclusions in these documents are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC)."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html|title=Information for Healthcare Providers {{!}} ME/CFS {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== The Institute of Medicine report ==

'''''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'''''

===Read the report===
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Key facts] (two pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Report brief] (four pages)
*[http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx Download full report] (282 pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm Diagnostic Algorithm Chart]
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ProposedDiagnosticCriteria Proposed Diagnostic Criteria Chart]
*[http://www.nap.edu/read/19012/chapter/1 Read the full 282 page report online]
**[http://www.nap.edu/read/19012/chapter/1 Front matter]
**[http://www.nap.edu/read/19012/chapter/2 Summary]
**[http://www.nap.edu/read/19012/chapter/3 1. Introduction]
**[http://www.nap.edu/read/19012/chapter/4 2. Background]
**[http://www.nap.edu/read/19012/chapter/5 3. Current Case Definitions and Diagnostic Criteria, Terminology, and Symptom Constructs and Clusters]
**[http://www.nap.edu/read/19012/chapter/6 4. Review of the Evidence on Major ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/7 5. Review of the Evidence on Other ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/8 6. Pediatric ME/CFS]
**[http://www.nap.edu/read/19012/chapter/9 7. Recommendations]
**[http://www.nap.edu/read/19012/chapter/10 8. Dissemination Strategy]
**[http://www.nap.edu/read/19012/chapter/11 Public Session Agendas]
**[http://www.nap.edu/read/19012/chapter/12 GRADE Grid Template]
**[http://www.nap.edu/read/19012/chapter/13 Disability in ME/CFS]
**[http://www.nap.edu/read/19012/chapter/14 Questionnaires and Tools That May Be Useful for Assessing ME/CFS Symptoms]
**[http://www.nap.edu/read/19012/chapter/15 Biographical Sketches of Committee Members, Consultants, and Staff]

[http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" Official video presentation]

== Videos ==
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]]
:[[CDC]] Posted Video - Dr. [[John Iskander]] of CDC interviews Dr. [[Anthony Komaroff]] (Feb 17, 2016)

*[https://www.youtube.com/watch?v=ZW2Tcsp75a0 SMCI IOM Briefing in Washington, D.C. Full Coverage]<ref>{{Cite web|url=https://www.youtube.com/watch?v=ZW2Tcsp75a0|title=SMCI IOM Briefing in Washington, D.C. Full Coverage|last=|first=|date=Mar 25, 2015|website=YouTube|publisher=SolveCFS|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:[[Carol Head]] of [[Solve ME/CFS]], Dr. [[Ellen Wright Clayton]] and [https://en.wikipedia.org/wiki/Morgan_Fairchild Morgan Fairchild]

*[https://www.youtube.com/watch?v=X4Tnt2d-5S8 New Clinical Definitions for ME/CFS - Dr. Lucinda Bateman]<ref>{{Cite web|url=https://www.youtube.com/watch?v=X4Tnt2d-5S8|title="New Clinical Definitions for ME/CFS" Dr. Lucinda Bateman|last=Bateman|first=Lucinda|date=Mar 8, 2015|website=YouTube|publisher=Bateman Horne Center|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:Dr. [[Lucinda Bateman]] of [[Bateman Horne Center]] discusses. (Mar 8, 2015)

==Notable studies==
* 2015, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556426/pdf/nihms699325.pdf Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease]<ref name="Jason, Sunn, 2015" />
* 2015, Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease<ref>{{Cite journal|last=Jason|first=Leonard A.|author-link=Leonard Jason|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Kot|first3=Bobby|author-link3=Bobby Kot|last4=Brown|first4=Abigail|author-link4=Abigail Brown|last5=|last7=|last8=|date=Jun 23, 2015|title=Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease|url=https://www.mdpi.com/2075-4418/5/2/272|journal=Diagnostics|language=en|volume=5|issue=2|pages=272–286|doi=10.3390/diagnostics5020272|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/5/2/272/htm (Full text)]
* 2016, Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward<ref>{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|last2=|first2=|author-link2=|author-link3=|author-link4=|author-link5=|date=Feb 6, 2016|title=Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward|url=https://www.mdpi.com/2075-4418/6/1/10|journal=Diagnostics|language=en|volume=6|issue=1|pages=10|doi=10.3390/diagnostics6010010|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/6/1/10 (Full text)]
* 2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20& Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria]<ref name="Chu, 2017" />

==Letters and commentary==
*2017, An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods<ref name=":1" /> [https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf (Full text)]
*2017, [http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1362750 Article commentary - Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox]<ref name="Chu, Valencia, Montoya, 2017" />
*2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1362780 Article commentary - Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.]<ref name="Jason, Sunnquist, Gleason, Fox, 2017" />

==In popular culture==
A February 2016 comic strip referred to SEID and implied it is simply tiredness. ''See'': [[Blondie comic]]

==See also==
* [[Chronic fatigue syndrome]]
* [[ME/CFS]]
* [[Myalgic encephalomyelitis]]

*[[NIH Post-Infectious ME/CFS Study]] - [[SEID]] will be used in this study.<ref>{{Cite news|url=http://www.meaction.net/2016/02/09/positive-answers-to-initial-questions-re-nih-clinical-center-protocol/|title=Positive Answers to Initial Questions re NIH Clinical Center Protocol - #MEAction|last=Alexander Miller|first=Courtney|date=2016-02-09|work=#MEAction|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Severe and very severe ME]]

===Generally accepted criteria for diagnosing ME/CFS and ME ===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria]] (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> This criterion will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegría|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*2015, [https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/ Chronic fatigue syndrome gets yet another name]<ref>{{Cite news|url=https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/|title=Chronic fatigue syndrome gets yet another name|last=Coghlan|first=Andy|date=Feb 10, 2015|work=New Scientist|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*2015, [http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract Systemic Exercise Intolerance Disease: What’s in a name?]<ref>{{Cite journal|last=Sen|first=Mahadev Singh|last2=Sahoo|first2=Swapnajeet|last3=Aggarwal|first3=Shivali|last4=Singh|first4=Shubh Mohan|date=2016|title=Systemic exercise intolerance disease: What’s in a name?|url=http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract|journal=Asian Journal of Psychiatry|language=English|volume=22|pages=157–158|doi=10.1016/j.ajp.2016.06.003|issn=1876-2018|via=}}</ref>
*2018, [https://youtu.be/RC9TjgE_PlU?t=89 Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome]<ref>{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=89|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=Oct 16, 2018|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.|at=1:29}}</ref> (Notes the IOM report's diagnostic criteria.)

== References ==
<references>
<ref name="Chu, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Norris | first2 = Jane | authorlink2 = Jane Norris
| last3 = Valencia | first3 = Ian J. | authorlink3 =
| last4 = Montoya | first4 = Jose G. | authorlink4 = Jose Montoya
| title = Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 5 | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1299079
}}
</ref>
<ref name="Chu, Valencia, Montoya, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Valencia | first2 = Ian J. | authorlink2 =
| last3 = Montoya | first3 = Jose G. | authorlink3 = Jose Montoya
| title = Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1362750
}}
</ref>
<ref name="Jason, Sunn, 2015">{{Citation
| last1 = Jason | first1 = L.A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = M. | authorlink2 = Madison Sunnquist
| last3 = Brown | first3 = A. | authorlink3 =
| last4 = Newton | first4 = J.L. | authorlink4 = Julia Newton
| last5 = Strand | first5 = E.B. | authorlink5 = Elin Strand
| last6 = Vernon | first6 = S.D. | authorlink6 = Suzanne Vernon
| title = Chronic fatigue syndrome versus systemic exertion intolerance disease
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 3 | issue = 3 | page = 127-141
| date = 2015
| pmid =
| doi = 10.1080/21641846.2015.1051291
}}</ref>
<ref name="Jason, Sunnquist, Gleason, Fox, 2017">{{Citation
| last1 = Jason | first1 = Leonard A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = Madison | authorlink2 = Madison Sunnquist
| last3 = Gleason | first3 = Kristen | authorlink3 = Kristen Gleason
| last4 = Fox | first4 = Pamela | authorlink4 = Pamela Fox
| title = Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| pmid =
| doi = 10.1080/21641846.2017.1362780
}}
</ref>
</references>

[[Category:Definitions]]
[[Category:Diagnoses]]
[[Category:Disease names]]

Systemic Exertion Intolerance Disease

2019-04-14T14:03:37Z

MEandCFS:/* Authors */ caption info

'''Systemic Exertion Intolerance Disease''' (SEID) was the new name proposed at the same time as the diagnostic criteria developed by the [[National Academy of Medicine]] (NAM) (formerly the Institute of Medicine, IOM) published on February 10, 2015. The report was titled ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', and is also referred to as the [[Institute of Medicine report]].

The IOM diagnostic criteria requires [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]; and [[Cognitive dysfunction|cognitive impairment]] and/or [[orthostatic intolerance]] (OI).<ref name=":2">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Diagnostic Algorithm for ME/CFS|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> It is also useful for a more severe presentation of the disease; symptom severity and other symptoms are outlined in the Institute of Medicine report.<ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/7|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=141-162|language=en|chapter=5|quote=|editor-last2=|editor-link2=}}</ref>

Adults can be diagnosed at six months of illness and [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|pediatric]] cases are diagnosed at three months.
[[File:Morgan Fairchild.png |300px|thumb|right|[[Morgan Fairchild]] is an [[United States|American]] actress of film and television. She was diagnosed with [[chronic fatigue syndrome]] (CFS) in 1989. On March 25, 2015, she gave a [https://www.youtube.com/watch?v=lWTF80daWtw speech] during the [[IOM]] briefing of the rollout of SEID where she says compared to others suffering with [[ME/CFS]] she has a mild case]]

==Authors==
[[File:Rosa SEID.JPG|400px|thumb|Rosa age 25 in 1986 and mildly ill with [[ME/CFS]] when she believes she would have met the SEID criteria developed in 2015 and first read about [[Post-exertional malaise|PEM]]. She became worse over the years and in 2003 was diagnosed and disabled with [[chronic fatigue syndrome]] (CFS) which was the name for ME/CFS at the time. Rosa now meets the [[CCC]] criteria with PEM "[[Canadian Consensus Criteria#Definition|option]]". ME/CFS onset was [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|age 17]] and [[fibromyalgia]] since puberty]]
The committee on the Diagnostic Criteria for [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) consisted of [[Ellen Wright Clayton]], [[Margarita Alegría]], [[Lucinda Bateman]], [[Lily Chu]], [[Charles Cleeland]], [[Ronald Davis]], [[Betty Diamond]], [[Theodore Ganiats]], [[Betsy Keller]], [[Nancy Klimas]], [[A Martin Lerner]], [[Cynthia Mulrow]], [[Benjamin Natelson]], [[Peter Rowe]], and [[Michael Shelanski]].

==Development==
In 2014, the [[U.S. Department of Health and Human Services]] (HHS), the [[National Institutes of Health]] (NIH), the [[Agency for Healthcare Research and Quality]] (AHRQ), the [[Centers for Disease Control & Prevention]] (CDC), the [[Food and Drug Administration]] (FDA), and the [[Social Security Administration]] (SSA) asked the [[Institute of Medicine]] (IOM) to convene an expert committee to examine the evidence base for [[ME/CFS]]. In ''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'', the committee proposes new diagnostic criteria that will facilitate timely diagnosis and care and enhance understanding among health care providers and the public. These criteria, based on expert analysis and the most up-to-date scientific literature, are streamlined for practical use in the clinical setting. The IOM committee also recommends that the name of the disease be changed—from ME/CFS to systemic exertion intolerance disease (SEID)—to more accurately capture the central characteristics of the illness.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=|website=nationalacademies.org|page=5|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

'''The proposed name and acronym SEID is meant to hone in on key aspects of''' ME/CFS'''.''' '''''S'''ystemic'' would give credence to the disease being body wide. '''''E'''xertion '''I'''ntolerance'' would key doctors into understanding that the patient CANNOT tolerate exertion of any kind; physical, cognitive or emotional.<ref>{{Cite news|url=http://www.shoutoutaboutme.com/about-mecfs/seid-diagnostic-criteria-proposed/|title=NIH/IOM 2015 Definition (SEID)|last=Logan|first=Russell|date=Jan 3, 2015|work=Shoutout about ME|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-us}}</ref> (Intolerance is well understood in the medical field in that there is a medical problem. Other diseases, such as gluten intolerance, is a serious medical condition; gluten CAN NOT be consumed.) '''''D'''isease'' gave the self-explanatory label of being an organic biological disease.

==Diagnostic criteria==
[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm<ref name=":2" />]]
'''Diagnosis requires that the patient have the following three symptoms:'''

1. A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied
by [[Chronic fatigue|fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest]], and

2. [[Post-exertional malaise]],* and

3. [[Unrefreshing sleep]]*

'''At least one of the two following manifestations is also required:'''

1. [[Cognitive impairment]]* or

2. [[Orthostatic intolerance]]

: * Frequency and severity of symptoms should be assessed. The diagnosis of ME/CFS (SEID) should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity.<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

===Centers for Disease Control and Prevention (CDC) website===

:Note: The name "Systemic Exertion Intolerance Disease" (SEID) has not been adopted but the new diagnostic criteria have been incorporated into the [[Centers for Disease Control and Prevention]] (CDC) ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html IOM 2015 Diagnostic Criteria].<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== SEID vs Other criteria ==
The SEID criteria are the most symptom liberal of the valid ''disease'' definition criteria. The [[Canadian Consensus Criteria]] (CCC) are for ME/CFS, and [[International Consensus Criteria]] (ICC) are for ME.<ref>{{Cite journal|last=Chu|first=Lily|last2=Norris|first2=Jane L.|last3=Valencia|first3=Ian J.|last4=Montoya|first4=Jose G.|date=2017-03-13|title=Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria|url=http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=114–128|doi=10.1080/21641846.2017.1299079|issn=2164-1846}}</ref>

The IOM report calls for the "retirement" of the [[Oxford criteria]] for [[chronic fatigue syndrome]] (CFS).<ref>{{Cite web|url=http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/|title=US NIH Report Calls for UK Definition of ME/CFS to be Scrapped|last=Swift|first=Penny|date=|website=theargusreport.com|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-03}}</ref> The [[Fukuda criteria]] are also for CFS.

Comparison chart of the [[International Consensus Criteria|ICC]] and SEID: [https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663 ICC compared to IOM (SEID)].<ref>{{Cite web|url=https://d3n8a8pro7vhmx.cloudfront.net/meadvocacy/pages/22/attachments/original/1531592663/ICC_compared_to_IOM.pdf?1531592663|title=International Consensus Criteria (ICC) vs Systemic Exertion Intolerance Disease (SEID)|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cloudfront.net|publisher=MEadvocacy.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

== Criticism ==
The main criticism is the missing of [[immune system]] and [[nervous system]] symptoms, and the unclear and wide criterion of the main symptom (PEM) and missing of important symptoms like pain, lab tests, and missing exclusions.

ME was the original name for CFS; the names are often used interchangeably or with the acronym ME/CFS.<ref name=":0">{{Cite news|url=https://www.verywellhealth.com/myalgic-encephalomyelitis-me-715663|title=Myalgic Encephalomyelitis or Chronic Fatigue Syndrome|last=Dellwo|first=Adrienne|date=Nov 24, 2018|work=Verywell Health|access-date=2018-11-28|archive-url=|archive-date=|dead-url=|quote=|author-link=}}</ref> The name SEID, although giving credence to the fact that patients are intolerant to [[exertion]], does not capture the debilitating [[central nervous system]] (CNS) symptoms patients experience as the name ME does.

[[Frank Twisk|Twisk]] (2017) stated that ME and CFS are different illnesses, with ME being a neuromuscular disease and CFS being a partially overlapping fatigue-based illness, and that it was not possible to replace both ME and CFS with a single diagnostic entity. Twisk also stated that SEID included some patients that did not meet either ME or CFS diagnostic criteria.<ref name=":1">{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|author-link2=|author-link3=|author-link4=|author-link5=|date=Jun 27, 2017|title=An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods|url=https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf|journal=Journal of Medical Diagnostic Methods|volume=6|issue=3|pages=|doi=10.4172/2168-9784.1000249|quote=|via=l}}</ref>

== Clinicians guide ==
The [http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Report Guide for Clinicians] explains the core symptoms, additional symptoms, diagnostic criteria and more. (Feb 10, 2015)

===Centers for Disease Control and Prevention (CDC) website===

: Note: This clinicians guide has been incorporated into the CDC's ME/CFS website under the tab [https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers] under the "Resources" heading with a page disclaimer: "The findings and conclusions in these documents are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC)."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html|title=Information for Healthcare Providers {{!}} ME/CFS {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-03}}</ref>

== The Institute of Medicine report ==

'''''Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness'''''

===Read the report===
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Key facts] (two pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Report brief] (four pages)
*[http://www.nationalacademies.org/hmd/Reports/2015/ME-CFS.aspx Download full report] (282 pages)
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm Diagnostic Algorithm Chart]
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ProposedDiagnosticCriteria Proposed Diagnostic Criteria Chart]
*[http://www.nap.edu/read/19012/chapter/1 Read the full 282 page report online]
**[http://www.nap.edu/read/19012/chapter/1 Front matter]
**[http://www.nap.edu/read/19012/chapter/2 Summary]
**[http://www.nap.edu/read/19012/chapter/3 1. Introduction]
**[http://www.nap.edu/read/19012/chapter/4 2. Background]
**[http://www.nap.edu/read/19012/chapter/5 3. Current Case Definitions and Diagnostic Criteria, Terminology, and Symptom Constructs and Clusters]
**[http://www.nap.edu/read/19012/chapter/6 4. Review of the Evidence on Major ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/7 5. Review of the Evidence on Other ME/CFS Symptoms and Manifestations]
**[http://www.nap.edu/read/19012/chapter/8 6. Pediatric ME/CFS]
**[http://www.nap.edu/read/19012/chapter/9 7. Recommendations]
**[http://www.nap.edu/read/19012/chapter/10 8. Dissemination Strategy]
**[http://www.nap.edu/read/19012/chapter/11 Public Session Agendas]
**[http://www.nap.edu/read/19012/chapter/12 GRADE Grid Template]
**[http://www.nap.edu/read/19012/chapter/13 Disability in ME/CFS]
**[http://www.nap.edu/read/19012/chapter/14 Questionnaires and Tools That May Be Useful for Assessing ME/CFS Symptoms]
**[http://www.nap.edu/read/19012/chapter/15 Biographical Sketches of Committee Members, Consultants, and Staff]

[http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" Official video presentation]

== Videos ==
*[[Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education]]
:[[CDC]] Posted Video - Dr. [[John Iskander]] of CDC interviews Dr. [[Anthony Komaroff]] (Feb 17, 2016)

*[https://www.youtube.com/watch?v=ZW2Tcsp75a0 SMCI IOM Briefing in Washington, D.C. Full Coverage]<ref>{{Cite web|url=https://www.youtube.com/watch?v=ZW2Tcsp75a0|title=SMCI IOM Briefing in Washington, D.C. Full Coverage|last=|first=|date=Mar 25, 2015|website=YouTube|publisher=SolveCFS|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:[[Carol Head]] of [[Solve ME/CFS]], Dr. [[Ellen Wright Clayton]] and [https://en.wikipedia.org/wiki/Morgan_Fairchild Morgan Fairchild]

*[https://www.youtube.com/watch?v=X4Tnt2d-5S8 New Clinical Definitions for ME/CFS - Dr. Lucinda Bateman]<ref>{{Cite web|url=https://www.youtube.com/watch?v=X4Tnt2d-5S8|title="New Clinical Definitions for ME/CFS" Dr. Lucinda Bateman|last=Bateman|first=Lucinda|date=Mar 8, 2015|website=YouTube|publisher=Bateman Horne Center|archive-url=|archive-date=|dead-url=|access-date=}}</ref>
:Dr. [[Lucinda Bateman]] of [[Bateman Horne Center]] discusses. (Mar 8, 2015)

==Notable studies==
* 2015, [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556426/pdf/nihms699325.pdf Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease]<ref name="Jason, Sunn, 2015" />
* 2015, Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease<ref>{{Cite journal|last=Jason|first=Leonard A.|author-link=Leonard Jason|last2=Sunnquist|first2=Madison|author-link2=Madison Sunnquist|last3=Kot|first3=Bobby|author-link3=Bobby Kot|last4=Brown|first4=Abigail|author-link4=Abigail Brown|last5=|last7=|last8=|date=Jun 23, 2015|title=Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease|url=https://www.mdpi.com/2075-4418/5/2/272|journal=Diagnostics|language=en|volume=5|issue=2|pages=272–286|doi=10.3390/diagnostics5020272|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/5/2/272/htm (Full text)]
* 2016, Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward<ref>{{Cite journal|last=Twisk|first=Frank N. M.|author-link=Frank Twisk|last2=|first2=|author-link2=|author-link3=|author-link4=|author-link5=|date=Feb 6, 2016|title=Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward|url=https://www.mdpi.com/2075-4418/6/1/10|journal=Diagnostics|language=en|volume=6|issue=1|pages=10|doi=10.3390/diagnostics6010010|quote=|via=}}</ref> [https://www.mdpi.com/2075-4418/6/1/10 (Full text)]
* 2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1299079?journalCode=rftg20& Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria]<ref name="Chu, 2017" />

==Letters and commentary==
*2017, An Accurate Diagnosis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome requires strict Clinical Case definitions and Objective Test Methods<ref name=":1" /> [https://www.researchgate.net/profile/Frank_Twisk/publication/318463814_An_Accurate_Diagnosis_of_Myalgic_Encephalomyelitis_and_Chronic_Fatigue_Syndrome_requires_strict_Clinical_Case_definitions_and_Objective_Test_Methods/links/596ca586aca2728ca689c2fa/An-Accurate-Diagnosis-of-Myalgic-Encephalomyelitis-and-Chronic-Fatigue-Syndrome-requires-strict-Clinical-Case-definitions-and-Objective-Test-Methods.pdf (Full text)]
*2017, [http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1362750 Article commentary - Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox]<ref name="Chu, Valencia, Montoya, 2017" />
*2017, [http://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1362780 Article commentary - Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.]<ref name="Jason, Sunnquist, Gleason, Fox, 2017" />

==In popular culture==
A February 2016 comic strip referred to SEID and implied it is simply tiredness. ''See'': [[Blondie comic]]

==See also==
* [[Chronic fatigue syndrome]]
* [[ME/CFS]]
* [[Myalgic encephalomyelitis]]

*[[NIH Post-Infectious ME/CFS Study]] - [[SEID]] will be used in this study.<ref>{{Cite news|url=http://www.meaction.net/2016/02/09/positive-answers-to-initial-questions-re-nih-clinical-center-protocol/|title=Positive Answers to Initial Questions re NIH Clinical Center Protocol - #MEAction|last=Alexander Miller|first=Courtney|date=2016-02-09|work=#MEAction|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome]]
*[[Severe and very severe ME]]

===Generally accepted criteria for diagnosing ME/CFS and ME ===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[International Consensus Criteria]] (ICC)<ref>{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref> This criterion will accurately diagnose [[myalgic encephalomyelitis]] (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=Clayton|first=Ellen Wright|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=Ellen Wright Clayton|last2=Alegria|first2=Margarita|authorlink2=Margarita Alegría|authorlink3=Lucinda Bateman|authorlink4=Lily Chu|authorlink5=Charles Cleeland|authorlink6=Ronald Davis|authorlink7=Betty Diamond|authorlink8=Theodore Ganiats|authorlink9=Betsy Keller|authors=|last3=Bateman|first3=Lucinda|last4=Chu|first4=Lily|last5=Cleeland|first5=Charles|last6=Davis|first6=Ronald|last7=Diamond|first7=Betty|last8=Ganiats|first8=Theodore|last9=Keller|first9=Betsy|last10=Klimas|first10=Nancy|authorlink10=Nancy Klimas|last11=Lerner|first11=A Martin|authorlink11=Martin Lerner|last12=Mulrow|first12=Cynthia|authorlink12=Cynthia Mulrow|last13=Natelson|first13=Benjamin|authorlink13=Benjamin Natelson|last14=Rowe|first14=Peter|authorlink14=Peter Rowe|last15=Shelanski |first15=Michael|authorlink15=Michael Shelanski}}</ref> ME/CFS ([[Systemic Exertion Intolerance Disease|SEID]]) is accurately diagnosed when the [[Systemic Exertion Intolerance Disease#Diagnostic criteria|core symptoms]] are met. The [[Institute of Medicine report]] as a whole is a comprehensive review of the medical literature available at time of publication (2015). Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.

==Learn more==
*2015, [https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/ Chronic fatigue syndrome gets yet another name]<ref>{{Cite news|url=https://www.newscientist.com/article/dn26945-chronic-fatigue-syndrome-gets-yet-another-name/|title=Chronic fatigue syndrome gets yet another name|last=Coghlan|first=Andy|date=Feb 10, 2015|work=New Scientist|access-date=2018-09-03|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>
*2015, [http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract Systemic Exercise Intolerance Disease: What’s in a name?]<ref>{{Cite journal|last=Sen|first=Mahadev Singh|last2=Sahoo|first2=Swapnajeet|last3=Aggarwal|first3=Shivali|last4=Singh|first4=Shubh Mohan|date=2016|title=Systemic exercise intolerance disease: What’s in a name?|url=http://www.asianjournalofpsychiatry.com/article/S1876-2018(16)30248-9/abstract|journal=Asian Journal of Psychiatry|language=English|volume=22|pages=157–158|doi=10.1016/j.ajp.2016.06.003|issn=1876-2018|via=}}</ref>
*2018, [https://youtu.be/RC9TjgE_PlU?t=89 Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome]<ref>{{Cite web|url=https://youtu.be/RC9TjgE_PlU?t=89|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|last=Kaufman|first=David|date=Oct 16, 2018|website=YouTube|publisher=Unrest Film|archive-url=|archive-date=|dead-url=|access-date=|quote=Part of the Unrest Continuing Education module.|at=1:29}}</ref> (Notes the IOM report's diagnostic criteria.)

== References ==
<references>
<ref name="Chu, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Norris | first2 = Jane | authorlink2 = Jane Norris
| last3 = Valencia | first3 = Ian J. | authorlink3 =
| last4 = Montoya | first4 = Jose G. | authorlink4 = Jose Montoya
| title = Patients diagnosed with Myalgic encephalomyelitis/chronic fatigue syndrome also fit systemic exertion intolerance disease criteria
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 5 | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1299079
}}
</ref>
<ref name="Chu, Valencia, Montoya, 2017">{{Citation
| last1 = Chu | first1 = Lily | authorlink1 = Lily Chu
| last2 = Valencia | first2 = Ian J. | authorlink2 =
| last3 = Montoya | first3 = Jose G. | authorlink3 = Jose Montoya
| title = Differences of opinion on systemic exercise intolerance disease are not ‘mistakes’: a rejoinder to Jason Sunnquist, Gleason and Fox
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| doi = 10.1080/21641846.2017.1362750
}}
</ref>
<ref name="Jason, Sunn, 2015">{{Citation
| last1 = Jason | first1 = L.A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = M. | authorlink2 = Madison Sunnquist
| last3 = Brown | first3 = A. | authorlink3 =
| last4 = Newton | first4 = J.L. | authorlink4 = Julia Newton
| last5 = Strand | first5 = E.B. | authorlink5 = Elin Strand
| last6 = Vernon | first6 = S.D. | authorlink6 = Suzanne Vernon
| title = Chronic fatigue syndrome versus systemic exertion intolerance disease
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 3 | issue = 3 | page = 127-141
| date = 2015
| pmid =
| doi = 10.1080/21641846.2015.1051291
}}</ref>
<ref name="Jason, Sunnquist, Gleason, Fox, 2017">{{Citation
| last1 = Jason | first1 = Leonard A. | authorlink1 = Leonard Jason
| last2 = Sunnquist | first2 = Madison | authorlink2 = Madison Sunnquist
| last3 = Gleason | first3 = Kristen | authorlink3 = Kristen Gleason
| last4 = Fox | first4 = Pamela | authorlink4 = Pamela Fox
| title = Mistaken conclusions about systemic exercise intolerance disease being comparable to research case definitions of CFS: A rebuttal to Chu et al.
| journal = Fatigue: Biomedicine, Health & Behavior | volume = | issue = | page =
| date = 2017
| pmid =
| doi = 10.1080/21641846.2017.1362780
}}
</ref>
</references>

[[Category:Definitions]]
[[Category:Diagnoses]]
[[Category:Disease names]]

Primer for the public

2019-04-14T13:52:36Z

MEandCFS:/* Symptoms */ caption info

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
'''Primer for the public''' offers a broad audience detailed information on [[myalgic encephalomyelitis]] (ME) and [[chronic fatigue syndrome]] (CFS), complex, chronic, and poorly understood medical conditions. ME was first categorized as a [[Nervous system|neurological]] disease by the [[World Health Organization]] (WHO) in 1969.<ref name=":32">{{Cite book|url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y|title=International Classification of Diseases|last=World Health Organization|first=|publisher=WHO|year=1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic), (myalgic, benign) 323|editor-last2=|editor-link2=}}</ref> [[Chronic fatigue syndrome|CFS]] was first formally defined by the United States [[Centers for Disease Control|Centers for Disease Control and Prevention]] (CDC) in 1988 as a framework for researching unexplained [[chronic fatigue]] (CF) associated with a [[mononucleosis]]-like syndrome. There remains a lack of consensus among members of the medical and research communities regarding the equivalence of [[Myalgic encephalomyelitis|ME]] and CFS. Some believe that CFS is intended to describe the same disease entity as ME, while others believe that they are distinct conditions but with overlapping symptom profiles. In deference to this lack of consensus, the combined term [[ME/CFS]] is often used.

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]]<ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":4">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] symptoms to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda19942">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":0232">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref> There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref>{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref> CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The CDC website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":03">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]
== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":043">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />
===Not a mental health disorder===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

===ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":0322">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":4" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":22">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-10-28}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":4" /><ref name="Carruthers, 20032" /><ref name=":5" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":12">{{Cite journal|last=Cairns|first=R.|last2=Hotopf|first2=M.|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":12" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

== Symptoms ==
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about PEM and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] including [[chronic fatigue]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":023">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":0">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref name=":2">[http://chronicfatigue.about.com/od/cfsglossary/g/malaise.htm Post-Exertional Malaise - About.com Health - FMS/ME/CFS]</ref> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":15">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":13">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":023" /><ref name=":0" /><ref name=":1" /><ref name=":2" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
* [[chronic fatigue]]

*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]]<ref name=":6" /><ref name=":4" />
==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[https://me-pedia.org/wiki/Category:Neurological_signs_and_symptoms?title= neurological signs and symptoms] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ)<ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Drugs, treatments, and therapies ==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [https://me-pedia.org/wiki/Category:Potential_treatments potential treatments], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.

===Drugs===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the [[United States]] have failed so it is unavailable to many.<ref>{{Cite web|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|title=Ampligen for Chronic Fatigue Syndrome|last=|first=|authorlink=Adrienne Dellwo|last2=Grant|first2=Hughes|authorlink2=|date=Sep 16, 2018|website=Verywell Health|archive-url=|archive-date=|dead-url=|access-date=2019-02-09}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the United States, known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] ([[LDN]]) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Controversy===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Psychiatry has taken an inappropriate lead and treatment path for a biological disease. In the [[United Kingdom|UK]], [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are employed by ME Clinics. [[Exercise]] exacerbates symptoms and can further injure patients.<ref>[http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS - Slightly Alive - By: Mary Schweitzer]</ref><ref>[https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients GET and CBT are dangerous treatments for ME patients - Petition - 38 Degrees - By Michael Evison]</ref> [[Depression]] and [[anxiety]] drugs are utilized usually with poor and even damaging results.<ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

Treating a biological disease as a mental illness is seen as cost-effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance, having clauses excluding a mental health illness/disease, stop any payment or shorten the payout time-frame.<ref>[http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/ Trial by error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really? - By: David Tuller Virology Blog]</ref><ref>[https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders Physical Illnesses May Soon Be Labeled “Mental Disorders” - Psychology Today - Toni Bernhard, J.D.]</ref><ref>[http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth People with mental illness face widespread discrimination - The Guardian - David Batty]</ref><ref>[http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/ Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits - Thoughts About ME]</ref>

====Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
[[Graded exercise therapy|GET]] and [[Cognitive behavioral therapy|CBT]] are usually employed in the UK, [[Ireland]] and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

===Claims of curative treatments===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":7" /><ref name=":8" /><ref name=":9" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>
=== Working with government to move forward ===

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[National Institutes of Health]] (NIH), the [[Centers for Disease Control and Prevention]] (CDC) reinstating and increasing funding and education based on [[Institute of Medicine report]] recommendations and the [[U.S. Department of Health and Human Services|Health and Human Services]] (HHS) funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> #[[MEAction]] reports on this ongoing process.

====CDC Website updates====
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #MEAction report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

== Recommended viewing ==

==== Documentary ====
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

==== Short film ====
*[[The Last Great Medical Cover Up]] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)

==== News media ====
*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)

==== Talks and interviews ====
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Canary in a Coal Mine]] (now called Unrest) at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20.] (2016)

== Recommended reading ==
====Government health organizations====
:'''US'''

:[[Centers for Disease Control]] (CDC)
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html ME/CFS in Children Fact Sheets] (2017) Fact Sheets for Healthcare Professionals, Parents/Guardians, Education Professionals

:[[National Institutes of Health]] (NIH)
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]

:[[Institute of Medicine]] (IOM)
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts] From the [[Institute of Medicine report]]. (2015)

:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness] Report Brief on the Institute of Medicine report. (2015)

==== ME/CFS research foundations ====
:'''UK'''

:[[Invest in ME]]
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]

:'''US'''

:[[Open Medicine Foundation]] (OMF)
:*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]

==== ME/CFS organizations ====
:'''Australia'''

:[[Emerge Australia]]
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]

:'''UK'''

:[[ME Association]]
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]

:[[Tymes Trust]] (Pediatric)
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs] (2016)

:'''US'''
:[[Massachusetts CFIDS/ME & FM Association]]
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]

:[[Solve ME/CFS]]
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?] (2017)

:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS] (2016)

:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?] (2013)

:'''International'''
:[[MEAction]]
:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)] (2015)

:*[http://www.meaction.net/reports-and-fact-sheets/?utm_content=bufferc2125&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Reports and Fact Sheets] (2015)

==== Other organizations ====
:*[https://rarediseases.org/ National Organization for Rare Disorders] (NORD) has a section for [https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]

==== Other reading====
:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?] By Suzan Jackson

==History==
=== 1980's to present day ===
*''[[Osler's Web]] i''s a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref>

=== Disease names and acronyms around the world ===
The [[United States]] and [[Australia]] usually refer to the disease as CFS, (chronic fatigue syndrome). Many European countries, the [[United Kingdom]] and [[Ireland]] mostly use the name ME, (Myalgic Encephalomyelitis). Most countries, as well as doctors and researchers worldwide, will also use the acronym ME/CFS and a few CFS/ME. ''See:'' [http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Definitions of ME and CFS].

The symptom [[chronic fatigue]] (CF) should not be used in place of the name [[chronic fatigue syndrome]] (CFS); this has been a source of confusion of CF the symptom and CFS the disease. CFS is a grossly misnamed disease whereas CF is a symptom of many diseases, illnesses and drug therapies.<ref>[http://chronicfatigue.about.com/od/whatischronicfatigue/a/cf_vs_cfs.htm?utm_content=bufferda812&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Chronic Fatigue vs. Chronic Fatigue Syndrome - One's a Symptom, One's a Disease - About.com Health FMS/ME/CFS By Adrienne Dellwo]</ref><ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome What's the Difference? - About.com Health FMS/ME/CFS - By Carol Eustice]</ref> Dr. [[Jarred Younger]] explains chronic fatigue and begins by stating "Fatigue is not a disease and it is not even a symptom. So fatigue is a alarm system and the most general alarm system the body has." [https://www.youtube.com/watch?v=wJB95m4FLa0 Webinar with Jarred Younger, Ph.D. (@6:04-7:54)]

==== Myalgic Encephalomyelitis (ME) ====
Although many similar diseases have occurred for centuries, in the 1920s - 1940s there were sporadic outbreaks around the world<ref>[[List of outbreaks]]</ref>, of both poliomyelitis, and what Dr. [[Melvin Ramsay]] called 'Benign Myalgic Encephalomyelitis' ('benign because it is disabling but not usually fatal). In 1969, the World Health Organisation included "Myalgic Encephalitis' in its 'International Classification of Diseases' (ICD), under the category 'Diseases of the Nervous System', code G93.3.<ref>[http://www.hfme.org/thewhoandme.htm The WHO and M.E. (in brief) - The Hummingbirds' Foundation for M.E.]</ref><ref>[http://www.meactionuk.org.uk/ME_CFS_TERMINOLOGY.pdf ME/CFS Terminology - By: Margaret Williams - April - 2009]</ref>

==== From ME to CFS ====
[[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]], Lake Tahoe, NV, USA experienced an outbreak during 1984-1985. The CDC were sent to investigate. Dr. [[Anthony Komaroff]] studied cases from the outbreak and eventually he and a body of clinicians settled on the name "Chronic Fatigue Syndrome".<ref>[https://www.masscfids.org/diagnosis Diagnosis of ME/CFS - What is a Syndrome]</ref> Dr. Komaroff discusses the name emerging in the documentary film Forgotten Plague.

==== From CFS to 'any unexplained fatigue' ====
Various groups invented new definitions, that required only 'medically unexplained fatigue' such as [[Reeves criteria]] and [[Oxford criteria]]. Fatigue is a common symptom in any population, with many different causes. These new definitions allowed some psychiatrists to claim that CFS could be 'cured' through exercise and positive thinking which has been promoted through the [[PACE trial]] and that this 'cure' also applied to people who are severely ill with Myalgic Encephalomyelitis.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/19855350/ A review on cognitive behavioral therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based but also potentially harmful for many patients with ME/CFS.]</ref><ref>[http://www.meassociation.org.uk/2009/12/statements-of-concern-about-cbtget-provided-for-the-high-court-judicial-review/ Statements of concern about CBT/GET provided for the High Court judicial review - ME Association]</ref> [[Postviral fatigue syndrome]] (PVFS) is the next frontier of the psychological paradigm keeping control of an organic disease and have been laying groundwork to do so.<ref>[http://forums.phoenixrising.me/index.php?threads/elle-anecdotes-used-to-promote-osullivan-complain-shes-being-trolled.46176/ Mind Games - ELLE Magazine September 2016 - Phoenix Rising - '''ELLE''' Anecdotes used to promote O'Sullivan, complain she's being trolled]</ref>

==== SEID name and diagnostic criteria ====
[[Systemic Exertion Intolerance Disease]] (SEID) is a diagnostic criteria proposed by the [[Institute of Medicine]] (IOM) in the [[Institute of Medicine report]]. This clinical criteria was developed for doctors in the United States to diagnose at 6 months instead of years or even decades. Doctors are encouraged to perform tests prior to six months, such as a [[Tilt table test]] or sleep study if symptoms require further investigation. Treating symptoms such as [[orthostatic intolerance]] or a sleep disorder can begin prior to the six months needed to diagnose.<ref name="IOM2015MECFS" />

=== Different diagnostic criteria used worldwide ===
==== Currently used ====
<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[Canadian Consensus Criteria]] (CCC)
*[[Fukuda criteria]] (Sometimes referred to as CDC Criteria)
*[[International Consensus Criteria]] (ICC)
*[[Oxford criteria]]
*[[Reeves criteria]] (Sometimes called [[Empirical definition]])
*[[SEID]] or IOM 2015 (Used by CDC on their [https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html ME/CFS Diagnostic Criteria for Healthcare providers] page.)
</div>

==== Currently not in use ====

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[Holmes criteria]]
*[[London criteria]]
*[[Nightingale definition]]
*[[NIOF]]
*[[Ramsay definition]]
</div>

The different criteria used from one doctor to another and researcher to researcher results in confusion for doctors trying to diagnose, poor research and discord between patients, medical professionals, and charitable organizations. Adding to the confusion is a clinical criteria will at times be used in research and a research criteria used by a clinician to diagnose. Many US researchers will use Fukuda (using the PEM "option") and CCC in a single research project.<ref>[http://www.meaction.net/2016/03/18/study-says-scientists-must-agree-on-classifying-patients/ Study says scientists must agree on classifying patients - By: Sasha Nimmo - #MEAction]</ref> The [[NIH Post-Infectious ME/CFS Study]] will be using four: SEID, Fukuda, CCC and Reeves.<ref>[http://www.meaction.net/2016/02/09/positive-answers-to-initial-questions-re-nih-clinical-center-protocol/#comment-2067 Positive Answers to Initial Questions re NIH Clinical Center Protocol - #MEAction - Comments Section - "Polly"]</ref> The ME/CFS community wanted to participate in this study's design.<ref>[https://my.meaction.net/petitions/nih-put-me-cfs-patients-at-heart-of-research-design-process NIH: Put ME/CFS patients at heart of research design process - Petition - #MEAction]</ref><ref>[https://my.meaction.net/petitions/keep-psychiatry-out-of-nih-study-on-me-cfs PETITION - Keep Psychiatry Out of NIH Study on ME/CFS - #MEAction - By: Mary Schweitzer]</ref>

==Notable studies==
*2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*[https://me-pedia.org/wiki/List_of_enterovirus_infection_studies List of enterovirus infection studies]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|dead-url=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref>
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)

<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

== See also ==
<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[25 Percent ME Group]]
*[[Blood donation]]
*[[Fibromyalgia]]
*[[Primer for family, friends and care providers]]
*[[Primer for patients]]
</div>
== Learn more ==
'''Potential treatments and research'''
* [[Ampligen]] Used in [[Argentina]] for the treatment of [[Severe and very severe ME|severe ME/CFS]].
* [[Brain imaging]]
* [[Natural killer cell]]
* [[Vagus nerve infection hypothesis]]
'''Guides and reports'''
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers
*"[[In the Expectation of Recovery]]" by [[Centre for Welfare Reform]] UK

'''[[Patient mental health]]'''

:Patients that had been deemed as suffering from mental health and not a biological illness.
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.
* ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref><ref>[http://www.sleepydust.net/CHRONIC-FATIGUE-SYNDROME-AND-DEPRESSION.html Are ME/CFS & Depression The Same Thing? - Sleepy Dust]</ref><ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>
'''Outbreaks'''
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]

* [[List of outbreaks]]

== Other resources ==
*[[Verywell FMS/CFS]] Well written articles on ME/CFS and Fibromyalgia.

== References ==
<references>
<ref name="IOM2015MECFS">{{citation
| last1 = Institute of Medicine (USA)
| last2 = Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
| display-authors =
| title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness
| date = 10 February 2015
| url = http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx
}}</ref>
</references>

[[Category:Primers]]

Primer for patients

2019-04-14T13:50:29Z

MEandCFS:/* Symptoms */ caption info

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
This '''Primer for patients''' will provide the information you need to better understand your personal diagnosis of [[chronic fatigue syndrome]] (CFS), [[myalgic encephalomyelitis]] (ME), or [[ME/CFS]], which can be very different with severity and symptoms from patient to patient.

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":042">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":6">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":2">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptoms and [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptoms and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":5">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda19942">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":0232">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing [[chronic fatigue syndrome]] (CFS), they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having [[Chronic fatigue syndrome|CFS]] when in fact they are suffering from the symptom [[chronic fatigue]] (CF).<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref> There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":7">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":8">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":9">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref>{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref>

CF is a symptom of many diseases, illnesses, and drug therapies and should not be confused with the grossly misnamed disease CFS.

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":4">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-22}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":3">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-22}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

Take time when you are able to review this Primer. Because you are not well, this can be overwhelming at times, so only do what you are mentally and physically able.

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu2">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":04">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmentally acquired illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":14">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":4" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":4" />
===Not a mental health disorder===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":4" />

===ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":0322">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":2" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":0">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":2" /><ref name="Carruthers, 20032" /> <ref name=":5" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS isconsidered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":1">{{Cite journal|last=Cairns|first=R.|author-link=|last2=Hotopf|first2=M.|author-link2=|author-link3=|author-link4=|author-link5=|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087|quote=|via=}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":1" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

== Symptoms ==
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-01}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about PEM and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] including [[chronic fatigue]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":02">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":03">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref><ref name=":1" /> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":152">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":132">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":02" /><ref name=":03" /><ref name=":0" /><ref name=":1" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]] <ref name=":6" /><ref name=":2" />
==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ)<ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]]
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]

== Tests to discuss with your doctor ==
* [[Natural killer cell]] (NKC) Blood Test

*[https://en.wikipedia.org/wiki/Sleep_study Sleep study] for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
*[[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Drugs and treatments==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood. There are many [https://me-pedia.org/wiki/Category:Potential_treatments potential treatments], though their evidence base is limited, as most research into treatments has gone into unsuccessful psychological approaches to treatment.

===Drugs===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />

===Controversy===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Psychiatry has taken an inappropriate lead and treatment path for a biological disease. In the UK, [[GET]] and [[CBT]] are employed by ME Clinics. [[Exercise]] exacerbates symptoms and can further injure patients.<ref>[http://slightlyalive.blogspot.com/2016/03/open-letter-to-dr-sanjay-gupta-on-in.html Open Letter to Dr. Sanjay Gupta on In-House NIH Study of ME/CFS - Slightly Alive - By: Mary Schweitzer]</ref><ref>[https://you.38degrees.org.uk/petitions/get-and-cbt-are-dangerous-treatments-for-me-patients GET and CBT are dangerous treatments for ME patients - Petition - 38 Degrees - By Michael Evison]</ref> [[Depression]] and [[anxiety]] drugs are utilized usually with poor and even damaging results.<ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

Treating a biological disease as a mental illness is cost effective. The drugs are inexpensive and biomedical research is not pursued. People struck down and disabled with ME/CFS are labeled with a mental health issue; disability insurance having clauses excluding a mental health illness/disease kick in stopping any payment or shortening the payout time-frame.<ref>[http://www.virology.ws/2015/11/17/trial-by-error-continued-pace-teams-work-for-insurance-companies-not-related-to-pace-really/ Trial by error, Continued: PACE Team’s Work for Insurance Companies Is “Not Related” to PACE. Really? - By: David Tuller Virology Blog]</ref><ref>[https://www.psychologytoday.com/blog/turning-straw-gold/201212/physical-illnesses-may-soon-be-labeled-mental-disorders Physical Illnesses May Soon Be Labeled “Mental Disorders” - Psychology Today - Toni Bernhard, J.D.]</ref><ref>[http://www.theguardian.com/society/2004/apr/28/equality.mentalhealth People with mental illness face widespread discrimination - The Guardian - David Batty]</ref><ref>[http://thoughtsaboutme.com/2016/03/21/keep-an-eye-on-your-walitt-nih-study-poses-dramatic-risk-to-long-term-disability-benefits/ Keep an Eye on Your Walitt: NIH Study Poses Dramatic Risk to Long-Term Disability Benefits - Thoughts About ME]</ref>

==== Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
[[Graded exercise therapy]] (GET) and [[Cognitive behavioral therapy]] (CBT) are usually employed in the UK, Ireland and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

===Claims of curative treatments===
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":7" /><ref name=":8" /><ref name=":9" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>
=== Working with government to move forward ===

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[National Institutes of Health]] (NIH), the [[Centers for Disease Control and Prevention]] (CDC) reinstating and increasing funding and education based on [[Institute of Medicine report]] recommendations and the [[U.S. Department of Health and Human Services|Health and Human Services]] (HHS) funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> #[[MEAction]] reports on this ongoing process.

===CDC Website updates===
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and [[GET]] and [[CBT]] recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref>
*Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>

'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

== Recommended viewing ==

==== Documentary ====
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

==== Short film ====

*[[The Last Great Medical Cover Up]] is a [https://vimeo.com/143904110 UK short Film on Vimeo] with several patient interviews. (2015)

==== News media ====
*[[Chronic Fatigue: Missing Millions (Carte Blanche DSTV)]] TV report, South Africa (2017)

==== Talks and interviews ====
*Jennifer Brea is interviewed for the upcoming BRIC Flix on her ME/CFS disease experience and her 2017 documentary film [[Canary in a Coal Mine]] (now titled [[Unrest]]) at [https://www.youtube.com/watch?v=zeIefNymFuw 5:30 and 10:20.] (2016)

== Recommended reading ==
====Government health organizations====
:'''US'''

:[[Centers for Disease Control]] (CDC)
:*[https://www.cdc.gov/me-cfs/me-cfs-children/factsheets.html ME/CFS in Children Fact Sheets] (2017) Fact Sheets for Healthcare Professionals, Parents/Guardians, Education Professionals

:[[National Institutes of Health]] (NIH)
:*[[Moving Toward Answers in ME/CFS - NIH Director's Blog (2017)]]

:[[Institute of Medicine]] (IOM)
:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts] From the [[Institute of Medicine report]]. (2015)

:*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_ReportBrief.pdf Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Redefining an Illness] Report Brief on the Institute of Medicine report. (2015)

==== ME/CFS research foundations ====
:'''UK'''

:[[Invest in ME]]
:*[http://www.investinme.org/faqs.shtml Frequently Asked Questions]

:'''US'''

:[[Open Medicine Foundation]] (OMF)
:*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?]

==== ME/CFS organizations ====
:'''Australia'''

:[[Emerge Australia]]
:*[https://emerge.org.au/about-mecfs/diagnosis/mecfs/ What is ME/CFS?]

:'''UK'''

:[[ME Association]]
:*[http://www.meassociation.org.uk/about/what-is-mecfs/ What is ME/CFS?]

:[[Tymes Trust]] (Pediatric)
:*[http://www.tymestrust.org/pdfs/mecfsseid.pdf Pediatric ME, CFS, SEID for Families and their GPs] (2016)

:'''US'''
:[[Massachusetts CFIDS/ME & FM Association]]
:*[https://www.masscfids.org/cfids-me-cfs About ME/CFS]

:[[Solve ME/CFS]]
:*[https://drive.google.com/file/d/0B6UlcglLsyp7WkgxbmdaWXVhbVU/view What, Exactly, is a Biomarker Anyway? And Why Don't We Have One for ME/CFS?] (2017)

:*[http://solvecfs.org/what-is-mecfs/ Get the Facts about ME/CFS] (2016)

:*[http://solvecfs.org/wp-content/uploads/2013/06/SMCI_MECFS_FactSheet.pdf What is ME/CFS?] (2013)

:'''International'''
:[[MEAction]]
:*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers

:*[http://www.meaction.net/wp-content/uploads/2015/10/ME-Facts-v2-1.pdf Facts about Myalgic Encephalomyelitis (ME) (Also called chronic fatigue syndrome or CFS)] (2015)

:*[http://www.meaction.net/reports-and-fact-sheets/?utm_content=bufferc2125&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer Reports and Fact Sheets] (2015)

==== Other organizations ====
:[https://rarediseases.org/ National Organization for Rare Disorders] (NORD)
:*[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis]

==== Other reading====
:*[http://thirdage.com/what-do-you-do-when-a-loved-one-becomes-chronically-ill/ What Do You Do When a Loved One Becomes Chronically Ill?] By: Suzan Jackson

==History==
*''[[Osler's Web]] i''s a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref>

==Notable studies==
*2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]

*[[Cytokine#Notable_Studies|Cytokine ("Notable studies")]]
*[https://me-pedia.org/wiki/List_of_enterovirus_infection_studies List of enterovirus infection studies]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''<ref name=":022">{{Cite web|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4?author_access_token=rNZAi4Qn9MGbc1YywGoHCve4RwlQNchNByi7wbcMAY4otkELpwVAg-M9CJyul_kO-cT6SC717CxfcGOGfesdx7f1AhmYrPeCJukInpp-Dq7L6ew7TkRsW7LllmoDMoo7GAglGA7edR1iMan4xy8-LA==|title=Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy|last=|first=|authorlink=Christina Mueller|last2=|first2=|authorlink2=Joanne Lin|date=2019|website=link.springer.com|doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|dead-url=|access-date=2019-01-17|authorlink3=Sulaiman Sheriff|authorlink4=Andrew Maudsley|authorlink5=Jarred Younger}}</ref>
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

== Connect with organizations and other persons with ME/CFS ==
*For information and support, you may want to review materials offered by a patient group in your area.

:''See:'' [http://me-pedia.org/wiki/Category:Patient_groups_by_country Patient groups by country]

:[[Science for ME]], [[Phoenix Rising]], r/cfs, and [[Health Rising]] are forums where you can ask questions, get support, and read about the latest research.

*There are many research initiatives around the world working on ME/CFS.

:''See'': [http://me-pedia.org/wiki/Category:Research_initiatives_by_country Research initiatives by country]

:[[Solve ME/CFS]] produces printed, online and e-mail newsletters. Take their [http://solvecfs.org/do-i-have-mecfs-quiz/ Do I have ME/CFS? QUIZ]

== See also ==
*[[Primer for family, friends and care providers]]
==Learn more==
'''[[Patient mental health]]'''

:Patients that had been deemed as suffering from mental health and not a biological illness.
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end to make him swim and put on a scary theme park ride to scare him into moving.

*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref><ref>[http://www.sleepydust.net/CHRONIC-FATIGUE-SYNDROME-AND-DEPRESSION.html Are ME/CFS & Depression The Same Thing? - Sleepy Dust]</ref><ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

'''Outbreaks'''
* [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak of 1984 began the research that led to the diagnostic construct [[Fukuda criteria|Fukuda]] and name of [[chronic fatigue syndrome]]

* [[List of outbreaks]]

===Other resources===
*[[Phoenix Rising]] Citizen Scientists debate the latest ME/CFS science.
*[[Science for ME]] Friendly forum on ME/CFS, FMS, and comorbid illnesses.
*[https://twitter.com/search?f=tweets&vertical=default&q=%23mecfs&src=tyah Twitter #mecfs] Connect with patients, caregivers, and ME/CFS organizations for support, articles, and research.
*[[Verywell FMS/CFS]] Well written articles with simply stated facts about ME/CFS and Fibromyalgia.

== References ==

[[Category:Primers]]
<references />

Primer for journalists

2019-04-14T13:48:25Z

MEandCFS:/* Evidence of a disease */ caption

{{mbox|text= Editors: Edits to this Primer may require the same edits to the other [[:Category:Primers|Primers]].}}
[[Myalgic Encephalomyelitis|Myalgic encephalomyelitis]] (ME), [[chronic fatigue syndrome]] (CFS), and [[chronic fatigue]] (CF) are widely misunderstood. In this '''Primer for journalists''', we provide evidence-based statements (with links to further reading & sources) to support journalists writing about the disease. ''Chronic Fatigue Syndrome'' must never be shortened to ''Chronic Fatigue'' in the body of an article or its headline. This has caused much confusion for readers who do not understand CFS is a debilitating lifelong illness and it is not the same as CF which is a symptom. There have been media reports of athletes diagnosed with ME or CFS who have recovered in a relatively short period of time after rest, supplementation, and diet changes; these athletes may have had [[overtraining syndrome]] (which has the symptom of CF) and not ME, CFS, or [[ME/CFS]].<ref name=":6">[https://inews.co.uk/news/health/marathon-runner-quit-work-me-cfs-diet-change/ Marathon runner forced to quit work after developing ME claims diet change gave him his life back by Claudia Tanner - iNews]</ref><ref name=":7">[https://www.thetimes.co.uk/article/muslim-fighter-with-me-who-left-an-arranged-marriage-to-win-world-title-svxhhzt57 Muslim fighter with ME who left an arranged marriage to win world title by Rick Broadbent - The Times]</ref><ref name=":8">[http://www.abc.net.au/7.30/committee-reviews-potentially-harmful-and-old/10010408 Video Mark 6:18 - Committee reviews 'potentially harmful and old fashioned' chronic fatigue treatments - by Andy Park and Clare O'Halloran - ABC 7.30]</ref><ref name=":9">{{Cite news|url=https://www.thetimes.co.uk/article/nathan-douglas-london-2012-was-the-darkest-period-of-my-life-vxt5gftcx|title=Nathan Douglas: London 2012 was the darkest period of my life|last=Broadbent|first=Rick|date=2019-02-27|work=The Times|access-date=2019-02-28|archive-url=|archive-date=|dead-url=|language=en|issn=0140-0460|quote=|author-link=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="''What is ME/CFS'' By Open Medicine Foundation - OMF. Linda Tannenbaum, Founder & CEO/President, talks about ME/CFS and how OMF is leading research and delivering hope (2018)">https://www.youtube.com/watch?v=pqDubEeIBtA</embedvideo>

The core [[List of symptoms in ME CFS|ME/CFS symptoms]] are: [[chronic fatigue]] (CF); [[post-exertional malaise]] (PEM); [[unrefreshing sleep]]/[[Sleep dysfunction|sleep problems]]; and [[Cognitive dysfunction|cognitive impairment]]/[[brain fog]] and/or [[orthostatic intolerance]] (OI).<ref name=":043">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref><ref>{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|pages=9 and 10}}</ref> A patient can have many more symptoms<ref name=":0223">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref> and meet different criteria. [[Systemic Exertion Intolerance Disease]] (SEID), an ME/CFS criteria, allows for a patient to be [[Systemic Exertion Intolerance Disease#Diagnostic criteria|diagnosed with the minimum core symptoms]] <ref name=":5">{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_DiagnosticAlgorithm|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness - Diagnostic Algorithm|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref name=":2">{{Cite web|url=http://iom.nationalacademies.org/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|last=|first=|date=2015|website=nationacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> and the patient may have other symptoms.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf|title=Beyond Myalgid Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness|date=2015|access-date=|website=nationalacademies.org|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|page=9}}</ref> The [[Canadian Consensus Criteria]] (CCC) requires the core symptomsand [[Nervous system|neurological]], [[Autonomic nervous system|autonomic]], [[Neuroendocrine system|neuroendocrine]], [[immune system]], and [[myalgia]] symptoms to meet [[Canadian Consensus Criteria#Definition|its ME/CFS diagnostic criteria]].<ref name="Carruthers, 20032">{{Citation
| last1 = Carruthers | first1 = Bruce M. | authorlink1 = Bruce Carruthers
| last2 = Jain | first2 = Anil Kumar | authorlink2 = Anil Kumar Jain
| last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir
| last4 = Peterson | first4 = Daniel L. | authorlink4 = Daniel Peterson
| last5 = Klimas | first5 = Nancy G. | authorlink5 = Nancy Klimas
| last6 = Lerner | first6 = A. Martin | authorlink6 = Martin Lerner
| last7 = Bested | first7 = Alison C. | authorlink7 = Alison Bested
| last8 = Flor-Henry | first8 = Pierre | authorlink8 = Pierre Flor-Henry
| last9 = Joshi | first9 = Pradip | authorlink9 = Pradip Joshi
| last10 = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles
| last11 = Sherkey | first11 = Jeffrey A. | authorlink11 = Jeffrey Sherkey
| last12 = van de Sande | first12 = Marjorie I. | authorlink12 = Marjorie van de Sande
| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols
| journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115
| date = 2003
| pmid =
| doi = 10.1300/J092v11n01_02
| url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf
}}</ref> The [[International Consensus Criteria]] (ICC) is used to diagnose [[myalgic encephalomyelitis]] (ME) which requires the core symptom and neurological, immune/[[Gastrointestinal system|gastrointestinal]]/[[genitourinary]] impairment, and [[portal:Energy metabolism|energy metabolism]]/[[Ion transportation|ion transport]] impairment [[International Consensus Criteria#Criteria|symptoms for a diagnosis]].<ref name=":4">{{Cite journal|last=Carruthers|first=Bruce M.|author-link=Bruce Carruthers|last2=van de Sande|first2=Marjorie I.|author-link2=Marjorie van de Sande|last3=De Meirleir|first3=Kenny L.|author-link3=Kenny De Meirleir|last4=Klimas|first4=Nancy G.|author-link4=Nancy Klimas|last5=Broderick|first5=Gordon|author-link5=Gordon Broderick|last6=Mitchell|first6=Terry|author-link6=Terry Mitchell|last7=Staines|first7=Donald|author-link7=Donald Staines|last8=Powles|first8=A. C. Peter|author-link8=A C Peter Powles|last9=Speight|first9=Nigel|author-link9=Nigel Speight|last10=Vallings|first10=Rosamund|author-link10=Rosamund Vallings|last11=Bateman|first11=Lucinda|author-link11=Lucinda Bateman|last12=Baumgarten-Austrheim|first12=Barbara|author-link12=Barbara Baumgarten-Austrheim|last13=Bell|first13=David|author-link13=David Bell|last14=Carlo-Stella|first14=Nicoletta|author-link14=Nicoletta Carlo-Stella|last15=Chia|first15=John|author-link15=John Chia|last16=Darragh|first16=Austin|author-link16=Austin Darragh|last17=Jo|first17=Daehyun|author-link17=Daehyun Jo|last18=Lewis|first18=Donald|author-link18=Donald Lewis|last19=Light|first19=Alan|author-link19=Alan Light|last20=Marshall-Gradisnik|first20=Sonya|author-link20=Sonya Marshall-Gradisnik|last21=Mena|first21=Ismael|author-link21=Ismael Mena|last22=Mikovits|first22=Judy|author-link22=Judy Mikovits|last23=Miwa|first23=Kunihisa|author-link23=Kunihisa Miwa|last24=Murovska|first24=Modra|author-link24=Modra Murovska|last25=Pall|first25=Martin|author-link25=Martin Pall|last26=Stevens|first26=Staci|author-link26=Staci Stevens|date=2011-08-22|title=Myalgic encephalomyelitis: International Consensus Criteria|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2011.02428.x|journal=Journal of Internal Medicine|language=en|volume=270|issue=4|pages=327–338|doi=10.1111/j.1365-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>

Although the [[Fukuda criteria|Fukuda]]<ref name="fukuda1994">{{Cite journal|last=Fukuda|first=K.|author-link=Keiji Fukuda|last2=Straus|first2=S. E.|author-link2=Stephen Straus|last3=Hickie|first3=I.|author-link3=Ian Hickie|last4=Sharpe|first4=M. C.|author-link4=Michael Sharpe|last5=Dobbins|first5=J. G.|author-link5=James Dobbins|last6=Komaroff|first6=A.|author-link6=Anthony Komaroff|date=1994-12-15|title=The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group|url=https://www.researchgate.net/profile/Michael_Sharpe2/publication/247808895_The_Chronic_Fatigue_Syndrome_A_Comprehensive_Approach_to_Its_Definition_and_Study/links/0c96053201643bfc4b000000/The-Chronic-Fatigue-Syndrome-A-Comprehensive-Approach-to-Its-Definition-and-Study.pdf|journal=Annals of Internal Medicine|volume=121|issue=12|pages=953–959|issn=0003-4819|pmid=7978722|via=|doi=10.7326/0003-4819-121-12-199412150-00009|publisher=American College of Physicians}}</ref> and the [[Oxford criteria|Oxford Criteria]]<ref name=":02">{{Cite journal|title=A report--chronic fatigue syndrome: guidelines for research.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/|journal=Journal of the Royal Society of Medicine|date=Feb 1991|issn=0141-0768|pmc=1293107|pmid=1999813|pages=118–121|volume=84|issue=2|first=M C|last=Sharpe|first2=L C|last2=Archard|first3=J E|last3=Banatvala|first4=L K|last4=Borysiewicz|first5=A W|last5=Clare|first6=A|last6=David|first7=R H|last7=Edwards|first8=K E|last8=Hawton|first9=H P|last9=Lambert}}</ref> are used for diagnosing CFS, they are both overly broad and there is criticism that patients are being misdiagnosed in both clinical and research settings as having CFS when in fact they are suffering from the symptom CF.<ref>[http://arthritis.about.com/od/fatigue/f/chronicfatigue.htm Chronic Fatigue Versus Chronic Fatigue Syndrome - About.com Health - By: Carol Eustice]</ref><ref>{{Cite web|title=What Does a True ME Definition Look Like?|url=https://www.meadvocacy.org/what_does_a_true_me_definition_look_like|website=MEadvocacy.org|access-date=2019-01-25|first=2015|last=Feb 02|first2=6|last2=Reactions}}</ref><ref>{{Cite web|title=Fukuda Definition (1994)|url=http://www.shoutoutaboutme.com/definitions/fukuda-definition-1994/|website=Shoutout about ME|access-date=2019-01-25|date=Mar 25, 2014|last=Logan|first=Russell|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref><ref>[http://theargusreport.com/us-nih-report-calls-uk-definition-mecfs-scrapped/ US NIH Report Calls for UK Definition of ME/CFS to be Scrapped - The Argus Report By: Penny Swift]</ref><ref>{{Cite web|url=http://occupyme.net/2016/08/16/ahrq-evidence-review-changes-its-conclusions/|website=occupyme.net|access-date=2019-01-25|title=AHRQ Evidence Review Changes Its Conclusions|date=Aug 16, 2016|last=|first=|authorlink=Jennie Spotila|last2=|first2=|authorlink2=Mary Dimmock|archive-url=|archive-date=|dead-url=}}</ref>

The acronym ME/CFS is widely used in research, by research and patient organizations, and patients.

"The most common overlapping condition with ME/CFS is [[fibromyalgia]]."<ref name=":30">{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions - American Myalgic Encephalomyelitis and Chronic Fatigue Syndrome Society|last=|first=|date=|website=ammes.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-08-12}}</ref><ref name=":31">{{Cite journal|last=Jason|first=Leonard|last2=Taylor|first2=R.R.|last3=Kennedy|first3=C.L.|last4=Song|first4=S|last5=Johnson|first5=D|last6=Torres|first6=S.R.|date=2001-01-01|title=Chronic fatigue syndrome: Comorbidity with fibromyalgia and psychiatric illness|url=https://www.researchgate.net/publication/285787383_Chronic_fatigue_syndrome_Comorbidity_with_fibromyalgia_and_psychiatric_illness|journal=Medicine and Psychiatry|volume=4|pages=29–34}}</ref> While some have posited ME/CFS and fibromyalgia are variants of the same illness, [[Benjamin Natelson]], MD summoned considerable amounts of data that suggest the two illnesses differ with different pathophysiologic processes leading to different treatments.<ref>{{Cite journal|last=Natelson|first=Benjamin H.|date=2019-02-19|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: Definitions, Similarities, and Differences|url=https://www.clinicaltherapeutics.com/article/S0149-2918(19)30003-7/abstract|journal=Clinical Therapeutics|language=English|volume=0|issue=0|doi=10.1016/j.clinthera.2018.12.016|issn=0149-2918|pmid=30795933}}</ref>

Unfortunately, a psychiatric approach has been taken with ME/CFS, but this is changing. At this time there are no approved drug treatments. [[Graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT) are used in the [[United Kingdom|UK]] inappropriately for treating ME/CFS. The [[Centers for Disease Control and Prevention]] (CDC) website states "ME/CFS is a biological illness''',''' not a psychologic disorder" and impacts multiple body systems.<ref name=":3">{{Cite web|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-22|language=en-us}}</ref> The CDC recognizes the hallmark symptom of PEM which is a worsening of symptoms after physical or mental activity<ref name=":04">{{Cite web|title=Symptoms of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-22|language=en-us}}</ref> and says [[ME/CFS]] is a "disabling and complex disease."<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-04-12}}</ref>

[[File:SEID algorithm.JPG|400px|thumb|right|Diagnostic Algorithm for [[Systemic Exertion Intolerance Disease|SEID]]'s minimum [[List of symptoms in ME CFS#Systemic Exertion Intolerance Disease (SEID) symptom list|ME/CFS core symptoms]]]]

==What do we know?==
ME is a debilitating illness that has been recognized as a neurological condition by the [[World Health Organization]] (WHO) since 1969.<ref name=":32">{{Cite book|url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf?sequence=3&isAllowed=y|title=International Classification of Diseases|last=World Health Organization|first=|publisher=WHO|year=1969|isbn=|editor-link=|edition=Eighth revision|volume=2|location=Geneva|pages=173|chapter=|quote=Encephalomyelitis (chronic), (myalgic, benign) 323|editor-last2=|editor-link2=}}</ref>

It is a systemic [[Neuro-immune disease|neuroimmune]] condition characterized by [[post-exertional malaise]] (PEM) (a severe worsening of symptoms after even minimal [[exertion]]). It causes dysregulation of both the [[immune system]] and the [[nervous system]]. The effects of ME are devastating enough to leave [[Severe and very severe ME|25% of patients housebound or bedbound]]. For moderate to severe patients, the disability of living with ME is like living with late-stage cancer, advanced stage AIDS, or congestive heart failure for decades.

In many parts of the world, it is commonly called chronic fatigue syndrome.

[[ME/CFS]] costs the US economy up to $24 billion per year in direct medical costs, and lost production.<ref name="IOM2015MECFS" /> Despite this, funding for research is not commensurate with the level of disease burden. In the 2015 financial year, the [[National Institutes of Health]] (NIH) provided only $5 million in research funding for ME/CFS, which is less funding than hayfever. This is in stark contrast to funding levels for other similarly disabling illnesses, like [[multiple sclerosis]] ($105 million) and HIV/AIDS ($3 billion).<ref>reference needed for NIH funding levels</ref> The [[Institute of Medicine]], a special advisory committee of the [[U.S. Department of Health and Human Services]] (HHS) (ref: [[Chronic Fatigue Syndrome Advisory Committee|CFSAC]] recommendations) and [[NIH]] expert advisory panel agree that it is imperative to increase research funding into ME/CFS.<ref name="NIHP2PFIN" />

== Disease onset and course of illness==
[[Onset of ME/CFS|ME/CFS can begin]] from many acute/sudden<ref name="Chu22">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref> events: usually [[Viral onset hypothesis|viral]] or [[Bacterial disease onset|bacterial]] infections, but also [[trauma]], surgery or childbirth, [[allergic reaction]], and [[stress]].<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is also a gradual onset in some people,<ref name="Chu3">{{Cite journal|last=Chu|first=Lily|author-link=Lily Chu|last2=Valencia|first2=Ian J.|author-link2=Ian Valencia|last3=Garvert|first3=Donn W.|author-link3=|last4=Montoya|first4=Jose G.|author-link4=Jose Montoya|author-link5=|date=14 Jan 2019|title=Onset patterns and course of myalgic encephalomyelitis/ chronic fatigue syndrome|url=https://www.frontiersin.org/articles/10.3389/fped.2019.00012/abstract|journal=Frontiers in Pediatrics|volume=|issue=|pages=|doi=10.3389/fped.2019.00012|quote=|via=}}</ref><ref name=":044">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/index.html|title=Presentation and Clinical Course of ME/CFS {{!}} Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS {{!}} CDC|date=2018-12-12|website=www.cdc.gov|language=en-us|access-date=2019-02-07}}</ref> that is not attributed to any one event. Occasionally, ME/CFS has been triggered by [[Environmental illness|environmental toxins]] or the receipt of an [[Vaccine|immunizing injection]].<ref>[https://www.masscfids.org/images/pdf/Primer_2014.pdf Chronic Fatigue Syndrome Myalgic Encephalomyelitis - Primer for Clinical Practitioners - 2014 Edition - Massachusettes CFIDS/FM Assoc]</ref> Some say that the disease [[Myalgic encephalomyelitis|ME]] always has an acute/sudden [[Infection|infectious]] onset.<ref name=":142">{{Cite journal|last=Evans|first=Meredyth|author-link=Meredyth Evans|author-link2=Leonard Jason|author-link3=|author-link4=|author-link5=|date=2018|title=Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf|journal=Research on Chronic Diseases|volume=|issue=|pages=2|quote=|via=|last2=Jason|first2=Leonard}}</ref>

The disease [[ME/CFS]] is often diagnosed when a person does not recover from a [[flu-like illness]], [[mononucleosis]] or another [[HHV|herpesvirus]], [[Q fever]], an unidentified [[virus]], or [[:Category:Infectious agents|other infection]], and meets one or more [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|diagnostic criteria for either ME, CFS, or ME/CFS]].<ref>[https://www.nap.edu/read/19012/chapter/7#157 IOM Report - INFECTION]</ref><ref>[http://www.cortjohnson.org/blog/2014/01/09/lipkin-study-vagus-nerve-hhv-6-loomis-hhv-6-foundation/ The Lipkin Study, The Vagus Nerve Infection Hypothesis and HHV-6: Kristin Loomis of the HHV-6 Foundation Talks – Pt. I - Health Rising - By: Cort Johnson - June 2014]</ref> Patients experience [[List of symptoms in ME CFS|numerous symptoms]] and disease severity which fluctuate from day to day, week to week, month to month, year to year, and even decade to decade. Furthermore, symptoms and disease severity vary among patients.<ref>[http://www.meassociation.org.uk/about/the-symptoms-and-diagnosis-of-mecfs/ Symptoms and diagnosis of ME/CFS - ME Association]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Symptoms - Web MD]</ref><ref>[http://phoenixrising.me/mecfs-basics/chronic-fatigue-syndrome-mecfs-facts-chronic-fatigue-syndrome-is-2 Facts (ME/CFS) Severity]</ref>

The CDC recognizes that there can be different causes and it is possible that two or more things could cause the illness. Areas of research include infections, [[immune system]] changes, [[stress]] affecting [[body chemistry]], changes in [[Metabolic|energy production]], and a possible [[Genetics of chronic fatigue syndrome|genetic link]].<ref>{{Cite web|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-27|language=en-us}}</ref><ref name=":3" /> The CDC notes there are abnormalities with the immune system, [[Metabolic|cellular metabolism]], neuroendocrine disturbances, and [[blood pressure]] or [[heart rate]] regulation.<ref name=":3" />
===Not a mental health disorder===
In the past, CFS was believed to be a mental health disorder. This is why the CDC now states: "ME/CFS is a biological illness, not a psychologic disorder. Patients with ME/CFS are neither malingering nor seeking secondary gain. These patients have multiple pathophysiological changes that affect multiple systems."<ref name=":3" />

=== ME/CFS is not contagious===
There is no evidence that ME/CFS patients are contagious.<ref name=":0322">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|last=|first=|authorlink=Suzanne Vernon|last2=|first2=|authorlink2=|date=|website=www.healthywomen.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> [[:Category:Infectious agents|Initial infectious triggers]] have led to [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] over the years and 72% of ME/CFS patients report an [[Onset of ME/CFS|onset]] of a viral or bacterial infection.<ref>{{Cite web|url=https://www.cdc.gov/grand-rounds/pp/2016/20160216-presentation-chronic-fatigue-H.pdf|title=CDC Public Health Grand Rounds - Chronic Fatigue Syndrome - Advancing Research and Clinical Education|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=cdc.gov|page=6|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Families, partners, and friends do not report contracting ME/CFS from someone ''with the disease'' ''ME/CFS'' nor do patients report passing it on to others.<ref>{{Cite web|url=http://forums.prohealth.com/forums/index.php?threads/is-cfs-contagious.189664/|title=Is CFS contagious? {{!}} ProHealth Fibromyalgia, ME/CFS and Lyme Disease Forums|website=forums.prohealth.com|access-date=2019-02-13}}</ref> Because ME/CFS can run in families, a [[Genetics of chronic fatigue syndrome|genetic link]] is a recommended line of research by the CDC.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html|title=Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-02-13}}</ref>
====Blood donation and organ transplant====
[[Blood donation]] prohibition had been enacted in the [[United States]] (US) and [[United Kingdom]] (UK)<ref name=":062">{{Cite web|url=https://www.healthywomen.org/content/ask-expert/9326/chronic-fatigue-syndrome-contagious|title=Is chronic fatigue syndrome contagious? {{!}} HealthyWomen|website=www.healthywomen.org|language=en|access-date=2019-02-13}}</ref><ref name=":442">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> at one time due to the research of [[Xenotropic murine leukemia virus-related virus|XMRV]] as being the infectious trigger of CFS<ref>{{Cite web|url=https://www.meassociation.org.uk/2010/04/xmrv-testing-in-the-uk/|title=XMRV testing in the UK|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2010|website=meassociation.org|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-13}}</ref> and that patients carried the virus.<ref name=":432">{{Cite web|url=http://voices.washingtonpost.com/checkup/2010/12/red_cross_bars_chronic_fatique.html|title=Red Cross bars chronic fatigue patients from donating blood|last=Stein|first=Rob|authorlink=|last2=|first2=|authorlink2=|date=Dec 3, 2010|website=washingtonpost.com|publisher=Washington Post|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Two papers on XMRV were retracted as it was a laboratory contamination.<ref name=":522">{{Cite journal|date=Dec 2012|title=Redaction, retraction and reaction|url=https://www.nature.com/articles/nrmicro2928|journal=Nature Reviews Microbiology|language=en|volume=10|issue=12|pages=799|doi=10.1038/nrmicro2928|issn=1740-1534}}</ref><ref name=":622">{{Cite web|url=https://transfusionnews.com/2012/10/05/multicenter-study-finds-no-correlation-between-chronic-fatigue-syndrome-and-xmrv/|title=Multicenter Study Finds No Correlation between Chronic Fatigue Syndrome and XMRV|website=transfusionnews.com|access-date=2019-02-13}}</ref> The US American Red Cross and UK [[National Health Service]] Blood and Transplant sites no longer have statements barring transfusions or transplants for CFS.<ref name=":322">{{Cite web|url=https://www.redcrossblood.org/faq.html#eligibility-health|website=www.aabb.org|access-date=2019-02-13|title=Frequently Asked Questions|date=|last=|first=|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=American Red Cross|at=|quote=Your search for “Chronic fatigue syndrome” returned no results.}}</ref><ref name=":162">{{Cite web|url=http://hospital.blood.co.uk/customer-services/blood-and-transplant-matters/|title=Error 404|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Feb 13, 2019|website=hospital.blood.co.uk|archive-url=|archive-date=|dead-url=|access-date=|publisher=NHSBT Hospitals and Science}}</ref> [[Australia]] has a prohibition on blood transfusion as a precaution.<ref name=":722">[https://www.donateblood.com.au/faq/chronic-fatigue-syndrome Chronic fatigue syndrome – I have/had chronic fatigue syndrome. Can I donate?]</ref>
== Mini-Docs ==
<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Jen Brea/TED (2016)">https://www.youtube.com/watch?v=Fb3yp4uJhq0</embedvideo>
[[What happens when you have a disease doctors can't diagnose - TED Talk (2016)|''What happens when you have a disease doctors can't diagnose'']] By [[Jennifer Brea|Jen Brea]]/TED

Five years ago, TED Fellow Jen Brea became progressively ill with myalgic encephalomyelitis, commonly known as chronic fatigue syndrome, a debilitating illness that severely impairs normal activities and on bad days makes even the rustling of bed sheets unbearable. In this poignant talk, Brea describes the obstacles she's encountered in seeking treatment for her condition, whose root causes and physical effects we don't fully understand, as well as her mission to document through film the lives of patients that medicine struggles to treat.<ref>{{Cite web|url=https://www.youtube.com/watch?v=Fb3yp4uJhq0|title=What happens when you have a disease doctors can't diagnose|date=Jan 17, 2017|access-date=|website=YouTube|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=TED}}</ref><ref>{{Cite web|url=https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose|title=What happens when you have a disease doctors can't diagnose|date=Jun 2016|access-date=|website=TED.com|last=|first=|authorlink=Jennifer Brea|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Veronica Weber/Palo Alto Online (2015)">https://www.youtube.com/watch?v=9_HwOUiImvw</embedvideo>

[[Invisible Illness - Stories of Chronic Fatigue Syndrome|''Invisible Illness - Stories of Chronic Fatigue Syndrome'']] By Veronica Weber/Palo Alto Online

This mini documentary reveals 3 stories of people who have been impacted by [[Chronic Fatigue Syndrome]] - a little known disease that affects roughly 836,000-2.5 million people in the U.S. and receives little research funding. They share emotions of treating loved ones with the disease, their frustrations of being ignored by members of society and the healthcare industry and express hopes of treatment and research. Video by Veronica Weber/Palo Alto Online<ref>{{Cite web|url=https://www.youtube.com/watch?v=9_HwOUiImvw|title=Invisible Illness - Stories of Chronic Fatigue Syndrome|date=Jul 10, 2015|access-date=|website=YouTube|last=Weber|first=Veronica|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Palo Alto Online}}</ref>

<embedvideo service="youtube" dimensions="400" alignment="right" container="frame" description="By Dr. David Kaufman/Unrest (2018)">https://www.youtube.com/watch?v=RC9TjgE_PlU</embedvideo>

''Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome'' By Dr. [[David Kaufman]]/[[Unrest|''Unrest'']]

This video on the diagnosis and management of myalgic encephalomyelitis and chronic fatigue syndrome is '''part of the Unrest Continuing Education module''', made available through the American Medical Women’s Association and Indiana University School of Medicine, and in partnership with #MEAction. US medical providers can visit: https://www.unrest.film/cme to register to watch [[Unrest]] online for free and receive Continuing Education credit.<ref>{{Cite web|url=https://www.youtube.com/watch?v=RC9TjgE_PlU|title=Diagnosis and Management of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome|date=Oct 16, 2018|access-date=|website=YouTube|last=|first=|authorlink=David Kaufman|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Unrest Film}}</ref>

==Epidemiology ==
In the [[United States]], 836,000 - 2.5 million people suffer from ME/CFS. "The total economic costs of ME/CFS are estimated at $17 to $24 billion annually."<ref name=":2" /> Some CFS patients can work with [https://www.dol.gov/general/topic/disability/jobaccommodations job accommodations] but 1/3 to 1/2 become unemployed and [[Disability|many rely on SSDI/SSI]].<ref>[http://phoenixrising.me/living-i-the-basics/disability-chronic-fatigue-syndrome-mecfs Disability for CFS - Phoenix Rising]</ref><ref>[http://www.womenshealth.gov/publications/our-publications/fact-sheet/chronic-fatigue-syndrome.html CFS - Womenshealth.gov]</ref><ref>[https://www.masscfids.org/job-accommodations Job Accommodations - MASS CFIDS]</ref>
*[[Epidemiology of myalgic encephalomyelitis and chronic fatigue syndrome|Epidemiology]]
:All races and cultures are afflicted with ME/CFS.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-9-91 Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in three regions of England: a repeated cross-sectional study in primary care - Bio-Med Central - July 2011]</ref><ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref> Children and adolescents are also diagnosed.<ref>{{Cite web|title=ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-01-29|language=en-us}}</ref><ref>{{Cite web|title=Pediatric ME/CFS Home Page|url=https://www.massmecfs.org/pediatric-me-cfs-home-page|website=www.massmecfs.org|access-date=2019-01-29}}</ref>
*[[Female predominant diseases]]
:Like many [[Autoimmune disease|autoimmune]] and [[Neuro-immune disease|neuro-immune]] diseases where mostly women are afflicted,<ref>[http://www.rightdiagnosis.com/artic/fact_sheet_autoimmune_disease_in_women_nwhic.htm Fact Sheet Autoimmune Disease in Women: NWHIC - Right Diagnosis - Aug 2015]</ref> the ME/CFS female/male patient ratio per Capelli et al. is 6:1<ref>{{Cite journal|title=Chronic fatigue syndrome/myalgic encephalomyelitis: an update|url=https://www.ncbi.nlm.nih.gov/pubmed/21244747|journal=International Journal of Immunopathology and Pharmacology|date=Oct 2010|issn=0394-6320|pmid=21244747|pages=981–989|volume=23|issue=4|doi=10.1177/039463201002300402|first=E.|last=Capelli|first2=R.|last2=Zola|first3=L.|last3=Lorusso|first4=L.|last4=Venturini|first5=F.|last5=Sardi|first6=G.|last6=Ricevuti}}</ref> while the CDC states 4:1.<ref>{{Cite web|title=Epidemiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/epidemiology.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-29|language=en-us}}</ref>
*[[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|Pediatric]]
:Pediatric ME/CFS is defined by the CDC<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/factsheet-healthcare-professional.html|title=Pediatric ME/CFS: Fact Sheet for Healthcare Professionals {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2017-10-10|website=www.cdc.gov|language=en-us|access-date=2018-10-13}}</ref> and the [[National Academy of Medicine]] (NAM)<ref>{{Cite journal|last=|first=|date=2015-03-16|title=Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.nap.edu/read/19012/chapter/8|journal=The National Academies Press|language=en|volume=|page=|pages=|at=Pediatric ME/CFS Chapter 6, p 181|doi=10.17226/19012|via=|issue=|quote=|author-link=|author-link2=|author-link3=|author-link4=|author-link5=}}</ref> although it is usually diagnosed in adults.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref> "Children below the age of 8 or 9 do not have the symptom pattern of adolescents past puberty. If the onset of the disease occurs during adolescence, the most common time of onset, the pattern is similar to that of adults."<ref>{{Cite news|url=https://www.omf.ngo/2016/06/25/mecfs-in-children-by-dr-david-s-bell-2/|title=ME/CFS in Children - by David S. Bell, MD {{!}} Open Medicine Foundation|date=2016-06-25|work=Open Medicine Foundation|access-date=2018-08-11|language=en-US}}</ref> The prognosis in adolescents is considered to be better than in adults.<ref name=":0">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html|title=Prognosis {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-11-08|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref><ref>{{Cite journal|last=Rowe|first=Peter C.|last2=Underhill|first2=Rosemary A.|last3=Friedman|first3=Kenneth J.|last4=Gurwitt|first4=Alan|last5=Medow|first5=Marvin S.|last6=Schwartz|first6=Malcolm S.|last7=Speight|first7=Nigel|last8=Stewart|first8=Julian M.|last9=Vallings|first9=Rosamund|date=2017|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer|url=https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref> Children are diagnosed with ME/CFS at three months of illness under SEID and CCC and ME is diagnosed immediately under ICC.<ref>{{Cite web|url=https://www.masscfids.org/pediatric-me-cfs-links|title=Pediatric ME/CFS links|website=www.masscfids.org|language=en-GB|access-date=2018-08-11}}</ref><ref name=":2" /><ref name="Carruthers, 20032" /><ref name=":4" />
*[[Prevalence of myalgic encephalomyelitis and chronic fatigue syndrome|Prevalence]]
:"Worldwide, there may be as many as 17 – 24 million people with ME/CFS."<ref>{{Cite web|url=https://ammes.org/how-many-people-have-mecfs/|title=How Many People Have ME/CFS? – American ME and CFS Society|language=en-US|access-date=2019-01-31}}</ref> 25% of ME/CFS patients are [[Severe and very severe ME|housebound or bedbound]] at some point in their illness.<ref>{{Cite web|url=http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFS_KeyFacts.pdf|title=Myalgic Encelphalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Key Facts|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2015|website=nationalacademies.org|archive-url=|archive-date=|dead-url=|access-date=}}</ref> <ref>{{Cite book|url=https://www.nap.edu/read/19012/chapter/4|title=Read "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness" at NAP.edu|last=|first=|publisher=National Academies of Medicine|year=2015|isbn=|editor-link=|location=|pages=32|language=en|chapter=|quote=|editor-last2=|editor-link2=}}</ref> 90% of patients are undiagnosed.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html|title=What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2019-01-18|website=www.cdc.gov|language=en-us|access-date=2019-01-31}}</ref>
*[[Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome|Prognosis]]
:The prognosis for a patient diagnosed with ME/CFS is considered to be poor with only a minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name=":1">{{Cite journal|last=Cairns|first=R.|author-link=|last2=Hotopf|first2=M.|author-link2=|author-link3=|author-link4=|author-link5=|date=Jan 2005|title=A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087|quote=|via=}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients.<ref name=":1" /><ref>{{Cite journal|last=Joyce|first=J.|last2=Hotopf|first2=M.|last3=Wessely|first3=S.|date=Mar 1997|title=The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review|url=https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600}}</ref>

==ME vs CFS vs CF==

The name myalgic encephalomyelitis (ME) was coined following an [[outbreak]] of an illness at the [[1955 Royal Free Hospital outbreak|Royal Free Hospital]] in the UK, in 1955. The name chronic fatigue syndrome (CFS) was coined by the [[Centers for Disease Control and Prevention]] (CDC) following an [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreak]] of a [[flu-like illness]] at [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]], at Lake Tahoe, in the 1980s. There is disagreement as to whether ME and CFS are the same condition, entirely separate conditions, or whether ME constitutes a more severe subset of CFS. Adding to the confusion, the diagnostic name given to patients is more often dependent on the country in which they live, than differing characteristics of their condition, as some countries use CFS (eg: US, [[Australia]]), and other countries (particularly in Europe) use ME. At this point in time, there is no clear biological evidence to resolve whether the conditions are the same or different, and there is unlikely to be a resolution until firm [[biomarkers]] have been identified. As such, many patients and researchers use the term ME/CFS.<ref name="Klimas20140621video" /> ''See:'' [http://me-pedia.org/wiki/Definitions_of_ME_and_CFS Definitions of ME and CFS].

The name Chronic Fatigue Syndrome is itself controversial, as many consider it stigmatizing. In February 2016, Dr [[Anthony Komaroff]], who was part of the CDC group of clinicians who coined the name Chronic Fatigue Syndrome, said of it:
<blockquote>"I think that was a big mistake because the name, in my opinion, and the opinion of a lot of people, it both trivializes and stigmatizes the illness. It makes it seem unimportant, maybe not even real"<ref name="Komaroff20160217video" /></blockquote>

It is important to distinguish between ME/CFS and chronic fatigue (CF), which is a symptom of many different medical conditions (eg: [[anemia]], [[hepatitis]], [[multiple sclerosis]], [[Thyroid disease|hypothyroidism]], [[depression]], ME/CFS). "Chronic fatigue" is not a condition in its own right and it is incorrect and misleading to refer to ME/CFS as "chronic fatigue". While [[fatigue]] is a component of ME/CFS, many consider [[post-exertional malaise]] (PEM) to be the cardinal feature of ME/CFS.<ref>reference needed CCC</ref><ref name="IOM2015MECFS" />

==Evidence of a disease==

=== Symptoms ===
[[List of symptoms in ME CFS|Symptom presentation varies enormously]] between individuals. Symptom presentation also varies within individuals, as individuals often report that symptoms change over time (increasing or decreasing) and new symptoms may appear while others disappear.<ref>{{Cite web|title=Symptoms and Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/index.html|website=www.cdc.gov|date=2019-01-18|access-date=2019-02-01|language=en-us}}</ref> There are many symptoms which people with ME/CFS experience, though those listed below are the core symptoms found in all patients.

[[File:Cfs woman sketch.jpg|435x435px|thumb|[[Post-exertional malaise]] (PEM) is a [[List of symptoms in ME CFS|''worsening'' of ME/CFS symptoms]] after minimal [[Exertion#Exertion in ME.2FCFS|''physical'' or ''mental'' exertion]]. Worsening symptoms may include [[chronic fatigue]]; [[flu-like symptoms]]; [[brain fog|brain fog,]] [[cognitive dysfunction]], and [[word-finding problems]]; [[unrefreshing sleep|unrefreshing sleep;]] [[Headache|headaches]] and [[Migraine|migraines]]; [[chronic pain]]; [[Myalgia|muscle pain]] and [[muscle fatigability]]; [[orthostatic intolerance]], [[neurally mediated hypotension|neurally mediated hypotension,]] or [[Postural orthostatic tachycardia syndrome|POTS]]; and more. The onset of PEM can be delayed 24-72 hours and depending on ME/CFS severity can last days, weeks, or even months]]

[[File:Rosa SEID.JPG|400px|thumb|left|Rosa age 25 in 1986 and mildly ill with [[Systemic Exertion Intolerance Disease#Diagnostic criteria|ME/CFS's core symptoms]]. In 2015 the [[SEID]] criteria were released. Rosa read about PEM and how it is delayed and makes [[List of symptoms in ME CFS|ME/CFS symptoms]] including [[chronic fatigue]] worse. Her life since [[Pediatric myalgic encephalomyelitis/chronic fatigue syndrome|age 17]] fell into place as she never connected her worsening symptoms with increased [[Exertion#Exertion in ME.2FCFS|physical or mental activity]] 24-72 hours prior. She believes not understanding PEM made her condition worsen over the years and is now disabled meeting the [[Canadian Consensus Criteria|CCC]] with PEM "[[Canadian Consensus Criteria#Definition|option]]"]]

[[File:Brian vastag.png|thumb|left|[[Brian Vastag]] is an American and award-winning journalist and an ME/CFS patient that won a disability case against Prudential, proving that PEM is a severe symptom that keeps him from gainful employment]]

[[File:PEM1.JPG|300px|thumb|right|I think [https://twitter.com/hashtag/twofacesofme?f=tweets&vertical=default&src=hash #TwoFacesofME] is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #[[ME/CFS|MEcfs]] research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.<ref>{{Cite web|url=https://twitter.com/JackCroxall/status/1085900441328803840|title=I think #TwoFacesofME is a really important hashtag. We’re only out and about at our best, and our (more frequent) worst often remains hidden. I’m convinced it’s why #MEcfs research funding is so low - the problem isn’t visible enough. I’m seriously ill in both these photos.pic.twitter.com/hNjK5140kv|last=Croxall|first=Jack|date=2019-01-17|website=@JackCroxall|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM4.JPG|300px|thumb|right|First photo, me in my [[Severe and very severe ME|wheelchair on a rare trip out]]. Second photo, the inevitable crash. Eye half closed, [[Speech difficulties|slurred speech]], [[Dizziness|dizzy]], weak etc., etc. #TwoFacesofME<ref>{{Cite web|url=https://twitter.com/hopeforMEyet/status/1085909800766980096|title=First photo, me in my wheelchair on a rare trip out. Second photo, the inevitable crash. Eye half closed, slurred speech, dizzy, weak etc., etc. #TwoFacesofMEpic.twitter.com/P2OPnnpQvF|last=Karen|date=2019-01-17|website=@hopeforMEyet|language=en|access-date=2019-01-17}}</ref>]]

[[File:PEM5.JPG|300px|thumb|right|#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not [[Severe and very severe ME|severely ill]], and my life is ok, even [so] I wish that one day science will help me & all the #MeCfs sufferers around the globe.<ref>{{Cite web|title=#TwoFacesofME First photo from the morning, the other one from the afternoon ( when I failed to nap 30-60 minutes). I am Not severely ill, and my life is ok, even do I wish that one day science will help me & all the #MeCfs sufferers around the globe.pic.twitter.com/wmhfHcfP0p|url=https://twitter.com/Authorportrait/status/1085815918846832640|website=@Authorportrait|date=2019-01-17|access-date=2019-01-17|language=en|first=Henry|last=Köhler}}</ref>]]

*[[Post-exertional malaise]] (PEM) is the hallmark symptom of ME/CFS. After ''physical or mental'' [[exertion]] (which for some patients can be a shower or making out a to-do list, others grocery shopping, socializing or reading a news article, while some just walking to the mailbox, getting to the doctor or mentally following a T.V. program)<ref name=":022">{{Cite web|url=https://www.omf.ngo/what-is-mecfs/|title=What is ME/CFS?|last=|first=|date=|website=omf.ngo|archive-url=|archive-date=|dead-url=|access-date=|authorlink=|last2=|first2=|authorlink2=|publisher=Open Medicine Foundation}}</ref><ref name=":032">{{Cite news|url=https://phoenixrising.me/archives/11883|title=Unraveling Post-exertional Malaise By Jennifer M. Spotila, J.D.|last=Spotlia|first=Jenny|date=Aug 6, 2010|work=Phoenix Rising|access-date=2018-10-16|archive-url=|archive-date=|dead-url=|publisher=Phoenix Rising|language=en-US}}</ref> <ref name=":1" /> there is a payback of ''worsening'' [[List of symptoms in ME CFS|ME/CFS symptoms]] which can be delayed 24-72 hours or more<ref>{{Cite web|url=http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html|title=International CFS/ME Awareness Day - 12th May 2019|last=Hartley|first=Simon|website=www.whathealth.com|language=en|access-date=2018-10-16}}</ref><ref>{{Cite journal|last=Lindheimer|first=Jacob B.|last2=Meyer|first2=Jacob D.|last3=Stegner|first3=Aaron J.|last4=Dougherty|first4=Ryan J.|last5=Van Riper|first5=Stephanie M.|last6=Shields|first6=Morgan|last7=Reisner|first7=Amanda|last8=Shukla|first8=Sanjay K.|last9=Light|first9=Alan R.|date=2017-04-03|title=Symptom variability following acute exercise in myalgic encephalomyelitis/chronic fatigue syndrome: a perspective on measuring post-exertion malaise|url=https://www.tandfonline.com/doi/full/10.1080/21641846.2017.1321166|journal=Fatigue: Biomedicine, Health & Behavior|language=en|volume=5|issue=2|pages=69–88|doi=10.1080/21641846.2017.1321166|issn=2164-1846}}</ref><ref name=":152">{{Cite journal|last=Yoshiuchi|first=Kazuhiro|last2=Cook|first2=Dane B.|last3=Ohashi|first3=Kyoko|last4=Kumano|first4=Hiroaki|last5=Kuboki|first5=Tomifusa|last6=Yamamoto|first6=Yoshiharu|last7=Natelson|first7=Benjamin H.|date=2007-12-05|title=A real-time assessment of the effect of exercise in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17655887|journal=Physiology & Behavior|volume=92|issue=5|pages=963–968|doi=10.1016/j.physbeh.2007.07.001|issn=0031-9384|pmc=2170105|pmid=17655887}}</ref> and can last 24 hours and even days, weeks, or months.<ref name=":132">{{Cite journal|last=VanNess|first=J. Mark|last2=Stevens|first2=Staci R.|last3=Bateman|first3=Lucinda|last4=Stiles|first4=Travis L.|last5=Snell|first5=Christopher R.|date=Feb 2010|title=Postexertional malaise in women with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/20095909|journal=Journal of Women's Health (2002)|volume=19|issue=2|pages=239–244|doi=10.1089/jwh.2009.1507|issn=1931-843X|pmid=20095909}}</ref><ref>[https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm368806.pdf The Voice of the Patient.] A series of reports from the U.S. Food and Drug Administration’s (FDA’s) Patient-Focused Drug Development Initiative. September 2013</ref> The patient will experience even greater fatigue as well as exasperate the [[flu-like symptoms]] and body [[pain]]. Every patient experiences different symptoms and symptom severity from different activities and exertion output according to how sick he or she is with the disease.<ref name=":0" /><ref name=":022" /><ref name=":032" /><ref name=":1" /> Regarding PEM the [[CFIDS Association of America]] states:
<blockquote>This is a term which describes a symptom in which exercise or exertion can bring on [[malaise]] (illness). In the case of people with ME/CFS, malaise often occurs during a period some 24-72 hours after exertion. For example, in some cases, a short walk can worsen ME/CFS symptoms two days later. This lack of understanding about the delayed onset of symptoms has, in the past, made it harder to test for ME/CFS. Follow up tests, taken less than 24 hours after an initial exercise test, may show that the patient can still perform activities at the same level (before post exertional malaise has a chance to take hold).<ref>[http://www.whathealth.com/awareness/event/internationalcfsmeawarenessday.html What Health - International CFS/ME Awareness Day 2017 - CFIDS Association of America]</ref></blockquote>
*[[chronic fatigue]]
*[[cognitive dysfunction]]

*[[orthostatic intolerance]] (OI) such as [[postural orthostatic tachycardia syndrome]] (POTS) or [[neurally mediated hypotension]] (NMH)
*[[unrefreshing sleep]] ''See also:'' [[sleep disturbance]] <ref name=":5" /><ref name=":2" />
==== Other possible symptoms ====
*[[chronic pain]]
*[[immune system]]
*[[:Category:Neurological signs and symptoms|neurological signs and symptoms]] ''See Also:'' [[neuroinflammation]].
*[[List of symptoms in ME CFS|List of symptoms in ME/CFS]]

=== Comorbids ===
*[[fibromyalgia]] (FMS)
*[[irritable bowel syndrome]] (IBS)
*[[multiple chemical sensitivity]] (MCS)
*[[temporomandibular joint disorder]] (TMJ) <ref>[http://solvecfs.org/what-is-mecfs/ What is ME/CFS? - Solve ME/CFS Initiative]</ref>

=== Government guides on symptoms ===
'''US Government guides on symptoms'''
*[http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2015/MECFS/MECFScliniciansguide.pdf Clinicians Guide] via The [[Institute of Medicine report]] (IOM)
*[https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html CDC - ME/CFS Symptoms]

'''Canada guides on symptoms'''
*[http://linkis.com/org/tUheh Alberta Clinicians Guide]

===Biological abnormalities===
Because there is currently no biomedical test for ME/CFS, many have incorrectly assumed that there are no medical abnormalities found in people with the condition. As a result, ME/CFS symptoms are often considered to be medically unexplained, and therefore psychological in origin. Whilst it is true that the condition is poorly understood, many biological abnormalities have been found in a range of different body systems that have been found in ME/CFS, particularly in the [[central nervous system]] (CNS), [[autonomic nervous system]], [[immune system]] and [[Metabolic|energy metabolism]].<ref name="IOM2015MECFS" /> Unfortunately, none have yet proved to be specific or practical enough to ME/CFS as to be useful as a [[biomarker]] of the condition, and many were identified in small studies, which are in need of replication. Whilst there have been abnormalities which have been identified to be associated with the condition, it cannot yet be determined whether these are a cause or consequence of the condition.
* [[Gastrointestinal system]]
* [[Natural killer cell]]

==== Notable studies ====
* [[Cytokine#Notable Studies|Cytokine ("Notable studies")]]
*Immune findings by [[Mady Hornig]] & [[Ian Lipkin]]<ref name="Hornig20150201immune" />
*[[List of enterovirus infection studies]]

*2014/15, [[Neuroinflammation]] Japanese Neuroinflammation study<ref name="NakatomiY2014" />, Younger's Leptin study <ref name="JohnsonC20150126younger" />
*2014, Right [[Arcuate Fasciculus]] Abnormality in Chronic Fatigue Syndrome<ref>{{Cite web|url=https://pubs.rsna.org/action/captchaChallenge?redirectUrl=https%3A%2F%2Fpubs.rsna.org%2Fdoi%2Fabs%2F10.1148%2Fradiol.14141079&|website=pubs.rsna.org|doi=10.1148/radiol.14141079|access-date=2019-01-30}}</ref>
<blockquote>Bilateral [[white matter]] atrophy is present in CFS. No differences in perfusion were noted. Right hemispheric increased FA may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right [[anterior arcuate]] FA may serve as a [[Diagnostic biomarker|biomarker]] for CFS.</blockquote>
:*2014, [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder - New York Times: Well (2014)|''Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder'' By David Tuller - New York Times: Well]]
[[File:ME-CFS Brain Images.jpg|500px|thumb|center|Top scans: Healthy control patient; Bottom scans: chronic fatigue syndrome (CFS) patient. Image By: [[Michael Zeineh]]]]
*2016, ''[[Metabolic features of chronic fatigue syndrome]]''

*2019, ''[[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy]]''
**2018, [https://www.youtube.com/watch?v=rxdzaWD5wfU ''ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study'']<ref>{{Cite web|url=https://www.youtube.com/watch?v=rxdzaWD5wfU|title=ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study|date=Dec 14, 2018|access-date=|website=YouTube|last=|first=|authorlink=Jarred Younger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=SolveCFS}}</ref> (TALK)
<gallery widths="200" heights="100" class="center" caption="Images from talk: "ME/CFS Involves Brain Inflammation: Results from a Ramsay Pilot Study"">
File:Younger Choline Results.JPG|Choline results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=981 @16:21]
File:Younger Lactate Results.JPG|Lactate results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1202 @20:02]
File:Younger Therm Results.JPG|Thermometry results: (L) ME/CFS patient (R) Healthy control patient. Image discussed [https://youtu.be/rxdzaWD5wfU?t=1560 @26:00]
</gallery>

===Causes & triggers===

*Outbreaks - see [[List of outbreaks]]
*Possible infectious triggers: [[Enterovirus]]es, [[Epstein-Barr virus]]<ref name="Hickie2006" />, [[Q fever]]<ref name="Hickie2006" />, [[Ross River virus]]<ref name="Hickie2006" />, [[mononucleosis]]<ref name="Jason, Katz, 2017" />, ([[Ebola virus disease|Ebola]]?)<ref name="Hickie2006" />
*Non-viral triggers - [[trauma]], [[Environmental trigger|chemical]]

== Tests ==
* [[Natural killer cell]] (NKC) Blood Test

* Sleep study for [[sleep apnea]], [[Restless legs syndrome|restless leg syndrome]], and other sleep disturbances.
* [[Tilt table test]] for [[Orthostatic intolerance|OI]] or [[Postural orthostatic tachycardia syndrome|POTS]].

==Treatments==
There are currently no [[U.S. Food and Drug Administration|Food and Drug Administration]] (FDA) approved treatments for ME/CFS. Treatments consist mostly of symptom management, rather than treatment of the underlying cause of the condition, which is not yet understood.<ref name="IACFSME2014primer" /> There are many [http://me-pedia.org/wiki/Welcome_to_MEpedia#Potential_treatments potential treatments], though their evidence-base is limited, as most research into treatments has gone into psychological approaches to treatment.

=== Drugs ===
[[File:Ampligen.jpg|200px|thumb|right|Ampligen]]
Two treatments that have garnered much attention are [[Ampligen]], produced by [[Hemispherx Biopharma]], and [[Rituximab]]. Many people have reported enormous benefit from Ampligen;{{Citation needed}} some doctors have been prescribing it for ME/CFS for decades.{{Citation needed}}

Attempts to obtain FDA approval for Ampligen in the US have failed so it is unavailable to many.<ref>{{Cite web|title=Ampligen for Chronic Fatigue Syndrome|url=https://www.verywellhealth.com/profile-of-ampligen-for-chronic-fatigue-syndrome-716071|website=Verywell Health|access-date=2019-02-09|first=|last=|last2=Grant|date=Sep 16, 2018|authorlink=Adrienne Dellwo|first2=Hughes|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref> [[Argentina]] has approved the use of Ampligen for [[Severe and very severe ME|severe ME/CFS]] in 2016.<ref>{{Cite news|url=http://www.globenewswire.com/news-release/2016/08/23/866212/0/en/Hemispherx-Biopharma-Announces-Major-Breakthrough-Approval-for-Commercial-Sale-of-Rintatolimod-U-S-Tradename-Ampligen-to-Treat-Severe-Cases-of-Myalgic-Encephalomyelitis-Chronic-Fat.html|title=Hemispherx Biopharma Announces Major Breakthrough: Approval for Commercial Sale of Rintatolimod (U.S. Tradename: Ampligen®) to Treat Severe Cases of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in the Argentine Republic|last=Inc.|first=Hemispherx Biopharma,|date=Aug 23, 2016|work=GlobeNewswire News Room|access-date=2018-08-13|archive-url=|archive-date=|dead-url=|language=en-US}}</ref><ref>{{Cite news|url=http://cdn2.hubspot.net/hubfs/150154/docs/Hemispherx-Executive-Informational-Overview-11-27-16.pdf?__hssc=75734090.1.1482434979170&__hstc=75734090.d484bcfed76166643c7e8f36a0c76637.1482434979170.1482434979170.1482434979170.1&__hsfp=4187238277&hsCtaTracking=afde00a7-b0f3-44d3-b072-5febf480affb%7Cb8ddd437-9009-4bb9-a8fe-65a376fff33f|title=Hemispherx Biopharma, Inc. Executive Informational Overview|last=|first=|date=Nov 27, 2016|work=Crystal Research Associates|access-date=|archive-url=|archive-date=|dead-url=|format=PDF}}</ref> Also in 2016, it was made available on a limited basis in Europe.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/news/2016/07/25/hemispherx-ships-ampligen-for-european-chronic.html|title=Hemispherx ships Ampligen for European chronic fatigue syndrome program|last=George|first=John|date=Jul 25, 2016|website=www.bizjournals.com|archive-url=|archive-date=|dead-url=|access-date=2018-08-13}}</ref> July of 2018, Hemispherx Biopharma, Inc "announced the immediate expansion of its Treatment Protocol/Expanded Access Programs for ME/CFS in the [[United States]], known as AMP-511, to new enrollees for the first time in more than a year."<ref>[http://www.4-traders.com/HEMISPHERX-BIOPHARMA-INC-31148494/news/Hemispherx-BioPharma-Opens-FDA-Approved-Reimbursement-Based-Expanded-Access-Treatment-Program-for-26862569/ Hemispherx BioPharma : Opens FDA-Approved Reimbursement Based Expanded Access Treatment Program for ME/CFS to New Enrollees - 4 Traders]</ref> AMP-511 "will allow treatment of up to 100 [[ME/CFS]] patients at any one time at approved clinical infusion therapy sites."<ref>{{Cite web|url=https://finance.yahoo.com/news/hemispherx-biopharma-inc-announces-advancement-133000883.html|title=Hemispherx Biopharma Inc. Announces Advancement in Expanded Access Program for Ampligen in the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=Jan 2, 2019|website=finance.yahoo.com|publisher=GlobeNewswire|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2019-02-10}}</ref>

[[Rituximab]], a lymphoma drug, had shown promising results in initial trials in Norway,{{Citation needed}} and there were groups crowdsourced funding for further trials in other countries. On Nov 21, 2017, Drs. [[Øystein Fluge]] and [[Olav Mella]] announced that their Rituximab trial had failed. They stated that they would focus their efforts on attempting to identify a subgroup of ME/CFS patients with an immune profile that would be responsive to Rituximab. The doctors will publish a paper next year with the specifics of the failed trial.<ref>http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/</ref>

[[Jarred Younger]] announced in March 2016 that he will be undertaking a trial of [[low dose naltrexone]] (LDN) in ME/CFS.<ref>http://www.psy.uab.edu/younger/research.html</ref>

=== Treating other conditions ===
Different forms of [[Orthostatic intolerance|OI]] are treated with [[wikipedia:Beta_blocker|Beta-blockers]] (Metopropol), [[Fludrocortisone]] (Florinef), and [[Mestinon|Pyridostigmine]].<ref>{{Cite news|url=https://www.prohealth.com/library/evergreen_pages/pharmaceutical-medications-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis|title=Pharmaceutical Medications for Chronic Fatigue Syndrome & Myalgic Encephalomyelitis - Prohealth|work=Prohealth|access-date=2018-08-28|language=en-US}}</ref> When treating other diseases, illnesses, and conditions, and ME/CFS comorbids and overlapping conditions such as sleep difficulties, cognitive problems, pain, and other symptoms it is important to remember that patients are [[Medicine sensitivities|sensitive to medications]].<ref name=":05">{{Cite web|title=Monitoring the Use of All Medicines and Supplements {{!}} Clinical Care of Patients {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|url=https://www.cdc.gov/me-cfs/healthcare-providers/clinical-care-patients-mecfs/monitoring-medication.html|website=www.cdc.gov|date=2018-11-08|access-date=2019-01-27|language=en-us}}</ref> The CDC advice to health care practitioners is to be aware that because all drugs can cause side effects, ME/CFS patient symptoms can worsen. "This is particularly true of any medication that acts on the [[central nervous system]], such as sedating medications: therapeutic benefits can often be achieved at lower-than-standard doses. Patients with ME/CFS might tolerate or need only a fraction of the usual recommended doses for medications. After initial management with lower dosing, one or more gradual increases may be considered as necessary and as tolerated by the patient."<ref name=":05" /> For instance, tricyclic drugs can improve mood and help with sleep and pain. However, in some in can worsen OI. <ref name=":05" />
===Exercise as treatment===
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an [[United States|American]] who was attending Harvard and while on a trip to [[Kenya]] she became very ill and never recovered. Brea began experiencing [[Nervous system|neurological]] problems. Her neurologist diagnosed her with "conversion disorder" ([[hysteria]]). When walking home from his office, she collapsed. [[Severe and very severe ME|Jen now needs to use a wheelchair]] keeping her legs up due to [[Postural orthostatic tachycardia syndrome|POTS]] as her blood pools into her legs]]
Previously, two common treatment recommendations for ME/CFS were [[graded exercise therapy]] (GET) and [[cognitive behavioral therapy]] (CBT). These treatments are based on the hypothesis that the condition might have begun with a viral infection but has been perpetuated by [[deconditioning]] from lack of activity, and fear and avoidance of activity. GET & CBT are aimed at addressing these hypothesized causes by challenging the unhelpful thoughts that result in avoidance of activity and reconditioning through a gradual increase in exercise. These treatments are controversial and are at odds with much of the research literature, which suggests that exercise may actually be harmful to people with ME/CFS. A large patient survey of treatment responses found that 74% of people who had tried GET, reported that their symptoms subsequently worsened,<ref name="MEASSUK20150529survey" /> which is consistent with other patient surveys.<ref name="Phoenix20160222Norway2012" />

The [[PACE trial]], published in 2011, is the largest GET ever conducted. It has received much publicity as a result of its claims of recovery rates, though it has come under strong criticism from within both the scientific and patient community, for significant flaws in its design, and for overstating (and in some cases misrepresenting) outcomes in both the initial trial, and follow-up studies.<ref>http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00551-9/fulltext</ref> From 2015 to present day, the study was the subject of a series of investigative pieces that were highly critical of the trial by journalist Dr. [[David Tuller]]<ref name="viroblogMECFS" />, science writer [[Julie Rehmeyer]], patient advocate [[Tom Kindlon]], Dr. [[Keith Geraghty]]<ref name="Geraghty, 2017" />, psychologist Dr. [[Carolyn Wilshire]]<ref name="Wilshire C, et al, 2017" /> and others. A petition signed by almost 12,000 ME/CFS patients and allies,<ref name="MEACTIONpacepetition" /> and an open letter signed by 42 ME/CFS experts from around the world,<ref name="openletrLANCET2" /> were sent to The Lancet, both calling for the data to be reanalysed. Twenty-four ME/CFS organizations from 14 different countries have written to Queen Mary University London requesting that the trial data be released for reanalysis.<ref name="MEACTION20160313openletr" /> To date, the authors of the trial and editor of The Lancet have refused such requests. Despite such criticism, the PACE trial continues to influence both government and the medical profession's approach to the treatment of ME/CFS in many countries.

One of the reasons that exercise may be harmful to people with ME/CFS, is the presence of PEM, which is an exacerbation of symptoms following physical, mental or even emotional exertion. Studies have revealed immunological, muscular, neurological, autonomic and cardiovascular abnormalities in response to exercise in people with ME/CFS. As these results are not also found in healthy sedentary controls, the adverse effects of exercise cannot be said to be due to [[deconditioning]].<ref name="TwiskF2015" /><ref>reference needed - Workwell Foundation studies</ref><ref>reference needed - the Lights epigenetic changes post-exercise</ref>

People with ME/CFS should approach exercise with caution, as there is much potential for harm.

[[Anaerobic]] threshold, use of heart rate monitors for activity and [[pacing]]. Analeptic, not [[aerobic]].
[[Energy Envelope Theory|Energy envelope]]/pacing - people do better if stay within their envelope, than push to increase activity

====Graded exercise therapy & Cognitive behavioral therapy ====
[[File:Emma Shorter.JPG|400px|thumb|right|[[Emma Shorter]], is a citizen of [[Scotland]]. Here, she gives testimony before Parliament's Petitions Committee on [[GET]] and how it put her in a wheelchair]]
GET and CBT are usually employed in the [[United Kingdom|UK]], [[Ireland]] and some parts of Europe through ME Clinics. They are highly controversial and not recommended by patients, most patient advocates, and research organizations nor by many doctors or researchers outside of the UK. Based on the flawed [[PACE trial]] which used the flawed [[Oxford criteria]] to diagnose and recruit patients, GET and CBT found its way into treating people with ME/CFS.

[[Exercise]], especially GET, can injure an ME/CFS patient further.

*[[Jennifer Brea]] walked home from her Neurologist's office and became wheelchair bound.
*This is an experience of serious injury due to GET shared [https://twitter.com/TomKindlon/status/846425974052966400 by K. Miles, via Tom Kindlon on Twitter].
*[[Emma Shorter]] was able to walk a few minutes a day until GET put her in a wheelchair.
*[[Doctor Speedy]] was also seriously injured by GET.

==== Claims of recovery and cures ====
Charlatans claim they can cure CFS (per the CDC "there is no cure"<ref>{{Cite web|url=https://www.theguardian.com/society/2004/apr/28/equality.mentalhealth|title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|last=|first=|date=2018-07-03|website=www.cdc.gov|language=en-us|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref>) when in reality they may be able to treat [[chronic fatigue]] (CF). ME/CFS patients experience an ongoing improper immune response and other abnormalities for at least 6 months straight with a reduction in activity with a specific symptom set for at least 50% of the time.<ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/etiology-pathophysiology.html|title=Etiology and Pathophysiology {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/iom-2015-diagnostic-criteria.html|title=IOM 2015 Diagnostic Criteria {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-10|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref><ref>{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/diagnosis/approach-to-diagnosis.html|title=Proposed Approach to ME/CFS Diagnosis in Children and Adults {{!}} Diagnosis {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) {{!}} CDC|date=2018-07-12|website=www.cdc.gov|language=en-us|access-date=2018-09-07}}</ref>

Additionally, there have been media reports of some athletes diagnosed with CFS that recovered were actually suffering from [[overtraining syndrome]], a condition they sometimes acquire,<ref name=":6" /><ref name=":7" /><ref name=":8" /><ref name=":9" /> while some people with [[adrenal fatigue]] are sometimes diagnosed with CFS.<ref>{{Cite web|title=Chronic Fatigue vs. Adrenal Fatigue – Are They The Same Thing?|url=https://adrenalfatiguesolution.com/chronic-fatigue-vs-adrenal-fatigue/|website=Adrenal Fatigue Solution|date=2017-11-14|access-date=2019-02-01|language=en-US|last=Hansen|first=Fawne|authorlink=|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=}}</ref>

==Severely ill patients==
Considerable variation exists in the severity of the condition. The [[International Consensus Criteria]] lists the following severity levels (it should be noted that even "mild" ME/CFS consists of significant debility):

*Mild = 50% reduction in pre-illness activity levels
*Moderate = mostly housebound
*Severe = mostly bedridden
*Very Severe = totally bedridden, and needing help with basic functions.

At least [[Severe and very severe ME|25% of people with ME/CFS are bedbound or housebound]], often for years or even decades, so are largely an invisible population.<ref name="IOM2015MECFS" /><ref name="DerekPrisk2009" /><ref>[http://iacfsme.org/PDFS/2017JanNewsletter/8-Japan-2014-Patient-Survey.aspx ME/CFS Patient Survey Report: Ministry of Health Survey Reveals Harsh Reality of ME/CFS Patients in Japan - IACFSME - By Mieko Shinohara]</ref> So invisible in fact, that they have rarely been included as part of research because their level of debility precludes them from traveling to laboratories for required testing. The [[Open Medicine Foundation]]'s [[ME/CFS Severely Ill, Big Data Study]] will be the first in-depth study of people with a severe form of ME/CFS. This study has so far produced the groundbreaking paper [[Metabolic features of chronic fatigue syndrome]].
It is estimated that 25% of ME/CFS patients are severely ill and are housebound or bedbound.

Notable patients with severe or very severe ME/CFS include [[Whitney Dafoe]], [[Karina Hansen]], [[Lynn Gilderdale]], [[Laura Hillenbrand]], [[Tom Kindlon]], [[Vanessa Li]], [[Doctor Speedy]], [[Naomi Whittingham]], [[Jamison Hill]] and [[Jessica Taylor-Bearman]].

Though uncommon, there have been instances of deaths which have been attributed to the condition (see [[Sophia Mirza]], [[Merryn Crofts]]).

==Patients & psychiatry/psychology==

*Objections & scope
*Mind-body dualism
*The [[PACE trial]]. See [http://www.meaction.net/wp-content/uploads/2015/05/MEAction%E2%80%93patient-view-of-the-PACE-Trial-Controversy.pdf Patient view of the PACE Trial controversy]
*[[Patient mental health]]

===Stigmatization===

*Pretty young women slumped on desk
*[[Yuppie Flu]]
*Accusations of laziness/lethargy
*Epidemiological evidence - age, gender, demographic, racial/cultural

===Accusations of harassment===

*No arrests or convictions<ref>{{Cite web|url=http://www.virology.ws/2016/02/01/trial-by-error-continued-a-few-words-about-harassment/|title=Trial By Error, Continued: A Few Words About “Harassment”|last=|first=|authorlink=David Tuller|last2=|first2=|authorlink2=|date=Feb 1, 2016|website=www.virology.ws|archive-url=|archive-date=|dead-url=|access-date=2019-01-21}}</ref>
*Poor treatment of patients not mentioned. [[Ean Proctor]] and "The Mental Health Movement: Persecution of Patients?"<ref>[http://www.theoneclickgroup.co.uk/documents/ME-CFS_docs/The%20Mental%20Health%20Movement%20-%20Persecution%20of%20Patients.pdf The Mental Health Movement: Persecution of Patients?]</ref>

== Working with government to move forward ==

Advocates met with senate staffers the week of March 16, 2016, and discussed research and drug development by the [[NIH]], the [[CDC]] reinstating and increasing funding and education based on [[IOM]] recommendations and the [[HHS]] funding to develop Centers of Excellence.<ref>[http://www.meaction.net/2016/03/16/meaction-meets-with-senate-staffers/ #MEAction meets with Senate staffers]</ref> [[MEAction]] reports on this ongoing process.

====CDC Website updates====
*Jul 3, 2017, the CDC's Chronic Fatigue Syndrome page has been changed to [[ME/CFS|Myalgic Encephalomyelitis/Chronic Fatigue Syndrome]] (ME/CFS) and GET and CBT recommendations have been removed.<ref>[http://www.virology.ws/2017/07/10/trial-by-error-the-cdc-drops-cbtget/ Trial By Error: The CDC Drops CBT/GET - Virology Blog]</ref><ref>[https://www.cdc.gov/me-cfs/index.html Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - CDC.gov]</ref>

*Jul 12, 2018, the "Information for Healthcare Providers" tab and its sub-tabs were updated.<ref>[https://www.cdc.gov/me-cfs/healthcare-providers/index.html Information for Healthcare Providers - ME/CFS - CDC]</ref><ref>[https://www.cdc.gov/media/releases/2018/a0712-new-website-me-cfs.html New ME/CFS Web Content for Healthcare Providers - CDC - Jul 12, 2018]</ref>

* Feb 25, 2019, Dr. [[Elizabeth Unger]], Chief of CDC's Chronic Viral Disease Branch (CVDB), that houses the ME/CFS program, in collaboration between ''Medscape'' and the CDC put out brief video and commentary page with links to the CDC's July 12th, 2018 updates for medical professionals: ''[https://www.medscape.com/viewarticle/908622?src=rss Chronic Fatigue Syndrome: It's Real, and We Can Do Better].''<ref>{{Cite web|title=Chronic Fatigue Syndrome: It's Real, and We Can Do Better|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzkwODYyMj9zcmM9cnNz&ac=401|website=medscape.com|access-date=2019-02-25|date=Feb 25, 2019|last=|first=|authorlink=Elizabeth Unger|last2=|first2=|authorlink2=|archive-url=|archive-date=|dead-url=|publisher=Medscape and CDC}}</ref>
'''MEAction input'''
*Jul 29, 2018, [https://www.meaction.net/2018/07/29/cdc-revises-its-information-on-me/ CDC Revises its Information on ME] #[[MEAction]] report on the CDC July 2017 and July 2018 website updates. Recommendations for the CDC's ME/CFS page have been created from patient feedback on the updates as well as asking for further patient input.

==Expert opinions==

===Quotes from ME/CFS experts and patients===
*[http://thoughtsaboutme.com/quotes/ Thoughts About ME - List of Quotes]
*[[Individual Quotes]]

===Doctors===
'''UK'''
*[[Jonathan Edwards]]
*[[Charles Shepherd]]

'''US'''
<div style="column-count:4;-moz-column-count:4;-webkit-column-count:4">

*[[Lucinda Bateman]]
*[[Lily Chu]]
*[[David Kaufman]]
*[[Nancy Klimas]]
*[[Anthony Komaroff]]
*[[Susan Levine]]
*[[Jose Montoya]]
*[[Benjamin Natelson]]
*[[Daniel Peterson]]
*[[Alan Pocinki]]
*[[Peter Rowe]]
*[[Ronald Tompkins]]
*[[David Tuller]]

</div>

===Researchers===
'''Australia'''
*[[Neil McGregor]]

'''UK'''
*[[Keith Geraghty]]

'''US'''
<div style="column-count:4;-moz-column-count:4;-webkit-column-count:4">
*[[Ron Davis]]
*[[Gunnar Gottschalk]]
*[[Maureen Hanson]]
*[[Mady Hornig]]
*[[Leonard Jason]]
*[[Betsy Keller]]
*[[Ian Lipkin]]
*[[Staci Stevens]]
*[[Suzanne Vernon]]
*[[Jarred Younger]]

</div>

===Patients===
====Australia====

===== Canada =====
*[[Scott Simpson]]

====Scotland====
*[[Emma Shorter]]

====US====
<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[Jennifer Brea]]
*[[Carol Head]]
*[[Ryan Prior]]
*[[Julie Rehmeyer]]
*[[Jaime Seltzer]]
</div>

====UK====
*[[Adam Lowe]]
*[[Graham McPhee]]
*[[Jessica Taylor-Bearman]]

====Ireland====
*[[Tom Kindlon]]

===Patient groups & charities===

'''[[:Category:Patient groups|Patient groups]]'''
<div style="column-count:3;-moz-column-count:3;-webkit-column-count:3">
*[[:Category:American patient groups|American patient groups]]
*[[:Category:Australian patient groups|Australian patient groups]]
*[[:Category:Belgian patient groups|Belgian patient groups]]
*[[:Category:British patient groups|British patient groups]]
*[[:Category:Canadian patient groups|Canadian patient groups]]
*[[:Category:Dutch patient groups|Dutch patient groups]]
*[[:Category:Irish patient groups|Irish patient groups]]
*[[:Category:Italian patient groups|Italian patient groups]]
*[[:Category:New Zealand patient groups|New Zealand patient groups]]
*[[:Category:Norwegian patient groups|Norwegian patient groups]]
*[[:Category:Scottish patient groups|Scottish patient groups]]
*[[:Category:Swedish patient groups|Swedish patient groups]]
</div>

==History==
*[[Osler's Web|''Osler's Web'']] is a book by [[Hillary Johnson]] on the early history of CFS.
*[[Thirty Years of Disdain|''Thirty Years of Disdain'']] by [[Mary Dimmock]] and Matthew Lazell-Fairman picks up on the ME/CFS history where Osler's Web leaves off.

=== Deaths of ME/CFS patients ===
*[[Causes of death]]
*[[Suicide]]

'''Death certificates with ME or CFS'''
*[[Merryn Crofts]]' death is attributed to ME.
*[[Sophia Mirza]]'s death is attributed to CFS.

In the UK, United States, and Australia there are claims loved ones have died due to ME/CFS.<ref>[https://www.newscientist.com/letter/mg19125620-600-not-sadly-the-first/ Sadly, not the first (Comment Section)]</ref> See Editor's Note<ref>[https://www.newscientist.com/article/dn9342-first-official-uk-death-from-chronic-fatigue-syndrome/ First official UK death from chronic fatigue syndrome - New Scientist]</ref>

==Other tips==

*Always interview a patient
*Interview more than one researcher (not just from the psychological etiology view)
*Avoid using derogatory, outdated & incorrect term "[[Yuppie Flu]]"
*Never shorten the disease name [[chronic fatigue syndrome]] (CFS) to the symptom [[chronic fatigue]] (CF). [[CFS]], [[ME]] or [[ME/CFS]] can be used to save print space.
*Use photographic imagery that represents the reality for patients - serious illness & disability - not well-groomed & slightly tired office workers at their computer or students with a pile of books sleeping at their desk. [[Solve ME/CFS Initiative]]'s [https://www.youtube.com/watch?v=cF2OuYFDriY Times Square Public Awareness Ad] shows the reality of the disease ME/CFS. Using photos of patients whether chronically ill yet functioning or a severely ill patient or stock photos that reflect life with this disease is necessary.

==Learn more==
'''Films'''
*''[[Forgotten Plague]] i''s a US documentary about [[Ryan Prior]], an afflicted journalist who investigates the disease and its history and why the CDC has left millions sidelined from life; available for [http://www.forgottenplague.com/ streaming and DVD ''purchase'']. (2015)
[[File:Forgotten Plague.jpeg|200px|thumb|center]]
*[[Unrest|''Unrest'']] is a US documentary film that aired on PBS's ''Independent Lens'' in 2018 and is available for [https://www.unrest.film/watch/#digital streaming] and [https://www.unrest.film/store/ DVD purchase]. [[Jennifer Brea]], a person with [[ME]], directs. (2017)
[[File:Unrest.jpg|400px|thumb|center]]

'''ME/CFS organization and researchers material'''
*[https://www.youtube.com/watch?v=hRdn4A2SGic Beyond the Data – Chronic Fatigue Syndrome: Advancing Research and Clinical Education] (The CDC's Dr. [[John Iskander]] interviews Dr. [[Anthony Komaroff]]. Video, 2016)
*[https://drive.google.com/file/d/1h_ZwdR4567k-mSoWahnC_id0F_fAA3Fb/view Caring for People with Myalgic Encephalomyelitis] (2018) Guide for Caretakers
*[http://youtu.be/c2vIQ92wU9Y ME/CFS Diagnosis and Name with Dr Nancy Klimas (video)]
*[http://www.openmedicinefoundation.org/what-is-mecfs/ What is ME/CFS?] By the [[Open Medicine Foundation]]

'''[[Patient mental health]]'''

:Patients
:*[[Karina Hansen]] is a young [[Denmark|Danish]] woman taken from her family for 3 1/2 years due to [[Per Fink]]'s insistence her ME was due to mental health issues.
:*[[Sophia Mirza]] was taken forcibly from her home to a mental hospital only to be returned shortly after and died.
:*[[Ean Proctor]] was taken from his parents as a young boy and he was told his "parents were letting him die." He had become paralyzed and mute and was let go in the deep end of a pool to make him swim and another time put him on a scary theme park ride to scare him into moving.

'''More mental health information'''
*ME/CFS is not [[depression]]. It is a lack of energy, not desire.<ref>[http://chronicfatigue.about.com/b/2011/12/17/chronic-fatigue-syndrome-vs-depression-one-doctors-view.htm Chronic Fatigue Syndrome vs. Depression: One Doctor's View Lack of Energy or Lack of Desire? About.com Health FMS/ME/CFS]</ref><ref>[http://www.sleepydust.net/CHRONIC-FATIGUE-SYNDROME-AND-DEPRESSION.html Are ME/CFS & Depression The Same Thing? - Sleepy Dust]</ref><ref>[http://drmyhill.co.uk/wiki/CFS_or_depression_-_what_are_the_differences CFS or depression - what are the differences - Dr. Myhill.co.uk]</ref>

'''Research'''
*[[Institute of Medicine report]] (2015) The CDC based its updated [https://www.cdc.gov/me-cfs/index.html ME/CFS page] on information in this report.
*[[Notable studies]]

==See also==
*[[Primer for the public#Disease_names_and_acronyms_around_the_world|Primer for the public (''Disease names and acronyms around the world'' section)]]

==References==
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[[Category:Primers]]