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Myalgic encephalomyelitis

2019-02-07T01:27:57Z

Alvin:

'''Myalgic Encephalomyelitis''' (ME) is a progressive, chronic, [[Inflammation|inflammatory]], physically and [[neurological|neurologically]] disabling disease that presents with symptoms involving multiple bodily systems. Frequently triggered by a [[viral infection]], it affects the [[central nervous system]] (CNS), [[autonomic nervous system]] (ANS), [[immune system]], [[cardiovascular system]], [[endocrine system]], [[digestive system]], and [[musculoskeletal system]].<ref name=":8">{{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><ref>{{Cite web|url=http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf|title=Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations|last=Petrison|first=Lisa|date=Apr 4, 2016|website=paradigmchange.me|archive-url=|archive-date=|dead-url=|access-date=}}</ref> It has been classified by the [[World Health Organization]] (WHO) as a neurological disease since 1969<ref>{{Cite journal|date=2018-07-22|title=History of chronic fatigue syndrome|url=https://en.wikipedia.org/w/index.php?title=History_of_chronic_fatigue_syndrome&oldid=851489536|journal=Wikipedia|language=en}}</ref><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=2018-09-08|language=en-US}}</ref> and has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic forms since at least the 1930s.

A hallmark symptom of ME is [[Post-exertional malaise|post-exertional malaise]] (PEM), which is an intolerance to previously achievable cognitive or physical [[exertion]].<ref name=":0">{{Cite news|url=https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs|title=Pathways to Prevention (P2P) Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|last=|first=|date=|work=Office of Disease Prevention|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en}}</ref><ref name=":1">[http://www.meactionuk.org.uk/definition.html Research Descriptions of M.E. - ME Action UK]</ref><ref name=":2">{{Cite web|url=http://www.cfids-me.org/ramsay86.html|title=The Clinical Features of Myalgic Encephalomyelitis|last=Ramsey|first=Melvin|date=1986|website=www.cfids-me.org|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref name=":3">{{Cite news|url=https://www.verywell.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=Aug 1, 2018|work=Verywell Health|access-date=2018-09-07|archive-url=|archive-date=|dead-url=}}</ref><ref name=":5">{{Cite news|url=http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms|title=Think You Might Have Chronic Fatigue Syndrome? Here are The Symptoms|work=WebMD|access-date=2018-09-07|language=en-US}}</ref><ref name=":6">{{Cite web|url=http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf|title=Post-Exertional Malaise in Chronic Fatigue Syndrome|last=Spotila|first=Jennifer|date=2010|website=solvecfs.org|publisher=The CFIDS Association of America|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Other key symptoms include [[muscle]] [[Muscle weakness|weakness]] and easy [[Muscle fatigability|fatiguability]], [[sleep disturbance]], and [[cognitive dysfunction]]. ANS dysfunction is frequent, although specific symptoms vary from patient to patient and may include [[Postural orthostatic tachycardia syndrome|postural orthostatic tachycardia]] (POTS), [[Orthostatic intolerance|orthostatic hypotension]] (OI), and both [[Body temperature|cold and heat intolerance]]. Other common symptoms include [[myalgia]] (muscle pain), [[neuralgia]] (neuropathic pain), [[Neck stiffness|neck]] and [[spine stiffness]], and sensory symptoms including [[sensitivity to light]], [[Hyperacusis|sound]], [[touch]], [[Paresthesia|paraesthesia]] (skin tingling or [[numbness]]) and hyperaesthesia (skin sensitivity and pain, and [[allodynia]]).

Among adults, ME is more common in women than men. New onset has been [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|observed in children]] and in adults as old as 80 years old. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or 'crashes') or accruing over time.<ref>{{Cite web|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzg3MTQ4Mg==&ac=401|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|last=|first=|date=|website=medscape.com|format=Login Needed|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>{{Cite web|url=http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf|title=Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report|last=Howes|first=S|date=Jul 7, 2015|website=meassocation.org|publisher=Physical Medicine and Rehabilitation - International|via=Austin Publishers Group|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

There are no approved pharmacological treatments for ME anywhere in the world, except in [[Argentina]], which has approved the immunomodulator [[Ampligen]] for [[Severe and very severe ME|severe ME/CFS]] as of August 23, 2016.<ref name=":9">{{Cite news|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|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|work=GlobeNewswire News Room|access-date=2018-08-12|language=en-US|first=Hemispherx Biopharma,|last=Inc.|date=Aug 23, 2016|archive-url=|archive-date=|dead-url=}}</ref>

ME is accurately diagnosed with the [[International Consensus Criteria]] (ICC) and a diagnosis should be made immediately. Other criterion such as the [[Canadian Consensus Criteria]] (CCC) and [[Systemic Exertion Intolerance Disease|SEID]] cannot be used to diagnose immediately nor speak to the array and severity of CNS, neurological, ANS, and immune system symptoms patients experience.

[[File:Linda Crowhurst.JPG|thumb|[[Linda Crowhurst]] is married to [[Greg Crowhurst]]; they reside in Belfast, [[Northern Ireland]]. Greg is Linda's full-time carer as she is [[Severe and very severe ME|very severely ill with ME]]. As of June 2018, Linda has been ill for 25 years. This image is a still from the video [https://www.youtube.com/watch?v=Z1z5O_cgQ7I Wasteland] which visually documents Linda's very severe ME. Greg posted a [https://www.youtube.com/watch?v=rVsOeZjhMFY YouTube video in 2006 (reposted in 2007)] of Linda speaking of her condition and showing her [[Nervous system|neurological]] symptoms which are the first known public visual document of very severe ME. She is now bedbound barely able to move and unable to feed herself]]

[[File:Jenny Spotlia.jpg|300px|thumb|right|[[Jennie Spotila]] is an American ME patient who fell ill on October 6, 1994. Jennie is [[Severe and very severe ME|disabled, mostly housebound, and uses a wheelchair]] but has been an [[ME/CFS]] advocate for many years. She writes the blog [[Occupy M.E.]] She served on the Board of Directors of [[Solve ME/CFS Initiative|The CFIDS Association of America]] and testified before the [[Chronic Fatigue Syndrome Advisory Committee|CFSAC]]]]

== History ==
[[File:Hillary Johnson.jpg|200px|thumb|[[Hillary Johnson]] is an [[United States|American]] journalist and while ill herself, wrote the book [[Osler's Web]] which is the historical account of the early years of a "new" illness that had an outbreak at [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] which she shared the same symptoms. The illness came to be known as [[chronic fatigue syndrome]] (CFS). Johnson spent nine years investigating the outbreak and the [[CDC]]'s refusal to acknowledge a devastating disease (deeming sufferers of Incline Village as having "[https://en.wikipedia.org/wiki/Mass_psychogenic_illness mass hysteria]") that can be spread through casual contact. She appears in the documentary ''[[Forgotten Plague]]'' and currently writes at
[https://www.oslersweb.com/ Oslersweb.com] ]]

{{Main article | page_name =History of myalgic encephalomyelitis and chronic fatigue syndrome}}<div role="note" class="hatnote navigation-not-searchable">

ME has occurred in both epidemic and sporadic form since at least the 1930s, although it has likely been occurring much longer but was not formally named. The first recorded outbreak of [[epidemic myalgic encephalomyelitis]] was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical [[polio]]. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called 'Akureyri Disease' or [[Icelandic disease]] through much of the 1940s and 1950s. It was named ME after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and [[Epidemic myalgic encephalomyelitis|epidemic neuromyasthenia]].

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[chronic fatigue syndrome]] (CFS). The most recent putative outbreak was in [[1996 Mohave Valley region, Arizona|Arizona in 1996]].

==Disease Name==

[[File:Merry Crofts sick.JPG|200px|thumb|[[Merryn Crofts]] was [[Severe and very severe ME|bedbound and unable to eat.]] Merryn weighed six stone (84 lbs) at her death; her autopsy revealed inflammation of the [[Dorsal root ganglia|ganglia]]. It is suspected that in the later years of her illness Merryn also suffered from [[Ehlers-Danlos syndrome|EDS]] and [[Mast cell activation disorder|MCAD]]. Her death certificate is the 2nd in the [[United Kingdom|UK]] to attribute a death to ME]]
{{Main article |page_name = Names of myalgic encephalomyelitis and chronic fatigue syndrome}}
* ''Myalgic adj. - of or relating to [[myalgia]].'' Is [[muscle pain]].<ref>{{Cite news|url=https://www.thefreedictionary.com/myalgic|title=myalgic|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Encephalo'': Refers to the [[brain]].<ref>{{Cite news|url=https://medical-dictionary.thefreedictionary.com/encephalo-|title=encephalo-|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Myel'': Relating to the [[spinal cord]].<ref>{{Cite news|url=https://www.thefreedictionary.com/myel-|title=myel-|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Itis'': [[Inflammation]].<ref>{{Cite news|url=https://www.thefreedictionary.com/-itis|title=Itis|work=TheFreeDictionary.com|access-date=2018-08-12|last=|first=|date=|archive-url=|archive-date=|dead-url=}}</ref>
The name ME<ref>{{Cite news|url=https://www.verywell.com/myalgic-encephalomyelitis-me-715663|title=Myalgic Encephalomyelitis: Chronic Fatigue Syndrome's Other Name|last=Dellwo|first=Adrienne|date=Jul 23, 2018|work=Verywell Health|access-date=2018-08-12|archive-url=|archive-date=|dead-url=}}</ref> was coined by Dr. [[Melvin Ramsay]] following the [[1955 Royal Free Hospital outbreak]]<ref>{{Cite journal|last=|first=|date=1957-10-19|title=An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/|journal=British Medical Journal|volume=2|issue=5050|pages=895–904|issn=0007-1447|pmid=13472002|via=}}</ref> and is a portmanteau of several of the key signs and symptoms of the disease: myalgic (muscle pain), encephalo (brain), myel (spinal cord), itis (inflammation).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref> The [[central nervous system]] (brain and spinal cord) are inflamed.<ref name=":02">{{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>

Several other names have been used or proposed throughout the history of the disease, including [[atypical polio]], [[Icelandic disease]], benign ME, [[epidemic neuromyasthenia]], CFS, and [[systemic exertion intolerance disease]] (SEID). This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|case definitions]].

A survey by [[The MEAction Network]] in 2016 found that the majority of patients prefer the name ME to other names including chronic fatigue syndrome.<ref>{{Cite news|url=http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/|title=#MEAction RFI Poll Report (Part 1 of 3) - #MEAction|date=2016-08-07|work=#MEAction|access-date=2018-09-08|language=en-US}}</ref>

Myalgic encephalomyelitis (ME) was the original name for [[chronic fatigue syndrome]] (CFS); the names are used interchangeably or with the acronym [[ME/CFS]].<ref name=":02" />

== Onset ==
Following after an incubation period of 4 to 7 days, the [[wikipedia:Prodrome|prodromal]] phase generally involve a [[flu-like illness]] with [[low-grade fever]]. In the majority but not all cases, an [[infection]] or infectious process is evident.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref> Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the CNS. It is this second phase, persistent phase that most characterizes ME.<ref>{{Cite web|url=https://www.scribd.com/document/32848597/Nightingale-ME-Definition-En|title=Nightingale ME Definition En {{!}} Chronic Fatigue Syndrome {{!}} Infection|last=|first=|date=|website=Scribd|page=5|pages=|at=|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref><ref name=":8" />

In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In theirs, an apparent remission was followed by relapses brought on by exertion, [[menstrual period]], or cold. In other patients there is no discernible triggering event.

==Signs and Symptoms==
Symptoms can range from mild to very severe and can include:
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an 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. View her TED Talk ''[https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose What happens when you have a disease doctors can't diagnose]'']]

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
* [[ataxia|ataxia (coordination difficulties)]]

* [[cognitive dysfunction]]
* [[Chronic fatigue|fatigability]]
* [[gastrointestinal]] symptoms
* [[headache]]

*[[low-grade fever]], [[Temperature dysregulation|temperature instability]]
*[[muscle]] [[Muscle weakness|weakness]] and [[Muscle fatigability|fatiguability]]
*[[myalgia|myalgia (muscle pain)]]
*neck and back or [[spinal cord]] stiffness
*[[neuralgia|neuralgia (nerve pain)]]
*[[Orthostatic intolerance|othostatic intolerance]]
*[[post-exertional malaise]]
*sensitivity to [[Temperature sensitivity|heat or cold]]
*sensitivity to [[Light sensitivity|light]], [[Hyperacusis|sound]] and/or [[Allodynia|touch]]
*[[sleep dysfunction]]

</div>

Symptom presentation and severity can vary considerably day to day and even hour to hour.<ref name=":8" /> Overexertion can exacerbate all symptoms, and Post Exertional Malaise often delayed by 24 hours or more.<ref>{{Cite web|url=http://www.investinme.org/landerP5.shtml|title=Invest in ME Research - Invest in ME Research Home Page|last=Research|first=Invest in ME|website=www.investinme.org|access-date=2018-09-08}}</ref> <ref name=":8" /> The US [[National Institutes of Health]] (NIH) notes that sensitivity to noise, light and [[Chemical sensitivities|chemical]]<nowiki/>s may force patients to withdraw from society.<ref>{{Cite news|url=https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs|title=Pathways to Prevention (P2P) Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|last=|first=|date=|work=Office of Disease Prevention|access-date=2018-09-08|archive-url=|archive-date=|dead-url=|language=en}}</ref>

The severity of a patient's symptoms often depends on the time period since the disease was contacted and rate of progression of each patient. The rate of progression can be accelerated by ''physical or cognitive activity'' beyond a patient's limits over long periods, which typically entails [[anaerobic]] activity <ref>{{Cite web|url=https://www.me-pedia.org/wiki/Unrest|title=Unrest - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

=== Post-exertional malaise ===
{{Main article | page_name =Post-exertional malaise}}
A core symptom, [[post-exertional malaise]], is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":5" /><ref name=":6" /><ref name=":4">{{Cite news|url=https://www.verywell.com/post-exertional-malaise-715670|title=What is Post-Exertional Malaise? Learn About a Key ME/CFS Symptom|work=Verywell Health|access-date=2018-09-07}}</ref>

== Clinical Findings ==
[[File:Alem Matthee.png|200px|thumb|right|[[Alem Matthees]] is an [[Australia|Australian]] ME patient that filed an FOI request for data from the [[PACE trial]]. At a [[Severe and very severe ME|great cost to his health]], Alem appealed the denial of the data and won. This data proved the results published in [[The Lancet|''The Lancet'']] were untrue. Alem's health suffered significantly in part from the efforts required for the FOI request and tribunal]]
Although there is no definitive [[biomarker]], several signs and findings have been frequently observed in clinical settings:<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*high antibody titers to specific infections (including [[Epstein-Barr virus|EBV]], [[Human herpesvirus 6|HHV-6]], and [[Coxsackie B virus|Coxsackie B]] among others)
*[[Hormones|hormone]] imbalance
*[[Immune system|immunological abnormalities]]
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]
*low red blood cell [[magnesium]]
*[[natural killer cell]] (NKC)
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]] (POTS)
*[[Post-exertional malaise|reaction to physical and mental activity and sensory input]] (PEM)
</div>

==Diagnosis==

[[File:Tom Kindlon.png|300px|thumb|[[Tom Kindlon]] became [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|ill at 16]] and never recovered. He is an ME/CFS advocate with published works in Research Gate and PubMed. Kindlon lives in [[Ireland]] and is Assistant Chairperson of the [[Irish ME/CFS Association]]. Tom and others analyzed the data for the PACE trial proving out that its published results were untrue. He uses a [[Severe and very severe ME|wheelchair and his full-time carer]] is his mother, Vera]]

{{Main article | page_name =Definitions of myalgic encephalomyelitis and chronic fatigue syndrome}}There are several proposed criteria for diagnosing ME including the [[International Consensus Criteria]] (ICC) and the [[Canadian Consensus Criteria]] (CCC). The original criteria developed by [[Melvin Ramsay]], the [[Ramsay definition]], is not used for diagnosing ME today.<span></span><span></span>
=== Other diagnostic criteria ===
Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on [[Epidemic myalgic encephalomyelitis|epidemic ME]], exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's [[Oxford criteria]] is the broadest and likely least discerning definition. (The US [[Institute of Medicine report]] called for its complete retirement.)<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=2018-09-08}}</ref> The US [[Centers for Disease Control and Prevention|Centers for Disease Control]]'s (CDC) [[Fukuda criteria]], in use since 1994, is also overly broad.

===Differential diagnosis===
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], [[Systemic lupus erythematosus|lupus]], [[brucellosis]], or another condition."<ref name=":8" /> Additional testing may be needed to help distinguish ME from these other problems.

==Course and Prognosis ==
{{Main article | page_name =Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome}}

ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, [[influenza]] and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

About 25% of patients become [https://www.me-pedia.org/wiki/Severe_and_very_severe_M.E. severe or very severely ill with ME].

==Clinical Subtypes==
Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:<ref name=":7">{{Cite web|url=http://me-ireland.com/genes2.pdf|title=Seven genomic subtypes of chronic fatigue phenotypes analysis of gene networks and clinical syndrome/myalgic encephalomyelitis: a detailed|last=Kerr|first=JR|last2=Burke|first2=R|date=May 30, 2008|website=me-ireland.com|doi=10.1136/jcp.2007.053553|archive-url=|archive-date=|dead-url=|access-date=|last3=Petty|first3=R|last4=Gough|first4=J|last5=Fear|first5=D|last6=Mattey|first6=D L|last7=Axford|first7=J S|last8=Dalgleish|first8=A G|last9=Nutt|first9=D J|publisher=JCP Online}}</ref><ref>{{Cite journal|last=Kerr|first=J. R.|last2=Burke|first2=B.|last3=Petty|first3=R.|last4=Gough|first4=J.|last5=Fear|first5=D.|last6=Mattey|first6=D. L.|last7=Axford|first7=J. S.|last8=Dalgleish|first8=A. G.|last9=Nutt|first9=D. J.|date=2008-06-01|title=Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes|url=https://jcp.bmj.com/content/61/6/730|journal=Journal of Clinical Pathology|language=en|volume=61|issue=6|pages=730–739|doi=10.1136/jcp.2007.053553|issn=0021-9746|pmid=18057078}}</ref>

[[File:Whitney.JPG|200px|thumb|[[Whitney Dafoe]] is an American photographer who has a [[Severe and very severe ME|very severe form]] of ME. Whitney can no longer speak or handle contact with anyone but his parents. His father is [[Ronald Davis|Ron Davis]], a world-renowned geneticist who is working to solve his son's disease]]

* Subtype 1 This is one of the more severe subtypes. Effects are cognitive, [[Musculoskeletal system|musculoskeletal]], [[Sleep dysfunction|sleep-related]] and [[anxiety]]/[[depression]].

* Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.

* Subtype 3 This subtype has the mildest symptoms.

* Subtype 4 This subtype is dominated by cognitive issues.

* Subtype 5 Effects are musculoskeletal and gastrointestinal.

* Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after [[exercise]] or exertion.)

* Subtype 7 This is one of the more severe subtypes. Effects are [[pain]], infections, musculoskeletal, sleep-related, [[Nervous system|neurological]], gastrointestinal, [[Cognitive dysfunction|neurocognitive]] and anxiety/depression.<ref name=":7" />

==Pathophysiology==
[[File:Vanessa Li.jpg|thumb|right|[[Vanessa Li]] lived in Hong Kong, the UK, and the US. She became ill with a [[flu-like illness]] while skiing in [[Italy]] and never recovered. Vanessa founded a crowdfund for the [[Microbe Discovery Project]]. She was in [[Severe and very severe ME|excruciating pain, suffered from breathing issues, and occasional paralysis]] for 15 years. She took her own life in 2015]]
{{Main article | page_name =List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis}}

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

=== Central nervous system ===
[[File:Sophia mirza.jpg|thumb|right|[[Sophia Mirza]] was a [[Severe and very severe ME|very severely ill]] ME patient who lived in the UK. Sophia's death came not long after a forced entry into her mother's home and being sectioned and taken to a mental hospital in 2003. An independent Neuropathologist found Sophia's spine contained a massive infection. Her death certificate was the first in the UK to attribute a death to CFS]]
{{Main article |page_name =Central nervous system}}Radiological research on ME has shown [https://medical-dictionary.thefreedictionary.com/hypoperfusion hypoperfusion] of the [[brain stem]] and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, some research stated that a reduced volume of [[grey matter]] may be a result of a lack of activity and is reversible with [[cognitive behavioral therapy]] (CBT).

=== Autonomic nervous system ===
{{Main article |page_name =Autonomic nervous system}}

=== Peripheral nervous system ===
{{Main article |page_name =Peripheral nervous system}}

=== Musculoskeletal system ===
{{Main article |page_name =Muscle}}

=== Immune system ===
{{Main article |page_name =Immune system}}<div role="note" class="hatnote navigation-not-searchable">{{Main article |page_name =Immune system}}</div><span></span>

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as [[RNase L|Rnase-L]]. [[Channelopathy]], a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.

=== Chronic infection ===
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the post-polio syndrome?].
[[File:Emma Shorter.JPG|400px|thumb|[[Emma Shorter]] is a [[Scotland|Scottish]] citizen who has ME. She did [[Graded exercise therapy]] (GET) and went from walking a few minutes a day to being [[Severe and very severe ME|in a wheelchair.]] Here, Emma gives testimony before Scotland's Parliament's Petitions Committee.
View her [https://youtu.be/wDayJXxZSQE?t=106 testimony] ]]

=== Cardiovascular ===
[[wikipedia:Hemodynamics|Hemodynamic]] abnormalities are widely found, including serum and RBC [[wikipedia:Hypovolemia|hypovolemia]], [[neurally mediated hypotension]], (NMH) and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr [[Paul Cheney]] to posit that CFS is form of partially compensated cardiomyopathy in which [[orthostatic intolerance]] and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with [[wikipedia:Holter_monitor|Holter monitors]].

=== Gastrointestinal system ===
{{Main article |page_name =Gastrointestinal system}}

== Sex Differences ==
[[File:Florence Nightingale.png|200px|thumb|right|[[Florence Nightingale]] was a British citizen and pioneer of modern nursing. Nightingale was stationed in Crimea when she developed "Crimean fever" (a bacterial infection now known as [[brucellosis]]) and never recovered. She remained [[Severe and very severe ME|mostly bedbound]] the rest of her life. Although ME and CFS were not defined in her lifetime, many current physicians and medical historians believe she developed ME/CFS as a result of a chronic brucellosis infection]]

{{Main article |page_name = Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome}}
A Norwegian [[CFS/ME]] study shows that the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.<ref>{{Cite journal|last=Bakken|first=Inger Johanne|last2=Tveito|first2=Kari|last3=Gunnes|first3=Nina|last4=Ghaderi|first4=Sara|last5=Stoltenberg|first5=Camilla|last6=Trogstad|first6=Lill|last7=H åberg|first7=Siri Eldevik|last8=Magnus|first8=Per|date=2014-10-01|title=Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012|url=http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5|journal=BMC Medicine|language=En|volume=12|issue=1|pages=|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmid=25274261|via=}}</ref> Research by the [[Open Medicine Foundation]] cited in its paper, [[Metabolic features of chronic fatigue syndrome|''Metabolic features of chronic fatigue syndrome'']] which studied severe [[CFS]], found that the disease is different in men and women but this is not related to testosterone or estrogen. [[Michael VanElzakker]] notes there are [http://me-pedia.org/wiki/Michael_VanElzakker#Male_and_female_differences_in_neuropathic_pain male and female differences in neuropathic pain]. A study of UK and Dutch cohorts found "younger children had a more equal gender balance compared to adolescents and adults."<ref>{{Cite journal|last=Collin|first=Simon M.|last2=Nuevo|first2=Roberto|last3=van de Putte|first3=Elise M.|last4=Nijhof|first4=Sanne L.|last5=Crawley|first5=Esther|date=2015-10-28|title=Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts|url=https://www.ncbi.nlm.nih.gov/pubmed/26510728|journal=BMJ open|volume=5|issue=10|pages=e008830|doi=10.1136/bmjopen-2015-008830|issn=2044-6055|pmid=26510728|via=}}</ref>

==Risk Factors and Potential Causes==

{{Main article | page_name =Risk factors and potential causes of myalgic encephalomyelitis and chronic fatigue syndrome}}

===Risk factors===

===Potential causes===
Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.<ref>{{Cite web|url=http://via.library.depaul.edu/csh_etd/117/|title=Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach|last=Evans|first=Meredyth|date=Aug 23, 2015|website=via.library.depaul.edu|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref>{{Cite web|url=http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis|title=Vagus nerve infection hypothesis - MEpedia|website=me-pedia.org|language=en|access-date=2018-09-08}}</ref><ref>{{Cite web|url=http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/chronic-fatigue/case3.htm|title=Case Presentation - Chronic Fatigue Syndrome|website=www.clevelandclinicmeded.com|access-date=2018-09-08}}</ref><ref>{{Cite journal|last=Magnus|first=Per|last2=Gunnes|first2=Nina|last3=Tveito|first3=Kari|last4=Bakken|first4=Inger Johanne|last5=Ghaderi|first5=Sara|last6=Stoltenberg|first6=Camilla|last7=Hornig|first7=Mady|last8=Lipkin|first8=W. Ian|last9=Trogstad|first9=Lill|date=2015-11-17|title=Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine|url=https://www.ncbi.nlm.nih.gov/pubmed/26475444/|journal=Vaccine|volume=33|issue=46|pages=6173–6177|doi=10.1016/j.vaccine.2015.10.018|issn=1873-2518|pmid=26475444}}</ref> It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.<ref>{{Cite journal|last=Underhill|first=R. A.|date=2015|title=Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease|url=https://www.ncbi.nlm.nih.gov/pubmed/26604026|journal=Medical Hypotheses|volume=85|issue=6|pages=765–773|doi=10.1016/j.mehy.2015.10.011|issn=1532-2777|pmid=26604026|via=}}</ref><ref>{{Cite journal|last=Schlauch|first=K A|last2=Khaiboullina|first2=S F|last3=De Meirleir|first3=K L|last4=Rawat|first4=S|last5=Petereit|first5=J|last6=Rizvanov|first6=A A|last7=Blatt|first7=N|last8=Mijatovic|first8=T|last9=Kulick|first9=D|date=2016|title=Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://www.nature.com/tp/journal/v6/n2/full/tp2015208a.html|journal=Translational Psychiatry|language=En|volume=6|issue=2|pages=e730–e730|doi=10.1038/tp.2015.208|issn=2158-3188|via=}}</ref> Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of [[autoimmune disease]].<ref>{{Cite web|url=https://www.facebook.com/permalink.php?story_fbid=564532390371988&id=564526123705948|title=Klimas ME CFS Genes Study|last=|first=|date=Nov 23, 2015|website=www.facebook.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref> There is also a shift from the [[Th1]] type of helper [[T cell]]s, which fight infection, to the [[Th2]] type, which are more active in [[allergy]] and more likely to attack the body.<ref>{{Cite journal|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=https://www.sciencedirect.com/science/article/abs/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref><ref>{{Cite web|url=http://www.m-hikari.com/bmgt/bmgt2014/bmgt1-4-2014/hardcastleBMGT1-4-2014.pdf|title=Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells|last=Hardcastle|first=S.L.|last2=Brenu|first2=E.W.|date=2014|website=m-hikari.com|archive-url=|archive-date=|dead-url=|access-date=|last3=Staines|first3=D.R.|last4=Marshall-Gradisni|first4=S.}}</ref>

[[File:Naomi Whittingham .png|300px|thumb|[[Naomi Whittingham]] lives in the UK with a [[Severe and very severe ME|severe case of ME]]. Naomi became ill at [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|age 12]] with a routine virus and never recovered. She advocates for ME by doing interviews, writing the blog [[A Life Hidden]], and supporting her brother [[Tom Whittingham]]'s marathon fund raising for [[ME Research UK]]]]
===Viruses===
{{Main article |page_name = Viruses}}

Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses<ref>{{Cite journal|last=Bell|first=E. J.|last2=McCartney|first2=R. A.|last3=Riding|first3=M. H.|date=1988|title=Coxsackie B viruses and myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/2841461|journal=Journal of the Royal Society of Medicine|volume=81|issue=6|pages=329–331|doi=10.1177/014107688808100609|issn=0141-0768|pmid=2841461|via=}}</ref><ref>{{Cite news|url=http://solvecfs.org/ramsay-research-team-5-the-potential-role-of-hhv-6-in-mecfs/|title=Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS - Solve ME/CFS Initiative|last=|first=|date=2016-12-16|work=Solve ME/CFS Initiative|access-date=2018-09-08|archive-url=|archive-date=|dead-url=|publisher=VOLKMEDIA|language=en-US}}</ref> <ref>{{Cite journal|last=Chapenko|first=Svetlana|last2=Krumina|first2=Angelika|last3=Logina|first3=Inara|last4=Rasa|first4=Santa|last5=Chistjakovs|first5=Maksims|last6=Sultanova|first6=Alina|last7=Viksna|first7=Ludmila|last8=Murovska|first8=Modra|date=2012|title=Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/22927850|journal=Advances in Virology|volume=2012|pages=205085|doi=10.1155/2012/205085|issn=1687-8647|pmid=22927850|via=}}</ref> suggests a potential viral contribution in at least some individuals. Evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

=== Bacteria ===
{{Main article |page_name = Bacteria}}

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as [[lyme disease]]. Another bacterium that has been implicated in ME is [[chlamydia pneumoniae]].<ref>{{Cite journal|date=2018-09-05|others=John E.Tovey|title=Chlamydia pneumoniae infection a treatable cause of Chronic Fatigue Syndrome|url=https://www.bmj.com/rapid-response/2011/11/01/chlamydia-pneumoniae-infection-treatable-cause-chronic-fatigue-syndrome|journal=The BMJ|language=en|last=|first=|volume=|pages=|via=}}</ref><ref>{{Cite news|url=https://www.prohealth.com/library/new-me-cfs-study-at-stanford-dr-montoya-to-test-for-scores-of-infections-27346|title=New ME/CFS Study at Stanford: Dr. Montoya to test for scores of Infections - Prohealth|date=2010-06-04|work=Prohealth|access-date=2018-09-08|language=en-US}}</ref> Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.<ref>{{Cite web|url=http://www.bjmp.org/content/role-chronic-bacterial-and-viral-infections-neurodegenerative-neurobehavioral-psychiatric-au|title=Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1 {{!}} British Journal of Medical Practitioners|last=|first=|date=2009|website=www.bjmp.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref>

The [[vagus nerve infection hypothesis]] (VNIH) accounts for why so many different infectious onsets could be responsible. The [[vagus nerve]] runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>{{Cite web|url=http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/|title=People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement|last=|first=|date=Aug 2010|website=www.meassociation.org.uk|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref><ref>{{Cite news|url=http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html|title=Chronic fatigue patients barred from blood donation|last=Stein|first=Rob|date=2010-12-03|access-date=2018-09-08|language=en-US|issn=0190-8286}}</ref><ref>{{Cite web|url=http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C|title=Detailed eligibility criteria|website=www.nzblood.co.nz|language=en-NZ|access-date=2018-09-08}}</ref>

==Treatments==
[[File:Karina Hansen.jpg|200px|thumb|right|[[Karina Hansen]] became [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|ill as an adult teenager]] and is [[Severe and very severe ME|severely ill]] with ME. She was forcibly institutionalized for 3 1/2 years as the [[Denmark]] healthcare system designates ME as psychosomatic. Karina is now home with her family where she received cards from well-wishers from around the world. Karina's Danish High Court case and return home were featured in the documentary film [[Unrest|''Unrest'']]]]

{{Main article |page_name = Potential treatments for myalgic encephalomyelitis and chronic fatigue syndrome}}

There is no cure for ME and no country has approved any pharmacological treatment for the disease except, [[Argentina]] which has approved [[Ampligen]] for the treatment of severe ME/CFS.<ref name=":9" /> However the effectiveness of Ampligen is under dispute.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|title=FDA rejects Hemispherx’s chronic fatigue drug Ampligen|website=www.bizjournals.com|access-date=2018-08-12|date=Dec 2, 2009|last=George|first=John|archive-url=|archive-date=|dead-url=}}</ref> Other off label medications have been used with varying effectiveness in some patients.<ref>{{Cite web|url=https://www.me-pedia.org/wiki/Valganciclovir|title=Valganciclovir - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref><ref>{{Cite web|url=https://www.me-pedia.org/wiki/Oxymatrine|title=Oxymatrine - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself.

Success of treating symptoms of ME is not well researched or documented.

An immune system modulator drug called [[Rituximab]] has failed in a phase III clinical trial.<ref>{{Cite news|url=http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/|title=Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails - Simmaron Research|last=Johnson|first=Cort|date=2017-11-26|work=Simmaron Research|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

==Epidemiology ==

{{Main article |page_name = Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome}}

ME has been found world-wide, in at least 75 [[Outbreaks|epidemics]] documented in published papers from the 1930s to the 1980s.<ref>{{Cite web|url=http://www.hfme.org/methemedicalfacts.htm|title=M.E.: The medical facts|last=Bassett|first=Jodi|date=Sep 2010|website=The Hummingbirds' Foundation for M.E.|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref> Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approximately 2-3 females for every male.<ref>{{Cite journal|last=Bakken|first=Inger Johanne|last2=Tveito|first2=Kari|last3=Gunnes|first3=Nina|last4=Ghaderi|first4=Sara|last5=Stoltenberg|first5=Camilla|last6=Trogstad|first6=Lill|last7=H åberg|first7=Siri Eldevik|last8=Magnus|first8=Per|date=2014-10-01|title=Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012|url=http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5|journal=BMC Medicine|language=En|volume=12|issue=1|pages=|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmid=25274261|via=}}</ref> In children the sex ratio is approximately equal.<ref>{{Cite journal|last=Collin|first=Simon M.|last2=Nuevo|first2=Roberto|last3=van de Putte|first3=Elise M.|last4=Nijhof|first4=Sanne L.|last5=Crawley|first5=Esther|date=2015-10-28|title=Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts|url=https://www.ncbi.nlm.nih.gov/pubmed/26510728|journal=BMJ open|volume=5|issue=10|pages=e008830|doi=10.1136/bmjopen-2015-008830|issn=2044-6055|pmid=26510728|via=}}</ref>

== Co-morbidities ==
[[File:Chronically_Hopeful_Char_Profile_Pic.jpg|250px|thumb|right|Char, author at [[Chronically Hopeful]], must use sunglasses due to light sensitivity ([[photophobia]]) and noise canceling ear protection due to sound sensitivity ([[hyperacusis]])]]
Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions,<ref>{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-08-12}}</ref> and increased risks for secondary diseases in patients with ME. However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little that can be said definitively about the rate or underlying biological reasons for these potentially related conditions. Overlapping diagnostic criteria and the lack of a biomarker in many of these conditions add to the confusion and diagnostic uncertainty. Moreover, certain conditions such as [[postural orthostatic tachycardia syndrome]] (POTS) and idiopathic [[intracranial hypertension]] (IH/IIH) are symptoms that can occur in or be co-morbid with numerous conditions, including ME.

The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[fibromyalgia]]
*[[Chronic lyme disease|chronic Lyme disease]]
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]
*[[mast cell activation disorder]]
*[[small intestinal bacterial overgrowth]] (SIBO)
*[[thyroid disease]]
*[[Ehlers-Danlos syndrome]]
*[[endometriosis]]
*[[Sjögren's syndrome]]
*[[mold illness]]
*[[multiple chemical sensitivity]]
*[[environmentally acquired illness]]
*[[chronic inflammatory response syndrome]]
*[[cancer]]
*[[idiopathic intracranial hypertension]]
*[[Chiari malformation]]
*[[craniocervical instability]]
*See more [[:Category:Diagnoses|diagnoses]].

</div>

== Notable studies ==
{{Main article |page_name = Notable studies}}Due to lack of [[funding]] by governments around the world there has been little biological research into [[ME/CFS]]. There are studies which do reveal [[Nervous system|neurological]] involvement, [[metabolic]] features, and other abnormalities.
* 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]]

* 2016, [[Metabolic features of chronic fatigue syndrome]]
* 2016, [[CDC Multi-site Clinical Assessment of CFS]]
* 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]]
* [[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]

== See also ==
* [[Chronic fatigue syndrome]]
* [[ME/CFS]]
* [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome]]
* [[Severe and very severe ME]]

*[[Systemic Exertion Intolerance Disease]]
===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=Alegría|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 ==

== References ==

[[Category:Diagnoses]]
[[Category:Disease names]]
<references />

Myalgic encephalomyelitis

2019-02-07T01:25:21Z

Alvin:lots of little changes

'''Myalgic Encephalomyelitis''' (ME) is a progressive chronic, [[Inflammation|inflammatory]], physically and [[neurological|neurologically]] disabling disease that presents with symptoms involving multiple bodily systems. Frequently triggered by a [[viral infection]], it affects the [[central nervous system]] (CNS), [[autonomic nervous system]] (ANS), [[immune system]], [[cardiovascular system]], [[endocrine system]], [[digestive system]], and [[musculoskeletal system]].<ref name=":8">{{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><ref>{{Cite web|url=http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf|title=Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations|last=Petrison|first=Lisa|date=Apr 4, 2016|website=paradigmchange.me|archive-url=|archive-date=|dead-url=|access-date=}}</ref> It has been classified by the [[World Health Organization]] (WHO) as a neurological disease since 1969<ref>{{Cite journal|date=2018-07-22|title=History of chronic fatigue syndrome|url=https://en.wikipedia.org/w/index.php?title=History_of_chronic_fatigue_syndrome&oldid=851489536|journal=Wikipedia|language=en}}</ref><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=2018-09-08|language=en-US}}</ref> and has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic forms since at least the 1930s.

A hallmark symptom of ME is [[Post-exertional malaise|post-exertional malaise]] (PEM), which is an intolerance to previously achievable cognitive or physical [[exertion]].<ref name=":0">{{Cite news|url=https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs|title=Pathways to Prevention (P2P) Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|last=|first=|date=|work=Office of Disease Prevention|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en}}</ref><ref name=":1">[http://www.meactionuk.org.uk/definition.html Research Descriptions of M.E. - ME Action UK]</ref><ref name=":2">{{Cite web|url=http://www.cfids-me.org/ramsay86.html|title=The Clinical Features of Myalgic Encephalomyelitis|last=Ramsey|first=Melvin|date=1986|website=www.cfids-me.org|archive-url=|archive-date=|dead-url=|access-date=2018-09-07}}</ref><ref name=":3">{{Cite news|url=https://www.verywell.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=Aug 1, 2018|work=Verywell Health|access-date=2018-09-07|archive-url=|archive-date=|dead-url=}}</ref><ref name=":5">{{Cite news|url=http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms|title=Think You Might Have Chronic Fatigue Syndrome? Here are The Symptoms|work=WebMD|access-date=2018-09-07|language=en-US}}</ref><ref name=":6">{{Cite web|url=http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf|title=Post-Exertional Malaise in Chronic Fatigue Syndrome|last=Spotila|first=Jennifer|date=2010|website=solvecfs.org|publisher=The CFIDS Association of America|archive-url=|archive-date=|dead-url=|access-date=}}</ref> Other key symptoms include [[muscle]] [[Muscle weakness|weakness]] and easy [[Muscle fatigability|fatiguability]], [[sleep disturbance]], and [[cognitive dysfunction]]. ANS dysfunction is frequent, although specific symptoms vary from patient to patient and may include [[Postural orthostatic tachycardia syndrome|postural orthostatic tachycardia]] (POTS), [[Orthostatic intolerance|orthostatic hypotension]] (OI), and both [[Body temperature|cold and heat intolerance]]. Other common symptoms include [[myalgia]] (muscle pain), [[neuralgia]] (neuropathic pain), [[Neck stiffness|neck]] and [[spine stiffness]], and sensory symptoms including [[sensitivity to light]], [[Hyperacusis|sound]], [[touch]], [[Paresthesia|paraesthesia]] (skin tingling or [[numbness]]) and hyperaesthesia (skin sensitivity and pain, and [[allodynia]]).

Among adults, ME is more common in women than men. New onset has been [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|observed in children]] and in adults as old as 80 years old. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or 'crashes') or accruing over time.<ref>{{Cite web|url=https://login.medscape.com/login/sso/getlogin?urlCache=aHR0cHM6Ly93d3cubWVkc2NhcGUuY29tL3ZpZXdhcnRpY2xlLzg3MTQ4Mg==&ac=401|title=Postexertion 'Crash,' not Fatigue per se, Marks Syndrome|last=|first=|date=|website=medscape.com|format=Login Needed|archive-url=|archive-date=|dead-url=|access-date=}}</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>{{Cite web|url=http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf|title=Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report|last=Howes|first=S|date=Jul 7, 2015|website=meassocation.org|publisher=Physical Medicine and Rehabilitation - International|via=Austin Publishers Group|archive-url=|archive-date=|dead-url=|access-date=}}</ref>

There are no approved pharmacological treatments for ME anywhere in the world, except in [[Argentina]], which has approved the immunomodulator [[Ampligen]] for [[Severe and very severe ME|severe ME/CFS]] as of August 23, 2016.<ref name=":9">{{Cite news|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|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|work=GlobeNewswire News Room|access-date=2018-08-12|language=en-US|first=Hemispherx Biopharma,|last=Inc.|date=Aug 23, 2016|archive-url=|archive-date=|dead-url=}}</ref>

ME is accurately diagnosed with the [[International Consensus Criteria]] (ICC) and a diagnosis should be made immediately. Other criterion such as the [[Canadian Consensus Criteria]] (CCC) and [[Systemic Exertion Intolerance Disease|SEID]] cannot be used to diagnose immediately nor speak to the array and severity of CNS, neurological, ANS, and immune system symptoms patients experience.

[[File:Linda Crowhurst.JPG|thumb|[[Linda Crowhurst]] is married to [[Greg Crowhurst]]; they reside in Belfast, [[Northern Ireland]]. Greg is Linda's full-time carer as she is [[Severe and very severe ME|very severely ill with ME]]. As of June 2018, Linda has been ill for 25 years. This image is a still from the video [https://www.youtube.com/watch?v=Z1z5O_cgQ7I Wasteland] which visually documents Linda's very severe ME. Greg posted a [https://www.youtube.com/watch?v=rVsOeZjhMFY YouTube video in 2006 (reposted in 2007)] of Linda speaking of her condition and showing her [[Nervous system|neurological]] symptoms which are the first known public visual document of very severe ME. She is now bedbound barely able to move and unable to feed herself]]

[[File:Jenny Spotlia.jpg|300px|thumb|right|[[Jennie Spotila]] is an American ME patient who fell ill on October 6, 1994. Jennie is [[Severe and very severe ME|disabled, mostly housebound, and uses a wheelchair]] but has been an [[ME/CFS]] advocate for many years. She writes the blog [[Occupy M.E.]] She served on the Board of Directors of [[Solve ME/CFS Initiative|The CFIDS Association of America]] and testified before the [[Chronic Fatigue Syndrome Advisory Committee|CFSAC]]]]

== History ==
[[File:Hillary Johnson.jpg|200px|thumb|[[Hillary Johnson]] is an [[United States|American]] journalist and while ill herself, wrote the book [[Osler's Web]] which is the historical account of the early years of a "new" illness that had an outbreak at [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] which she shared the same symptoms. The illness came to be known as [[chronic fatigue syndrome]] (CFS). Johnson spent nine years investigating the outbreak and the [[CDC]]'s refusal to acknowledge a devastating disease (deeming sufferers of Incline Village as having "[https://en.wikipedia.org/wiki/Mass_psychogenic_illness mass hysteria]") that can be spread through casual contact. She appears in the documentary ''[[Forgotten Plague]]'' and currently writes at
[https://www.oslersweb.com/ Oslersweb.com] ]]

{{Main article | page_name =History of myalgic encephalomyelitis and chronic fatigue syndrome}}<div role="note" class="hatnote navigation-not-searchable">

ME has occurred in both epidemic and sporadic form since at least the 1930s, although it has likely been occurring much longer but was not formally named. The first recorded outbreak of [[epidemic myalgic encephalomyelitis]] was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical [[polio]]. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called 'Akureyri Disease' or [[Icelandic disease]] through much of the 1940s and 1950s. It was named ME after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and [[Epidemic myalgic encephalomyelitis|epidemic neuromyasthenia]].

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[chronic fatigue syndrome]] (CFS). The most recent putative outbreak was in [[1996 Mohave Valley region, Arizona|Arizona in 1996]].

==Disease Name==

[[File:Merry Crofts sick.JPG|200px|thumb|[[Merryn Crofts]] was [[Severe and very severe ME|bedbound and unable to eat.]] Merryn weighed six stone (84 lbs) at her death; her autopsy revealed inflammation of the [[Dorsal root ganglia|ganglia]]. It is suspected that in the later years of her illness Merryn also suffered from [[Ehlers-Danlos syndrome|EDS]] and [[Mast cell activation disorder|MCAD]]. Her death certificate is the 2nd in the [[United Kingdom|UK]] to attribute a death to ME]]
{{Main article |page_name = Names of myalgic encephalomyelitis and chronic fatigue syndrome}}
* ''Myalgic adj. - of or relating to [[myalgia]].'' Is [[muscle pain]].<ref>{{Cite news|url=https://www.thefreedictionary.com/myalgic|title=myalgic|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Encephalo'': Refers to the [[brain]].<ref>{{Cite news|url=https://medical-dictionary.thefreedictionary.com/encephalo-|title=encephalo-|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Myel'': Relating to the [[spinal cord]].<ref>{{Cite news|url=https://www.thefreedictionary.com/myel-|title=myel-|work=TheFreeDictionary.com|access-date=2018-08-12}}</ref>

* ''Itis'': [[Inflammation]].<ref>{{Cite news|url=https://www.thefreedictionary.com/-itis|title=Itis|work=TheFreeDictionary.com|access-date=2018-08-12|last=|first=|date=|archive-url=|archive-date=|dead-url=}}</ref>
The name ME<ref>{{Cite news|url=https://www.verywell.com/myalgic-encephalomyelitis-me-715663|title=Myalgic Encephalomyelitis: Chronic Fatigue Syndrome's Other Name|last=Dellwo|first=Adrienne|date=Jul 23, 2018|work=Verywell Health|access-date=2018-08-12|archive-url=|archive-date=|dead-url=}}</ref> was coined by Dr. [[Melvin Ramsay]] following the [[1955 Royal Free Hospital outbreak]]<ref>{{Cite journal|last=|first=|date=1957-10-19|title=An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/|journal=British Medical Journal|volume=2|issue=5050|pages=895–904|issn=0007-1447|pmid=13472002|via=}}</ref> and is a portmanteau of several of the key signs and symptoms of the disease: myalgic (muscle pain), encephalo (brain), myel (spinal cord), itis (inflammation).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref> The [[central nervous system]] (brain and spinal cord) are inflamed.<ref name=":02">{{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>

Several other names have been used or proposed throughout the history of the disease, including [[atypical polio]], [[Icelandic disease]], benign ME, [[epidemic neuromyasthenia]], CFS, and [[systemic exertion intolerance disease]] (SEID). This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|case definitions]].

A survey by [[The MEAction Network]] in 2016 found that the majority of patients prefer the name ME to other names including chronic fatigue syndrome.<ref>{{Cite news|url=http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/|title=#MEAction RFI Poll Report (Part 1 of 3) - #MEAction|date=2016-08-07|work=#MEAction|access-date=2018-09-08|language=en-US}}</ref>

Myalgic encephalomyelitis (ME) was the original name for [[chronic fatigue syndrome]] (CFS); the names are used interchangeably or with the acronym [[ME/CFS]].<ref name=":02" />

== Onset ==
Following after an incubation period of 4 to 7 days, the [[wikipedia:Prodrome|prodromal]] phase generally involve a [[flu-like illness]] with [[low-grade fever]]. In the majority but not all cases, an [[infection]] or infectious process is evident.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref> Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the CNS. It is this second phase, persistent phase that most characterizes ME.<ref>{{Cite web|url=https://www.scribd.com/document/32848597/Nightingale-ME-Definition-En|title=Nightingale ME Definition En {{!}} Chronic Fatigue Syndrome {{!}} Infection|last=|first=|date=|website=Scribd|page=5|pages=|at=|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref><ref name=":8" />

In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In theirs, an apparent remission was followed by relapses brought on by exertion, [[menstrual period]], or cold. In other patients there is no discernible triggering event.

==Signs and Symptoms==
Symptoms can range from mild to very severe and can include:
[[File:J Brea TED.JPG|200px|thumb|right|[[Jen Brea|Jennifer Brea]] is an 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. View her TED Talk ''[https://www.ted.com/talks/jen_brea_what_happens_when_you_have_a_disease_doctors_can_t_diagnose What happens when you have a disease doctors can't diagnose]'']]

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
* [[ataxia|ataxia (coordination difficulties)]]

* [[cognitive dysfunction]]
* [[Chronic fatigue|fatigability]]
* [[gastrointestinal]] symptoms
* [[headache]]

*[[low-grade fever]], [[Temperature dysregulation|temperature instability]]
*[[muscle]] [[Muscle weakness|weakness]] and [[Muscle fatigability|fatiguability]]
*[[myalgia|myalgia (muscle pain)]]
*neck and back or [[spinal cord]] stiffness
*[[neuralgia|neuralgia (nerve pain)]]
*[[Orthostatic intolerance|othostatic intolerance]]
*[[post-exertional malaise]]
*sensitivity to [[Temperature sensitivity|heat or cold]]
*sensitivity to [[Light sensitivity|light]], [[Hyperacusis|sound]] and/or [[Allodynia|touch]]
*[[sleep dysfunction]]

</div>

Symptom presentation and severity can vary considerably day to day and even hour to hour.<ref name=":8" /> Overexertion can exacerbate all symptoms, and Post Exertional Malaise often delayed by 24 hours or more.<ref>{{Cite web|url=http://www.investinme.org/landerP5.shtml|title=Invest in ME Research - Invest in ME Research Home Page|last=Research|first=Invest in ME|website=www.investinme.org|access-date=2018-09-08}}</ref> <ref name=":8" /> The US [[National Institutes of Health]] (NIH) notes that sensitivity to noise, light and [[Chemical sensitivities|chemical]]<nowiki/>s may force patients to withdraw from society.<ref>{{Cite news|url=https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs|title=Pathways to Prevention (P2P) Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)|last=|first=|date=|work=Office of Disease Prevention|access-date=2018-09-08|archive-url=|archive-date=|dead-url=|language=en}}</ref>

The severity of a patient's symptoms often depends on the time period since the disease was contacted and rate of progression of each patient. The rate of progression can be accelerated by ''physical or cognitive activity'' beyond a patient's limits over long periods, which typically entails [[anaerobic]] activity <ref>{{Cite web|url=https://www.me-pedia.org/wiki/Unrest|title=Unrest - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

=== Post-exertional malaise ===
{{Main article | page_name =Post-exertional malaise}}
A core symptom, [[post-exertional malaise]], is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":5" /><ref name=":6" /><ref name=":4">{{Cite news|url=https://www.verywell.com/post-exertional-malaise-715670|title=What is Post-Exertional Malaise? Learn About a Key ME/CFS Symptom|work=Verywell Health|access-date=2018-09-07}}</ref>

== Clinical Findings ==
[[File:Alem Matthee.png|200px|thumb|right|[[Alem Matthees]] is an [[Australia|Australian]] ME patient that filed an FOI request for data from the [[PACE trial]]. At a [[Severe and very severe ME|great cost to his health]], Alem appealed the denial of the data and won. This data proved the results published in [[The Lancet|''The Lancet'']] were untrue. Alem's health suffered significantly in part from the efforts required for the FOI request and tribunal]]
Although there is no definitive [[biomarker]], several signs and findings have been frequently observed in clinical settings:<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*high antibody titers to specific infections (including [[Epstein-Barr virus|EBV]], [[Human herpesvirus 6|HHV-6]], and [[Coxsackie B virus|Coxsackie B]] among others)
*[[Hormones|hormone]] imbalance
*[[Immune system|immunological abnormalities]]
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]
*low red blood cell [[magnesium]]
*[[natural killer cell]] (NKC)
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]] (POTS)
*[[Post-exertional malaise|reaction to physical and mental activity and sensory input]] (PEM)
</div>

==Diagnosis==

[[File:Tom Kindlon.png|300px|thumb|[[Tom Kindlon]] became [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|ill at 16]] and never recovered. He is an ME/CFS advocate with published works in Research Gate and PubMed. Kindlon lives in [[Ireland]] and is Assistant Chairperson of the [[Irish ME/CFS Association]]. Tom and others analyzed the data for the PACE trial proving out that its published results were untrue. He uses a [[Severe and very severe ME|wheelchair and his full-time carer]] is his mother, Vera]]

{{Main article | page_name =Definitions of myalgic encephalomyelitis and chronic fatigue syndrome}}There are several proposed criteria for diagnosing ME including the [[International Consensus Criteria]] (ICC) and the [[Canadian Consensus Criteria]] (CCC). The original criteria developed by [[Melvin Ramsay]], the [[Ramsay definition]], is not used for diagnosing ME today.<span></span><span></span>
=== Other diagnostic criteria ===
Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on [[Epidemic myalgic encephalomyelitis|epidemic ME]], exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's [[Oxford criteria]] is the broadest and likely least discerning definition. (The US [[Institute of Medicine report]] called for its complete retirement.)<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=2018-09-08}}</ref> The US [[Centers for Disease Control and Prevention|Centers for Disease Control]]'s (CDC) [[Fukuda criteria]], in use since 1994, is also overly broad.

===Differential diagnosis===
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], [[Systemic lupus erythematosus|lupus]], [[brucellosis]], or another condition."<ref name=":8" /> Additional testing may be needed to help distinguish ME from these other problems.

==Course and Prognosis ==
{{Main article | page_name =Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome}}

ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, [[influenza]] and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

About 25% of patients become [https://www.me-pedia.org/wiki/Severe_and_very_severe_M.E. severe or very severely ill with ME].

==Clinical Subtypes==
Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:<ref name=":7">{{Cite web|url=http://me-ireland.com/genes2.pdf|title=Seven genomic subtypes of chronic fatigue phenotypes analysis of gene networks and clinical syndrome/myalgic encephalomyelitis: a detailed|last=Kerr|first=JR|last2=Burke|first2=R|date=May 30, 2008|website=me-ireland.com|doi=10.1136/jcp.2007.053553|archive-url=|archive-date=|dead-url=|access-date=|last3=Petty|first3=R|last4=Gough|first4=J|last5=Fear|first5=D|last6=Mattey|first6=D L|last7=Axford|first7=J S|last8=Dalgleish|first8=A G|last9=Nutt|first9=D J|publisher=JCP Online}}</ref><ref>{{Cite journal|last=Kerr|first=J. R.|last2=Burke|first2=B.|last3=Petty|first3=R.|last4=Gough|first4=J.|last5=Fear|first5=D.|last6=Mattey|first6=D. L.|last7=Axford|first7=J. S.|last8=Dalgleish|first8=A. G.|last9=Nutt|first9=D. J.|date=2008-06-01|title=Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes|url=https://jcp.bmj.com/content/61/6/730|journal=Journal of Clinical Pathology|language=en|volume=61|issue=6|pages=730–739|doi=10.1136/jcp.2007.053553|issn=0021-9746|pmid=18057078}}</ref>

[[File:Whitney.JPG|200px|thumb|[[Whitney Dafoe]] is an American photographer who has a [[Severe and very severe ME|very severe form]] of ME. Whitney can no longer speak or handle contact with anyone but his parents. His father is [[Ronald Davis|Ron Davis]], a world-renowned geneticist who is working to solve his son's disease]]

* Subtype 1 This is one of the more severe subtypes. Effects are cognitive, [[Musculoskeletal system|musculoskeletal]], [[Sleep dysfunction|sleep-related]] and [[anxiety]]/[[depression]].

* Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.

* Subtype 3 This subtype has the mildest symptoms.

* Subtype 4 This subtype is dominated by cognitive issues.

* Subtype 5 Effects are musculoskeletal and gastrointestinal.

* Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after [[exercise]] or exertion.)

* Subtype 7 This is one of the more severe subtypes. Effects are [[pain]], infections, musculoskeletal, sleep-related, [[Nervous system|neurological]], gastrointestinal, [[Cognitive dysfunction|neurocognitive]] and anxiety/depression.<ref name=":7" />

==Pathophysiology==
[[File:Vanessa Li.jpg|thumb|right|[[Vanessa Li]] lived in Hong Kong, the UK, and the US. She became ill with a [[flu-like illness]] while skiing in [[Italy]] and never recovered. Vanessa founded a crowdfund for the [[Microbe Discovery Project]]. She was in [[Severe and very severe ME|excruciating pain, suffered from breathing issues, and occasional paralysis]] for 15 years. She took her own life in 2015]]
{{Main article | page_name =List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis}}

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

=== Central nervous system ===
[[File:Sophia mirza.jpg|thumb|right|[[Sophia Mirza]] was a [[Severe and very severe ME|very severely ill]] ME patient who lived in the UK. Sophia's death came not long after a forced entry into her mother's home and being sectioned and taken to a mental hospital in 2003. An independent Neuropathologist found Sophia's spine contained a massive infection. Her death certificate was the first in the UK to attribute a death to CFS]]
{{Main article |page_name =Central nervous system}}Radiological research on ME has shown [https://medical-dictionary.thefreedictionary.com/hypoperfusion hypoperfusion] of the [[brain stem]] and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, some research stated that a reduced volume of [[grey matter]] may be a result of a lack of activity and is reversible with [[cognitive behavioral therapy]] (CBT).

=== Autonomic nervous system ===
{{Main article |page_name =Autonomic nervous system}}

=== Peripheral nervous system ===
{{Main article |page_name =Peripheral nervous system}}

=== Musculoskeletal system ===
{{Main article |page_name =Muscle}}

=== Immune system ===
{{Main article |page_name =Immune system}}<div role="note" class="hatnote navigation-not-searchable">{{Main article |page_name =Immune system}}</div><span></span>

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as [[RNase L|Rnase-L]]. [[Channelopathy]], a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.

=== Chronic infection ===
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the post-polio syndrome?].
[[File:Emma Shorter.JPG|400px|thumb|[[Emma Shorter]] is a [[Scotland|Scottish]] citizen who has ME. She did [[Graded exercise therapy]] (GET) and went from walking a few minutes a day to being [[Severe and very severe ME|in a wheelchair.]] Here, Emma gives testimony before Scotland's Parliament's Petitions Committee.
View her [https://youtu.be/wDayJXxZSQE?t=106 testimony] ]]

=== Cardiovascular ===
[[wikipedia:Hemodynamics|Hemodynamic]] abnormalities are widely found, including serum and RBC [[wikipedia:Hypovolemia|hypovolemia]], [[neurally mediated hypotension]], (NMH) and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr [[Paul Cheney]] to posit that CFS is form of partially compensated cardiomyopathy in which [[orthostatic intolerance]] and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with [[wikipedia:Holter_monitor|Holter monitors]].

=== Gastrointestinal system ===
{{Main article |page_name =Gastrointestinal system}}

== Sex Differences ==
[[File:Florence Nightingale.png|200px|thumb|right|[[Florence Nightingale]] was a British citizen and pioneer of modern nursing. Nightingale was stationed in Crimea when she developed "Crimean fever" (a bacterial infection now known as [[brucellosis]]) and never recovered. She remained [[Severe and very severe ME|mostly bedbound]] the rest of her life. Although ME and CFS were not defined in her lifetime, many current physicians and medical historians believe she developed ME/CFS as a result of a chronic brucellosis infection]]

{{Main article |page_name = Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome}}
A Norwegian [[CFS/ME]] study shows that the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.<ref>{{Cite journal|last=Bakken|first=Inger Johanne|last2=Tveito|first2=Kari|last3=Gunnes|first3=Nina|last4=Ghaderi|first4=Sara|last5=Stoltenberg|first5=Camilla|last6=Trogstad|first6=Lill|last7=H åberg|first7=Siri Eldevik|last8=Magnus|first8=Per|date=2014-10-01|title=Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012|url=http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5|journal=BMC Medicine|language=En|volume=12|issue=1|pages=|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmid=25274261|via=}}</ref> Research by the [[Open Medicine Foundation]] cited in its paper, [[Metabolic features of chronic fatigue syndrome|''Metabolic features of chronic fatigue syndrome'']] which studied severe [[CFS]], found that the disease is different in men and women but this is not related to testosterone or estrogen. [[Michael VanElzakker]] notes there are [http://me-pedia.org/wiki/Michael_VanElzakker#Male_and_female_differences_in_neuropathic_pain male and female differences in neuropathic pain]. A study of UK and Dutch cohorts found "younger children had a more equal gender balance compared to adolescents and adults."<ref>{{Cite journal|last=Collin|first=Simon M.|last2=Nuevo|first2=Roberto|last3=van de Putte|first3=Elise M.|last4=Nijhof|first4=Sanne L.|last5=Crawley|first5=Esther|date=2015-10-28|title=Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts|url=https://www.ncbi.nlm.nih.gov/pubmed/26510728|journal=BMJ open|volume=5|issue=10|pages=e008830|doi=10.1136/bmjopen-2015-008830|issn=2044-6055|pmid=26510728|via=}}</ref>

==Risk Factors and Potential Causes==

{{Main article | page_name =Risk factors and potential causes of myalgic encephalomyelitis and chronic fatigue syndrome}}

===Risk factors===

===Potential causes===
Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.<ref>{{Cite web|url=http://via.library.depaul.edu/csh_etd/117/|title=Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach|last=Evans|first=Meredyth|date=Aug 23, 2015|website=via.library.depaul.edu|archive-url=|archive-date=|dead-url=|access-date=}}</ref><ref>{{Cite web|url=http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis|title=Vagus nerve infection hypothesis - MEpedia|website=me-pedia.org|language=en|access-date=2018-09-08}}</ref><ref>{{Cite web|url=http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/chronic-fatigue/case3.htm|title=Case Presentation - Chronic Fatigue Syndrome|website=www.clevelandclinicmeded.com|access-date=2018-09-08}}</ref><ref>{{Cite journal|last=Magnus|first=Per|last2=Gunnes|first2=Nina|last3=Tveito|first3=Kari|last4=Bakken|first4=Inger Johanne|last5=Ghaderi|first5=Sara|last6=Stoltenberg|first6=Camilla|last7=Hornig|first7=Mady|last8=Lipkin|first8=W. Ian|last9=Trogstad|first9=Lill|date=2015-11-17|title=Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine|url=https://www.ncbi.nlm.nih.gov/pubmed/26475444/|journal=Vaccine|volume=33|issue=46|pages=6173–6177|doi=10.1016/j.vaccine.2015.10.018|issn=1873-2518|pmid=26475444}}</ref> It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.<ref>{{Cite journal|last=Underhill|first=R. A.|date=2015|title=Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease|url=https://www.ncbi.nlm.nih.gov/pubmed/26604026|journal=Medical Hypotheses|volume=85|issue=6|pages=765–773|doi=10.1016/j.mehy.2015.10.011|issn=1532-2777|pmid=26604026|via=}}</ref><ref>{{Cite journal|last=Schlauch|first=K A|last2=Khaiboullina|first2=S F|last3=De Meirleir|first3=K L|last4=Rawat|first4=S|last5=Petereit|first5=J|last6=Rizvanov|first6=A A|last7=Blatt|first7=N|last8=Mijatovic|first8=T|last9=Kulick|first9=D|date=2016|title=Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome|url=http://www.nature.com/tp/journal/v6/n2/full/tp2015208a.html|journal=Translational Psychiatry|language=En|volume=6|issue=2|pages=e730–e730|doi=10.1038/tp.2015.208|issn=2158-3188|via=}}</ref> Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of [[autoimmune disease]].<ref>{{Cite web|url=https://www.facebook.com/permalink.php?story_fbid=564532390371988&id=564526123705948|title=Klimas ME CFS Genes Study|last=|first=|date=Nov 23, 2015|website=www.facebook.com|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref> There is also a shift from the [[Th1]] type of helper [[T cell]]s, which fight infection, to the [[Th2]] type, which are more active in [[allergy]] and more likely to attack the body.<ref>{{Cite journal|date=2015-03-01|title=Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis|url=https://www.sciencedirect.com/science/article/abs/pii/S1043466614006024|journal=Cytokine|language=en|volume=72|issue=1|pages=1–8|doi=10.1016/j.cyto.2014.11.019|issn=1043-4666}}</ref><ref>{{Cite web|url=http://www.m-hikari.com/bmgt/bmgt2014/bmgt1-4-2014/hardcastleBMGT1-4-2014.pdf|title=Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells|last=Hardcastle|first=S.L.|last2=Brenu|first2=E.W.|date=2014|website=m-hikari.com|archive-url=|archive-date=|dead-url=|access-date=|last3=Staines|first3=D.R.|last4=Marshall-Gradisni|first4=S.}}</ref>

[[File:Naomi Whittingham .png|300px|thumb|[[Naomi Whittingham]] lives in the UK with a [[Severe and very severe ME|severe case of ME]]. Naomi became ill at [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|age 12]] with a routine virus and never recovered. She advocates for ME by doing interviews, writing the blog [[A Life Hidden]], and supporting her brother [[Tom Whittingham]]'s marathon fund raising for [[ME Research UK]]]]
===Viruses===
{{Main article |page_name = Viruses}}

Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses<ref>{{Cite journal|last=Bell|first=E. J.|last2=McCartney|first2=R. A.|last3=Riding|first3=M. H.|date=1988|title=Coxsackie B viruses and myalgic encephalomyelitis|url=https://www.ncbi.nlm.nih.gov/pubmed/2841461|journal=Journal of the Royal Society of Medicine|volume=81|issue=6|pages=329–331|doi=10.1177/014107688808100609|issn=0141-0768|pmid=2841461|via=}}</ref><ref>{{Cite news|url=http://solvecfs.org/ramsay-research-team-5-the-potential-role-of-hhv-6-in-mecfs/|title=Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS - Solve ME/CFS Initiative|last=|first=|date=2016-12-16|work=Solve ME/CFS Initiative|access-date=2018-09-08|archive-url=|archive-date=|dead-url=|publisher=VOLKMEDIA|language=en-US}}</ref> <ref>{{Cite journal|last=Chapenko|first=Svetlana|last2=Krumina|first2=Angelika|last3=Logina|first3=Inara|last4=Rasa|first4=Santa|last5=Chistjakovs|first5=Maksims|last6=Sultanova|first6=Alina|last7=Viksna|first7=Ludmila|last8=Murovska|first8=Modra|date=2012|title=Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/22927850|journal=Advances in Virology|volume=2012|pages=205085|doi=10.1155/2012/205085|issn=1687-8647|pmid=22927850|via=}}</ref> suggests a potential viral contribution in at least some individuals. Evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

=== Bacteria ===
{{Main article |page_name = Bacteria}}

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as [[lyme disease]]. Another bacterium that has been implicated in ME is [[chlamydia pneumoniae]].<ref>{{Cite journal|date=2018-09-05|others=John E.Tovey|title=Chlamydia pneumoniae infection a treatable cause of Chronic Fatigue Syndrome|url=https://www.bmj.com/rapid-response/2011/11/01/chlamydia-pneumoniae-infection-treatable-cause-chronic-fatigue-syndrome|journal=The BMJ|language=en|last=|first=|volume=|pages=|via=}}</ref><ref>{{Cite news|url=https://www.prohealth.com/library/new-me-cfs-study-at-stanford-dr-montoya-to-test-for-scores-of-infections-27346|title=New ME/CFS Study at Stanford: Dr. Montoya to test for scores of Infections - Prohealth|date=2010-06-04|work=Prohealth|access-date=2018-09-08|language=en-US}}</ref> Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.<ref>{{Cite web|url=http://www.bjmp.org/content/role-chronic-bacterial-and-viral-infections-neurodegenerative-neurobehavioral-psychiatric-au|title=Role of Chronic Bacterial and Viral Infections in Neurodegenerative, Neurobehavioral, Psychiatric, Autoimmune and Fatiguing Illnesses: Part 1 {{!}} British Journal of Medical Practitioners|last=|first=|date=2009|website=www.bjmp.org|language=en|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref>

The [[vagus nerve infection hypothesis]] (VNIH) accounts for why so many different infectious onsets could be responsible. The [[vagus nerve]] runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>{{Cite web|url=http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/|title=People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement|last=|first=|date=Aug 2010|website=www.meassociation.org.uk|language=en-US|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref><ref>{{Cite news|url=http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html|title=Chronic fatigue patients barred from blood donation|last=Stein|first=Rob|date=2010-12-03|access-date=2018-09-08|language=en-US|issn=0190-8286}}</ref><ref>{{Cite web|url=http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C|title=Detailed eligibility criteria|website=www.nzblood.co.nz|language=en-NZ|access-date=2018-09-08}}</ref>

==Treatments==
[[File:Karina Hansen.jpg|200px|thumb|right|[[Karina Hansen]] became [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|ill as an adult teenager]] and is [[Severe and very severe ME|severely ill]] with ME. She was forcibly institutionalized for 3 1/2 years as the [[Denmark]] healthcare system designates ME as psychosomatic. Karina is now home with her family where she received cards from well-wishers from around the world. Karina's Danish High Court case and return home were featured in the documentary film [[Unrest|''Unrest'']]]]

{{Main article |page_name = Potential treatments for myalgic encephalomyelitis and chronic fatigue syndrome}}

There is no cure for ME and no country has approved any pharmacological treatment for the disease except, [[Argentina]] which has approved [[Ampligen]] for the treatment of severe ME/CFS.<ref name=":9" /> However the effectiveness of Ampligen is under dispute.<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|title=FDA rejects Hemispherx’s chronic fatigue drug Ampligen|website=www.bizjournals.com|access-date=2018-08-12|date=Dec 2, 2009|last=George|first=John|archive-url=|archive-date=|dead-url=}}</ref> Other off label medications have been used with varying effectiveness in some patients.<ref>{{Cite web|url=https://www.me-pedia.org/wiki/Valganciclovir|title=Valganciclovir - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref><ref>{{Cite web|url=https://www.me-pedia.org/wiki/Oxymatrine|title=Oxymatrine - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself.

Success of treating symptoms of ME is not well researched or documented.

An immune system modulator drug called [[Rituximab]] has failed in a phase III clinical trial.<ref>{{Cite news|url=http://simmaronresearch.com/2017/11/norwegian-rituximab-chronic-fatigue-syndrome-mecfs-trial-fails/|title=Norwegian Rituximab Chronic Fatigue Syndrome (ME/CFS) Trial Fails - Simmaron Research|last=Johnson|first=Cort|date=2017-11-26|work=Simmaron Research|access-date=2018-09-07|archive-url=|archive-date=|dead-url=|language=en-US}}</ref>

==Epidemiology ==

{{Main article |page_name = Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome}}

ME has been found world-wide, in at least 75 [[Outbreaks|epidemics]] documented in published papers from the 1930s to the 1980s.<ref>{{Cite web|url=http://www.hfme.org/methemedicalfacts.htm|title=M.E.: The medical facts|last=Bassett|first=Jodi|date=Sep 2010|website=The Hummingbirds' Foundation for M.E.|archive-url=|archive-date=|dead-url=|access-date=2018-09-08}}</ref> Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approximately 2-3 females for every male.<ref>{{Cite journal|last=Bakken|first=Inger Johanne|last2=Tveito|first2=Kari|last3=Gunnes|first3=Nina|last4=Ghaderi|first4=Sara|last5=Stoltenberg|first5=Camilla|last6=Trogstad|first6=Lill|last7=H åberg|first7=Siri Eldevik|last8=Magnus|first8=Per|date=2014-10-01|title=Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012|url=http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5|journal=BMC Medicine|language=En|volume=12|issue=1|pages=|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmid=25274261|via=}}</ref> In children the sex ratio is approximately equal.<ref>{{Cite journal|last=Collin|first=Simon M.|last2=Nuevo|first2=Roberto|last3=van de Putte|first3=Elise M.|last4=Nijhof|first4=Sanne L.|last5=Crawley|first5=Esther|date=2015-10-28|title=Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts|url=https://www.ncbi.nlm.nih.gov/pubmed/26510728|journal=BMJ open|volume=5|issue=10|pages=e008830|doi=10.1136/bmjopen-2015-008830|issn=2044-6055|pmid=26510728|via=}}</ref>

== Co-morbidities ==
[[File:Chronically_Hopeful_Char_Profile_Pic.jpg|250px|thumb|right|Char, author at [[Chronically Hopeful]], must use sunglasses due to light sensitivity ([[photophobia]]) and noise canceling ear protection due to sound sensitivity ([[hyperacusis]])]]
Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions,<ref>{{Cite web|url=https://ammes.org/overlapping-conditions/|title=Overlapping Conditions – American ME and CFS Society|website=ammes.org|language=en-US|access-date=2018-08-12}}</ref> and increased risks for secondary diseases in patients with ME. However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little that can be said definitively about the rate or underlying biological reasons for these potentially related conditions. Overlapping diagnostic criteria and the lack of a biomarker in many of these conditions add to the confusion and diagnostic uncertainty. Moreover, certain conditions such as [[postural orthostatic tachycardia syndrome]] (POTS) and idiopathic [[intracranial hypertension]] (IH/IIH) are symptoms that can occur in or be co-morbid with numerous conditions, including ME.

The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[fibromyalgia]]
*[[Chronic lyme disease|chronic Lyme disease]]
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]
*[[mast cell activation disorder]]
*[[small intestinal bacterial overgrowth]] (SIBO)
*[[thyroid disease]]
*[[Ehlers-Danlos syndrome]]
*[[endometriosis]]
*[[Sjögren's syndrome]]
*[[mold illness]]
*[[multiple chemical sensitivity]]
*[[environmentally acquired illness]]
*[[chronic inflammatory response syndrome]]
*[[cancer]]
*[[idiopathic intracranial hypertension]]
*[[Chiari malformation]]
*[[craniocervical instability]]
*See more [[:Category:Diagnoses|diagnoses]].

</div>

== Notable studies ==
{{Main article |page_name = Notable studies}}Due to lack of [[funding]] by governments around the world there has been little biological research into [[ME/CFS]]. There are studies which do reveal [[Nervous system|neurological]] involvement, [[metabolic]] features, and other abnormalities.
* 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]]

* 2016, [[Metabolic features of chronic fatigue syndrome]]
* 2016, [[CDC Multi-site Clinical Assessment of CFS]]
* 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]]
* [[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]

== See also ==
* [[Chronic fatigue syndrome]]
* [[ME/CFS]]
* [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome]]
* [[Severe and very severe ME]]

*[[Systemic Exertion Intolerance Disease]]
===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=Alegría|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 ==

== References ==

[[Category:Diagnoses]]
[[Category:Disease names]]
<references />

Myalgic encephalomyelitis

2018-08-12T02:43:09Z

Alvin:first paragraph

'''Myalgic Encephalomyelitis''' (ME) is a chronic, [[inflammatory]], physically and [[neurological|neurologically]] disabling disease that is progressive and multi-systemic. Frequently triggered by a [[viral infection]], it affects the [[central nervous system]] (CNS), [[immune system]], [[cardiovascular system]], [[endocrine system]], and [[musculoskeletal system]].<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref><ref>[http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF]</ref> It has been classified by the [[World Health Organization]] (WHO) as a neurological disease since 1969<ref>[https://en.wikipedia.org/wiki/History_of_chronic_fatigue_syndrome#International_classifications History of chronic fatigue syndrome - International Classifications]</ref><ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper - PDF]</ref> and has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic forms since at least the 1930s, although has likely been around for much longer before being classified as a distinct disease.

A hallmark symptom of ME is [[Post-exertional malaise|Post-Exertional Malaise]] (PEM), which is an intolerance to previously achievable cognitive or physical effort.<ref name=":0">[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - NIH]</ref><ref name=":1">[http://www.meactionuk.org.uk/definition.html Research Descriptions of M.E. - ME Action UK]</ref><ref name=":2">[http://www.cfids-me.org/ramsay86.html The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986]</ref><ref name=":3">[https://www.verywell.com/what-is-post-exertional-malaise-716023 What Is Post-exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":4">[https://www.verywell.com/post-exertional-malaise-715670 Post Exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":5">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Web MD]</ref><ref name=":6">[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf PEM Series - Solve ME/CFS - Jenny Spotila]</ref> Other key symptoms include [[muscle]] [[Muscle weakness|weakness]] and easy [[Muscle fatigability|fatiguability]], [[sleep disturbance]], and [[cognitive dysfunction]]. [[Autonomic nervous system]] dysfunction is frequent, although specific symptoms vary from patient to patient and may include [[Postural orthostatic tachycardia syndrome|postural orthostatic tachycardia]], [[Orthostatic intolerance|orthostatic hypotension]], [[cold intolerance]] and [[heat intolerance]]. Other common symptoms include [[myalgia]] (muscle pain), [[neuralgia]] (neuropathic pain), neck and spine stiffness, and sensory symptoms including [[sensitivity to light]], sound, [[touch]], [[Paresthesia|paraesthesia]] (skin tingling or numbness) and hyperaesthesia (skin sensitivity and pain).

Among adults, ME is more common in women than men. New onset has been observed in children and in adults as old as 80 years old. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or 'crashes') or accruing over time.<ref>[http://www.medscape.com/viewarticle/871482 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape]</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>[http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report]</ref>

There is no cure for ME/CFS though [[Argentina]] has approved [[Ampligen]] for the treatment of [[chronic fatigue syndrome]]. However the effectiveness of Ampligen is under dispute<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|title=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|website=www.bizjournals.com|access-date=2018-08-12}}</ref>. Other off label medications have been used with varying effectiveness in some patients.<ref>{{Cite web|url=https://www.me-pedia.org/wiki/Valganciclovir|title=Valganciclovir - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref><ref>{{Cite web|url=https://www.me-pedia.org/wiki/Oxymatrine|title=Oxymatrine - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

== History ==

{{Main article | History of myalgic encephalomyelitis and chronic fatigue syndrome}}

ME has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic form since at least the 1930s, although is probably much older. The first recorded outbreak of epidemic myalgic encephalomyelitis was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical [[polio]]. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called 'Akureyri Disease' or [[Icelandic disease]] through much of the 1940s and 1950s. It was named [[Myalgic Encephalomyelitis|myalgic encephalomyelitis]] after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[Chronic Fatigue Syndrome]]. The most recent was putative outbreak was in Arizona in 1996.

==Disease Name==

{{Main article | Names of myalgic encephalomyelitis and chronic fatigue syndrome}}

The name myalgic encephalomyelitis was coined by Dr. [[Melvin Ramsay]] following the [[1955 Royal Free Hospital outbreak]]<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/ An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 - The Medical Staff Of The Royal Free Hospital]</ref> and is a portmanteau of several of the key signs and symptoms of the disease: myalgic ([[muscle pain]]), encephalo ([[brain]]), myel ([[spinal cord]]), itis ([[inflammation]]).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref>

Several other names have been used or proposed throughout the history of the disease, including [[atypical polio]], [[Icelandic disease]], benign myalgic encephalomyelitis, [[epidemic neuromyasthenia]], [[chronic fatigue syndrome]], and [[systemic exertion intolerance disease]]. This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|case definitions]].

A survey by [[The MEAction Network]] in 2016 found that the majority of patients prefer the name myalgic encephalomyelitis to other names including [[Chronic Fatigue Syndrome|chronic fatigue syndrome]].<ref>[http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/ MEAction RFI Poll Report (Part 1 of 3)]</ref> Most government agencies and researchers around the world use the term [[ME/CFS]].{{Citation needed}}

== Onset ==
Following after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever. In the majority but not all cases, an infection or infectious process is evident.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref> Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the [[central nervous system]]. It is this second phase, persistent phase that is most ME.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref>

In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In others, an apparent remission was followed by relapses brought on by exertion, [[menstrual period]], or cold.
==Signs and Symptoms==

Symptoms can range from mild to very severe and can include:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*low-grade fever, temperature instability
*[[post-exertional malaise]]
*[[Cognitive dysfunction]]
*[[muscle]] [[Muscle weakness|weakness]] and [[Muscle fatigability|fatiguability]]
*[[Headache]]
*[[myalgia|myalgia (muscle pain)]]
*[[neuralgia|neuralgia (nerve pain)]]
*[[ataxia|ataxia (coordination difficulties)]]
*[[gastrointestinal]] symptoms
*[[sleep dysfunction]]
*neck and back or spinal cord stiffness
*sensitivity to light, sound and/or touch
*sensitivity to heat or cold

</div>

Symptoms presentation and severity can vary considerably day to day and even hour to hour.<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> Overexertion can make all symptoms worse, the effects are often delayed and may not be seen within 24 hours.<ref>[http://www.investinme.org/landerP5.shtml What is ME - Invest in ME Research]</ref> <ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> The US [[National Institutes of Health]] notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.<ref>[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic encephalomyelitis/Chronic Fatigue Syndrome]</ref>

The severity of a patient's symptoms often depends on the time period since the disease was contacted and rate of progression of each patient. The rate of progression can be accelerated by physical or cognitive activity beyond a patient's limits, which typically entails anaerobic activity <ref>{{Cite web|url=https://www.me-pedia.org/wiki/Unrest|title=Unrest - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

=== Post-exertional malaise ===
{{Main article | Post-exertional malaise}}
A core symptom, [[Post-exertional malaise]], is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":5" /><ref name=":6" />

== Clinical Findings ==
Although there is no definitive [[biomarker]], several signs and findings have been frequently observed in clinical settings:<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*reaction to physical and mental activity and sensory input
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]]
*[[Hormones|hormone]] imbalance
*[[Immune system|immunological abnormalities]]
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]
*high titers to specific infection
*low red blood cell [[magnesium]]

</div>
==Diagnosis==

{{Main article | Definitions of myalgic encephalomyelitis and chronic fatigue syndrome}}

There are several proposed criteria for diagnosing ME including the [[International Consensus Criteria]] (ICC) and the [[Canadian Consensus Criteria]] (CCC). The original criteria developed by [[Melvin Ramsay]], the [[Ramsay definition]], is not used for diagnosing ME today.

=== Other diagnostic criteria ===
Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on [[Epidemic myalgic encephalomyelitis|epidemic ME]], exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's [[Oxford criteria]] is the broadest and likely most heterogenous definition. (The US [[Institute of Medicine report]] called for its complete retirement<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]</ref>). The US [[Centers for Disease Control and Prevention|Centers for Disease Control]]'s [[Fukuda criteria]], in use since 1994, is also overly broad.

===Differential diagnosis===
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], lupus, [[brucellosis]], or another condition."<ref>[https://www.dartmouth-hitchcock.org/medical-information/health_encyclopedia/nord792 Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.]</ref> Additional testing may be needed to help distinguish ME from these other problems.

==Course and Prognosis ==
ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, influenza and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

"The later course of ME is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

==Clinical Subtypes==
There are no standard subtypes. Some researchers and clinicians have proposed distinguishing between a relapsing-remitting and progressive course.{{Citation needed}} However, it is difficult to distinguish between natural variation in the population of ME patients who might share a common disease process but owing to individual, genetic, or environmental differences, have different symptom clusters or disease course versus heterogeneity created by imprecise criteria and misdiagnosis.<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:<ref>[http://me-ireland.com/genes2.pdf Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes - JCP Online]</ref>

* Subtype 1 This is one of the more severe subtypes. Effects are cognitive, musculoskeletal, sleep-related and anxiety/depression.

* Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.

* Subtype 3 This subtype has the mildest symptoms.

* Subtype 4 This subtype is dominated by cognitive issues.

* Subtype 5 Effects are musculoskeletal and gastrointestinal.

* Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after exercise or exertion.)

* Subtype 7 This is one of the more severe subtypes. Effects are pain, infections, musculoskeletal, sleep-related, neurological, gastrointestinal, neurocognitive and anxiety/depression.

==Pathophysiology==
{{Main article | List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis}}

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

=== Central nervous system ===
{{Main article |Central nervous system}}Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, some research stated that a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.

=== Autonomic nervous system ===
{{Main article |Autonomic nervous system}}

=== Peripheral nervous system ===
{{Main article |Peripheral nervous system}}

=== Musculoskeletal system ===
{{Main article |Muscle}}

=== Immune system ===
{{Main article |Immune system}}

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as [[RNase L|Rnase-L]]. [[Channelopathy]], a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.

=== Chronic infection ===
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the post-polio syndrome?].

=== Cardiovascular ===
Hemodynamic abnormalities are widely found, including serum and RBC hypovolemia, NMH, and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr Paul Cheney to posit that CFS is form of partially compensated cardiomyopathy in which [[orthostatic intolerance]] and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with Holter monitors.

=== Gastrointestinal system ===
{{Main article |Gastrointestinal system}}

== Sex Differences ==
{{Main article | Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome}}
A Norwegian [[CFS/ME]] study shows that the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> Research by the [[Open Medicine Foundation]] cited in its paper, [[Metabolic features of chronic fatigue syndrome]] which studied severe [[CFS]], found that the disease is different in men and women but this is not related to testosterone or estrogen. [[Michael VanElzakker]] notes there are [http://me-pedia.org/wiki/Michael_VanElzakker#Male_and_female_differences_in_neuropathic_pain male and female differences in neuropathic pain]. A study of UK and Dutch cohorts found "younger children had a more equal gender balance compared to adolescents and adults."<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

==Risk Factors and Potential Causes==

{{Main article | Risk factors and potential causes of myalgic encephalomyelitis and chronic fatigue syndrome}}

===Risk factors===

===Potential causes===

Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.<ref>[http://via.library.depaul.edu/csh_etd/117/ Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach - Meredyth Evans - DePaul University]</ref><ref>[http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis Vagus nerve infection hypothesis - MEpedia]</ref><ref>[http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/chronic-fatigue/case3.htm Chronic Fatigue Syndrome - Cleveland Clinic]</ref><ref>[https://www.ncbi.nlm.nih.gov/pubmed/26475444/ Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. - PubMed]</ref> It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26604026 Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. RA Underhill - PubMed]</ref><ref>[http://www.nature.com/tp/journal/v6/n2/full/tp2015208a.html Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome]</ref> Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of [[autoimmune disease]].<ref>[https://www.facebook.com/permalink.php?story_fbid=564532390371988&id=564526123705948 Klimas ME/CFS Genes Study - Face Book - Video]</ref> There is also a shift from the [[Th1]] type of helper [[T cell]]s, which fight infection, to the [[Th2]] type, which are more active in allergy and more likely to attack the body.<ref>[http://www.sciencedirect.com/science/article/pii/S1043466614006024 Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis - ScienceDirect]</ref><ref>[http://www.m-hikari.com/bmgt/bmgt2014/bmgt1-4-2014/hardcastleBMGT1-4-2014.pdf Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells - Biological Markers and Guided Therapy, Vol. 1, 2014, no. 1, 25 -38 - PDF]</ref>

===Viruses===

{{Main article | Viruses}}

Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses<ref>[https://www.ncbi.nlm.nih.gov/pubmed/2841461 Coxsackie B viruses and myalgic encephalomyelitis.]</ref><ref>[http://solvecfs.org/ramsay-research-team-5-the-potential-role-of-hhv-6-in-mecfs/ Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS]</ref> <ref>[https://www.ncbi.nlm.nih.gov/pubmed/22927850 Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.]</ref> suggests a potential viral contribution in at least some individuals. Evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

=== Bacteria ===

{{Main article | Bacteria}}

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as [[Lyme disease]]. Another bacterium that has been implicated in ME is [[Chlamydia pneumoniae]].<ref>[http://med.stanford.edu/chronicfatiguesyndrome/infections/chlamydia/chlamydia-experts.html Chlamydia Pneumoniae - Stanford Myalgic Encephalomyelitis/Chronic Fatigue syndrome Initiative]</ref> Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.<ref>[http://www.nytimes.com/health/guides/test/csf-oligoclonal-banding/overview.html CSF Oligoclonal Banding - NY Times]</ref>

The [[Vagus nerve infection hypothesis]] accounts for why so many different infectious onsets could be responsible. The vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>[http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/ People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association]</ref><ref>[http://www.redcrossblood.org/news/northcentral/american-red-cross-statement-xmrv-and-chronic-fatigue-syndrome American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross]</ref><ref>[http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html Chronic fatigue patients barred from blood donation - Washington Post - By: Rob Stein - Dec 3, 2010]</ref><ref>[http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C - NZBlood]</ref>

==Treatments==

{{Main article | Potential treatments for myalgic encephalomyelitis and chronic fatigue syndrome}}

There is no known cure for ME.

Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself.

Success of treating symptoms of ME is not well researched or documented.

Treatments being trialled include an antiviral drug called [[Ampligen]] (now approved for use on [[ME/CFS]] patients in [[Argentina]]) and an immune system modulator drug called [[Rituximab]].<ref>[http://www.prohealth.com/me-cfs/me-chronic-fatigue-syndrome-experimental-treatments.cfm Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs]</ref>

==Epidemiology==

{{Main article | Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome}}

ME has been found world-wide, in at least 75 [[Outbreaks|epidemics]] documented in published papers from the 1930s to the 1980s.<ref>[http://www.hfme.org/methemedicalfacts.htm Myalgic Encephalomyelitis: The medical facts - What causes Myalgic Encephalomyelitis? Are there outbreaks of M.E.?]</ref> Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approxmately 2-3 females for every male.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> In children the sex ratio is approximately equal.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

== Co-morbidities ==
Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions, and increased risks for secondary diseases in patients with ME. However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little that can be said definitively about the rate or underlying biological reasons for these potentially related conditions. Overlapping diagnostic criteria and the lack of a biomarker in many of these conditions add to the confusion and diagnostic uncertainty. Moreover, certain conditions such as [[postural orthostatic tachycardia syndrome]] (POTS) and [[idiopathic intracranial hypertension|intracranial hypertension]] (IIH) are symptoms that can occur in or be co-morbid with numerous conditions, including ME.

The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[fibromyalgia]]
*[[Chronic lyme disease|chronic Lyme disease]]
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]
*[[mast cell activation disorder]]
*[[small intestinal bacterial overgrowth]] (SIBO)
*[[thyroid disease]]
*[[Ehlers-Danlos syndrome]]
*[[endometriosis]]
*[[Sjögren's syndrome]]
*[[mold illness]]
*[[multiple chemical sensitivity]]
*[[environmentally acquired illness]]
*[[chronic inflammatory response syndrome]]
*[[cancer]]
*[[idiopathic intracranial hypertension]]
*[[Chiari malformation]]
*[[craniocervical instability]]
*See more [[:Category:Diagnoses|diagnoses]].

</div>

== See also ==

*[[Pediatric|Pediatric myalgic encephalomyelitis]]
*[[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]

== References ==

[[Category:Diagnoses]]
[[Category:Disease names]]
<references />

Myalgic encephalomyelitis

2018-08-12T02:37:21Z

Alvin:added some sentences and some references

'''Myalgic Encephalomyelitis''' (ME) is a chronic, [[inflammatory]], physically and [[neurological|neurologically]] disabling disease that is progressive and multi-systemic. Frequently triggered by a [[viral infection]], it affects the [[central nervous system]] (CNS), [[immune system]], [[cardiovascular system]], [[endocrine system]], and [[musculoskeletal system]].<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref><ref>[http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF]</ref> It has been classified by the [[World Health Organization]] (WHO) as a neurological disease since 1969<ref>[https://en.wikipedia.org/wiki/History_of_chronic_fatigue_syndrome#International_classifications History of chronic fatigue syndrome - International Classifications]</ref><ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper - PDF]</ref> and has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic forms since at least the 1930s, although has likely been around for much longer before being classified as a distinct disease.

A hallmark symptom of ME is [[Post-exertional malaise|Post-Exertional Malaise]] (PEM), which is an intolerance to previously achievable cognitive or physical effort.<ref name=":0">[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - NIH]</ref><ref name=":1">[http://www.meactionuk.org.uk/definition.html Research Descriptions of M.E. - ME Action UK]</ref><ref name=":2">[http://www.cfids-me.org/ramsay86.html The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986]</ref><ref name=":3">[https://www.verywell.com/what-is-post-exertional-malaise-716023 What Is Post-exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":4">[https://www.verywell.com/post-exertional-malaise-715670 Post Exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":5">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Web MD]</ref><ref name=":6">[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf PEM Series - Solve ME/CFS - Jenny Spotila]</ref> Other key symptoms include [[muscle]] [[Muscle weakness|weakness]] and easy [[Muscle fatigability|fatiguability]], [[sleep disturbance]], and [[cognitive dysfunction]]. [[Autonomic nervous system]] dysfunction is frequent, although specific symptoms vary from patient to patient and may include [[Postural orthostatic tachycardia syndrome|postural orthostatic tachycardia]], [[Orthostatic intolerance|orthostatic hypotension]], [[cold intolerance]] and [[heat intolerance]]. Other common symptoms include [[myalgia]] (muscle pain), [[neuralgia]] (neuropathic pain), neck and spine stiffness, and sensory symptoms including [[sensitivity to light]], sound, [[touch]], [[Paresthesia|paraesthesia]] (skin tingling or numbness) and hyperaesthesia (skin sensitivity and pain).

Among adults, ME is more common in women than men. New onset has been observed in children and in adults as old as 80 years old. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or 'crashes') or accruing over time.<ref>[http://www.medscape.com/viewarticle/871482 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape]</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>[http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report]</ref>

There are no approved pharmacological treatments for ME/CFS though [[Argentina]] has approved [[Ampligen]] for the treatment of [[chronic fatigue syndrome]]. However the evidence for the effectiveness of Ampligen is under dispute<ref>{{Cite web|url=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|title=https://www.bizjournals.com/philadelphia/stories/2009/11/30/daily23.html|website=www.bizjournals.com|access-date=2018-08-12}}</ref>. Other off label medications have been used with varying effectiveness.<ref>{{Cite web|url=https://www.me-pedia.org/wiki/Valganciclovir|title=Valganciclovir - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref><ref>{{Cite web|url=https://www.me-pedia.org/wiki/Oxymatrine|title=Oxymatrine - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

== History ==

{{Main article | History of myalgic encephalomyelitis and chronic fatigue syndrome}}

ME has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic form since at least the 1930s, although is probably much older. The first recorded outbreak of epidemic myalgic encephalomyelitis was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical [[polio]]. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called 'Akureyri Disease' or [[Icelandic disease]] through much of the 1940s and 1950s. It was named [[Myalgic Encephalomyelitis|myalgic encephalomyelitis]] after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[Chronic Fatigue Syndrome]]. The most recent was putative outbreak was in Arizona in 1996.

==Disease Name==

{{Main article | Names of myalgic encephalomyelitis and chronic fatigue syndrome}}

The name myalgic encephalomyelitis was coined by Dr. [[Melvin Ramsay]] following the [[1955 Royal Free Hospital outbreak]]<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/ An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 - The Medical Staff Of The Royal Free Hospital]</ref> and is a portmanteau of several of the key signs and symptoms of the disease: myalgic ([[muscle pain]]), encephalo ([[brain]]), myel ([[spinal cord]]), itis ([[inflammation]]).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref>

Several other names have been used or proposed throughout the history of the disease, including [[atypical polio]], [[Icelandic disease]], benign myalgic encephalomyelitis, [[epidemic neuromyasthenia]], [[chronic fatigue syndrome]], and [[systemic exertion intolerance disease]]. This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|case definitions]].

A survey by [[The MEAction Network]] in 2016 found that the majority of patients prefer the name myalgic encephalomyelitis to other names including [[Chronic Fatigue Syndrome|chronic fatigue syndrome]].<ref>[http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/ MEAction RFI Poll Report (Part 1 of 3)]</ref> Most government agencies and researchers around the world use the term [[ME/CFS]].{{Citation needed}}

== Onset ==
Following after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever. In the majority but not all cases, an infection or infectious process is evident.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref> Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the [[central nervous system]]. It is this second phase, persistent phase that is most ME.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref>

In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In others, an apparent remission was followed by relapses brought on by exertion, [[menstrual period]], or cold.
==Signs and Symptoms==

Symptoms can range from mild to very severe and can include:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*low-grade fever, temperature instability
*[[post-exertional malaise]]
*[[Cognitive dysfunction]]
*[[muscle]] [[Muscle weakness|weakness]] and [[Muscle fatigability|fatiguability]]
*[[Headache]]
*[[myalgia|myalgia (muscle pain)]]
*[[neuralgia|neuralgia (nerve pain)]]
*[[ataxia|ataxia (coordination difficulties)]]
*[[gastrointestinal]] symptoms
*[[sleep dysfunction]]
*neck and back or spinal cord stiffness
*sensitivity to light, sound and/or touch
*sensitivity to heat or cold

</div>

Symptoms presentation and severity can vary considerably day to day and even hour to hour.<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> Overexertion can make all symptoms worse, the effects are often delayed and may not be seen within 24 hours.<ref>[http://www.investinme.org/landerP5.shtml What is ME - Invest in ME Research]</ref> <ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> The US [[National Institutes of Health]] notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.<ref>[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic encephalomyelitis/Chronic Fatigue Syndrome]</ref>

The severity of a patient's symptoms often depends on the time period since the disease was contacted and rate of progression of each patient. The rate of progression can be accelerated by physical or cognitive activity beyond a patient's limits, which typically entails anaerobic activity <ref>{{Cite web|url=https://www.me-pedia.org/wiki/Unrest|title=Unrest - MEpedia|website=www.me-pedia.org|language=en|access-date=2018-08-12}}</ref>

=== Post-exertional malaise ===
{{Main article | Post-exertional malaise}}
A core symptom, [[Post-exertional malaise]], is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":5" /><ref name=":6" />

== Clinical Findings ==
Although there is no definitive [[biomarker]], several signs and findings have been frequently observed in clinical settings:<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*reaction to physical and mental activity and sensory input
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]]
*[[Hormones|hormone]] imbalance
*[[Immune system|immunological abnormalities]]
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]
*high titers to specific infection
*low red blood cell [[magnesium]]

</div>
==Diagnosis==

{{Main article | Definitions of myalgic encephalomyelitis and chronic fatigue syndrome}}

There are several proposed criteria for diagnosing ME including the [[International Consensus Criteria]] (ICC) and the [[Canadian Consensus Criteria]] (CCC). The original criteria developed by [[Melvin Ramsay]], the [[Ramsay definition]], is not used for diagnosing ME today.

=== Other diagnostic criteria ===
Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on [[Epidemic myalgic encephalomyelitis|epidemic ME]], exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's [[Oxford criteria]] is the broadest and likely most heterogenous definition. (The US [[Institute of Medicine report]] called for its complete retirement<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]</ref>). The US [[Centers for Disease Control and Prevention|Centers for Disease Control]]'s [[Fukuda criteria]], in use since 1994, is also overly broad.

===Differential diagnosis===
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], lupus, [[brucellosis]], or another condition."<ref>[https://www.dartmouth-hitchcock.org/medical-information/health_encyclopedia/nord792 Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.]</ref> Additional testing may be needed to help distinguish ME from these other problems.

==Course and Prognosis ==
ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, influenza and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

"The later course of ME is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

==Clinical Subtypes==
There are no standard subtypes. Some researchers and clinicians have proposed distinguishing between a relapsing-remitting and progressive course.{{Citation needed}} However, it is difficult to distinguish between natural variation in the population of ME patients who might share a common disease process but owing to individual, genetic, or environmental differences, have different symptom clusters or disease course versus heterogeneity created by imprecise criteria and misdiagnosis.<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:<ref>[http://me-ireland.com/genes2.pdf Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes - JCP Online]</ref>

* Subtype 1 This is one of the more severe subtypes. Effects are cognitive, musculoskeletal, sleep-related and anxiety/depression.

* Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.

* Subtype 3 This subtype has the mildest symptoms.

* Subtype 4 This subtype is dominated by cognitive issues.

* Subtype 5 Effects are musculoskeletal and gastrointestinal.

* Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after exercise or exertion.)

* Subtype 7 This is one of the more severe subtypes. Effects are pain, infections, musculoskeletal, sleep-related, neurological, gastrointestinal, neurocognitive and anxiety/depression.

==Pathophysiology==
{{Main article | List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis}}

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

=== Central nervous system ===
{{Main article |Central nervous system}}Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, some research stated that a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.

=== Autonomic nervous system ===
{{Main article |Autonomic nervous system}}

=== Peripheral nervous system ===
{{Main article |Peripheral nervous system}}

=== Musculoskeletal system ===
{{Main article |Muscle}}

=== Immune system ===
{{Main article |Immune system}}

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as [[RNase L|Rnase-L]]. [[Channelopathy]], a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.

=== Chronic infection ===
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the post-polio syndrome?].

=== Cardiovascular ===
Hemodynamic abnormalities are widely found, including serum and RBC hypovolemia, NMH, and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr Paul Cheney to posit that CFS is form of partially compensated cardiomyopathy in which [[orthostatic intolerance]] and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with Holter monitors.

=== Gastrointestinal system ===
{{Main article |Gastrointestinal system}}

== Sex Differences ==
{{Main article | Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome}}
A Norwegian [[CFS/ME]] study shows that the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> Research by the [[Open Medicine Foundation]] cited in its paper, [[Metabolic features of chronic fatigue syndrome]] which studied severe [[CFS]], found that the disease is different in men and women but this is not related to testosterone or estrogen. [[Michael VanElzakker]] notes there are [http://me-pedia.org/wiki/Michael_VanElzakker#Male_and_female_differences_in_neuropathic_pain male and female differences in neuropathic pain]. A study of UK and Dutch cohorts found "younger children had a more equal gender balance compared to adolescents and adults."<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

==Risk Factors and Potential Causes==

{{Main article | Risk factors and potential causes of myalgic encephalomyelitis and chronic fatigue syndrome}}

===Risk factors===

===Potential causes===

Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.<ref>[http://via.library.depaul.edu/csh_etd/117/ Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach - Meredyth Evans - DePaul University]</ref><ref>[http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis Vagus nerve infection hypothesis - MEpedia]</ref><ref>[http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/chronic-fatigue/case3.htm Chronic Fatigue Syndrome - Cleveland Clinic]</ref><ref>[https://www.ncbi.nlm.nih.gov/pubmed/26475444/ Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. - PubMed]</ref> It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26604026 Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. RA Underhill - PubMed]</ref><ref>[http://www.nature.com/tp/journal/v6/n2/full/tp2015208a.html Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome]</ref> Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of [[autoimmune disease]].<ref>[https://www.facebook.com/permalink.php?story_fbid=564532390371988&id=564526123705948 Klimas ME/CFS Genes Study - Face Book - Video]</ref> There is also a shift from the [[Th1]] type of helper [[T cell]]s, which fight infection, to the [[Th2]] type, which are more active in allergy and more likely to attack the body.<ref>[http://www.sciencedirect.com/science/article/pii/S1043466614006024 Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis - ScienceDirect]</ref><ref>[http://www.m-hikari.com/bmgt/bmgt2014/bmgt1-4-2014/hardcastleBMGT1-4-2014.pdf Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells - Biological Markers and Guided Therapy, Vol. 1, 2014, no. 1, 25 -38 - PDF]</ref>

===Viruses===

{{Main article | Viruses}}

Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses<ref>[https://www.ncbi.nlm.nih.gov/pubmed/2841461 Coxsackie B viruses and myalgic encephalomyelitis.]</ref><ref>[http://solvecfs.org/ramsay-research-team-5-the-potential-role-of-hhv-6-in-mecfs/ Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS]</ref> <ref>[https://www.ncbi.nlm.nih.gov/pubmed/22927850 Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.]</ref> suggests a potential viral contribution in at least some individuals. Evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

=== Bacteria ===

{{Main article | Bacteria}}

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as [[Lyme disease]]. Another bacterium that has been implicated in ME is [[Chlamydia pneumoniae]].<ref>[http://med.stanford.edu/chronicfatiguesyndrome/infections/chlamydia/chlamydia-experts.html Chlamydia Pneumoniae - Stanford Myalgic Encephalomyelitis/Chronic Fatigue syndrome Initiative]</ref> Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.<ref>[http://www.nytimes.com/health/guides/test/csf-oligoclonal-banding/overview.html CSF Oligoclonal Banding - NY Times]</ref>

The [[Vagus nerve infection hypothesis]] accounts for why so many different infectious onsets could be responsible. The vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>[http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/ People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association]</ref><ref>[http://www.redcrossblood.org/news/northcentral/american-red-cross-statement-xmrv-and-chronic-fatigue-syndrome American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross]</ref><ref>[http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html Chronic fatigue patients barred from blood donation - Washington Post - By: Rob Stein - Dec 3, 2010]</ref><ref>[http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C - NZBlood]</ref>

==Treatments==

{{Main article | Potential treatments for myalgic encephalomyelitis and chronic fatigue syndrome}}

There is no known cure for ME.

Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself.

Success of treating symptoms of ME is not well researched or documented.

Treatments being trialled include an antiviral drug called [[Ampligen]] (now approved for use on [[ME/CFS]] patients in [[Argentina]]) and an immune system modulator drug called [[Rituximab]].<ref>[http://www.prohealth.com/me-cfs/me-chronic-fatigue-syndrome-experimental-treatments.cfm Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs]</ref>

==Epidemiology==

{{Main article | Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome}}

ME has been found world-wide, in at least 75 [[Outbreaks|epidemics]] documented in published papers from the 1930s to the 1980s.<ref>[http://www.hfme.org/methemedicalfacts.htm Myalgic Encephalomyelitis: The medical facts - What causes Myalgic Encephalomyelitis? Are there outbreaks of M.E.?]</ref> Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approxmately 2-3 females for every male.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> In children the sex ratio is approximately equal.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

== Co-morbidities ==
Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions, and increased risks for secondary diseases in patients with ME. However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little that can be said definitively about the rate or underlying biological reasons for these potentially related conditions. Overlapping diagnostic criteria and the lack of a biomarker in many of these conditions add to the confusion and diagnostic uncertainty. Moreover, certain conditions such as [[postural orthostatic tachycardia syndrome]] (POTS) and [[idiopathic intracranial hypertension|intracranial hypertension]] (IIH) are symptoms that can occur in or be co-morbid with numerous conditions, including ME.

The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[fibromyalgia]]
*[[Chronic lyme disease|chronic Lyme disease]]
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]
*[[mast cell activation disorder]]
*[[small intestinal bacterial overgrowth]] (SIBO)
*[[thyroid disease]]
*[[Ehlers-Danlos syndrome]]
*[[endometriosis]]
*[[Sjögren's syndrome]]
*[[mold illness]]
*[[multiple chemical sensitivity]]
*[[environmentally acquired illness]]
*[[chronic inflammatory response syndrome]]
*[[cancer]]
*[[idiopathic intracranial hypertension]]
*[[Chiari malformation]]
*[[craniocervical instability]]
*See more [[:Category:Diagnoses|diagnoses]].

</div>

== See also ==

*[[Pediatric|Pediatric myalgic encephalomyelitis]]
*[[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]

== References ==

[[Category:Diagnoses]]
[[Category:Disease names]]
<references />

Myalgic encephalomyelitis

2018-08-12T00:57:05Z

Alvin:

'''Myalgic Encephalomyelitis''' (ME) is a chronic, [[inflammatory]], physically and [[neurological|neurologically]] disabling disease that is progressive and multi-systemic. Frequently triggered by a [[viral infection]], it affects the [[central nervous system]] (CNS), [[immune system]], [[cardiovascular system]], [[endocrine system]], and [[musculoskeletal system]].<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref><ref>[http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF]</ref> It has been classified by the [[World Health Organization]] (WHO) as a neurological disease since 1969<ref>[https://en.wikipedia.org/wiki/History_of_chronic_fatigue_syndrome#International_classifications History of chronic fatigue syndrome - International Classifications]</ref><ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper - PDF]</ref> and has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic form since at least the 1930s, although has likely been around for much longer before being classified as a distinct disease.

A hallmark symptom of ME is [[Post-exertional malaise|Post-Exertional Malaise]] (PEM), which is an intolerance to previously achievable cognitive or physical effort.<ref name=":0">[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - NIH]</ref><ref name=":1">[http://www.meactionuk.org.uk/definition.html Research Descriptions of M.E. - ME Action UK]</ref><ref name=":2">[http://www.cfids-me.org/ramsay86.html The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986]</ref><ref name=":3">[https://www.verywell.com/what-is-post-exertional-malaise-716023 What Is Post-exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":4">[https://www.verywell.com/post-exertional-malaise-715670 Post Exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref name=":5">[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Web MD]</ref><ref name=":6">[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf PEM Series - Solve ME/CFS - Jenny Spotila]</ref> Other key symptoms include [[muscle]] [[Muscle weakness|weakness]] and [[Muscle fatigability|fatiguability]], [[sleep disturbance]], and [[cognitive dysfunction]]. [[Autonomic nervous system]] dysfunction is frequent, although specific symptoms vary from patient to patient and may include [[Postural orthostatic tachycardia syndrome|postural orthostatic tachycardia]], [[Orthostatic intolerance|orthostatic hypotension]], [[cold intolerance]] and [[heat intolerance]]. Other common symptoms include [[myalgia]] (muscle pain), [[neuralgia]] (neuropathic pain), neck and spine stiffness, and sensory symptoms including [[sensitivity to light]], sound, [[touch]], [[Paresthesia|paraesthesia]] (skin tingling or numbness) and hyperaesthesia (skin sensitivity and pain).

Among adults, ME is more common in women than men. New onset has been observed in children and in adults as old as 80 years old. Its course is usually relapsing-remitting with new symptoms occurring either in discrete relapses (or 'crashes') or accruing over time.<ref>[http://www.medscape.com/viewarticle/871482 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape]</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>[http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report]</ref>

There are no approved pharmacological treatments in any country except for [[Argentina]], which has approved [[Ampligen]] for the treatment of [[chronic fatigue syndrome]]. The evidence for the effectiveness of Ampligen is under dispute.

== History ==

{{Main article | History of myalgic encephalomyelitis and chronic fatigue syndrome}}

ME has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and sporadic form since at least the 1930s, although is probably much older. The first recorded outbreak of epidemic myalgic encephalomyelitis was in [[1934 Los Angeles atypical polio outbreak|1934 in Los Angeles]] and was thought to be an outbreak of atypical [[polio]]. After the outbreak in [[Akureyri]], Iceland in 1946, the disease came to be called 'Akureyri Disease' or [[Icelandic disease]] through much of the 1940s and 1950s. It was named [[Myalgic Encephalomyelitis|myalgic encephalomyelitis]] after London's [[Royal Free Hospital outbreak]] in 1955. Other names included benign myalgic encephalomyelitis and epidemic neuromyasthenia.

After the [[1984 Incline Village chronic fatigue syndrome outbreak|Incline Village]] outbreak in Nevada in 1984, the disease came to be called and redefined as [[Chronic Fatigue Syndrome]]. The most recent was putative outbreak was in Arizona in 1996.

==Disease Name==

{{Main article | Names of myalgic encephalomyelitis and chronic fatigue syndrome}}

The name myalgic encephalomyelitis was coined by Dr. [[Melvin Ramsay]] following the [[1955 Royal Free Hospital outbreak]]<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1962472/ An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955 - The Medical Staff Of The Royal Free Hospital]</ref> and is a portmanteau of several of the key signs and symptoms of the disease: myalgic ([[muscle pain]]), encephalo ([[brain]]), myel ([[spinal cord]]), itis ([[inflammation]]).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref>

Several other names have been used or proposed throughout the history of the disease, including [[atypical polio]], [[Icelandic disease]], benign myalgic encephalomyelitis, [[epidemic neuromyasthenia]], [[chronic fatigue syndrome]], and [[systemic exertion intolerance disease]]. This has lead to much confusion as a variety of names have been used at different times to describe discrete outbreaks as well as a larger and potentially more heterogenous population of sporadic cases, defined by a wide variety of [[Definitions of myalgic encephalomyelitis and chronic fatigue syndrome|case definitions]].

A survey by [[The MEAction Network]] in 2016 found that the majority of patients prefer the name myalgic encephalomyelitis to other names including [[Chronic Fatigue Syndrome|chronic fatigue syndrome]].<ref>[http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/ MEAction RFI Poll Report (Part 1 of 3)]</ref> Most government agencies and researchers around the world use the term [[ME/CFS]].{{Citation needed}}

== Onset ==
Following after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever. In the majority but not all cases, an infection or infectious process is evident.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref> Two to seven days later, a chronic phase commences, characterized by a measurable diffuse change in the function of the [[central nervous system]]. It is this second phase, persistent phase that is most ME.<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref>

In some patients, the initial presentation involved a severe, incapacitating prolonged illness. In others, an apparent remission was followed by relapses brought on by exertion, [[menstrual period]], or cold.
==Signs and Symptoms==

Symptoms can range from mild to very severe and can include:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*low-grade fever, temperature instability
*[[post-exertional malaise]]
*[[Cognitive dysfunction]]
*[[muscle]] [[Muscle weakness|weakness]] and [[Muscle fatigability|fatiguability]]
*[[Headache]]
*[[myalgia|myalgia (muscle pain)]]
*[[neuralgia|neuralgia (nerve pain)]]
*[[ataxia|ataxia (coordination difficulties)]]
*[[gastrointestinal]] symptoms
*[[sleep dysfunction]]
*neck and back or spinal cord stiffness
*sensitivity to light, sound and/or touch
*sensitivity to heat or cold

</div>

Symptoms presentation and severity can vary considerably day to day and even hour to hour.<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> Overexertion can make all symptoms worse, the effects are often delayed and may not be seen within 24 hours.<ref>[http://www.investinme.org/landerP5.shtml What is ME - Invest in ME Research]</ref> <ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> The US [[National Institutes of Health]] notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.<ref>[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic encephalomyelitis/Chronic Fatigue Syndrome]</ref>

=== Post-exertional malaise ===
{{Main article | Post-exertional malaise}}
A core symptom, [[Post-exertional malaise]], is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":5" /><ref name=":6" />

== Clinical Findings ==
Although there is no definitive [[biomarker]], several signs and findings have been frequently observed in clinical settings:<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">

*reaction to physical and mental activity and sensory input
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]]
*[[Hormones|hormone]] imbalance
*[[Immune system|immunological abnormalities]]
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]
*high titers to specific infection
*low red blood cell [[magnesium]]

</div>
==Diagnosis==

{{Main article | Definitions of myalgic encephalomyelitis and chronic fatigue syndrome}}

There are several proposed criteria for diagnosing ME including the [[International Consensus Criteria]] (ICC) and the [[Canadian Consensus Criteria]] (CCC). The original criteria developed by [[Melvin Ramsay]], the [[Ramsay definition]], is not used for diagnosing ME today.

=== Other diagnostic criteria ===
Several, overly broad criteria have been proposed and are in use. These criteria likely capture some patients with the disease characterized in the medical literature on [[Epidemic myalgic encephalomyelitis|epidemic ME]], exclude others, and also include patients with a wide range of other undiagnosed conditions including cancer, depression, and a range of autoimmune diseases. The United Kingdom's [[Oxford criteria]] is the broadest and likely most heterogenous definition. (The US [[Institute of Medicine report]] called for its complete retirement<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]</ref>). The US [[Centers for Disease Control and Prevention|Centers for Disease Control]]'s [[Fukuda criteria]], in use since 1994, is also overly broad.

===Differential diagnosis===
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], lupus, [[brucellosis]], or another condition."<ref>[https://www.dartmouth-hitchcock.org/medical-information/health_encyclopedia/nord792 Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.]</ref> Additional testing may be needed to help distinguish ME from these other problems.

==Course and Prognosis ==
ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, influenza and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

"The later course of ME is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

==Clinical Subtypes==
There are no standard subtypes. Some researchers and clinicians have proposed distinguishing between a relapsing-remitting and progressive course.{{Citation needed}} However, it is difficult to distinguish between natural variation in the population of ME patients who might share a common disease process but owing to individual, genetic, or environmental differences, have different symptom clusters or disease course versus heterogeneity created by imprecise criteria and misdiagnosis.<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>

Kerr et al proposed 7 different subsets for 'CFS' as it is defined today:<ref>[http://me-ireland.com/genes2.pdf Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes - JCP Online]</ref>

* Subtype 1 This is one of the more severe subtypes. Effects are cognitive, musculoskeletal, sleep-related and anxiety/depression.

* Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.

* Subtype 3 This subtype has the mildest symptoms.

* Subtype 4 This subtype is dominated by cognitive issues.

* Subtype 5 Effects are musculoskeletal and gastrointestinal.

* Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after exercise or exertion.)

* Subtype 7 This is one of the more severe subtypes. Effects are pain, infections, musculoskeletal, sleep-related, neurological, gastrointestinal, neurocognitive and anxiety/depression.

==Pathophysiology==
{{Main article | List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis}}

ME is a multi-system disease. Numerous biological abnormalities have been found in multiple bodily system, however no common, central cause or mechanism has yet been elucidated.

=== Central nervous system ===
{{Main article |Central nervous system}}Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, some research stated that a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.

=== Autonomic nervous system ===
{{Main article |Autonomic nervous system}}

=== Peripheral nervous system ===
{{Main article |Peripheral nervous system}}

=== Musculoskeletal system ===
{{Main article |Muscle}}

=== Immune system ===
{{Main article |Immune system}}

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as [[RNase L|Rnase-L]]. [[Channelopathy]], a reduced ability to move metabolites in and out of cells has been implicated in this process. This may also be applicable to ME.

=== Chronic infection ===
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the post-polio syndrome?].

=== Cardiovascular ===
Hemodynamic abnormalities are widely found, including serum and RBC hypovolemia, NMH, and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr Paul Cheney to posit that CFS is form of partially compensated cardiomyopathy in which [[orthostatic intolerance]] and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with Holter monitors.

=== Gastrointestinal system ===
{{Main article |Gastrointestinal system}}

== Sex Differences ==
{{Main article | Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome}}
A Norwegian [[CFS/ME]] study shows that the disease affects all ages, with two peak ages of 10-19 years and 30-39 years; it is more common in women than in men.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> Research by the [[Open Medicine Foundation]] cited in its paper, [[Metabolic features of chronic fatigue syndrome]] which studied severe [[CFS]], found that the disease is different in men and women but this is not related to testosterone or estrogen. [[Michael VanElzakker]] notes there are [http://me-pedia.org/wiki/Michael_VanElzakker#Male_and_female_differences_in_neuropathic_pain male and female differences in neuropathic pain]. A study of UK and Dutch cohorts found "younger children had a more equal gender balance compared to adolescents and adults."<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

==Risk Factors and Potential Causes==

{{Main article | Risk factors and potential causes of myalgic encephalomyelitis and chronic fatigue syndrome}}

===Risk factors===

===Potential causes===

Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.<ref>[http://via.library.depaul.edu/csh_etd/117/ Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach - Meredyth Evans - DePaul University]</ref><ref>[http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis Vagus nerve infection hypothesis - MEpedia]</ref><ref>[http://www.clevelandclinicmeded.com/online/casebased/decisionmaking/chronic-fatigue/case3.htm Chronic Fatigue Syndrome - Cleveland Clinic]</ref><ref>[https://www.ncbi.nlm.nih.gov/pubmed/26475444/ Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. - PubMed]</ref> It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26604026 Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. RA Underhill - PubMed]</ref><ref>[http://www.nature.com/tp/journal/v6/n2/full/tp2015208a.html Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome]</ref> Several theories suggest that ME is an inappropriate immune response to an infection, a theory bolstered by the observation that there is sometimes a family history of [[autoimmune disease]].<ref>[https://www.facebook.com/permalink.php?story_fbid=564532390371988&id=564526123705948 Klimas ME/CFS Genes Study - Face Book - Video]</ref> There is also a shift from the [[Th1]] type of helper [[T cell]]s, which fight infection, to the [[Th2]] type, which are more active in allergy and more likely to attack the body.<ref>[http://www.sciencedirect.com/science/article/pii/S1043466614006024 Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis - ScienceDirect]</ref><ref>[http://www.m-hikari.com/bmgt/bmgt2014/bmgt1-4-2014/hardcastleBMGT1-4-2014.pdf Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells - Biological Markers and Guided Therapy, Vol. 1, 2014, no. 1, 25 -38 - PDF]</ref>

===Viruses===

{{Main article | Viruses}}

Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses<ref>[https://www.ncbi.nlm.nih.gov/pubmed/2841461 Coxsackie B viruses and myalgic encephalomyelitis.]</ref><ref>[http://solvecfs.org/ramsay-research-team-5-the-potential-role-of-hhv-6-in-mecfs/ Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS]</ref> <ref>[https://www.ncbi.nlm.nih.gov/pubmed/22927850 Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.]</ref> suggests a potential viral contribution in at least some individuals. Evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.

=== Bacteria ===

{{Main article | Bacteria}}

Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as [[Lyme disease]]. Another bacterium that has been implicated in ME is [[Chlamydia pneumoniae]].<ref>[http://med.stanford.edu/chronicfatiguesyndrome/infections/chlamydia/chlamydia-experts.html Chlamydia Pneumoniae - Stanford Myalgic Encephalomyelitis/Chronic Fatigue syndrome Initiative]</ref> Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.<ref>[http://www.nytimes.com/health/guides/test/csf-oligoclonal-banding/overview.html CSF Oligoclonal Banding - NY Times]</ref>

The [[Vagus nerve infection hypothesis]] accounts for why so many different infectious onsets could be responsible. The vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.

Given the uncertainty regarding the cause, ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>[http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/ People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association]</ref><ref>[http://www.redcrossblood.org/news/northcentral/american-red-cross-statement-xmrv-and-chronic-fatigue-syndrome American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross]</ref><ref>[http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html Chronic fatigue patients barred from blood donation - Washington Post - By: Rob Stein - Dec 3, 2010]</ref><ref>[http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C - NZBlood]</ref>

==Treatments==

{{Main article | Potential treatments for myalgic encephalomyelitis and chronic fatigue syndrome}}

There is no known cure for ME.

Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself.

Success of treating symptoms of ME is not well researched or documented.

Treatments being trialled include an antiviral drug called [[Ampligen]] (now approved for use on [[ME/CFS]] patients in [[Argentina]]) and an immune system modulator drug called [[Rituximab]].<ref>[http://www.prohealth.com/me-cfs/me-chronic-fatigue-syndrome-experimental-treatments.cfm Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs]</ref>

==Epidemiology==

{{Main article | Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome}}

ME has been found world-wide, in at least 75 [[Outbreaks|epidemics]] documented in published papers from the 1930s to the 1980s.<ref>[http://www.hfme.org/methemedicalfacts.htm Myalgic Encephalomyelitis: The medical facts - What causes Myalgic Encephalomyelitis? Are there outbreaks of M.E.?]</ref> Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approxmately 2-3 females for every male.<ref>[http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0167-5 Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine]</ref> In children the sex ratio is approximately equal.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/26510728 Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed]</ref>

== Co-morbidities ==
Clinicians have observed several predisposing conditions, co-morbidities, overlapping conditions, and increased risks for secondary diseases in patients with ME. However, as no large-scale epidemiological studies, genetic studies, or family studies have been done, there is little that can be said definitively about the rate or underlying biological reasons for these potentially related conditions. Overlapping diagnostic criteria and the lack of a biomarker in many of these conditions add to the confusion and diagnostic uncertainty. Moreover, certain conditions such as [[postural orthostatic tachycardia syndrome]] (POTS) and [[idiopathic intracranial hypertension|intracranial hypertension]] (IIH) are symptoms that can occur in or be co-morbid with numerous conditions, including ME.

The following are some syndromes and diseases that have been associated with or misdiagnosed as ME:

<div style="column-count:2;-moz-column-count:2;-webkit-column-count:2">
*[[fibromyalgia]]
*[[Chronic lyme disease|chronic Lyme disease]]
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]
*[[mast cell activation disorder]]
*[[small intestinal bacterial overgrowth]] (SIBO)
*[[thyroid disease]]
*[[Ehlers-Danlos syndrome]]
*[[endometriosis]]
*[[Sjögren's syndrome]]
*[[mold illness]]
*[[multiple chemical sensitivity]]
*[[environmentally acquired illness]]
*[[chronic inflammatory response syndrome]]
*[[cancer]]
*[[idiopathic intracranial hypertension]]
*[[Chiari malformation]]
*[[craniocervical instability]]
*See more [[:Category:Diagnoses|diagnoses]].

</div>

== See also ==

*[[Pediatric|Pediatric myalgic encephalomyelitis]]
*[[List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis]]

== References ==

[[Category:Diagnoses]]
[[Category:Disease names]]
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