Myalgic encephalomyelitis: Difference between revisions

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'''Myalgic encephalomyelitis''' (ME) is a chronic, [[Inflammation|inflammatory]], physically and [[nervous system|neurological]] and immune-mediated disease that presents with symptoms involving multiple bodily systems. It is frequently triggered by a [[viral infection]] or a [[flu-like illness]].<ref name="ICC2011primer" /><ref name="CDC-causes" /> ME presents with symptoms in the [[central nervous system]] (CNS), [[autonomic nervous system]] (ANS), [[immune system]], [[cardiovascular system]], [[endocrine system]], [[digestive system]], and [[musculoskeletal system]].<ref name="ICC2011primer" /><ref name="CDC-symptoms" />
'''Myalgic encephalomyelitis''' (ME) is a chronic, [[Inflammation|inflammatory]], physically and [[nervous system|neurological]] and immune-mediated disease that presents with symptoms involving multiple bodily systems. It is frequently triggered by a [[viral infection]] or a [[flu-like illness]].<ref name="ICC2011primer" /><ref name="CDC-causes" /> ME presents with symptoms in the [[central nervous system]] (CNS), [[autonomic nervous system]] (ANS), [[immune system]], [[cardiovascular system]], [[endocrine system]], [[digestive system]], and [[musculoskeletal system]].<ref name="ICC2011primer" /><ref name="CDC-symptoms" />


Myalgic encephalomyelitis was first classified as a [[nervous system|neurological]] disease by the [[World Health Organization]] (WHO) in 1969, with the publication of the [[World Health Organization#icd8|World Health Organization's ICD-8]] manual.<ref name="ICD-8">{{Cite book |url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf | title=Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death Based on the Recommendations of the Eighth Revision Conference | last = World Health Organization | first = |authorlink=World Health Organization|publisher=WHO|year=1969|isbn=|editor-link=|edition=8th|volume=2|location=Geneva | page = 173|chapter=|quote=Encephalomyelitis (chronic),<br>(myalgic, benign) 323}}</ref>
Myalgic encephalomyelitis was first classified as a [[nervous system|neurological]] disease by the [[World Health Organization]] (WHO) in 1969, with the publication of the [[World Health Organization#icd8|World Health Organization's ICD-8]] manual.<ref name="ICD-8">{{Cite book |url=https://apps.who.int/iris/bitstream/handle/10665/70934/ICD_10_1969_eng_v2a.pdf | title=Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death Based on the Recommendations of the Eighth Revision Conference | last = World Health Organization | first = |authorlink=World Health Organization|publisher=WHO| year = 1969|isbn=|editor-link=|edition=8th|volume=2|location=Geneva | page = 173|chapter=|quote=Encephalomyelitis (chronic),<br>(myalgic, benign) 323}}</ref>


ME has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|sporadic]] forms.
ME has occurred in both [[Epidemic myalgic encephalomyelitis|epidemic]] and [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|sporadic]] forms.


According to the [[Centers for Disease Control|CDC]] the hallmark symptom of myalglc encephalomyelitis is [[post-exertional malaise]] (PEM), which is the worsening of ME/CFS symptoms after minimal physical, mental, or emotional [[exertion|effort]].<ref name="CDC-doctors">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html | title = Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = Dec 27, 2021 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2022-03-28}}</ref><ref name="Friedman2021">{{Cite journal | title = Our Evolving Understanding of ME/CFS | date = Mar 2021|url=https://www.mdpi.com/1648-9144/57/3/200/htm|journal=Medicina|volume=57|issue=3|pages=200 | last = Friedman | first = Kenneth J.|author-link=Kenneth Friedman | last2 = Murovska |  first2 = Modra|authorlink2 = Modra Murovska|last3 = Pheby | first3 = Derek F. H. | authorlink3 = Derek Pheby | last4 = Zalewski | first4 = Paweł | authorlink4 = Paweł Zalewski|language=en|doi=10.3390/medicina57030200|pmc=|pmid=33652622|access-date=|issn=1648-9144|quote=|via=}}</ref><ref name="Carruthers, 2003" /><ref name="Speight2013">{{Cite journal|url=https://www.sjmms.net/article.asp?issn=1658-631X;year=2013;volume=1;issue=1;spage=11;epage=13;aulast=Speight | title = Myalgic encephalomyelitis/chronic fatigue syndrome: Review of history, clinical features, and controversies | last = Speight | first = Nigel|authorlink=Nigel Speight | date = 2013|pages=11-13|doi=10.4103/1658-631x.112905|archive-url=|archive-date=|url-status=|access-date=|volume=1|issue=1|journal=Saudi J Med Med Sci}}</ref><ref name="CDC-symptoms" /> Other key symptoms include [[muscle weakness]] and easy [[muscle fatigability]], [[sleep dysfunction|sleep disturbance]], plus either [[orthostatic intolerance]] or [[cognitive dysfunction]]. Orthostic intolerance is [[autonomic nervous system]] dysfunction causing the worsening of symptoms when standing or sitting upright, and may include feeling [[syncope|faint], [[dizziness]], feeling weak, [[blurred vision]], [[postural orthostatic tachycardia]] (POTS), reduced [[heart rate variability]] at night, and both [[Body temperature|cold and heat intolerance]]. Other ME/CFS common symptoms include [[myalgia|muscle pain]], [[neuralgia|nerve pain]], neck and spine stiffness, and sensory symptoms including [[sensitivity to light]], [[Hyperacusis|sound]], [[touch]], [[Paresthesia|skin tingling or numbness]] and hyperaesthesia (skin sensitivity and pain, and [[allodynia]]). There is a progressive form of ME, but it is rarer than the relapsing-remitting type.<ref name="Howes2015">{{Cite journal|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 |authorlink=Sandra Howes | last2 = Goudsmit | first2=EM |authorlink2 = Ellen Goudsmit | date = Jul 7, 2015|journal=Physical Medicine and Rehabilitation - International|volume=2|issue=6|pages=1052|doi=}}</ref>   
According to the [[Centers for Disease Control|CDC]] the hallmark symptom of myalglc encephalomyelitis is [[post-exertional malaise]] (PEM), which is the worsening of ME/CFS symptoms after minimal physical, mental, or emotional [[exertion|effort]].<ref name="CDC-doctors">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/index.html | title = Information for Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = Dec 27, 2021 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2022-03-28}}</ref><ref name="Friedman2021">{{Cite journal | title = Our Evolving Understanding of ME/CFS | date = Mar 2021|url=https://www.mdpi.com/1648-9144/57/3/200/htm|journal=Medicina|volume=57|issue=3|pages=200 | last = Friedman | first = Kenneth J. | authorlinklink=Kenneth Friedman | last2 = Murovska |  first2 = Modra | authorlink2 = Modra Murovska|last3 = Pheby | first3 = Derek F.H. | authorlink3 = Derek Pheby | last4 = Zalewski | first4 = Paweł | authorlink4 = Paweł Zalewski|language=en|doi=10.3390/medicina57030200|pmc=|pmid=33652622|access-date=|issn=1648-9144|quote=|via=}}</ref><ref name="Carruthers, 2003" /><ref name="Speight2013">{{Cite journal|url=https://www.sjmms.net/article.asp?issn=1658-631X;year=2013;volume=1;issue=1;spage=11;epage=13;aulast=Speight | title = Myalgic encephalomyelitis/chronic fatigue syndrome: Review of history, clinical features, and controversies | last = Speight | first = Nigel | authorlink=Nigel Speight | date = 2013|pages=11-13|doi=10.4103/1658-631x.112905|archive-url=|archive-date=|url-status=|access-date=|volume=1|issue=1|journal=Saudi J Med Med Sci}}</ref><ref name="CDC-symptoms" /> Other key symptoms include [[muscle weakness]] and easy [[muscle fatigability]], [[sleep dysfunction|sleep disturbance]], plus either [[orthostatic intolerance]] or [[cognitive dysfunction]]. Orthostic intolerance is [[autonomic nervous system]] dysfunction causing the worsening of symptoms when standing or sitting upright, and may include feeling [[syncope|faint], [[dizziness]], feeling weak, [[blurred vision]], [[postural orthostatic tachycardia]] (POTS), reduced [[heart rate variability]] at night, and both [[Body temperature|cold and heat intolerance]]. Other ME/CFS common symptoms include [[myalgia|muscle pain]], [[neuralgia|nerve pain]], neck and spine stiffness, and sensory symptoms including [[sensitivity to light]], [[Hyperacusis|sound]], [[touch]], [[Paresthesia|skin tingling or numbness]] and hyperaesthesia (skin sensitivity and pain, and [[allodynia]]). There is a progressive form of ME, but it is rarer than the relapsing-remitting type.<ref name="Howes2015">{{Cite journal|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 |authorlink=Sandra Howes | last2 = Goudsmit | first2=EM |authorlink2 = Ellen Goudsmit | date = Jul 7, 2015|journal=Physical Medicine and Rehabilitation - International|volume=2|issue=6|pages=1052|doi=}}</ref>   


Among adults, ME is [[Female predominant diseases|more common in women]] than men.<ref name="CDC-causes">{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html | title = Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-04-13}}</ref> [[Onset of ME/CFS|New onset]] has been [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|observed in children]]<ref name="CDC-children">{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html | title = ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-04-13}}</ref> and in adults usually between the ages of 40-60.<ref name="what-is">{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html | title = What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-04-13}}</ref> [[Inger Johanne Bakken|Bakken]] et. al notes two age peaks for [[CFS/ME]]; age group 10 to 19 years and a second peak in the age group 30 to 39  years.<ref name="Bakken2014">{{Cite journal | last1 = Bakken | first1 = Inger Johanne|authorlink=Inger Johanne Bakken | last2 = Tveito | first2 = Kari|last3 = Gunnes | first3=Nina | last4 = Ghaderi | first4 = Sara | last5 = Stoltenberg|first5=Camilla | last6 = Trogstad | first6 = Lill | last7 = Håberg | 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=https://doi.org/10.1186/s12916-014-0167-5|journal=BMC Medicine|volume=12|issue=1|pages=167|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmc=4189623|pmid=25274261}}</ref>  
Among adults, ME is [[Female predominant diseases|more common in women]] than men.<ref name="CDC-causes">{{Cite web|url=https://www.cdc.gov/me-cfs/about/possible-causes.html | title = Possible Causes {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-04-13}}</ref> [[Onset of ME/CFS|New onset]] has been [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|observed in children]]<ref name="CDC-children">{{Cite web|url=https://www.cdc.gov/me-cfs/me-cfs-children/index.html | title = ME/CFS in Children {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-04-13}}</ref> and in adults usually between the ages of 40-60.<ref name="what-is">{{Cite web|url=https://www.cdc.gov/me-cfs/about/index.html | title = What is ME/CFS? {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2019-01-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2019-04-13}}</ref> [[Inger Johanne Bakken|Bakken]] et. al notes two age peaks for [[CFS/ME]]; age group 10 to 19 years and a second peak in the age group 30 to 39  years.<ref name="Bakken2014">{{Cite journal | last1 = Bakken | first1 = Inger Johanne | authorlink=Inger Johanne Bakken | last2 = Tveito | first2 = Kari|last3 = Gunnes | first3=Nina | last4 = Ghaderi | first4 = Sara | last5 = Stoltenberg | first5 = Camilla | last6 = Trogstad | first6 = Lill | last7 = Håberg | 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=https://doi.org/10.1186/s12916-014-0167-5|journal=BMC Medicine|volume=12|issue=1|pages=167|doi=10.1186/s12916-014-0167-5|issn=1741-7015|pmc=4189623|pmid=25274261}}</ref>  


There are no approved pharmacological treatments for ME anywhere in the world except in [[Argentina]], which has approved the immunomodulator [[Ampligen]] (rintatolimod) for [[Severe and very severe ME|severe ME/CFS]] as of August 23, 2016.<ref name="Hemispherx">{{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 =  | last = Hemispherx Biopharma, Inc | date = Aug 23, 2016|archive-url=|archive-date=|url-status=}}</ref>[[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. Image source: [https://www.youtube.com/watch?v=Z1z5O_cgQ7I Wasteland (video)] 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.]]
There are no approved pharmacological treatments for ME anywhere in the world except in [[Argentina]], which has approved the immunomodulator [[Ampligen]] (rintatolimod) for [[Severe and very severe ME|severe ME/CFS]] as of August 23, 2016.<ref name="Hemispherx">{{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 =  | last = Hemispherx Biopharma, Inc | date = Aug 23, 2016|archive-url=|archive-date=|url-status=}}</ref>[[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. Image source: [https://www.youtube.com/watch?v=Z1z5O_cgQ7I Wasteland (video)] 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.]]
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The World Health Organization's [[World Health Organization#icd8|ICD-8]] manual did not include any alternative names for myalgic encephalomyelitis although postinfectious encephalomyelitis and all other encephalomyelitis diseases were classified under the same code; fatigue-related alternative names were not added in any later revisions.<ref name="ICD-8" /><ref name="icd10-2016">{{Cite web|url=https://icd.who.int/browse10/2016/en#/G93 | title = G93 Other diseases of the nervous system - ICD-10 Version:2016 | last = World Health Organization | first = |authorlink=World Health Organization | date = 2016 | website = World Health Organization|archive-url=|archive-date=|url-status=|access-date=2019-04-13}}</ref> The alternative name [[chronic fatigue syndrome]] (CFS) was not in use at this time; it was proposed in 1987 by the [[Centers for Disease Control]], which adopted [[Holmes criteria|new diagnostic criteria]] the following year.<ref name="IOM-full" />{{Rp|29}}
The World Health Organization's [[World Health Organization#icd8|ICD-8]] manual did not include any alternative names for myalgic encephalomyelitis although postinfectious encephalomyelitis and all other encephalomyelitis diseases were classified under the same code; fatigue-related alternative names were not added in any later revisions.<ref name="ICD-8" /><ref name="icd10-2016">{{Cite web|url=https://icd.who.int/browse10/2016/en#/G93 | title = G93 Other diseases of the nervous system - ICD-10 Version:2016 | last = World Health Organization | first = |authorlink=World Health Organization | date = 2016 | website = World Health Organization|archive-url=|archive-date=|url-status=|access-date=2019-04-13}}</ref> The alternative name [[chronic fatigue syndrome]] (CFS) was not in use at this time; it was proposed in 1987 by the [[Centers for Disease Control]], which adopted [[Holmes criteria|new diagnostic criteria]] the following year.<ref name="IOM-full" />{{Rp|29}}


In the ICD-9, which was published in 1989, the entry for myalglc encephalomyelitis is uses code 323.9:<ref name="ICD-9">{{Cite book |url=https://apps.who.int/iris/bitstream/handle/10665/40492/9241540052_eng_v2_p1.pdf?sequence=3&isAllowed=y|title =Manual of the international statistical classification of diseases, injuries, and causes of death : based on the recommendations of the ninth revision conference, 1975, and adopted by the Twenty-ninth World Health Assembly, 1975 revision: alphabetic index | first =  | last = World Health Organization & International Conference for the Ninth Revision of the International Classification of Diseases|publisher=World Health Organization |year=1978|isbn=9241540044|editor-link=|edition=9th|volume=2|location=Geneva | page = 182|chapter=|quote=}}</ref>
In the ICD-9, which was published in 1989, the entry for myalglc encephalomyelitis is uses code 323.9:<ref name="ICD-9">{{Cite book |url=https://apps.who.int/iris/bitstream/handle/10665/40492/9241540052_eng_v2_p1.pdf?sequence=3&isAllowed=y| title = Manual of the international statistical classification of diseases, injuries, and causes of death : based on the recommendations of the ninth revision conference, 1975, and adopted by the Twenty-ninth World Health Assembly, 1975 revision: alphabetic index | first =  | last = World Health Organization & International Conference for the Ninth Revision of the International Classification of Diseases|publisher=World Health Organization | year = 1978|isbn=9241540044|editor-link=|edition=9th|volume=2|location=Geneva | page = 182|chapter=|quote=}}</ref>
{{Main article | page_name =History of myalgic encephalomyelitis and chronic fatigue syndrome}}
{{Main article | page_name =History of myalgic encephalomyelitis and chronic fatigue syndrome}}


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* '''-itis''': [[Inflammation]].<ref name="Terminology" />
* '''-itis''': [[Inflammation]].<ref name="Terminology" />
The name '''myalgic encephalomyelitis''' was first used in 1956 in an article in the ''Lancet'' medical journal to describ findings from the [[1955 Royal Free Hospital outbreak]] in London, UK.<ref name="MyalgicEncephalomyelitis-first-coines">{{Cite journal|journal=Lancet|volume=1|issue= | pages = 789–790|date = 1956 | title = A new clinical entity?|url=https://mecfsj.files.wordpress.com/2019/05/lancet_e383a9e383b3e382bbe38383e383881956_me.pdf}}</ref><ref name="Terminology" /><ref name="Ramsay1965">{{Cite journal | last = Ramsay | first = A. Melvin|author-link=Melvin Ramsay|date = 1965-10-30 | title = Hysteria and “Royal Free Disease.”|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847119/|journal=British Medical Journal|volume=2|issue=5469|pages=1062|doi=|issn=0007-1447|pmc=1847119|pmid=|access-date=|quote=|via=}}</ref> The term myalgic encephalomyelitis 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 name="Terminology">{{Cite web|url=https://www.investinme.org/Article%20010-Encephalopathy%20Hooper.shtml | title = The Terminology of ME & CFS | first = Malcolm | last = Hooper |author-link=Malcolm Hooper}}</ref><ref name="Smith1989">{{Cite book | title = Understanding M.E.: The Phenomenon of Myalgic Encephalomyelitis and Acute Onset Post Viral Fatigue Syndrome | page = 20 | last = Smith | first = David G|date = 1989}}</ref> The [[central nervous system]] (brain and spinal cord) are inflamed.<ref name="Terminology"/>
The name '''myalgic encephalomyelitis''' was first used in 1956 in an article in the ''Lancet'' medical journal to describ findings from the [[1955 Royal Free Hospital outbreak]] in London, UK.<ref name="MyalgicEncephalomyelitis-first-coines">{{Cite journal | journal = Lancet|volume=1|issue= | pages = 789–790|date = 1956 | title = A new clinical entity?|url=https://mecfsj.files.wordpress.com/2019/05/lancet_e383a9e383b3e382bbe38383e383881956_me.pdf}}</ref><ref name="Terminology" /><ref name="Ramsay1965">{{Cite journal | last = Ramsay | first = A. Melvin | author-link=Melvin Ramsay|date = 1965-10-30 | title = Hysteria and “Royal Free Disease.”|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847119/|journal=British Medical Journal|volume=2|issue=5469|pages=1062|doi=|issn=0007-1447|pmc=1847119|pmid=|access-date=|quote=|via=}}</ref> The term myalgic encephalomyelitis 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 name="Terminology">{{Cite web|url=https://www.investinme.org/Article%20010-Encephalopathy%20Hooper.shtml | title = The Terminology of ME & CFS | first = Malcolm | last = Hooper | authorlink = Malcolm Hooper}}</ref><ref name="Smith1989">{{Cite book | title = Understanding M.E.: The Phenomenon of Myalgic Encephalomyelitis and Acute Onset Post Viral Fatigue Syndrome | page = 20 | last = Smith | first = David G|date = 1989}}</ref> The [[central nervous system]] (brain and spinal cord) are inflamed.<ref name="Terminology"/>
===Benign myalgic encephalomyelitis ===
===Benign myalgic encephalomyelitis ===
''Benign'' myalgic encephalomyelitis was the  term used by the [[World Health Organization]] from 1969,<ref name="ICD-8" /> with the prefix "benign" used to denote that M.E. was not fatal, the prefix benign was later dropped since M.E. can [[causes of death|cause death]], for example the deaths of [[Merryn Crofts]] and [[Sophia Mirza]].<ref name="Terminology" /><ref name="Vindication" /><ref name="ICD-11">{{Cite web|url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/569175314 | title = 8E49 Postviral fatigue syndrome {{!}} ICD-11 - Mortality and Morbidity Statistics | last = World Health Organization | first = |authorlink=World Health Organization | date = |website=World Health Organization|language=en|archive-url=|archive-date=|access-date=2022-03-19|quote='''8E49 Postviral fatigue syndrome'''<br />Other disorders of the nervous system<br />Inclusions<br/>chronic fatigue syndrome<br/>myalgic encephalomyelitis<br />Exclusions<br/>Fatigue (MG22)}}</ref>
''Benign'' myalgic encephalomyelitis was the  term used by the [[World Health Organization]] from 1969,<ref name="ICD-8" /> with the prefix "benign" used to denote that M.E. was not fatal, the prefix benign was later dropped since M.E. can [[causes of death|cause death]], for example the deaths of [[Merryn Crofts]] and [[Sophia Mirza]].<ref name="Terminology" /><ref name="Vindication" /><ref name="ICD-11">{{Cite web|url=https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/569175314 | title = 8E49 Postviral fatigue syndrome {{!}} ICD-11 - Mortality and Morbidity Statistics | last = World Health Organization | first = |authorlink=World Health Organization | date = |website=World Health Organization|language=en|archive-url=|archive-date=|access-date=2022-03-19|quote='''8E49 Postviral fatigue syndrome'''<br />Other disorders of the nervous system<br />Inclusions<br/>chronic fatigue syndrome<br/>myalgic encephalomyelitis<br />Exclusions<br/>Fatigue (MG22)}}</ref>
[[Merryn Crofts]] had [[Severe and very severe ME#verysevere|very severe ME]], was bedbound and unable to eat. Merryn weighed under six stone (84 lbs) at her death, and was just 21 years-old. Merryn's death certificate was the second in the [[United Kingdom|UK]] to attribute a death to ME.<ref name="Vindication">{{Cite web |url=https://www.bbc.co.uk/news/health-44969741 | title =  'Vindication' for woman who wanted ME on death certificate | first = Jim  | last = Taylor|publisher=BBC Radio 5 Live | date = Jul 27, 2018}}</ref>
[[Merryn Crofts]] had [[Severe and very severe ME#verysevere|very severe ME]], was bedbound and unable to eat. Merryn weighed under six stone (84 lbs) at her death, and was just 21 years-old. Merryn's death certificate was the second in the [[United Kingdom|UK]] to attribute a death to ME.<ref name="Vindication">{{Cite web |url=https://www.bbc.co.uk/news/health-44969741 | title =  'Vindication' for woman who wanted ME on death certificate | first = Jim  | last = Taylor|publisher=BBC Radio 5 Live | date = Jul 27, 2018}}</ref>
===Disease of a thousand names ===
===Disease of a thousand names ===
Myalgic Encephalomyelitis has been referred to as the ''"disease of a thousand names"''.<ref name="Bell1991">{{Cite book | last = Bell | first = David S.|authorlink=David Bell | title = Chronic Fatigue/Immune Dysfunction Syndrome. CFIDS: The disease of a thousand names|location = Lyndonville, NY|publisher=Pollard Publications | date = 1991 | url=https://books.google.com/books/about/Chronic_Fatigue_immune_Dysfunction_Syndr.html?id=QYvkugAACAAJ|archive-url=https://archive.org/details/cfidsdiseaseofth00bell|archive-date=2010-02-16}}</ref> Other names used or proposed in the history of the myalgic encephalomyelitis include [[atypical polio]], [[Icelandic disease]], benign ME, [[epidemic neuromyasthenia]], [[chronic fatigue syndrome]], [[Chronic Fatigue Immune Dysfunction Syndrome]] (CFIDS), and [[systemic exertion intolerance disease]] (SEID).<ref name="Bell1991" /><ref name="IOM-full" /> 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|diagnostic criteria]]. Some names have emphasized particular symptoms or pathology, including chronic fatigue syndrome and myalgic encephalomyelitis.<ref name="Terminology" />  
Myalgic Encephalomyelitis has been referred to as the ''"disease of a thousand names"''.<ref name="Bell1991">{{Cite book | last = Bell | first = David S.|authorlink=David Bell | title = Chronic Fatigue/Immune Dysfunction Syndrome. CFIDS: The disease of a thousand names|location = Lyndonville, NY|publisher=Pollard Publications | date = 1991 | url=https://books.google.com/books/about/Chronic_Fatigue_immune_Dysfunction_Syndr.html?id=QYvkugAACAAJ|archive-url=https://archive.org/details/cfidsdiseaseofth00bell|archive-date=2010-02-16}}</ref> Other names used or proposed in the history of the myalgic encephalomyelitis include [[atypical polio]], [[Icelandic disease]], benign ME, [[epidemic neuromyasthenia]], [[chronic fatigue syndrome]], [[Chronic Fatigue Immune Dysfunction Syndrome]] (CFIDS), and [[systemic exertion intolerance disease]] (SEID).<ref name="Bell1991" /><ref name="IOM-full" /> 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|diagnostic criteria]]. Some names have emphasized particular symptoms or pathology, including chronic fatigue syndrome and myalgic encephalomyelitis.<ref name="Terminology" />  


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>  
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 sometimes used interchangeably or with the acronym [[ME/CFS]].<ref name="Smith1989" />
Myalgic encephalomyelitis (ME) was the original name for [[chronic fatigue syndrome]] (CFS); the names are sometimes used interchangeably or with the acronym [[ME/CFS]].<ref name="Smith1989" />
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== Onset ==
== Onset ==
{{Main article |page_name =Onset of ME/CFS}}
{{Main article |page_name =Onset of ME/CFS}}
According to Dr [[Byron Hyde]], after an incubation period of 4 to 7 days, the prodromal phase generally involve a [[flu-like illness]] with [[low-grade fever]].<ref name="Evans2018" /> In the majority but not all cases, an [[infection]] or infectious process is evident.<ref name="Evans2018">{{Cite journal | last = Evans | first = Meredyth |author-link=Meredyth Evans | last2 = Jason | first2 =Leonard |authorlink2 = Leonard Jason | date = 2018 | title = Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf | journal=Research on Chronic diseases|volume=2|issue=1|pages=2-3|quote=|via=}}</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 name="Nightingale">{{Citation | title = The Nightingale Research Foundation Definition of Myalgic Encephalomyelitis (M.E.)|pages=|language=en|title-link=Nightingale Research Foundation definition | date = 2016 | publisher=IACFS/ME | last = Hyde | first = Byron|author-link=Byron Hyde|others=|oclc=|quote=|location=}}</ref><ref name="Evans2018" />
According to Dr [[Byron Hyde]], after an incubation period of 4 to 7 days, the prodromal phase generally involve a [[flu-like illness]] with [[low-grade fever]].<ref name="Evans2018" /> In the majority but not all cases, an [[infection]] or infectious process is evident.<ref name="Evans2018">{{Cite journal | last = Evans | first = Meredyth | authorlink = Meredyth Evans | last2 = Jason | first2 =Leonard |authorlink2 = Leonard Jason | date = 2018 | title = Onset patterns of chronic fatigue syndrome and myalgic encephalomyelitis|url=https://www.openaccessjournals.com/articles/Onset%20patterns%20of%20chronic%20fatigue%20syndrome%20and%20myalgic%20encephalomyelitis.pdf | journal=Research on Chronic diseases|volume=2|issue=1|pages=2-3|quote=|via=}}</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 name="Nightingale">{{Citation | title = The Nightingale Research Foundation Definition of Myalgic Encephalomyelitis (M.E.)|pages=|language=en|title-link=Nightingale Research Foundation definition | date = 2016 | publisher=IACFS/ME | last = Hyde | first = Byron | author-link=Byron Hyde|others=|oclc=|quote=|location=}}</ref><ref name="Evans2018" />


==Signs and symptoms==
==Signs and symptoms==
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*sensitivity to [[Temperature sensitivity|heat or cold]]
*sensitivity to [[Temperature sensitivity|heat or cold]]
*sensitivity to [[Light sensitivity|light]], [[Hyperacusis|sound]] and/or [[Allodynia|touch]]
*sensitivity to [[Light sensitivity|light]], [[Hyperacusis|sound]] and/or [[Allodynia|touch]]
*[[sleep dysfunction]]<ref name="ICC">{{Cite journal | last = Carruthers | first = Bruce M.|author-link=Bruce Carruthers | last2 = van de Sande |  first2 = Marjorie I.|authorlink2 = Marjorie van de Sande|last3 = De Meirleir | first3=Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Klimas | first4=Nancy G. | author-link4 = Nancy Klimas | last5 = Broderick | first5 = Gordon | author-link5 = Gordon Broderick | last6 = Mitchell | first6 = Terry | authorlink6 = Terry Mitchell | last7 = Staines | first7 = Donald | author-link7 = Donald  Staines | last8 = Powles | first8 = A. C. Peter  | authorlink8 = A C Peter Powles | last9 = Speight | first9 = Nigel | authorlink9 = Nigel Speight | last10 = Vallings | first10 = Rosamund | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = Lucinda | authorlink11 = Lucinda Bateman | last12 = Baumgarten-Austrheim | first12 = Barbara | authorlink12 = 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.1365q-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
*[[sleep dysfunction]]<ref name="ICC">{{Cite journal | last = Carruthers | first = Bruce M. | authorlinklink=Bruce Carruthers | last2 = van de Sande |  first2 = Marjorie I.|authorlink2 = Marjorie van de Sande|last3 = De Meirleir | first3=Kenny L. | authorlink3 = Kenny De Meirleir | last4 = Klimas | first4 = Nancy G. | author-link4 = Nancy Klimas | last5 = Broderick | first5 = Gordon | author-link5 = Gordon Broderick | last6 = Mitchell | first6 = Terry | authorlink6 = Terry Mitchell | last7 = Staines | first7 = Donald | author-link7 = Donald  Staines | last8 = Powles | first8 = A.C. Peter  | authorlink8 = AC Peter Powles | last9 = Speight | first9 = Nigel | authorlink9 = Nigel Speight | last10 = Vallings | first10 = Rosamund | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = Lucinda | authorlink11 = Lucinda Bateman | last12 = Baumgarten-Austrheim | first12 = Barbara | authorlink12 = 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.1365q-2796.2011.02428.x|issn=0954-6820|pmc=3427890|pmid=21777306|via=}}</ref>
</div>
</div>
[[File:ME CFS.png|alt=Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features.  - International Consensus Criteria|thumb|upright=1.6|left]]
[[File:ME CFS.png|alt=Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features.  - International Consensus Criteria|thumb|upright=1.6|left]]


Symptom presentation and [[:Category:Severity definitions|severity]] can vary considerably day to day and even hour to hour.<ref name="CDC-symptoms" /><ref name="Primer2014">{{Citation| date = 2014 |url=https://www.massmecfs.org/images/pdf/Primer_2014.pdf | title=Chronic Fatigue Syndrome Myalgic Encephalomyelitis Primer for Clinical Practitioners | last1 = ((International Association for Chronic Fatigue Syndrome / Myalgic Encephalomyelitis))|author-link=International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis | last2 = Friedberg | first2 = Fred | authorlink2 = Fred Friedberg | last3 = Bateman | first3 = Lucinda | authorlink3 = Lucinda Bateman | last4 = Bested | first4 = Alison C | authorlink4 = Alison Bested | last5 = Davenport | first5 = Todd | authorlink5 = Todd Davenport | last6 = Friedman | first6 = Kenneth J | authorlink6 = Kenneth Friedman | last7 = Gurwitt | first7 = Alan R | authorlink7 = Alan Gurwitt | last8 = Jason | first8 = Leonard A | authorlink8 = Leonard Jason | last9 = Lapp | first9 = Charles W | authorlink9 = Charles Lapp | last10 = Stevens | first10 = Staci R | authorlink10= Staci Stevens | last11 = Underhill | first11 =  Rosemary A | authorlink11 = Rosemary Underhill | last12 = Vallings | first12 = Rosamund | authorlink12 = Rosamund Vallings|location=Chicago, USA|publisher= International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis |quote=The illness can vary from mild to severe, with symptoms that may fluctuate significantly from hour to hour and day to day.}}</ref> Overexertion can exacerbate all symptoms, and [[post-exertional malaise]] is often [[Delayed onset of post-exertional symptoms|delayed by 24 hours or more]].<ref name="CDC-symptoms" /> The US [[National Institutes of Health]] (NIH) notes that sensitivity to noise, light and [[multiple chemical sensitivity|chemical]]s may force patients to withdraw from society.<ref name="P2P2016">{{Cite web|url=https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs | title = ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | last =  | first =  | date = Dec 8, 2016 | website = [[National Institutes of Health]]|access-date=2022-03-28|quote=Effects of the illness can range from moderate to debilitating, and can substantially impact everyday functioning. Routine daily activities such as cooking meals, brushing teeth, and caring for children become difficult. Additionally, sensitivity to environmental factors (e.g., noise, light, chemicals) may force many individuals with ME/CFS into seclusion or withdrawal from society.|archive-url=|archive-date=|url-status=|language=en}}</ref>
Symptom presentation and [[:Category:Severity definitions|severity]] can vary considerably day to day and even hour to hour.<ref name="CDC-symptoms" /><ref name="Primer2014">{{Citation| date = 2014 |url=https://www.massmecfs.org/images/pdf/Primer_2014.pdf | title=Chronic Fatigue Syndrome Myalgic Encephalomyelitis Primer for Clinical Practitioners | last1 = ((International Association for Chronic Fatigue Syndrome / Myalgic Encephalomyelitis))|author-link=International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis | last2 = Friedberg | first2 = Fred | authorlink2 = Fred Friedberg | last3 = Bateman | first3 = Lucinda | authorlink3 = Lucinda Bateman | last4 = Bested | first4 = Alison C | authorlink4 = Alison Bested | last5 = Davenport | first5 = Todd | authorlink5 = Todd Davenport | last6 = Friedman | first6 = Kenneth J | authorlink6 = Kenneth Friedman | last7 = Gurwitt | first7 = Alan R | authorlink7 = Alan Gurwitt | last8 = Jason | first8 = Leonard A | authorlink8 = Leonard Jason | last9 = Lapp | first9 = Charles W | authorlink9 = Charles Lapp | last10 = Stevens | first10 = Staci R | authorlink10 = Staci Stevens | last11 = Underhill | first11 =  Rosemary A | authorlink11 = Rosemary Underhill | last12 = Vallings | first12 = Rosamund | authorlink12 = Rosamund Vallings|location=Chicago, USA|publisher= International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis |quote=The illness can vary from mild to severe, with symptoms that may fluctuate significantly from hour to hour and day to day.}}</ref> Overexertion can exacerbate all symptoms, and [[post-exertional malaise]] is often [[Delayed onset of post-exertional symptoms|delayed by 24 hours or more]].<ref name="CDC-symptoms" /> The US [[National Institutes of Health]] (NIH) notes that sensitivity to noise, light and [[multiple chemical sensitivity|chemical]]s may force patients to withdraw from society.<ref name="P2P2016">{{Cite web|url=https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs | title = ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | last =  | first =  | date = Dec 8, 2016 | website = [[National Institutes of Health]]|access-date=2022-03-28|quote=Effects of the illness can range from moderate to debilitating, and can substantially impact everyday functioning. Routine daily activities such as cooking meals, brushing teeth, and caring for children become difficult. Additionally, sensitivity to environmental factors (e.g., noise, light, chemicals) may force many individuals with ME/CFS into seclusion or withdrawal from society.|archive-url=|archive-date=|url-status=|language=en}}</ref>


=== Post-exertional malaise ===
=== Post-exertional malaise ===
Line 85: Line 85:
[[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]]
[[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;">
Although there is no definitive [[biomarker]], several signs and findings have been frequently observed in clinical settings:<div style="column-count:2;">
*high [[:Category:Antibodies|antibody]] titers to specific infections (including [[Epstein-Barr virus|EBV]],<ref>{{Cite journal | last = Schmaling | first = K. B. | last2 = Jones | first2=J. F. | date = Jan 1996 | title = MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1 | pages = 67–74|issn=0022-3999|pmid=8730646}}</ref> [[Human herpesvirus 6|HHV-6]],<ref name="Cuende1997">{{cite journal| vauthors=Cuende JI, Civeira P, Diez N, Prieto J| title=[High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome]. | journal=An Med Interna | year= 1997 | volume= 14 | issue= 9 | pages = 441-4 | pmid=9453750 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/pubmed/9453750}}</ref><ref name="Komaroff2006">{{cite journal | last=Komaroff  | first = AL | authorlink = Anthony Komaroff | title=Is human herpesvirus-6 a trigger for chronic fatigue syndrome? | journal=J Clin Virol | year= 2006 | volume= 37 | issue= Suppl 1 | pages = S39-46 | pmid=17276367 | doi=10.1016/S1386-6532(06)70010-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/pubmed/17276367}}</ref> and [[Coxsackie B virus|Coxsackie B]]<ref>{{Cite journal | last = Landay | first = AL | date = September 1991 | title = Chronic fatigue syndrome: clinical condition associated with immune activation | url =https://www.ncbi.nlm.nih.gov/pubmed/1679864|journal=Lancet|volume=|pages=|via=}}</ref><ref name="Chia2005">{{Cite journal | last = Chia | first = John | date = November 2005 | title = The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref> among others)
*high [[:Category:Antibodies|antibody]] titers to specific infections (including [[Epstein-Barr virus|EBV]],<ref>{{Cite journal | last = Schmaling | first = K.B. |last2 = Jones | first2=J.F. |date = Jan 1996 | title = MMPI profiles of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8730646|journal=Journal of Psychosomatic Research|volume=40|issue=1 | pages = 67–74|issn=0022-3999|pmid=8730646}}</ref> [[Human herpesvirus 6|HHV-6]],<ref name="Cuende1997">{{cite journal| vauthors=Cuende JI, Civeira P, Diez N, Prieto J| title=[High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome]. | journal=An Med Interna | year= 1997 | volume= 14 | issue= 9 | pages = 441-4 | pmid=9453750 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/pubmed/9453750}}</ref><ref name="Komaroff2006">{{cite journal | last=Komaroff  | first = AL | authorlink = Anthony Komaroff | title=Is human herpesvirus-6 a trigger for chronic fatigue syndrome? | journal=J Clin Virol | year= 2006 | volume= 37 | issue= Suppl 1 | pages = S39-46 | pmid=17276367 | doi=10.1016/S1386-6532(06)70010-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/pubmed/17276367}}</ref> and [[Coxsackie B virus|Coxsackie B]]<ref>{{Cite journal | last = Landay | first = AL | date = September 1991 | title = Chronic fatigue syndrome: clinical condition associated with immune activation | url =https://www.ncbi.nlm.nih.gov/pubmed/1679864|journal=Lancet|volume=|pages=|via=}}</ref><ref name="Chia2005">{{Cite journal | last = Chia | first = John | date = November 2005 | title = The role of enterovirus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/|journal=Journal of Clinical Pathology|volume=|pages=|via=}}</ref> among others)
*[[Hormone]] imbalance<ref name="Ruiz-Núñez, 2018">{{Cite journal | last1  = Ruiz-Núñez | first1 = Begoña | authorlink1 =  | last2 = Tarasse  | first2 = Rabab  | authorlink2 =  | last3 = Vogelaar | first3 = Emar F. | authorlink3 =  | last4 =  Janneke Dijck-Brouwer  | first4 = D.A.  | authorlink4 =  | last5 =Muskiet  | first5 = Frits A. J.  | authorlink5 = | title = Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study | url = https://doi.org/10.3389%2Ffendo.2018.00097 | journal = Frontiers in Endocrinology    | volume = 9  | issue =  | page = 97 | date = 2018| pmid    = 29615976
*[[Hormone]] imbalance<ref name="Ruiz-Núñez, 2018">{{Cite journal | last1  = Ruiz-Núñez | first1 = Begoña | authorlink1 =  | last2 = Tarasse  | first2 = Rabab  | authorlink2 =  | last3 = Vogelaar | first3 = Emar F. | authorlink3 =  | last4 =  Janneke Dijck-Brouwer  | first4 = D.A.  | authorlink4 =  | last5 =Muskiet  | first5 = Frits A. J.  | authorlink5 = | title = Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study | url = https://doi.org/10.3389%2Ffendo.2018.00097 | journal = Frontiers in Endocrinology    | volume = 9  | issue =  | page = 97 | date = 2018| pmid    = 29615976
| doi = 10.3389/fendo.2018.00097}}</ref>
| doi = 10.3389/fendo.2018.00097}}</ref>
*[[Immune system|immunological abnormalities]]<ref name="ICC" /><ref name="Brenu2014">{{Cite journal | last = Brenu | first = Ekua Weba | last2 = Huth | first2 = Teilah K. | last3 = Hardcastle | first3=Sharni L. | last4 = Fuller | first4=Kirsty | last5 = Kaur | first5=Manprit | last6 = Johnston | first6 = Samantha | last7 = Ramos | first7 = Sandra B. | last8 = Staines | first8 = Don R. | last9 = Marshall-Gradisnik | first9 = Sonya M. | date = Apr 2014 | title = Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref><ref name="CDC-etiology"/>
*[[Immune system|immunological abnormalities]]<ref name="ICC" /><ref name="Brenu2014">{{Cite journal | last = Brenu | first = Ekua Weba | last2 = Huth | first2 = Teilah K. | last3 = Hardcastle | first3=Sharni L. | last4 = Fuller | first4=Kirsty | last5 = Kaur | first5=Manprit | last6 = Johnston | first6 = Samantha | last7 = Ramos | first7 = Sandra B. | last8 = Staines | first8 = Don R. | last9 = Marshall-Gradisnik | first9 = Sonya M. | date = Apr 2014 | title = Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref><ref name="CDC-etiology"/>
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]<ref name="Brenu2014" />
*[[Natural Killer Cell (NKC) function|low natural killer cell function]]<ref name="Brenu2014" />
*low red blood cell [[magnesium]]<ref name="Cox1991">{{Cite journal | title = Red blood cell magnesium and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/1672392|journal=Lancet (London, England)|date = 1991-03-30|issn=0140-6736|pmid=1672392 | pages = 757–760|volume=337|issue=8744 | first = I. M. | last=Cox |  first2 = M. J. | last2 = Campbell | first3 =  D. | last3 = Dowson}}</ref>
*low red blood cell [[magnesium]]<ref name="Cox1991">{{Cite journal | title = Red blood cell magnesium and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/1672392|journal=Lancet (London, England)|date = 1991-03-30|issn=0140-6736|pmid=1672392 | pages = 757–760|volume=337|issue=8744 | first = I.M. | last=Cox |  first2 = M.J. | last2 = Campbell | first3 =  D. | last3 = Dowson}}</ref>
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]] (POTS)<ref name="ICC2011primer" /><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>
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia]] (POTS)<ref name="ICC2011primer" /><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>
*[[Post-exertional malaise|physical and mental exertion, sensory input cause relapse]] (PEM)<ref name="ICC2011primer" /><ref name="Arroll2014">{{Cite journal | last = Arroll | first = Megan A.|authorlink=Megan Arroll | last2 = Attree | first2=Elizabeth A. | last3 = O'Leary | first3 = John M. | last4 = Dancey | first4 = Christine P. | date = 2014-04-03 | title = The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2014.892755|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=2|issue=2 | pages = 57–63|doi=10.1080/21641846.2014.892755|issn=2164-1846}}</ref><ref name="CDC-symptoms">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html | title = Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-05-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-21}}</ref>
*[[Post-exertional malaise|physical and mental exertion, sensory input cause relapse]] (PEM)<ref name="ICC2011primer" /><ref name="Arroll2014">{{Cite journal | last = Arroll | first = Megan A.|authorlink=Megan Arroll | last2 = Attree | first2=Elizabeth A. | last3 = O'Leary | first3 = John M. | last4 = Dancey | first4 = Christine P. | date = 2014-04-03 | title = The delayed fatigue effect in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2014.892755|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=2|issue=2 | pages = 57–63|doi=10.1080/21641846.2014.892755|issn=2164-1846}}</ref><ref name="CDC-symptoms">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/symptoms.html | title = Symptoms {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-05-18 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-11-21}}</ref>
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===Generally accepted criteria for diagnosing ME/CFS and ME===
===Generally accepted criteria for diagnosing ME/CFS and ME===
*[[Canadian Consensus Criteria]] (CCC)<ref name="Carruthers, 2003">{{Citation | last1  = Carruthers  | first1 = Bruce M. | authorlink1 = Bruce Carruthers  | last2 = Jain | first2 = Anil Kumar  | authorlink2 = Anil Kumar Jain | last3 = De Meirleir | first3 = Kenny L. | authorlink3 = Kenny De Meirleir | last4 =  Peterson  | first4 = Daniel L.  | authorlink4 = Daniel Peterson | last5 =Klimas  | first5 = Nancy G. | authorlink5 = Nancy Klimas | last6 = Lerner  | first6 = A. Martin  | authorlink6 = Martin Lerner | last7 = Bested  | first7 = Alison C.  | authorlink7 = Alison Bested | last8 = Flor-Henry  | first8 = Pierre | authorlink8 = Pierre Flor-Henry  | last9 = Joshi | first9 = Pradip  | authorlink9 = Pradip Joshi | last10  = Powles | first10 = A C Peter | authorlink10 = A C Peter Powles | last11  = Sherkey  | first11 = Jeffrey A.  | authorlink11 = Jeffrey Sherkey | last12  = van de Sande  | first12 = Marjorie I.  | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols | journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115 | date = 2003 | pmid = | doi = 10.1300/J092v11n01_02 | url = http://phoenixrising.me/wp-content/uploads/Canadian-definition.pdf }}</ref>  A diagnosis of moderate and severe forms of [[ME/CFS]] are accurately made using this criterion. Adults can be diagnosed at 6 months while pediatric cases are diagnosed at three months.
*[[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 = AC Peter | authorlink10 = AC 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 name="ICC" /><ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10= Rosamund Vallings | last11 = Bateman | first11 =  L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 =  N | authorlink13= Nicoletta Carlo-Stella | last14 = Chia | first14 =  J | authorlink14= John Chia | last15 = Darragh | first15 =  A | authorlink15= Austin Darragh | last16 = Gerken | first16 =  A | authorlink16= Anne Gerken | last17 = Jo | first17 =  D | authorlink17= Daehyun Jo | last18 = Lewis | first18 =  DP | authorlink18= Donald Lewis | last19 = Light | first19 =  AR | authorlink19= Alan Light | last20 = Light  | first20 =  KC | authorlink20= Kathleen Light | last21 = Marshall-Gradisnik | first21 =  S | authorlink21= Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 =  J | authorlink22= John McLaren-Howard | last23 = Mena  | first23 =  I | authorlink23= Ismael Mena | last24 = Miwa | first24 =  K | authorlink24= Kunihisa Miwa | last25 = Murovska  | first25 =  M | authorlink25= Modra Murovska | last26 = Stevens  | first26 =  SR | authorlink26= Staci Stevens | title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012
*[[International Consensus Criteria]] (ICC)<ref name="ICC" /><ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = AC Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 =  L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 =  N | authorlink13= Nicoletta Carlo-Stella | last14 = Chia | first14 =  J | authorlink14= John Chia | last15 = Darragh | first15 =  A | authorlink15= Austin Darragh | last16 = Gerken | first16 =  A | authorlink16= Anne Gerken | last17 = Jo | first17 =  D | authorlink17= Daehyun Jo | last18 = Lewis | first18 =  DP | authorlink18= Donald Lewis | last19 = Light | first19 =  AR | authorlink19= Alan Light | last20 = Light  | first20 =  KC | authorlink20= Kathleen Light | last21 = Marshall-Gradisnik | first21 =  S | authorlink21= Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 =  J | authorlink22= John McLaren-Howard | last23 = Mena  | first23 =  I | authorlink23= Ismael Mena | last24 = Miwa | first24 =  K | authorlink24= Kunihisa Miwa | last25 = Murovska  | first25 =  M | authorlink25= Modra Murovska | last26 = Stevens  | first26 =  SR | authorlink26= Staci Stevens | title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012
| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf }}</ref> This criteria will accurately diagnose myalgic encephalomyelitis (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf }}</ref> This criteria will accurately diagnose myalgic encephalomyelitis (ME). There is no requirement that the individual have symptoms for a specified period of time for diagnosis, as opposed to CCC, [[Fukuda criteria|Fukuda]], and [[Systemic Exertion Intolerance Disease|SEID]], which all require 6 months in adults.
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref name="IOM-full">{{Cite book | last = Institute of Medicine | first =  | authorlink = Institute of Medicine|date = 2015 |title =Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.|location = Washington, DC|publisher =The National Academies Press|doi=10.17226/19012 | url = http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx}}</ref>
*[[Systemic Exertion Intolerance Disease]] (SEID)<ref name="IOM-full">{{Cite book | last = Institute of Medicine | first =  | authorlink = Institute of Medicine|date = 2015 | title = Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.|location = Washington, DC|publisher =The National Academies Press|doi=10.17226/19012 | url = http://iom.nationalacademies.org/Reports/2015/ME-CFS.aspx}}</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]] is 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.
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]] is 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.
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{{Main article|page_name =Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome}}
{{Main article|page_name =Prognosis for myalgic encephalomyelitis and chronic fatigue syndrome}}


The [[prognosis for myalgic encephalomyelitis and chronic fatigue syndrome]] (ME and CFS) is considered to be poor with only a small minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name="Cairns2005">{{Cite journal | last = Cairns | first = R. | last2 = Hotopf | first2 = M. | date = Jan 2005 | title = A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients<ref name="Joyce1997">{{Cite journal | last= Joyce | first = J. | last2 = Hotopf | first2 = M. | last3 = Wessely | first3 = S. | date = Mar 1997 | title = The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review | url =https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600|doi=|pmc=|quote=|authorlink2 = Matthew Hotopf|access-date= | authorlink3 = Simon Wessely|via=}}</ref> and the prognosis in [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|adolescents]] is considered to be better than in adults.<ref name="CDC-prognosis">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html | title = Prognosis  {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-07-10 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-10-28}}</ref><ref name="Rowe2017>{{Cite journal | last = Rowe | first = Peter C. | last2 = Underhill | first2 = Rosemary A. | last3 = Friedman | first3=Kenneth J. | last4 = Gurwitt | first4=Alan | last5 = Medow|first5=Marvin S. | last6 = Schwartz | first6 = Malcolm S. | last7 = Speight | first7 = Nigel | last8 = Stewart | first8 = Julian M. | last9 = Vallings | first9 = Rosamund | date = 2017 | title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer |url =https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref>
The [[prognosis for myalgic encephalomyelitis and chronic fatigue syndrome]] (ME and CFS) is considered to be poor with only a small minority (a median estimate of 5%) returning to pre-morbid levels of functioning.<ref name="Cairns2005">{{Cite journal | last = Cairns | first = R. | last2 = Hotopf | first2 = M. | date = Jan 2005 | title = A systematic review describing the prognosis of chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/15699087|journal=Occupational Medicine (Oxford, England)|volume=55|issue=1|pages=20–31|doi=10.1093/occmed/kqi013|issn=0962-7480|pmid=15699087}}</ref> The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients<ref name="Joyce1997">{{Cite journal | last= Joyce | first = J. | last2 = Hotopf | first2 = M. | last3 = Wessely | first3 = S. | date = Mar 1997 | title = The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review | url =https://www.ncbi.nlm.nih.gov/pubmed/9093600|journal=QJM: monthly journal of the Association of Physicians|volume=90|issue=3|pages=223–233|issn=1460-2725|pmid=9093600|doi=|pmc=|quote=|authorlink2 = Matthew Hotopf|access-date= | authorlink3 = Simon Wessely|via=}}</ref> and the prognosis in [[Pediatric myalgic encephalomyelitis and chronic fatigue syndrome|adolescents]] is considered to be better than in adults.<ref name="CDC-prognosis">{{Cite web|url=https://www.cdc.gov/me-cfs/healthcare-providers/presentation-clinical-course/prognosis.html | title = Prognosis  {{!}} Presentation and Clinical Course {{!}} Healthcare Providers {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | date = 2018-07-10 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2018-10-28}}</ref><ref name="Rowe2017>{{Cite journal | last = Rowe | first = Peter C. | last2 = Underhill | first2 = Rosemary A. | last3 = Friedman | first3=Kenneth J. | last4 = Gurwitt | first4=Alan | last5 = Medow | first5 = Marvin S. | last6 = Schwartz | first6 = Malcolm S. | last7 = Speight | first7 = Nigel | last8 = Stewart | first8 = Julian M. | last9 = Vallings | first9 = Rosamund | date = 2017 | title=Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer |url =https://www.frontiersin.org/articles/10.3389/fped.2017.00121/full|journal=Frontiers in Pediatrics|language=English|volume=5|doi=10.3389/fped.2017.00121|issn=2296-2360}}</ref>


==Pathophysiology==
==Pathophysiology==
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{{Main article |page_name = Sex differences in myalgic encephalomyelitis and chronic fatigue syndrome}}
{{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 name="Bakken2014" />  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 [[chronic fatigue syndrome|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 [[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 name="Collin2015">{{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>
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 name="Bakken2014" />  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 [[chronic fatigue syndrome|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 [[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 name="Collin2015">{{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==
==Risk factors and potential causes==
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===Genetic risks===
===Genetic risks===


Myalgic encephalomyelitis and chronic fatigue syndrome have been reported to run in families, although ME and CFS are not considered inherited illnesses, there is evidence of a genetic predisposition.<ref name="Schlauch, 2016" /><ref name="Dibble2020">{{Cite journal | title = Genetic risk factors of ME/CFS: a critical review | date = 2020-08-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530519/|journal=Human Molecular Genetics|volume=29|issue=R1|pages=R117–R124 | last = Dibble | first = Joshua J|author-link= | last2 = McGrath | first2 = Simon J|authorlink2 = Simon McGrath|last3 = Ponting | first3 = Chris P  | authorlink3 = Chris Ponting|doi=10.1093/hmg/ddaa169|pmc=7530519|pmid=32744306|access-date=|issn=0964-6906|quote=|via=}}</ref><ref name="Hajdarevic2022">{{Cite journal | title = Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci | date = 2022-05-01|url=https://www.sciencedirect.com/science/article/pii/S0889159122000782|journal=Brain, Behavior, and Immunity|volume=102|issue=|pages=362–369 | last = Hajdarevic | first = Riad|author-link=Riad Hajdarevic | last2 = Lande | first2=Asgeir |authorlink2 = Asgeir Lande|last3 = Mehlsen | first3=Jesper  | authorlink3 =  | last4 = Rydland | first4=Anne | authorlink4 =  | last5 = Sosa | first5=Daisy D.  | authorlink5 =  | last6 = Strand | first6 = Elin B. | authorlink6 = Elin Strand | last7 = Mella | first7 = Olav | authorlink7 = Olav Mella | last8 = Pociot | first8 = Flemming | last9 = Fluge | first9 = Øystein | authorlink9 = Øystein Fluge | last10 = Lie | first10 = Benedicte A. | last11 = Viken | first11 = Marte K.|language=en|doi=10.1016/j.bbi.2022.03.010|pmc=|pmid=|access-date=|issn=0889-1591|quote=|via=}}</ref>
Myalgic encephalomyelitis and chronic fatigue syndrome have been reported to run in families, although ME and CFS are not considered inherited illnesses, there is evidence of a genetic predisposition.<ref name="Schlauch, 2016" /><ref name="Dibble2020">{{Cite journal | title = Genetic risk factors of ME/CFS: a critical review | date = 2020-08-03|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530519/|journal=Human Molecular Genetics|volume=29|issue=R1|pages=R117–R124 | last = Dibble | first = Joshua J|author-link= | last2 = McGrath | first2 = Simon J|authorlink2 = Simon McGrath|last3 = Ponting | first3 = Chris P  | authorlink3 = Chris Ponting|doi=10.1093/hmg/ddaa169|pmc=7530519|pmid=32744306|access-date=|issn=0964-6906|quote=|via=}}</ref><ref name="Hajdarevic2022">{{Cite journal | title = Genetic association study in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) identifies several potential risk loci | date = 2022-05-01|url=https://www.sciencedirect.com/science/article/pii/S0889159122000782|journal=Brain, Behavior, and Immunity|volume=102|issue=|pages=362–369 | last = Hajdarevic | first = Riad | author-link=Riad Hajdarevic | last2 = Lande | first2=Asgeir |authorlink2 = Asgeir Lande|last3 = Mehlsen | first3 = Jesper  | authorlink3 =  | last4 = Rydland | first4=Anne | authorlink4 =  | last5 = Sosa | first5=Daisy D.  | authorlink5 =  | last6 = Strand | first6 = Elin B. | authorlink6 = Elin Strand | last7 = Mella | first7 = Olav | authorlink7 = Olav Mella | last8 = Pociot | first8 = Flemming | last9 = Fluge | first9 = Øystein | authorlink9 = Øystein Fluge | last10 = Lie | first10 = Benedicte A. | last11 = Viken | first11 = Marte K.|language=en|doi=10.1016/j.bbi.2022.03.010|pmc=|pmid=|access-date=|issn=0889-1591|quote=|via=}}</ref>


{{Main article|page_name = Genetics of chronic fatigue syndrome}}
{{Main article|page_name = Genetics of chronic fatigue syndrome}}


===Potential causes===
===Potential causes===
Although risk factors for myalgic encephalomyelitis have been identified, no single [[Vagus nerve infection hypothesis|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 name="Rasa2018">{{Cite journal | last = Rasa | first = Santa|author-link=Santa Rasa | last2 = Nora-Krukle | first2=Zaiga|authorlink2 = Zaiga Nora-Krukle|last3 = Henning | first3 = Nina | authorlink3 =  | last4 = Eliassen | first4=Eva | authorlink4 =  | last5 = Shikova | first5=Evelina | authorlink5 = Evelina Shikova | last6 = Harrer | first6 = Thomas | authorlink6 = Thomas Harrer | last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen | last8 = Murovska | first8 = Modra | authorlink8 = Modra Murovska | last9 = Prusty | first9 = Bhupesh K. | authorlink9 = Bhupesh Prusty | last10 = European Network on ME/CFS (EUROMENE) | first10 =  | authorlink10 = EUROMENE | date = 2018-10-01 | title = Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y|journal=Journal of Translational Medicine|language=en|volume=16|issue=1|pages=|doi=10.1186/s12967-018-1644-y|issn=1479-5876|pmc=|pmid=30285773|quote=|via=}}</ref><ref name="Magnus2015">{{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 name="Schlauch, 2016">{{Cite journal | last1  = Schlauch | first1 = Karen A.  | authorlink1 = Karen Schlauch | last2 = Khaiboullina | first2 = Svetlana F.| authorlink2 = Svetlana Khaiboullina | last3 = De Meirleir  | first3 = Kenny L. | authorlink3 = Kenny de Meirleir  | last4 =  Rawat  | first4 = Shanti  | authorlink4 = Shanti Rawat | last5 = Petereit | first5 = J  | authorlink5 =  | last6 = Rizvanov | first6 = Albert A | authorlink6 = Albert Rizvanov | last7 = Blatt  | first7 = Nataliya | authorlink7 = Nataliya Blatt | last8 = Mijatovic  | first8 = Tatjana  | authorlink8 = Tatjana Mijatovic | last9 = Kulick | first9 = D  | authorlink9 =  | last10  = Palotás | first10 = András | authorlink10 = András Palotás | last11  = Lombardi | first11 = Vincent C.| authorlink11 = Vincent Lombardi | title = Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome | journal = Translational Psychiatry  | volume = 6  | issue = 2 | page = e730 | date = 2016 | pmid = | doi = 10.1038/tp.2015.208 }}</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 name="Sotzny, 2018">{{Cite journal | last1  = Sotzny  | first1 = Franziska  | authorlink1 = Franziska Sotzny | last2 = Blanco  | first2 = Julià | authorlink2 = Julià Blanco | last3 = Capelli | first3 = Enrica  | authorlink3 = Enrica Capelli | last4 =  Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero | last5 =Steiner | first5 = Sophie  | authorlink5 =  | last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska  | last7 = Scheibenbogen  | first7 = Carmen  | authorlink7 = Carmen Scheibenbogen| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease | url = https://www.sciencedirect.com/science/article/pii/S1568997218300880 | journal = Autoimmunity Reviews  | volume = 17  | issue = 6 | page =  601-609 | date = 2018| pmid    = | doi = 10.1016/j.autrev.2018.01.009}}</ref><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 = facebook.com|language=en|archive-url=|archive-date=|url-status=|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 name="Hardcastle2014">{{Cite journal|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. | last3 = Staines | first3= D.R. | authorlink3 = Donald Staines | last4 = Marshall-Gradisnik | first4 = S. | authorlink4 = Sonya Marshall-Gradisnik| date = 2014 |journal=Biological Markers and Guided Therapy|volume=1|issue=1=|pages=25|doi=10.12988/bmgt.2014.3122}}</ref>
Although risk factors for myalgic encephalomyelitis have been identified, no single [[Vagus nerve infection hypothesis|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 name="Rasa2018">{{Cite journal | last = Rasa | first = Santa | author-link=Santa Rasa | last2 = Nora-Krukle | first2=Zaiga | authorlink2 = Zaiga Nora-Krukle|last3 = Henning | first3 = Nina | authorlink3 =  | last4 = Eliassen | first4=Eva | authorlink4 =  | last5 = Shikova | first5=Evelina | authorlink5 = Evelina Shikova | last6 = Harrer | first6 = Thomas | authorlink6 = Thomas Harrer | last7 = Scheibenbogen | first7 = Carmen | authorlink7 = Carmen Scheibenbogen | last8 = Murovska | first8 = Modra | authorlink8 = Modra Murovska | last9 = Prusty | first9 = Bhupesh K. | authorlink9 = Bhupesh Prusty | last10 = European Network on ME/CFS (EUROMENE) | first10 =  | authorlink10 = EUROMENE | date = 2018-10-01 | title = Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)|url=https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y|journal=Journal of Translational Medicine|language=en|volume=16|issue=1|pages=|doi=10.1186/s12967-018-1644-y|issn=1479-5876|pmc=|pmid=30285773|quote=|via=}}</ref><ref name="Magnus2015">{{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 name="Schlauch, 2016">{{Cite journal | last1  = Schlauch | first1 = Karen A.  | authorlink1 = Karen Schlauch | last2 = Khaiboullina | first2 = Svetlana F. | authorlink2 = Svetlana Khaiboullina | last3 = De Meirleir  | first3 = Kenny L. | authorlink3 = Kenny de Meirleir  | last4 =  Rawat  | first4 = Shanti  | authorlink4 = Shanti Rawat | last5 = Petereit | first5 = J  | authorlink5 =  | last6 = Rizvanov | first6 = Albert A | authorlink6 = Albert Rizvanov | last7 = Blatt  | first7 = Nataliya | authorlink7 = Nataliya Blatt | last8 = Mijatovic  | first8 = Tatjana  | authorlink8 = Tatjana Mijatovic | last9 = Kulick | first9 = D  | authorlink9 =  | last10  = Palotás | first10 = András | authorlink10 = András Palotás | last11  = Lombardi | first11 = Vincent C. | authorlink11 = Vincent Lombardi | title = Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome | journal = Translational Psychiatry  | volume = 6  | issue = 2 | page = e730 | date = 2016 | pmid = | doi = 10.1038/tp.2015.208 }}</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 name="Sotzny, 2018">{{Cite journal | last1  = Sotzny  | first1 = Franziska  | authorlink1 = Franziska Sotzny | last2 = Blanco  | first2 = Julià | authorlink2 = Julià Blanco | last3 = Capelli | first3 = Enrica  | authorlink3 = Enrica Capelli | last4 =  Castro-Marrero | first4 = Jesús | authorlink4 = Jesús Castro-Marrero | last5 =Steiner | first5 = Sophie  | authorlink5 =  | last6 = Murovska | first6 = Modra | authorlink6 = Modra Murovska  | last7 = Scheibenbogen  | first7 = Carmen  | authorlink7 = Carmen Scheibenbogen| title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease | url = https://www.sciencedirect.com/science/article/pii/S1568997218300880 | journal = Autoimmunity Reviews  | volume = 17  | issue = 6 | page =  601-609 | date = 2018| pmid    = | doi = 10.1016/j.autrev.2018.01.009}}</ref><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 = facebook.com|language=en|archive-url=|archive-date=|url-status=|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 name="Hardcastle2014">{{Cite journal|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. | last3 = Staines | first3= D.R. | authorlink3 = Donald Staines | last4 = Marshall-Gradisnik | first4 = S. | authorlink4 = Sonya Marshall-Gradisnik| date = 2014 |journal=Biological Markers and Guided Therapy|volume=1|issue=1=|pages=25|doi=10.12988/bmgt.2014.3122}}</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]]]]
[[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]]]]
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{{Main article |page_name = Virus}}
{{Main article |page_name = Virus}}


Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[Human herpesvirus 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=|url-status=|publisher=VOLKMEDIA|language=en-US}}</ref><ref name="Chapenko2012">{{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=|pages=205085|doi=10.1155/2012/205085|issn=1687-8647|pmid=22927850|via=}}</ref> suggests a potential viral contribution in at least some individuals. Some researchers have stated that evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.<ref name="Chia2005"/><ref name="Hanson2021">{{Cite journal | title = The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review | date = 2021 | url=https://www.frontiersin.org/article/10.3389/fmed.2021.688486|journal=Frontiers in Medicine|volume=8|issue= | pages = 688486 | last = O'Neal | first = Adam J.|author-link= | last2 = Hanson |  first2 = Maureen R.|authorlink2 = Maureen Hanson|doi=10.3389/fmed.2021.688486/abstract|pmc=|pmid=|access-date=|issn=2296-858X|quote=|via=}}</ref>  
Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[Human herpesvirus 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=|url-status=|publisher=VOLKMEDIA|language=en-US}}</ref><ref name="Chapenko2012">{{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=|pages=205085|doi=10.1155/2012/205085|issn=1687-8647|pmid=22927850|via=}}</ref> suggests a potential viral contribution in at least some individuals. Some researchers have stated that evidence from [[epidemic myalgic encephalomyelitis]] strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.<ref name="Chia2005"/><ref name="Hanson2021">{{Cite journal | title = The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review | date = 2021 | url=https://www.frontiersin.org/article/10.3389/fmed.2021.688486|journal=Frontiers in Medicine|volume=8|issue= | pages = 688486 | last = O'Neal | first = Adam J. | authorlinklink= | last2 = Hanson |  first2 = Maureen R.|authorlink2 = Maureen Hanson|doi=10.3389/fmed.2021.688486/abstract|pmc=|pmid=|access-date=|issn=2296-858X|quote=|via=}}</ref>  


=== Bacteria ===
=== Bacteria ===
{{Main article |page_name = 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 name="Tovey2018">{{Cite journal | date = 2018-09-05 | last = Tovey | first = JE | 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|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 name="Nicholson2009">{{Cite journal|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 | first = Garth L. | last=Nicolson | first2=Jörg | last2 = Haier | date = 2009|journal=British Journal of Medical Practitioners|volume=2|issue=4|pages = 20-28|doi=|pmid=}}</ref>  
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 name="Tovey2018">{{Cite journal | date = 2018-09-05 | last = Tovey | first = JE | 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|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 name="Nicholson2009">{{Cite journal|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 | first = Garth L. | last=Nicolson | first2=Jörg | last2 = Haier | date = 2009|journal=British Journal of Medical Practitioners|volume=2|issue=4|pages = 20-28|doi=|pmid=}}</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.
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 name="MEA2010blood">{{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 = [[The ME Association]]|language=en-US|archive-url=|archive-date=|url-status=|access-date=2018-09-08}}</ref><ref name="USblood">{{Cite news|url=http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html | title = Chronic fatigue patients barred from blood donation|publisher=Washington Post | last = Stein | first = Rob | date = 2010-12-03|access-date=2018-09-08|language=en-US|issn=0190-8286}}</ref><ref name="NZblood">{{Cite web|url=http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C | title = Detailed eligibility criteria|website=NZ Blood|language=en-NZ|access-date=2018-09-08}}</ref>
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 name="MEA2010blood">{{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 = [[The ME Association]]|language=en-US|archive-url=|archive-date=|url-status=|access-date=2018-09-08}}</ref><ref name="USblood">{{Cite news | url=http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html | title = Chronic fatigue patients barred from blood donation|publisher=Washington Post | last = Stein | first = Rob | date = 2010-12-03|access-date=2018-09-08|language=en-US|issn=0190-8286}}</ref><ref name="NZblood">{{Cite web|url=http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C | title = Detailed eligibility criteria|website=NZ Blood|language=en-NZ|access-date=2018-09-08}}</ref>


==Treatments==
==Treatments==
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Success of treating symptoms of ME is not well researched or documented.
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=|url-status=|language=en-US}}</ref>  The antiviral Valganciclovir failed in a controlled nine month study against ME patients positive for Herpes Simplex 6 and Epstein Barr viral infections.<ref>{{Cite journal | last = Montoya | first = Jose G. | last2 = Kogelnik | first2 = Andreas M. | last3 = Bhangoo | first3 = Munveer | last4 = Lunn | first4=Mitchell R. | last5 = Flamand | first5=Louis | last6 = Merrihew | first6 = Lindsey E. | last7 = Watt | first7 = Tessa | last8 = Kubo | first8 = Jessica T. | last9 = Paik | first9 = Jane | date = Dec 2013 | title = Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23959519|journal=Journal of Medical Virology|volume=85|issue=12|pages=2101–2109|doi=10.1002/jmv.23713|issn=1096-9071|pmid=23959519|pmc=|quote=|author-link=Jose Montoya|authorlink2 = Andreas Kogelnik|access-date=|via=}}</ref>
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=|url-status=|language=en-US}}</ref>  The antiviral Valganciclovir failed in a controlled nine month study against ME patients positive for Herpes Simplex 6 and Epstein Barr viral infections.<ref>{{Cite journal | last = Montoya | first = Jose G. | last2 = Kogelnik | first2 = Andreas M. | last3 = Bhangoo | first3 = Munveer | last4 = Lunn | first4=Mitchell R. | last5 = Flamand | first5 = Louis | last6 = Merrihew | first6 = Lindsey E. | last7 = Watt | first7 = Tessa | last8 = Kubo | first8 = Jessica T. | last9 = Paik | first9 = Jane | date = Dec 2013 | title = Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/23959519|journal=Journal of Medical Virology|volume=85|issue=12|pages=2101–2109|doi=10.1002/jmv.23713|issn=1096-9071|pmid=23959519|pmc=|quote=|author-link=Jose Montoya | authorlink2 = Andreas Kogelnik|access-date=|via=}}</ref>


==Epidemiology ==
==Epidemiology ==
{{Main article |page_name = Epidemiology of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome}}
{{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 name="HFME">{{Cite web|url=http://www.hfme.org/methemedicalfacts.htm | title = M.E.: The medical facts | last = Bassett | first = Jodi|authorlink=Jodi Bassett | date = Sep 2010 | website = The Hummingbirds' Foundation for M.E.|archive-url=|archive-date=|url-status=|access-date=2018-09-08}}</ref> Epidemics often occur in enclosed communities such as schools and hospitals.
ME has been found world-wide, in at least 75 [[Outbreaks|epidemics]] documented in published papers from the 1930s to the 1980s.<ref name="HFME">{{Cite web|url=http://www.hfme.org/methemedicalfacts.htm | title = M.E.: The medical facts | last = Bassett | first = Jodi | authorlink=Jodi Bassett | date = Sep 2010 | website = The Hummingbirds' Foundation for M.E.|archive-url=|archive-date=|url-status=|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 name="Bakken2014" /> In children the sex ratio is approximately equal.<ref name="Collin2015" />
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 name="Bakken2014" /> In children the sex ratio is approximately equal.<ref name="Collin2015" />
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* [[Lyme disease]] and [[Chronic lyme disease|chronic Lyme disease]]<ref name="ICC" />
* [[Lyme disease]] and [[Chronic lyme disease|chronic Lyme disease]]<ref name="ICC" />
*[[Intracranial hypertension|idiopathic intracranial hypertension]]<ref name="Dankaerts2018" />
*[[Intracranial hypertension|idiopathic intracranial hypertension]]<ref name="Dankaerts2018" />
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]<ref name="ICC" /><ref name="Hoad2008">{{Cite journal | last = Hoad | first = A.|author-link= | last2 = Spickett | first2=G.|authorlink2 = Gavin Spickett‎|last3 = Elliott | first3=J. | authorlink3 =  | last4 = Newton | first4=J. | authorlink4 = Julia Newton | date = 2008 | title = Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/18805903|journal=QJM: monthly journal of the Association of Physicians|volume=101|issue=12 | pages = 961–965|doi=10.1093/qjmed/hcn123|issn=1460-2393|pmid=18805903|quote=|via=}}</ref>
*[[Postural orthostatic tachycardia syndrome|postural orthostatic tachychardia syndrome]]<ref name="ICC" /><ref name="Hoad2008">{{Cite journal | last = Hoad | first = A. | authorlinklink= | last2 = Spickett | first2=G.|authorlink2 = Gavin Spickett‎|last3 = Elliott | first3 = J. | authorlink3 =  | last4 = Newton | first4=J. | authorlink4 = Julia Newton | date = 2008 | title = Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/18805903|journal=QJM: monthly journal of the Association of Physicians|volume=101|issue=12 | pages = 961–965|doi=10.1093/qjmed/hcn123|issn=1460-2393|pmid=18805903|quote=|via=}}</ref>
*[[irritable bowel syndrome]]<ref name="CDC-comorbid" /><ref name="Carruthers, 2003" />
*[[irritable bowel syndrome]]<ref name="CDC-comorbid" /><ref name="Carruthers, 2003" />
*[[Hashimoto's thyroiditis (hypothyroidism)]]<ref name="CDC-differentialdiagnosis" />
*[[Hashimoto's thyroiditis (hypothyroidism)]]<ref name="CDC-differentialdiagnosis" />
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</div>
</div>


A Swedish study of 234 ME/CFS patients meeting the [[Canadian Consensus Criteria]] found that 13.2% had tonsillar herniations severe enough to be considered a [[Chiari malformation|Chiari Malformation]]. 49% had hypermobility and 20% met criteria for hEDS (Ehlers-Danlos syndrome with hypermobility), while 96% had fibromyalgia trigger point pain, with 67% meeting the diagnostic criteria for fibromyalgia.<ref name="Bragee2020">{{Cite journal | last = Bragée | first = Björn|author-link=Björn Bragée | last2 = Michos | first2=Anastasios|authorlink2 = |last3 = Drum | first3 = Brandon | authorlink3 =  | last4 = Fahlgren | first4=Mikael | authorlink4 =  | last5 = Szulkin | first5=Robert | authorlink5 =  | last6 = Bertilson | first6 = Bo C. | authorlink6 =  | date = 2020 | title=Signs of Intracranial Hypertension, Hypermobility, and Craniocervical Obstructions in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fneur.2020.00828/full|journal=Frontiers in Neurology|language=English|volume=11|issue=|pages=|doi=10.3389/fneur.2020.00828|issn=1664-2295|pmc=|pmid=|access-date=|quote=|via=}}</ref>
A Swedish study of 234 ME/CFS patients meeting the [[Canadian Consensus Criteria]] found that 13.2% had tonsillar herniations severe enough to be considered a [[Chiari malformation|Chiari Malformation]]. 49% had hypermobility and 20% met criteria for hEDS (Ehlers-Danlos syndrome with hypermobility), while 96% had fibromyalgia trigger point pain, with 67% meeting the diagnostic criteria for fibromyalgia.<ref name="Bragee2020">{{Cite journal | last = Bragée | first = Björn | author-link=Björn Bragée | last2 = Michos | first2=Anastasios | authorlink2 = |last3 = Drum | first3 = Brandon | authorlink3 =  | last4 = Fahlgren | first4=Mikael | authorlink4 =  | last5 = Szulkin | first5=Robert | authorlink5 =  | last6 = Bertilson | first6 = Bo C. | authorlink6 =  | date = 2020 | title=Signs of Intracranial Hypertension, Hypermobility, and Craniocervical Obstructions in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|url=https://www.frontiersin.org/articles/10.3389/fneur.2020.00828/full|journal=Frontiers in Neurology|language=English|volume=11|issue=|pages=|doi=10.3389/fneur.2020.00828|issn=1664-2295|pmc=|pmid=|access-date=|quote=|via=}}</ref>


== Notable studies ==
== Notable studies ==

Revision as of 17:53, November 30, 2022

Myalgic encephalomyelitis (ME) is a chronic, inflammatory, physically and neurological and immune-mediated disease that presents with symptoms involving multiple bodily systems. It is frequently triggered by a viral infection or a flu-like illness.[1][2] ME presents with symptoms in the central nervous system (CNS), autonomic nervous system (ANS), immune system, cardiovascular system, endocrine system, digestive system, and musculoskeletal system.[1][3]

Myalgic encephalomyelitis was first classified as a neurological disease by the World Health Organization (WHO) in 1969, with the publication of the World Health Organization's ICD-8 manual.[4]

ME has occurred in both epidemic and sporadic forms.

According to the CDC the hallmark symptom of myalglc encephalomyelitis is post-exertional malaise (PEM), which is the worsening of ME/CFS symptoms after minimal physical, mental, or emotional effort.[5][6][7][8][3] Other key symptoms include muscle weakness and easy muscle fatigability, sleep disturbance, plus either orthostatic intolerance or cognitive dysfunction. Orthostic intolerance is autonomic nervous system dysfunction causing the worsening of symptoms when standing or sitting upright, and may include feeling [[syncope|faint], dizziness, feeling weak, blurred vision, postural orthostatic tachycardia (POTS), reduced heart rate variability at night, and both cold and heat intolerance. Other ME/CFS common symptoms include muscle pain, nerve pain, neck and spine stiffness, and sensory symptoms including sensitivity to light, sound, touch, skin tingling or numbness and hyperaesthesia (skin sensitivity and pain, and allodynia). There is a progressive form of ME, but it is rarer than the relapsing-remitting type.[9]

Among adults, ME is more common in women than men.[2] New onset has been observed in children[10] and in adults usually between the ages of 40-60.[11] Bakken et. al notes two age peaks for CFS/ME; age group 10 to 19 years and a second peak in the age group 30 to 39  years.[12]

There are no approved pharmacological treatments for ME anywhere in the world except in Argentina, which has approved the immunomodulator Ampligen (rintatolimod) for severe ME/CFS as of August 23, 2016.[13]

Linda Crowhurst is married to Greg Crowhurst; they reside in Belfast, Northern Ireland. Greg is Linda's full-time carer as she is very severely ill with ME. As of June 2018, Linda has been ill for 25 years. Image source: Wasteland (video) which visually documents Linda's very severe ME. Greg posted a YouTube video in 2006 (reposted in 2007) of Linda speaking of her condition and showing her 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.
Jennie Spotila is an American ME patient who fell ill on October 6, 1994. Jennie is 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 The CFIDS Association of America and testified before the CFSAC

History[edit | edit source]

Myalgic encephalomyelitis was first classified as a neurological disease by the World Health Organization in 1969, with the publication of the ICD-8 manual.[4]

Hillary Johnson is an 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 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 "mass hysteria") that can be spread through casual contact and she appears in the documentary Forgotten Plague.

The World Health Organization's ICD-8 manual did not include any alternative names for myalgic encephalomyelitis although postinfectious encephalomyelitis and all other encephalomyelitis diseases were classified under the same code; fatigue-related alternative names were not added in any later revisions.[4][14] The alternative name chronic fatigue syndrome (CFS) was not in use at this time; it was proposed in 1987 by the Centers for Disease Control, which adopted new diagnostic criteria the following year.[15]:29

In the ICD-9, which was published in 1989, the entry for myalglc encephalomyelitis is uses code 323.9:[16]

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 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 neuromyasthenia.

After the Incline Village outbreak in Nevada in 1984, the disease came to be called and redefined as chronic fatigue syndrome (CFS). The most recent myalgic encephalomyelitis outbreak was caused by the 2019-2022 Coronavirus pandemic outbreak.

Disease name[edit | edit source]

Poster of breakdown of parts of the name myalgic encephalomyelitis

The name myalgic encephalomyelitis was first used in 1956 in an article in the Lancet medical journal to describ findings from the 1955 Royal Free Hospital outbreak in London, UK.[18][17][19] The term myalgic encephalomyelitis is a portmanteau of several of the key signs and symptoms of the disease: myalgic (muscle pain), encephalo (brain), myel (spinal cord), itis (inflammation).[17][20] The central nervous system (brain and spinal cord) are inflamed.[17]

Benign myalgic encephalomyelitis[edit | edit source]

Benign myalgic encephalomyelitis was the term used by the World Health Organization from 1969,[4] with the prefix "benign" used to denote that M.E. was not fatal, the prefix benign was later dropped since M.E. can cause death, for example the deaths of Merryn Crofts and Sophia Mirza.[17][21][22] Merryn Crofts had very severe ME, was bedbound and unable to eat. Merryn weighed under six stone (84 lbs) at her death, and was just 21 years-old. Merryn's death certificate was the second in the UK to attribute a death to ME.[21]

Disease of a thousand names[edit | edit source]

Myalgic Encephalomyelitis has been referred to as the "disease of a thousand names".[23] Other names used or proposed in the history of the myalgic encephalomyelitis include atypical polio, Icelandic disease, benign ME, epidemic neuromyasthenia, chronic fatigue syndrome, Chronic Fatigue Immune Dysfunction Syndrome (CFIDS), and systemic exertion intolerance disease (SEID).[23][15] 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 diagnostic criteria. Some names have emphasized particular symptoms or pathology, including chronic fatigue syndrome and myalgic encephalomyelitis.[17]

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.[24]

Myalgic encephalomyelitis (ME) was the original name for chronic fatigue syndrome (CFS); the names are sometimes used interchangeably or with the acronym ME/CFS.[20]

Onset[edit | edit source]

According to Dr Byron Hyde, after an incubation period of 4 to 7 days, the prodromal phase generally involve a flu-like illness with low-grade fever.[25] In the majority but not all cases, an infection or infectious process is evident.[25] 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.[26][25]

Signs and symptoms[edit | edit source]

Myalgic encephalomyelitis is a neurological disease that affects multiple bodily systems, causing a widespread combination of symptoms.[27] Symptoms can range from mild to very severe and can include:

Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features. - International Consensus Criteria

Symptom presentation and severity can vary considerably day to day and even hour to hour.[3][28] Overexertion can exacerbate all symptoms, and post-exertional malaise is often delayed by 24 hours or more.[3] The US National Institutes of Health (NIH) notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.[29]

Post-exertional malaise[edit | edit source]

A core symptom, post-exertional malaise (PEM), is intolerance to previously trivial mental or physical effort such as attending a child's school event, running an errand or grocery shopping, taking a shower or brushing teeth; this causes a worsening of symptoms, and deterioration of health from persistent or repeated exertion.[1][3]

Jennifer Brea is an American who was studying at Harvard; while on a trip to Kenya she became very ill with what would eventually be diagnosed as ME/CFS. Brea began experiencing neurological problems. Her neurologist diagnosed her with "conversion disorder" (hysteria). When walking home from his office, she collapsed. Jen needed to use a wheelchair to keep her legs up due to POTS as her blood pools into her legs. View her TED Talk What happens when you have a disease doctors can't diagnose

Some studies show that patients who have been ill for longer are more likely to uave severe ME/CFS. ME/CFS oftens becomes more severe when patients try to push through their symptoms and continue to repeatedly exceed their personal physical or cognitive limits, for instance by attempting to keep working, which typically entails anaerobic activity.[30][31]

Clinical findings[edit | edit source]

Alem Matthees is an Australian ME patient that filed an FOI request for data from the PACE trial. At a great cost to his health, Alem appealed the denial of the data and won. This data proved the results published in 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:

Diagnosis[edit | edit source]

Tom Kindlon became 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 wheelchair and his full-time carer is his mother, Vera

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.

Generally accepted criteria for diagnosing ME/CFS and ME[edit | edit source]

ME/CFS (SEID) is accurately diagnosed when the core symptoms are met. The Institute of Medicine report is 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.

Other diagnostic criteria[edit | edit source]

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 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 for chronic fatigue syndrome is the broadest and likely least discerning definition and has been retired due to the risk of many different fatiguing illnesses being misdiagnosed as chronic fatigue syndrome.[43] The US Centers for Disease Control's (CDC) Fukuda criteria, in use since 1994, is also overly broad. The Institute of Medicine report developed the criteria of Systemic Exertion Intolerance Disease (SEID) and although it can diagnose ME patients with the minimum core symptoms,[44][45] it does not describe the array of symptoms those suffering with ME experience. Symptoms such as neurological, immune/gastrointestinal/genitourinary impairment, and energy metabolism/ion transport impairment; these symptoms are necessary for a diagnosis under the ICC.[27] The CCC requires neurological, autonomic, neuroendocrine, immune system, and myalgia symptoms to meet its ME/CFS diagnostic criteria.[7]

Differential diagnosis[edit | edit source]

The signs and symptoms of myalgic encephalomyelitis can be similar to other medical illnesses, including cancer, multiple sclerosis, lupus, Hashimoto's thyroiditis (hypothyroidism), diabetes mellitus, brucellosis, anemia and others.[46][7] Standard medical tests are needed to help distinguish ME from these other illnesses, and additional testing may also be needed.[45][46][47]

Course and prognosis[edit | edit source]

The prognosis for myalgic encephalomyelitis and chronic fatigue syndrome (ME and CFS) is considered to be poor with only a small minority (a median estimate of 5%) returning to pre-morbid levels of functioning.[48] The majority of patients remains significantly impaired. A substantial improvement however is noted in an estimated 40% of patients[49] and the prognosis in adolescents is considered to be better than in adults.[50][51]

Pathophysiology[edit | edit source]

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 excruciating pain, suffered from breathing issues, and occasional paralysis for 15 years. She took her own life in 2015

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[edit | edit source]

Sophia Mirza was a 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 forcibly taken to a mental hospital in 2003. An independent neuropathologist found Sophia's spine contained a massive inflammation. Her death certificate was the first in the UK to attribute a death to CFS.[30]

Autonomic nervous system[edit | edit source]

Cardiovascular[edit | edit source]

Gastrointestinal system[edit | edit source]

Immune system[edit | edit source]

Musculoskeletal system[edit | edit source]

Peripheral nervous system[edit | edit source]

Sex differences[edit | edit source]

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 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

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.[12] 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 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."[52]

Risk factors and potential causes[edit | edit source]

Genetic risks[edit | edit source]

Myalgic encephalomyelitis and chronic fatigue syndrome have been reported to run in families, although ME and CFS are not considered inherited illnesses, there is evidence of a genetic predisposition.[53][54][55]

Potential causes[edit | edit source]

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.[56][57] 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.[58][53] 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.[59][60] There is also a shift from the Th1 type of helper T cells, which fight infection, to the Th2 type, which are more active in allergy and more likely to attack the body.[61][62]

Naomi Whittingham lives in the UK with a severe case of ME. Naomi became ill at 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[edit | edit source]

Other theories describe ME as an immune response to a chronic infection. The association between ME and the Coxsackie B, Human herpesvirus 6, and HHV-7 viruses[63][64][65] suggests a potential viral contribution in at least some individuals. Some researchers have stated that evidence from epidemic myalgic encephalomyelitis strongly point to an enterovirus, however, in most outbreaks, no virus was successfully isolated.[36][66]

Bacteria[edit | edit source]

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.[67][68] Protein findings relating to several infections have seen found in the oligoclonal bands ME of patients.[69]

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.[70][71][72]

Treatments[edit | edit source]

Karina Hansen became ill as an adult teenager and is 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

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.[13] However the effectiveness of Ampligen is under dispute.[73] Other medications have been used off-label for ME with varying effectiveness in some patients.[7][27]

Treatments for sleep problems, headaches, pain or other symptoms are utilized by some doctors for some patients although these are treating symptoms and not ME itself.[27]

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.[74] The antiviral Valganciclovir failed in a controlled nine month study against ME patients positive for Herpes Simplex 6 and Epstein Barr viral infections.[75]

Epidemiology[edit | edit source]

ME has been found world-wide, in at least 75 epidemics documented in published papers from the 1930s to the 1980s.[76] 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.[12] In children the sex ratio is approximately equal.[52]

Co-morbidities[edit | edit source]

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, and increased risks for secondary diseases in patients with ME.[7][3] 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 neurally mediated hypotension (NMH) and idiopathic intracranial hypertension (IIH/IH) and fibromyalgia (FM/FMS) can occur in or be co-morbid with numerous conditions, including ME.[39][77]

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

A Swedish study of 234 ME/CFS patients meeting the Canadian Consensus Criteria found that 13.2% had tonsillar herniations severe enough to be considered a Chiari Malformation. 49% had hypermobility and 20% met criteria for hEDS (Ehlers-Danlos syndrome with hypermobility), while 96% had fibromyalgia trigger point pain, with 67% meeting the diagnostic criteria for fibromyalgia.[80]

Notable studies[edit | edit source]

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 neurological involvement, metabolic features, and other abnormalities.

News and articles[edit | edit source]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

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