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{{Cleanup | reason=This article needs citations. Please see the discussion page | date=November 2015}}
{{Cleanup | reason=This article needs citations. Please see the discussion page | date=November 2015}}


Myalgic Encephalomyelitis (ME) is a chronic, inflammatory, post-viral, primarily neurological disease that is multisystemic, i.e. affecting the [[central nervous system]] (CNS), [[immune system]], [[cardiovascular system]], endocrinological system, and musculoskeletal system.<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref><ref>[http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF]</ref> It has been classified by the World Health Organisation (WHO) as a neurological disease since 1969.<ref>[https://en.wikipedia.org/wiki/History_of_chronic_fatigue_syndrome#International_classifications History of chronic fatigue syndrome - International Classifications]</ref><ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper - PDF]</ref> An ''M.E. Support'' article [http://www.mesupport.co.uk/index.php?page=the-symptoms-of-m-e#Cardinal-Symptoms The Symptoms of Myalgic Encephalomyelitis] has the headings: ''Cardinal Symptoms'', ''Secondary Features'', and ''Characterised Symptoms'' headings. An extensive list of symptoms can be found at the [[The Hummingbirds' Foundation for ME]] article ''Myalgic Encephalomyelitis: The medical facts'' under the heading [http://www.hfme.org/methemedicalfacts.htm What are some of the symptoms of Myalgic Encephalomyelitis?]
'''Myalgic Encephalomyelitis''' (ME) is a chronic, [[inflammatory]], post-viral, primarily [[neurological]] disease that is multisystemic, i.e. affecting the [[central nervous system]] (CNS), [[immune system]], [[cardiovascular system]], [[endocrinological system]], and [[musculoskeletal system]].<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref><ref>[http://paradigmchange.me/wp-content/uploads/2016/04/ME-CFS-Medical-Abormalities-040416.pdf Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF]</ref> It has been classified by the ''World Health Organization'' (WHO) as a neurological disease since 1969.<ref>[https://en.wikipedia.org/wiki/History_of_chronic_fatigue_syndrome#International_classifications History of chronic fatigue syndrome - International Classifications]</ref><ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper - PDF]</ref> An ''M.E. Support'' article [http://www.mesupport.co.uk/index.php?page=the-symptoms-of-m-e#Cardinal-Symptoms The Symptoms of Myalgic Encephalomyelitis] covers cardinal symptoms, secondary features, and characterized symptoms.  


A hallmark of ME is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or tooth brushing, and deterioration of health from persistent or repeated exertion.<ref>[http://www.meactionuk.org.uk/definition.html - Research Descriptions of M.E. - ME Action UK]</ref><ref>[http://www.cfids-me.org/ramsay86.html The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986]</ref><ref>[https://www.verywell.com/what-is-post-exertional-malaise-716023 What Is Post-exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref>[https://www.verywell.com/post-exertional-malaise-715670 Post Exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Web MD]</ref><ref>[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf PEM Series - Solve ME/CFS - Jenny Spotila]</ref> Myalgic encephalomyelitis is usually a relapsing-remitting disease with new symptoms occurring either in discrete relapses (or “crashes”) or accruing over time.<ref>[http://www.medscape.com/viewarticle/871482 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape]</ref> The ''National Organization for Rare Disorders'' (NORD) notes that "Symptoms and their severity can fluctuate over the course of the illness, even from hour to hour."<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref>  
A hallmark symptom of ME, [[Post-exertional malaise]], is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.<ref>[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - NIH]</ref><ref>[http://www.meactionuk.org.uk/definition.html Research Descriptions of M.E. - ME Action UK]</ref><ref>[http://www.cfids-me.org/ramsay86.html The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986]</ref><ref>[https://www.verywell.com/what-is-post-exertional-malaise-716023 What Is Post-exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref>[https://www.verywell.com/post-exertional-malaise-715670 Post Exertional Malaise - Very Well - Adrienne Dellwo]</ref><ref>[http://www.webmd.com/chronic-fatigue-syndrome/chronic-fatigue-syndrome-symptoms Chronic Fatigue Syndrome - Web MD]</ref><ref>[http://solvecfs.org/wp-content/uploads/2013/10/pem-series.pdf PEM Series - Solve ME/CFS - Jenny Spotila]</ref> Myalgic encephalomyelitis is usually a relapsing-remitting disease with new symptoms occurring either in discrete relapses (or “crashes”) or accruing over time.<ref>[http://www.medscape.com/viewarticle/871482 Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape]</ref> The ''National Organization for Rare Disorders'' (NORD) states: "Symptoms and their severity can fluctuate over the course of the illness, even from hour to hour."<ref>[https://rarediseases.org/rare-diseases/myalgic-encephalomyelitis/ Myalgic Encephalomyelitis - NORD]</ref> The US [[National Institutes of Health]] notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.<ref>[https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/me-cfs ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic encephalomyelitis/Chronic Fatigue Syndrome]</ref>  


ME does not have a cure, though treatments including the antiviral [[Ampligen]] (now approved for use on [[ME/CFS]] patients in [[Argentina]]) and immune system modulator [[Rituximab]] are being trialled.<ref>[http://www.prohealth.com/me-cfs/me-chronic-fatigue-syndrome-experimental-treatments.cfm Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs]</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>[http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report]</ref>
ME does not have a cure, though treatments including the antiviral [[Ampligen]] (now approved for use on [[ME/CFS]] patients in [[Argentina]]) and immune system modulator [[Rituximab]] are being trialled.<ref>[http://www.prohealth.com/me-cfs/me-chronic-fatigue-syndrome-experimental-treatments.cfm Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs]</ref> There is a progressive form of ME but it is rarer than the relapsing-remitting type.<ref>[http://www.meassociation.org.uk/wp-content/uploads/fulltext_pmr-v2-id10521.pdf Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report]</ref>


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


There is a controversial view that ME is not a chronic infectious or autoimmune disease, but rather a psychosocial illness triggered by infection or stress and noting a "high attack rate in females compared with males".<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700894/ Royal Free Epidemic of 1955: A Reconsideration - McEvedy and Beard - NCBI NLM NIH - PMC]</ref>.  
There is a controversial view that ME is not a chronic infectious or autoimmune disease, but rather a psychosocial illness triggered by infection or stress and with a "high attack rate in females compared with males".<ref>[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1700894/ Royal Free Epidemic of 1955: A Reconsideration - McEvedy and Beard - NCBI NLM NIH - PMC]</ref> The [[BPS model]] is being applied to ME, CFS and [[PVFS]] by psychiatrists in the UK. However, Dr. VanElzakker said, “Everyone here [at Harvard] recognizes that it’s a neuroimmune condition and approaches it that way.”<ref>[http://www.meaction.net/2016/12/12/dr-vanelzakker-two-new-mecfs-studies-at-harvard/ Dr VanElzakker: two new ME/CFS studies at Harvard - Jaime S - MEAction]</ref>


ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>[http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/ People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association]</ref><ref>[http://www.redcrossblood.org/news/northcentral/american-red-cross-statement-xmrv-and-chronic-fatigue-syndrome American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross]</ref><ref>[http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html Chronic fatigue patients barred from blood donation - Washington Post -  By: Rob Stein - Dec 3, 2010]</ref><ref>[http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C - NZBlood]</ref>
ME and CFS patients are barred from donating blood or organs in the [[United Kingdom]], [[United States]] and [[New Zealand]] while symptoms persist.<ref>[http://www.meassociation.org.uk/2010/08/people-with-mecfs-to-be-permanently-excluded-from-giving-blood-in-the-uk-from-1-november-this-year-department-of-health-announcement/ People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association]</ref><ref>[http://www.redcrossblood.org/news/northcentral/american-red-cross-statement-xmrv-and-chronic-fatigue-syndrome American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross]</ref><ref>[http://www.washingtonpost.com/wp-dyn/content/article/2010/12/03/AR2010120305888.html Chronic fatigue patients barred from blood donation - Washington Post -  By: Rob Stein - Dec 3, 2010]</ref><ref>[http://www.nzblood.co.nz/Give-blood/Donating/Detailed-eligibility-criteria#C - NZBlood]</ref>
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The name Myalgic Encephalomyelitis describes the disease: Myalgic (muscle pain), Encephalo (brain), myel (spinal cord), itis (inflammation).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref> The patient has muscle pain and the brain and spinal cord are inflamed.  
The name Myalgic Encephalomyelitis describes the disease: Myalgic (muscle pain), Encephalo (brain), myel (spinal cord), itis (inflammation).<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref> The patient has muscle pain and the brain and spinal cord are inflamed.  


Dr. [[Melvin Ramsay]] used the term ME<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref> which is now proving accurate due to brain fMRI's that detail the inflammation. The ''NY Times'' article [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder]] by [[David Tuller]] has brain images of a patient diagnosed with [[ME/CFS]] that clearly indicates brain inflammation. Other [http://me-pedia.org/wiki/Brain_imaging#Research brain imaging research] has been completed. Michael VanElzakker proposed the [[Vagus nerve infection hypothesis]].
Dr. [[Melvin Ramsay]] used the term ME<ref>[http://www.name-us.org/DefintionsPages/DefinitionsArticles/Hoopersdescription.pdf The Terminology of ME & CFS By Professor Malcolm Hooper]</ref> which is now proving accurate due to brain fMRI's that detail the brain inflammation. The ''NY Times'' article [[Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder]] by [[David Tuller]] has images of a patient diagnosed with [[ME/CFS]] that clearly show brain inflammation. Other [http://me-pedia.org/wiki/Brain_imaging#Research brain imaging research] has been completed. Dr. VanElzakker proposed the [[Vagus nerve infection hypothesis]] in which he hypothesizes a [[Vagus nerve]] infection causing symptoms of [[ME/CFS]].<ref>[http://www.meaction.net/2016/12/12/dr-vanelzakker-two-new-mecfs-studies-at-harvard/ Dr VanElzakker: two new ME/CFS studies at Harvard - Jaime S. - MEAction]</ref>


A survey by [[The MEAction Network]] in 2016 found patients much preferred the name myalgic encephalomyelitis to other names including [[Chronic Fatigue Syndrome]].<ref>[http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/ MEAction RFI Poll Report (Part 1 of 3)]</ref>
A survey by [[The MEAction Network]] in 2016 found patients much preferred the name myalgic encephalomyelitis to other names including [[Chronic Fatigue Syndrome]].<ref>[http://www.meaction.net/2016/08/07/meaction-rfi-poll-report-1-of-3/ MEAction RFI Poll Report (Part 1 of 3)]</ref>
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===Differential diagnosis===
===Differential diagnosis===
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], lupus, brucellosis, or another condition."<ref>[https://www.dartmouth-hitchcock.org/medical-information/health_encyclopedia/nord792 Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.]</ref> Additional testing may be needed to help distinguish ME from these other problems.
The signs and symptoms of ME can be similar to other medical problems, "such as cancer, [[multiple sclerosis]], lupus, [[brucellosis]], or another condition."<ref>[https://www.dartmouth-hitchcock.org/medical-information/health_encyclopedia/nord792 Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.]</ref> Additional testing may be needed to help distinguish ME from these other problems.


==Disease course and clinical subtypes==
==Disease course and clinical subtypes==
The initial presentation takes one of two forms: a severe, incapacitating prolonged illness, or an apparent remission followed by increasing relapses until the patient is forced to recognise exertional limitation. The most common initial symptoms reported are: Pain in the spine, neck or head; mild fever and flu-like symptoms; nausea or vomiting; flaccid muscle weakness; and muscle pain or tenderness. For some people, ME is triggered by Hepatitis B vaccination <ref>[http://www.meassociation.org.uk/2016/01/were-collecting-information-on-hepatitis-b-vaccination-and-mecfs-can-you-help-13-january-2016/ ME Association Survey Report, 2010]</ref>, blood transfusion<ref>[https://www.masscfids.org/resource-library/3-research/119-can-blood-transfusions-cause-cfids- Can Blood Transfusions Cause ME/CFS? - Massachusetts CFIDS/ME & FM Association]</ref>, or chemical poisoning<ref>[http://www.prohealth.com/library/showarticle.cfm?libid=8267 Tired or Toxic? Chronic Fatigue Syndrome and Environmental Toxicity - Michael A. Schmidt - ProHealth]</ref><ref>[http://drmyhill.co.uk/wiki/Toxic_causes_of_CFS_-_the_more_I_ask,_the_more_I_find! Toxic causes of CFS - the more I ask, the more I find! - Dr. Myhill.co.uk]</ref> (See: [[Countess of Mar]]), although it is now thought organophosphate poisoning is a different illness.<ref>[http://apt.rcpsych.org/content/aptrcpsych/6/3/187.full.pdf Chronic exposure to organophosphates: background and clinical picture - Robert Davies, Ghouse Ahmed & Tegwedd Freer]</ref>
'''Primary Phase'''


The later course of ME. is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement.
"The first phase is an epidemic or endemic (sporadic) infectious disease generally with an incubation period of 4 to 7 days; in most, but not all cases, an infection or infectious process is evident."<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref>


The evidence for subgroups is strengthened by research using heterogeneous CFS criteria, although this artificial heterogeneity also hampers consensus. It is likely that subtypes exist within the ME milieu based on the clinical findings, history, and perhaps gender of patients.
'''Secondary Chronic Phase'''
 
"The second and chronic phase follows closely on the first phase, usually within two to seven days; it is
characterized by a measurable diffuse change in the function of the Central Nervous System. This
second phase is the persisting disease that most characterizes M.E."<ref>[http://www.nightingale.ca/documents/Nightingale_ME_Definition_en.pdf ME Definition - Nightingale - PDF pg. 6]</ref>
 
'''Presentation'''
 
"The initial presentation takes one of two forms: a severe, incapacitating prolonged illness, or an apparent remission followed by increasing relapses until the patient is forced to recognize exertional limitation. The most common initial symptoms reported are: Pain in the spine, neck or head; mild fever and flu-like symptoms; nausea or vomiting; flaccid muscle weakness; and muscle pain or tenderness."<ref>[https://arainbowatnight.com/whatisme/ https://arainbowatnight.com/whatisme/ What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref> For some people, ME is triggered by Hepatitis B vaccination <ref>[http://www.meassociation.org.uk/2016/01/were-collecting-information-on-hepatitis-b-vaccination-and-mecfs-can-you-help-13-january-2016/ ME Association Survey Report, 2010]</ref>, blood transfusion<ref>[https://www.masscfids.org/resource-library/3-research/119-can-blood-transfusions-cause-cfids- Can Blood Transfusions Cause ME/CFS? - Massachusetts CFIDS/ME & FM Association]</ref>, or chemical poisoning<ref>[http://www.prohealth.com/library/showarticle.cfm?libid=8267 Tired or Toxic? Chronic Fatigue Syndrome and Environmental Toxicity - Michael A. Schmidt - ProHealth]</ref><ref>[http://drmyhill.co.uk/wiki/Toxic_causes_of_CFS_-_the_more_I_ask,_the_more_I_find! Toxic causes of CFS - the more I ask, the more I find! - Dr. Myhill.co.uk]</ref> (See: [[Countess of Mar]]), although it is now thought organophosphate poisoning is a different illness.<ref>[http://apt.rcpsych.org/content/aptrcpsych/6/3/187.full.pdf Chronic exposure to organophosphates: background and clinical picture - Robert Davies, Ghouse Ahmed & Tegwedd Freer]</ref><ref>[https://arainbowatnight.com/whatisme/ https://arainbowatnight.com/whatisme/ What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>
 
'''Later course'''
 
"The later course of ME. is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>
 
'''Subgroups/types'''
 
"The evidence for subgroups is strengthened by research using heterogeneous CFS criteria, although this artificial heterogeneity also hampers consensus. It is likely that subtypes exist within the ME milieu based on the clinical findings, history, and perhaps gender of patients."<ref>[https://arainbowatnight.com/whatisme/#Signs_and_symptoms What Is ME? - Disease course and clinical subtypes - A rainbow at night]</ref>


=== Subtypes proposed ===
=== Subtypes proposed ===
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==Pathophysiology==
==Pathophysiology==


Although much is known about abnormalities in ME., the reasons why they occur is not known. There are two ME. conferences held in the UK each year attended by international research luminaries, and other conferences held worldwide.
Although much is known about abnormalities in ME., the reasons why they occur are not known. There are two ME. conferences held in the UK each year attended by international research luminaries, and other conferences held worldwide.


ME is a complex disease in which the immune and neurological systems appear dysregulated and in conflict, producing a wide variety of findings.
ME is a complex disease in which the immune and neurological systems appear dysregulated and in conflict, producing a wide variety of findings.
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According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as Rnase-L. A reduced ability to move metabolites in and out of cells (channelopathy) has been implicated in this process. This may also be applicable to ME.
According to a strictly immunological explanation of CFS, the inflammatory processes triggered by [[T cell]]s create leaks in the [[blood-brain barrier]] (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of [[cytokine]]s and other destructive proteins such as Rnase-L. A reduced ability to move metabolites in and out of cells (channelopathy) has been implicated in this process. This may also be applicable to ME.


Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the Post-polio syndrome?]. Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behaviour therapy.
Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the Post-polio syndrome?]. Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.


An inquest into the death of [[Sophia Mirza]] from ME found inflammation of the dorsal spine ganglia and liver abnormalities. However, she had co-morbid disorders.
An inquest into the death of [[Sophia Mirza]] from ME found inflammation of the dorsal spine ganglia and liver abnormalities. However, she had co-morbid disorders.


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


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


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


===Environmental===
===Viral cause===
 
Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses<ref>[https://www.ncbi.nlm.nih.gov/pubmed/2841461 Coxsackie B viruses and myalgic encephalomyelitis.]</ref><ref>[http://solvecfs.org/ramsay-research-team-5-the-potential-role-of-hhv-6-in-mecfs/ Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS]</ref> <ref>[https://www.ncbi.nlm.nih.gov/pubmed/22927850 Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.]</ref> suggests a potential viral contribution in at least some individuals. Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as [[Lyme disease]]. Another bacterium that has been implicated in ME is [[Chlamydia pneumoniae]].<ref>[http://med.stanford.edu/chronicfatiguesyndrome/infections/chlamydia/chlamydia-experts.html Chlamydia Pneumoniae - Stanford Myalgic Encephalomyelitis/Chronic Fatigue syndrome Initiative]</ref> Protein findings relating to several infections have seen found in the oligoclonal bands ME patients.<ref>[http://www.nytimes.com/health/guides/test/csf-oligoclonal-banding/overview.html CSF Oligoclonal Banding - NY Times]</ref>
The most popular hypothesis is that a viral infection or retroviral reactivation primes a susceptible immune system for an abnormal reaction later in life. On a molecular level, this might occur if there is a structural similarity between the infectious virus and some component of the central nervous system, leading to eventual confusion in the immune system.
 
Since ME seems to be more common in people who live farther from the equator, another theory proposes that decreased sunlight exposure and possibly decreased [[vitamin D]] production may help cause ME. This theory is bolstered by recent research into the biochemistry of vitamin D, which has shown that it is an important immune system regulator.


Other theories describe ME as an immune response to a chronic infection. The association between ME and the [[Coxsackie B]], [[HHV-6]], and [[HHV-7]] viruses suggests a potential viral contribution in at least some individuals. 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]]. Protein findings relating to several infections have seen found in the oligoclonal bands ME patients. Research has shown that, much like the relationship between HIV and AIDS, the immune dysfunction accompanying ME can lead to temporary or permanent disease progression, regardless of the infection or combination of infections to which the ME sufferer is exposed. Additionally, ME sufferers can be more prone to opportunistic infections.
The [[Vagus nerve infection hypothesis]] accounts for why so many different viral onsets could be responsible. The Vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.


==Treatments==
==Treatments==
There is no known cure for ME. Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself. Success of treating symptoms of ME is not well researched or documented.
There is no known cure for ME. Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself. Success of treating symptoms of ME is not well researched or documented.


[[Ampligen]] (Approved for ME/CFS in [[Argentina]]) and [[Rituximab]] are being trialed.
[[Ampligen]] (Approved for ME/CFS in [[Argentina]]) and [[Rituximab]] are being trialled.


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


==History==
== Learn more ==
 
*[[Pediatric]]
=== The Formative Years ===
 
==== First descriptions ====
 
 
The first definitive description of an illness resembling poliomyelitis was by Gilliam after the [[Los Angeles atypical polio outbreak|1934 Los Angeles outbreak]]. Careful clinical observation in all the epidemics repeatedly found reproducible signs and a distinctive pattern of CNS and sensory nerve involvement, muscle weakness with pain or tenderness, and emotional liability with a chronic, relapsing course.
 
In the 1950s, the public eye was caught by several outbreaks of a mysterious illness that incapacitated communities, often in hospitals. In the Iceland epidemic it was noted patients who contracted the illness developed immunity to poliomyelitis, suggesting confirmation of an association.
 
Autopsy findings on experimentally infected monkeys during the Adelaide epidemic led to the conclusion that the disorder was caused by inflammation of the brain and spinal cord. Accordingly, names such as atypical polio and Akiyuri disease were replaced in 1956 in the UK by the term Benign myalgic encephalomyelitis. However, autopsies on humans have revealed only evidence of infection, notably in the brain, heart, and skeletal muscle.
 
==== WHO Classification ====
 
ME has been classified by WHO as a disease of the [[Central nervous system]] under ICD-8 since 1969.<ref>[https://en.wikipedia.org/wiki/History_of_chronic_fatigue_syndrome#International_classifications History of chronic fatigue syndrome - International Classifications]</ref>
 
In the ICD-10, ME is the only disorder listed in the tabular classification under G93.3, Post-viral fatigue syndrome ([[PVFS]]).<ref>[http://www.icd10data.com/ICD10CM/Codes/G00-G99/G89-G99/G93-/G93.3 2016/17 ICD-10-CM Diagnosis Code G93.3 - Post Viral Fatigue Syndrome - ICD10Data.com]</ref>
 
Despite the increasing prevalence of non-epidemic cases, the disorder was soon dismissed by some as mass hysteria due to the 1970 McEvedy and Beard review, in which no actual patients were examined.<ref>[https://www.ncbi.nlm.nih.gov/pubmed/5411596 Concept of benign myalgic encephalomyelitis. McEvedy CP, Beard AW. - PubMed]</ref>
 
=== CDC Intervention ===
 
In 1987, researchers from the US [[Centers for Disease Control]] & Prevention ([[CDC]]) decided to treat the Lake Tahoe outbreak of M.E. as well as other M.E. outbreaks from the mid-1980s as an entirely new illness, yet another decision based on a complete lack of patient examination.<ref>[https://www.cdc.gov/mmwr/preview/mmwrhtml/00000740.htm Chronic Fatigue Possibly Related to Epstein-Barr Virus -- Nevada  - MMWR - CDC]</ref> It was only after the doctors managing the epidemics used over $200,000 of their own money to fund MRIs, that they found their patients had brain lesions indistinguishable from those found in people with AIDS.
 
Nonetheless, these findings were dismissed because they were not present in all patients and in 1988 the CDC christened the illness [[chronic fatigue syndrome]] (CFS) instead of ME, effectively because three ME experts left the committee meeting early due to (1) a lack of patient information and (2) the remaining members’ preoccupation with Epstein-Barr Virus, which was biologically incapable of causing the outbreaks due to the virus’s extensive latency period. CFS is a highly contentious concept to patients and specialists. Because of the similarity in terminology, CFS is often confused with “chronic fatigue”; many believe this to have been intentional for the benefit of disability insurance companies. ([[Osler's Web]], [[Hillary Johnson]], pp 217 – 219).
 
In 1993 the term chronic fatigue syndrome was added to the alphabetic list of the WHO ICD classification under R53.82 “Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified.”
 
Although neither CFS nor its criteria were developed to replace ME, many, particularly in the psychiatry field, falsely promoted the notion that ME was synonymous with CFS. The first CFS criteria ([[Holmes criteria]]) published in 1988 by Holmes (5) were in fact created “to provide a rational basis for evaluating patients who have chronic fatigue of undetermined cause.”
 
==== CFS research and Psychiatric paradigm ====
 
Research increased after the CFS criteria were further relaxed in 1994, but it was criticized for its over-inclusiveness. With all objective signs now expunged, the obvious possibility of misdiagnosis bedeviled clinical and research work. Lacking a diagnostic laboratory test of any kind, CFS is frequently misdiagnosed in patients presenting symptoms to other similar biological conditions, infections such as [[Lyme disease]] (for which standard testing produces an extremely high rate of false-negatives) or [[Epstein-Barr Virus]] (the cause of glandular fever/infectious mononucleosis), or psychological conditions.
 
A lack of information and awareness has led to both ME and CFS patients being stigmatized, sometimes as hypochondriacs or lazy, yet at other times as over-active and perfectionist.
 
More accurate criteria should help to increase homogeneity and identify pathology. It has also been noted that some journals operate pro-psychiatric editorial policies, resulting in a narrow range of opinions and undermining the physicians’ understanding of the illness.
 
A major recurrent criticism of CFS is that it does not make [[post-exertional malaise]] or muscle weakness an essential criteria, thus leading to the uncertainty and controversy over the appropriateness of physical rehabilitation programmes.
 
==== ME Redux ====
Recent research on CFS may be relevant to ME. For example, studies have revealed pathologically delayed recovery of muscle strength, cardiac and vascular abnormalities, and defects in cellular metabolism. Neurocognitive dysfunction has been objectively observed; and physiological abnormalities relating to immune activity, [[gene expression]], oxidative stress, and nervous system have also been found, plus many psychological and psychiatric studies have also been done.
 
The CDC now recognizes CFS as a serious illness but also [listed] ME as a differential diagnosis on their website [until 2011], reflecting the incompatibility of the traditional definitions by stating the following:
 
“Various terms are often used interchangeably with CFS. CFS is the preferred term because it has an internationally accepted case definition that is used in research and clinical settings. The name [[Chronic Fatigue Immune Dysfunction Syndrome]] (CFIDS) was introduced soon after CFS was defined; there is no case definition for CFIDS, and the name implies an understanding about the pathophysiology of CFS that does not currently exist. Chronic active Epstein-Barr virus (EBV) infection (chronic mononucleosis) was thought to be the cause of CFS during the 1980s, and this association is now known to be rare. However, post-infection fatigue syndromes have been associated with EBV and other infectious agents. The name myalgic encephalomyelitis (ME) was coined in the 1950s to clarify well-documented outbreaks of disease; however, ME is accompanied by neurologic and muscular signs and has a case definition distinct from that of CFS” (Centers for Disease Control and Prevention).
 
Patients and specialists alike have long lobbied for a name and definition change or reversal of “CFS”. In January 2007, the American “CFS Name Change Advisory Board” consisting of doctors [[Lucinda Bateman]], [[David Bell]], [[Paul Cheney]], [[Leonard Jason]], [[Nancy Klimas]], [[Charles Lapp]], and [[Daniel Peterson]]–several of whom were present in the 1980s outbreaks–agreed that “CFS downplays the severity of the disease and is hurtful to patients” and publicized their deliberation that CFS should now be termed ME. However, no statement was made on definition, and considering the slew of misdiagnosed individuals accrued within the “CFS” umbrella since 1988, other doctors, researchers, and ME experts insist that the CFS illness described by the CDC and [[Oxford criteria]] in the UK, no longer represents ME. There are historical reasons for choosing myalgic encephalomyelitis as the name, however the acute post-viral onset, brain inflammation, neurological damage, and extremely specific pattern of muscle fatigue inherent in ME are not a required part of any CFS diagnosis. Multiple studies from Jason et al. show most people with a CFS diagnosis do not have myalgic encephalomyelitis.
 
In 2003 a group of international specialists published the consensus definition of an illness now termed [[ME/CFS]] the criteria of which, including CNS and exertional signs, was more like that of ME than CFS. However, there is no ICD code for “ME/CFS” or “CFS/ME.” Although ME remains under ICD G93.3 as “benign myalgic encephalomyelitis,” Professor [[Malcolm Hooper]] (6) explains: “The word ‘benign’ was used because it was thought at the time that the disorder was not fatal (as poliomyelitis could be, with which it had some similarity), but it was quickly realised by clinicians that ME was not a benign condition, as it has such high morbidity… By 1988 clinicians had stopped using the word ‘benign’ and referred to it as ME, the first to do so being Dr. [[Melvin Ramsay]].”
 
The ICD-10-CM officially states that ME and CFS are two separate entities, each mutually exclusive of the other. ME is listed as subset of G93.3 [[Post Viral Fatigue Syndrome]] under Diseases of the nervous system, while CFS is listed under R53.82 as a subset of Malaise and fatigue. Both entities have “a type 1 exclusion” listed for the other, which is “used when two conditions cannot occur together.” The World Health Organization’s (WHO) International Classification of Diseases (ICD) page for ME explicitly states R53.82 Chronic Fatigue Syndrome as a type 1 exclusion that “should never be used at the same time as G93.3. A type 1 excludes note is used when two conditions cannot occur together.”


== References ==
== References ==

Revision as of 21:30, March 28, 2017

Myalgic Encephalomyelitis (ME) is a chronic, inflammatory, post-viral, primarily neurological disease that is multisystemic, i.e. affecting the central nervous system (CNS), immune system, cardiovascular system, endocrinological system, and musculoskeletal system.[1][2] It has been classified by the World Health Organization (WHO) as a neurological disease since 1969.[3][4] An M.E. Support article The Symptoms of Myalgic Encephalomyelitis covers cardinal symptoms, secondary features, and characterized symptoms.

A hallmark symptom of ME, Post-exertional malaise, is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.[5][6][7][8][9][10][11] Myalgic encephalomyelitis is usually a relapsing-remitting disease with new symptoms occurring either in discrete relapses (or “crashes”) or accruing over time.[12] The National Organization for Rare Disorders (NORD) states: "Symptoms and their severity can fluctuate over the course of the illness, even from hour to hour."[13] The US National Institutes of Health notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.[14]

ME does not have a cure, though treatments including the antiviral Ampligen (now approved for use on ME/CFS patients in Argentina) and immune system modulator Rituximab are being trialled.[15] There is a progressive form of ME but it is rarer than the relapsing-remitting type.[16]

A CFS/ME Norwegian study shows 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.[17] 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 co-horts found "younger children had a more equal gender balance compared to adolescents and adults."[18]

There is a controversial view that ME is not a chronic infectious or autoimmune disease, but rather a psychosocial illness triggered by infection or stress and with a "high attack rate in females compared with males".[19] The BPS model is being applied to ME, CFS and PVFS by psychiatrists in the UK. However, Dr. VanElzakker said, “Everyone here [at Harvard] recognizes that it’s a neuroimmune condition and approaches it that way.”[20]

ME and CFS patients are barred from donating blood or organs in the United Kingdom, United States and New Zealand while symptoms persist.[21][22][23][24]

Name describes disease[edit | edit source]

The name Myalgic Encephalomyelitis describes the disease: Myalgic (muscle pain), Encephalo (brain), myel (spinal cord), itis (inflammation).[25] The patient has muscle pain and the brain and spinal cord are inflamed.

Dr. Melvin Ramsay used the term ME[26] which is now proving accurate due to brain fMRI's that detail the brain inflammation. The NY Times article Brains of People With Chronic Fatigue Syndrome Offer Clues About Disorder by David Tuller has images of a patient diagnosed with ME/CFS that clearly show brain inflammation. Other brain imaging research has been completed. Dr. VanElzakker proposed the Vagus nerve infection hypothesis in which he hypothesizes a Vagus nerve infection causing symptoms of ME/CFS.[27]

A survey by The MEAction Network in 2016 found patients much preferred the name myalgic encephalomyelitis to other names including Chronic Fatigue Syndrome.[28]

Signs and symptoms[edit | edit source]

Over-exertion can make ME worse and the effects are often delayed and may not be seen within 24 hours.[29] [30]

Invest in ME outlines ME symptoms and notes symptoms can range from mild to very severe and can include:

Post-exertional malaise[edit | edit source]

A core symptom, Post-exertional malaise, is used in diagnosing ME, CFS, ME/CFS and SEID.

Diagnosis[edit | edit source]

The International Consensus Criteria (ICC) is thought to be the best tool for diagnosing ME while the Canadian Consensus Criteria (CCC) diagnoses both ME and Chronic Fatigue Syndrome (CFS) and is an ME/CFS diagnostic tool.

The original criteria developed by Melvin Ramsay, the Ramsay definition, is not used for diagnosing ME today.

Other diagnostic criteria[edit | edit source]

The UK Oxford criteria (the US Institute of Medicine report has called for its retirement)[31] and the US CDC Fukuda criteria (used in some research worldwide) are not describing ME but instead describe Chronic fatigue (CF). CF should not be confused with CFS. Many patients and ME organizations believe CFS must not be confused with ME nor its diagnostic criteria used to describe, diagnose or research ME.

Differential diagnosis[edit | edit source]

The signs and symptoms of ME can be similar to other medical problems, "such as cancer, multiple sclerosis, lupus, brucellosis, or another condition."[32] Additional testing may be needed to help distinguish ME from these other problems.

Disease course and clinical subtypes[edit | edit source]

Primary Phase

"The first phase is an epidemic or endemic (sporadic) infectious disease generally with an incubation period of 4 to 7 days; in most, but not all cases, an infection or infectious process is evident."[33]

Secondary Chronic Phase

"The second and chronic phase follows closely on the first phase, usually within two to seven days; it is characterized by a measurable diffuse change in the function of the Central Nervous System. This second phase is the persisting disease that most characterizes M.E."[34]

Presentation

"The initial presentation takes one of two forms: a severe, incapacitating prolonged illness, or an apparent remission followed by increasing relapses until the patient is forced to recognize exertional limitation. The most common initial symptoms reported are: Pain in the spine, neck or head; mild fever and flu-like symptoms; nausea or vomiting; flaccid muscle weakness; and muscle pain or tenderness."[35] For some people, ME is triggered by Hepatitis B vaccination [36], blood transfusion[37], or chemical poisoning[38][39] (See: Countess of Mar), although it is now thought organophosphate poisoning is a different illness.[40][41]

Later course

"The later course of ME. is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."[42]

Subgroups/types

"The evidence for subgroups is strengthened by research using heterogeneous CFS criteria, although this artificial heterogeneity also hampers consensus. It is likely that subtypes exist within the ME milieu based on the clinical findings, history, and perhaps gender of patients."[43]

Subtypes proposed[edit | edit source]

Kerr et al proposed 7 different subsets for “CFS” as it is defined today:[44]

  • Subtype 1 This is one of the more severe subtypes. Effects are cognitive, musculoskeletal, sleep-related and anxiety/depression.
  • Subtype 2 This is one of the more severe subtypes. Effects are musculoskeletal, pain and anxiety/depression.
  • Subtype 3 This subtype has the mildest symptoms.
  • Subtype 4 This subtype is dominated by cognitive issues.
  • Subtype 5 Effects are musculoskeletal and gastrointestinal.
  • Subtype 6 This subtype is dominated by post-exertional malaise (extreme crash after exercise or exertion.)
  • Subtype 7 This is one of the more severe subtypes. Effects are pain, infections, musculoskeletal, sleep-related, neurological, gastrointestinal, neurocognitive and anxiety/depression.

Severity[edit | edit source]

Factors triggering a relapse[edit | edit source]

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

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

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

Pathophysiology[edit | edit source]

Although much is known about abnormalities in ME., the reasons why they occur are not known. There are two ME. conferences held in the UK each year attended by international research luminaries, and other conferences held worldwide.

ME is a complex disease in which the immune and neurological systems appear dysregulated and in conflict, producing a wide variety of findings.

The problem is that most of the research in recent years has been conducted on people with CFS. This is a heterogeneous population, and includes patients with psychiatric disorders, as well as vitamin and nutritional deficiencies (especially vitamin D) and post-viral states such as ME.

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

Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the Post-polio syndrome?]. Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.

An inquest into the death of Sophia Mirza from ME found inflammation of the dorsal spine ganglia and liver abnormalities. However, she had co-morbid disorders.

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

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

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.[45][46][47][48] 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.[49][50] Although most accept an infectious explanation, several theories suggest that ME is an inappropriate immune response to an underlying condition, a theory bolstered by the observation that there is sometimes a family history of autoimmune disease.[51] 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.[52][53]

Viral cause[edit | edit source]

Other theories describe ME as an immune response to a chronic infection. The association between ME and the Coxsackie B, HHV-6, and HHV-7 viruses[54][55] [56] suggests a potential viral contribution in at least some individuals. 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.[57] Protein findings relating to several infections have seen found in the oligoclonal bands ME patients.[58]

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

Treatments[edit | edit source]

There is no known cure for ME. Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself. Success of treating symptoms of ME is not well researched or documented.

Ampligen (Approved for ME/CFS in Argentina) and Rituximab are being trialled.

Epidemiology[edit | edit source]

ME has been found world-wide, in at least 63 epidemics documented in published papers from the 1930s to the 1980s.[59] (See: List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks.) Epidemics often occur in enclosed communities such as schools and hospitals.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approxmately 2-3 females for every male.[60] In children the sex ratio is approximately equal.[61]

Learn more[edit | edit source]

References[edit | edit source]

  1. Myalgic Encephalomyelitis - NORD
  2. Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) Medical Abnormalities Research Citations Compiled by Lisa Petrison, Ph.D.Updated April 4, 2016 - PDF
  3. History of chronic fatigue syndrome - International Classifications
  4. The Terminology of ME & CFS By Professor Malcolm Hooper - PDF
  5. ME/CFS - Pathways to Prevention - NIH
  6. Research Descriptions of M.E. - ME Action UK
  7. The Clinical Features of Myalgic Encephalomyelitis Melvin Ramsay, M.D., 1986
  8. What Is Post-exertional Malaise - Very Well - Adrienne Dellwo
  9. Post Exertional Malaise - Very Well - Adrienne Dellwo
  10. Chronic Fatigue Syndrome - Web MD
  11. PEM Series - Solve ME/CFS - Jenny Spotila
  12. Postexertion 'Crash,' not Fatigue per se, Marks Syndrome - MedScape
  13. Myalgic Encephalomyelitis - NORD
  14. ME/CFS - Pathways to Prevention - Advancing the Research on Myalgic encephalomyelitis/Chronic Fatigue Syndrome
  15. Chronic Fatigue Syndrome & Myalgic Encephalomyelitis Experimental Treatments - ProHealth (Ampligen and Rituximab Tabs
  16. Progressive Myalgic Encephalomyelitis (ME) or A New Disease? A Case Report
  17. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine
  18. Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed
  19. Royal Free Epidemic of 1955: A Reconsideration - McEvedy and Beard - NCBI NLM NIH - PMC
  20. Dr VanElzakker: two new ME/CFS studies at Harvard - Jaime S - MEAction
  21. People with ME/CFS to be permanently excluded from giving blood in the UK from 1 November this year – Department of Health announcement - ME Association
  22. American Red Cross Statement on XMRV and Chronic Fatigue Syndrome - American Red Cross
  23. Chronic fatigue patients barred from blood donation - Washington Post - By: Rob Stein - Dec 3, 2010
  24. - NZBlood
  25. The Terminology of ME & CFS By Professor Malcolm Hooper
  26. The Terminology of ME & CFS By Professor Malcolm Hooper
  27. Dr VanElzakker: two new ME/CFS studies at Harvard - Jaime S. - MEAction
  28. MEAction RFI Poll Report (Part 1 of 3)
  29. What is ME - Invest in ME Research
  30. Myalgic Encephalomyelitis - NORD
  31. US NIH Report Calls for UK Definition of ME/CFS to be Scrapped
  32. Dartmouth Hitchock - Myalgic Encephalomyelitis National Organization for Rare Disorders, Inc.
  33. ME Definition - Nightingale - PDF pg. 6
  34. ME Definition - Nightingale - PDF pg. 6
  35. https://arainbowatnight.com/whatisme/ What Is ME? - Disease course and clinical subtypes - A rainbow at night
  36. ME Association Survey Report, 2010
  37. Can Blood Transfusions Cause ME/CFS? - Massachusetts CFIDS/ME & FM Association
  38. Tired or Toxic? Chronic Fatigue Syndrome and Environmental Toxicity - Michael A. Schmidt - ProHealth
  39. Toxic causes of CFS - the more I ask, the more I find! - Dr. Myhill.co.uk
  40. Chronic exposure to organophosphates: background and clinical picture - Robert Davies, Ghouse Ahmed & Tegwedd Freer
  41. https://arainbowatnight.com/whatisme/ What Is ME? - Disease course and clinical subtypes - A rainbow at night
  42. What Is ME? - Disease course and clinical subtypes - A rainbow at night
  43. What Is ME? - Disease course and clinical subtypes - A rainbow at night
  44. Seven genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis: a detailed analysis of gene networks and clinical phenotypes - JCP Online
  45. Onset Patterns of Chronic Fatigue Syndrome and Myalgic Encephalomyelitis: A Mixed Method Approach - Meredyth Evans - DePaul University
  46. Vagus nerve infection hypothesis - MEpedia
  47. Chronic Fatigue Syndrome - Cleveland Clinic
  48. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. - PubMed
  49. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease. RA Underhill - PubMed
  50. Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome
  51. Klimas ME/CFS Genes Study - Face Book - Video
  52. Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis - ScienceDirect
  53. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells - Biological Markers and Guided Therapy, Vol. 1, 2014, no. 1, 25 -38 - PDF
  54. Coxsackie B viruses and myalgic encephalomyelitis.
  55. Ramsay Research Team 5 – The Potential Role of HHV-6 in ME/CFS
  56. Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome.
  57. Chlamydia Pneumoniae - Stanford Myalgic Encephalomyelitis/Chronic Fatigue syndrome Initiative
  58. CSF Oligoclonal Banding - NY Times
  59. Myalgic Encephalomyelitis: The medical facts - What causes Myalgic Encephalomyelitis? Are there outbreaks of M.E.?
  60. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012 - BMC Medicine
  61. Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open - PubMed