Multiple sclerosis: Difference between revisions

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'''Multiple sclerosis''' (MS) is a chronic, irreversible, [[Autoimmune disease|autoimmune]] and [[neurological disorder|neurological disease]] that affects the [[central nervous system]], including the [[brain]] and [[spinal cord]].<ref>{{Cite book|last=Javalkar|first=Vijaykumar|last2=McGee|first2=Jeanie|last3=Minagar|first3=Alireza|date=2016|title=Multiple Sclerosis: A Mechanistic View | chapter=Clinical Manifestations of Multiple Sclerosis: An Overview|url=https://linkinghub.elsevier.com/retrieve/pii/B9780128007631000014|language=en|publisher=Academic Press|pages=1–12|doi=10.1016/b978-0-12-800763-1.00001-4|isbn=9780128007631}}</ref><ref>{{Cite web|url=https://www.uclh.nhs.uk/OurServices/ServiceA-Z/Neuro/MS2/Pages/WhatisMultipleSclerosis.aspx|title=What is multiple sclerosis?|last=|first=|authorlink=|date=|website=University College London Hospitals NHS trust|archive-url=|archive-date=|url-status=|access-date=2019-04-17}}</ref> In multiple sclerosis the insulating covers of [[Neurons|nerve cells]] in the brain and spinal cord are damaged.  This damage disrupts the ability of parts of the [[nervous system]] to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes [[Mental illness|psychiatric problems]]. Specific symptoms can include [[double vision]], [[blindness]] in one eye, [[Paresis|muscle weakness]], trouble with sensation, or trouble with coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent [[Nervous system|neurological]] problems often remain, especially as the disease advances.{{Citation needed}}
'''Multiple sclerosis''' (MS) is a chronic, irreversible, [[Autoimmune disease|autoimmune]] and [[neurological disorder|neurological disease]] that affects the [[central nervous system]], including the [[brain]] and [[spinal cord]].<ref>{{Cite book | last= Javalkar | first = Vijaykumar | last2 = McGee | first2 = Jeanie | last3 = Minagar | first3 = Alireza | date = 2016 | title=Multiple Sclerosis: A Mechanistic View | chapter=Clinical Manifestations of Multiple Sclerosis: An Overview | url =https://linkinghub.elsevier.com/retrieve/pii/B9780128007631000014|language=en|publisher=Academic Press|pages=1–12|doi=10.1016/b978-0-12-800763-1.00001-4|isbn=9780128007631}}</ref><ref>{{Cite web|url=https://www.uclh.nhs.uk/OurServices/ServiceA-Z/Neuro/MS2/Pages/WhatisMultipleSclerosis.aspx | title = What is multiple sclerosis? | last = | first = | authorlink = | date = | website = University College London Hospitals NHS trust|archive-url=|archive-date=|url-status=|access-date=2019-04-17}}</ref> In multiple sclerosis the insulating covers of [[Neurons|nerve cells]] in the brain and spinal cord are damaged.  This damage disrupts the ability of parts of the [[nervous system]] to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes [[Mental illness|psychiatric problems]]. Specific symptoms can include [[double vision]], [[blindness]] in one eye, [[Paresis|muscle weakness]], trouble with sensation, or trouble with coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent [[Nervous system|neurological]] problems often remain, especially as the disease advances.{{Citation needed}}


== Epidemiology ==
== Epidemiology ==
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=== Gender differences ===
=== Gender differences ===
Over the last decades, the ratio of women to men with MS has increased markedly, representing a true increase in MS among women but not men.<ref name="Harbo2013">{{Cite journal|title=Sex and gender issues in multiple sclerosis|date=Jul 2013|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707353/|journal=Therapeutic Advances in Neurological Disorders|volume=6|issue=4|pages=237–248|last=Harbo|first=Hanne F.|author-link=|last2=Gold|first2=Ralf|author-link2=|last3=Tintoré|first3=Mar|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|doi=10.1177/1756285613488434|pmc=3707353|pmid=23858327|access-date=|issn=1756-2856|quote=|via=}}</ref>
Over the last decades, the ratio of women to men with MS has increased markedly, representing a true increase in MS among women but not men.<ref name="Harbo2013">{{Cite journal | title = Sex and gender issues in multiple sclerosis | date = Jul 2013|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707353/|journal=Therapeutic Advances in Neurological Disorders|volume=6|issue=4|pages=237–248 | last = Harbo | first = Hanne F. | authorlink = | last2 = Gold | first2 = Ralf|authorlink2 = | last3 = Tintoré | first3 = Mar | authorlink3 = |doi=10.1177/1756285613488434|pmc=3707353|pmid=23858327|access-date=|issn=1756-2856|quote=|via=}}</ref>


== Disease mechanisms ==
== Disease mechanisms ==
== Demyelination of the myelin sheath ==
In multiple sclerosis, the [[myelin]] sheath, which is the layers of myelin surrounding the nerves of the [[brain]] and [[spinal cord]], is destroyed, disrupting the transmission of signals in the nerves.<ref name="MSD-consumer">{{Cite web|url=https://www.msdmanuals.com/en-gb/home/brain,-spinal-cord,-and-nerve-disorders/multiple-sclerosis-ms-and-related-disorders/overview-of-demyelinating-disorders|title=Overview of Demyelinating Disorders - Brain, Spinal Cord, and Nerve Disorders|last=Levin|first=Michael C.|date=2023|website=MSD Manual Consumer Version|language=en-GB|access-date=2023-12-30}}</ref>


===Epstein-Barr virus ===
===Epstein-Barr virus ===
In 2022, clear evidence was found of the role of [[Epstein-Barr virus]] infection in triggering multiple sclerosis,<ref name="Bjornevik2022">{{Cite journal|title=Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis|date=2022-01-21|url=https://www.science.org/doi/abs/10.1126/science.abj8222|journal=Science|last=Bjornevik|first=Kjetil|last2=Cortese|first2=Marianna|last3=Healy|first3=Brian C.|last4=Kuhle|first4=Jens|last5=Mina|first5=Michael J.|last6=Leng|first6=Yumei|last7=Elledge|first7=Stephen J.|last8=Niebuhr|first8=David W.|last9=Scher|first9=Ann I.|last10=Munger|first10=Kassandra L.|last11=Ascherio|first11=Alberto|language=EN|doi=10.1126/science.abj8222}}</ref> the strength of the link was higher than that between smoking and lung cancer.<ref name="SciAmJan2922">{{Cite web|url=https://www.scientificamerican.com/article/epstein-barr-virus-found-to-trigger-multiple-sclerosis/|title=Epstein-Barr Virus Found to Trigger Multiple Sclerosis|last=Denworth|first=Lydia|authorlink=|date=Jan 13, 2022|website=Scientific American|language=en|archive-url=|archive-date=|url-status=|access-date=2022-01-15}}</ref>
In 2022, clear evidence was found of the role of [[Epstein-Barr virus]] infection in triggering multiple sclerosis,<ref name="Bjornevik2022">{{Cite journal | title = Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis | date = 2022-01-21|url=https://www.science.org/doi/abs/10.1126/science.abj8222|journal=Science | last = Bjornevik | first = Kjetil | last2 = Cortese | first2 = Marianna | last3 = Healy | first3 = Brian C. | last4 = Kuhle | first4 = Jens | last5 = Mina | first5 = Michael J. | last6 = Leng | first6 = Yumei | last7 = Elledge | first7 = Stephen J. | last8 = Niebuhr | first8 = David W. | last9 = Scher | first9 = Ann I. | last10 = Munger | first10 = Kassandra L. | last11 = Ascherio | first11 = Alberto|language=EN|doi=10.1126/science.abj8222}}</ref> the strength of the link was higher than that between smoking and lung cancer.<ref name="SciAmJan2922">{{Cite web|url=https://www.scientificamerican.com/article/epstein-barr-virus-found-to-trigger-multiple-sclerosis/ | title = Epstein-Barr Virus Found to Trigger Multiple Sclerosis | last = Denworth | first = Lydia | authorlink= | date = Jan 13, 2022 | website = Scientific American|language=en|archive-url=|archive-date=|url-status=|access-date=2022-01-15}}</ref>


{{Quote frame|quote=The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality...This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.<ref name="Harv13Jan22"/>|source=Alberto Ascherio, Harvard Chan School}}
{{Quote frame|quote=The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality...This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.<ref name="Harv13Jan22"/>|source=Alberto Ascherio, Harvard Chan School}}


===Genes===
===Genes===
Genetic factors have been recognized as important in multiple sclerosis, and may combine with certain environmental factors, such as smoking and [[vitamin D deficiency]], as well as Epstein-Barr virus infection.<ref name="Harv13Jan22">{{Cite web|url=https://www.hsph.harvard.edu/news/press-releases/epstein-barr-virus-may-be-leading-cause-of-multiple-sclerosis/|title=Epstein-Barr virus may be leading cause of multiple sclerosis|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=2022-01-13|website=Harvard T.H. Chan School of Public Health|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-01-15}}</ref>
Genetic factors have been recognized as important in multiple sclerosis, and may combine with certain environmental factors, such as smoking and [[vitamin D deficiency]], as well as Epstein-Barr virus infection.<ref name="Harv13Jan22">{{Cite web|url=https://www.hsph.harvard.edu/news/press-releases/epstein-barr-virus-may-be-leading-cause-of-multiple-sclerosis/ | title = Epstein-Barr virus may be leading cause of multiple sclerosis | last = | first = | authorlink = | date = 2022-01-13 | website = Harvard T.H. Chan School of Public Health|language=en-us|archive-url=|archive-date=|url-status=|access-date=2022-01-15}}</ref>


===Immune system===
===Immune system===
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=== Microbiome ===
=== Microbiome ===
Specific changes in the gut [[microbiome]] might increase the risk of MS<ref name="Costandi2016">{{Cite news | title   = Gut bacteria regulate nerve fibre insulation
Specific changes in the gut [[microbiome]] might increase the risk of MS<ref name="Costandi2016">{{Cite news | title = Gut bacteria regulate nerve fibre insulation | journal = The Guardian - Science | date = 2016-04-05 | url = https://www.theguardian.com/science/neurophilosophy/2016/apr/05/gut-bacteria-brain-myelin}}</ref>, and the risk might be reduced using [[probiotic]]s, [[antibiotic]]s, a combination, or a change of [[diet]]. An International Multiple Sclerosis Microbiome Study commenced in 2015.<ref name="Conway2016" />
| journal = The Guardian - Science | date   = 2016-04-05 | url     = https://www.theguardian.com/science/neurophilosophy/2016/apr/05/gut-bacteria-brain-myelin}}</ref>, and the risk might be reduced using [[probiotic]]s, [[antibiotic]]s, a combination, or a change of [[diet]]. An International Multiple Sclerosis Microbiome Study commenced in 2015.<ref name="Conway2016" />


== Treatments ==
== Treatments ==
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=== Experimental treatments ===
=== Experimental treatments ===
Another discovery was that a commonly available and inexpensive [[antihistamine]], can be used to induce remyelination of the nerve cells.<ref name="Conway2016">{{Cite web  
Another discovery was that a commonly available and inexpensive [[antihistamine]], can be used to induce remyelination of the nerve cells.<ref name="Conway2016">{{Cite web | last1 = Conway | first1 = Claire | authorlink1 = | title = Wrapping Up Multiple Sclerosis | date = 2016-04-25
| last1   = Conway           | first1 = Claire             | authorlink1 =  
| website = UC San Francisco News Center | url = https://www.ucsf.edu/news/2016/04/402521/wrapping-multiple-sclerosis}}</ref>
| title   = Wrapping Up Multiple Sclerosis
| date   = 2016-04-25
| website = UC San Francisco News Center
| url     = https://www.ucsf.edu/news/2016/04/402521/wrapping-multiple-sclerosis}}</ref>


Dietary [[tryptophan]] can help reduce brain inflammation and [[Brain fog|'cognitive fog]]'.<ref name="Rothhammer2016">{{Cite journal
Dietary [[tryptophan]] can help reduce brain inflammation and [[Brain fog|'cognitive fog]]'.<ref name="Rothhammer2016">{{Cite journal | last1 = Rothhammer | first1 = Veit | last2 = Mascanfroni | first2 = Ivan D | last3 = Bunse | first3 = Lukas | last4 = Takenaka | first4 = Maisa C | last5 = Kenison | first5 = Jessica E | last6 = Mayo | first6 = Lior | last7 = Chao | first7 = Chun-Cheih | last8 = Patel | first8 = Bonny | last9 =Yan | first9 = Raymond | last10 = Blain | first10 = Manon | last11 = Alvarez | first11 = Jorge I | last12 = Kébir | first12 = Hania | last13 = Anandasabapathy | first13 = Niroshana | last14 = Izquierdo | first14 = Guillermo | last15 = Jung | first15 = Steffen | last16 = Obholzer | first16 = Nikolaus | last17 = Pochet | first17 = Nathalie | last18 = Clish | first18 = Clary B | last19 = Prinz | first19 = Marco | last20 = Prat | first20 = Alexandre | last21 = Antel | first21 = Jack | last22 = Quintana | first22 = Francisco J | title = Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor | journal = Nature Medicine| issn = 1078-8956| volume = | issue = | pages = | date = 2016-05-09 | doi = 10.1038/nm.4106 | url = http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4106.html}}</ref>
| last1   = Rothhammer       | first1 = Veit
| last2   = Mascanfroni     | first2 = Ivan D
| last3   = Bunse           | first3 = Lukas
| last4   = Takenaka         | first4 = Maisa C
| last5   = Kenison         | first5 = Jessica E
| last6   = Mayo             | first6 = Lior
| last7   = Chao             | first7 = Chun-Cheih
| last8   = Patel           | first8 = Bonny
| last9   = Yan             | first9 = Raymond
| last10 = Blain           | first10 = Manon
| last11 = Alvarez         | first11 = Jorge I
| last12 = Kébir           | first12 = Hania
| last13 = Anandasabapathy | first13 = Niroshana
| last14 = Izquierdo       | first14 = Guillermo
| last15 = Jung             | first15 = Steffen
| last16 = Obholzer         | first16 = Nikolaus
| last17 = Pochet           | first17 = Nathalie
| last18 = Clish           | first18 = Clary B
| last19 = Prinz           | first19 = Marco
| last20 = Prat             | first20 = Alexandre
| last21 = Antel           | first21 = Jack
| last22 = Quintana         | first22 = Francisco J
| display-authors =
| title   = Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor
| journal = Nature Medicine| issn = 1078-8956| volume = | issue = | pages =  
| date   = 2016-05-09
| doi     = 10.1038/nm.4106
| url     = http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4106.html}}</ref>


==Comparison of Multiple Sclerosis and ME/CFS==
==Comparison of Multiple Sclerosis and ME/CFS==


Multiple Sclerosis patients or samples are sometimes used for comparison with in [[ME/CFS]] in research studies, for instance at the [[CureME|UK ME/CFS biobank]], and both are [[female predominant diseases]] of the [[central nervous system]].<ref name="Lacerda2017">{{Cite journal|last=Lacerda|first=Eliana M.|author-link=Eliana Lacerda|last2=Bowman|first2=Erinna W.|author-link2=Erinna Bowman|last3=Cliff|first3=Jacqueline M.|author-link3=Jacqueline Cliff|last4=Kingdon|first4=Caroline C.|author-link4=Caroline Kingdon|last5=King|first5=Elizabeth C.|author-link5=Elizabeth King|last6=Lee|first6=Ji-Sook|last7=Clark|first7=Taane G.|last8=Dockrell|first8=Hazel M.|last9=Riley|first9=Eleanor M.|date=2017|title=The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482226/|journal=Open journal of bioresources|volume=4|issue=|pages=|doi=10.5334/ojb.28|issn=2056-5542|pmc=5482226|pmid=28649428|quote=|via=|access-date=|author-link6=|author-link7=Taane Clark|author-link8=Hazel Dockrell|author-link9=Eleanor Riley}}</ref><ref name="Morris2013">{{Cite journal|last=Morris|first=Gerwyn|author-link=Gerwyn Morris|last2=Maes|first2=Michael|author-link2=Michael Maes|date=Dec 2013|title=Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics|url=http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-205|journal=BMC Medicine|language=en|volume=11|issue=1|pages=205|doi=10.1186/1741-7015-11-205|issn=1741-7015|pmc=3847236|pmid=24229326|quote=|via=}}</ref><ref name="White2012">{{Cite journal|last=White|first=Andrea T.|author-link=Andrea White|last2=Light|first2=Alan R.|author-link2=Alan Light|last3=Hughen|first3=Ronald W.|author-link3=Ronald Hughen|last4=VanHaitsma|first4=Timothy A.|author-link4=Timothy VanHaitsma|last5=Light|first5=Kathleen C.|author-link5=Kathleen Light|date=Jan 2012|title=Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/|journal=Psychosomatic Medicine|volume=74|issue=1|pages=46–54|doi=10.1097/PSY.0b013e31824152ed|issn=0033-3174|pmc=PMC3256093|pmid=22210239|quote=|via=}}</ref>
Multiple sclerosis patients or samples are sometimes used for comparison with in [[ME/CFS]] in research studies, for instance at the [[CureME|UK ME/CFS biobank]], and both are [[female predominant diseases]] of the [[central nervous system]].<ref name="Lacerda2017">{{Cite journal | last = Lacerda | first = Eliana M. | authorlink = Eliana Lacerda | last2 = Bowman | first2 = Erinna W. | author-link2 = Erinna Bowman | last3 = Cliff | first3 = Jacqueline M. | authorlink3 = Jacqueline Cliff | last4 = Kingdon | first4 = Caroline C. | authorlink4 = Caroline Kingdon | last5 = King | first5 = Elizabeth C. | authorlink5 = Elizabeth King | last6 = Lee | first6 = Ji-Sook | last7 = Clark | first7 = Taane G. | last8 = Dockrell | first8 = Hazel M. | last9 = Riley | first9 = Eleanor M. | date = 2017 | title=The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482226/|journal=Open journal of bioresources|volume=4|issue=|pages=|doi=10.5334/ojb.28|issn=2056-5542|pmc=5482226|pmid=28649428|quote=|via=|access-date= | authorlink6 = | authorlink7 = Taane Clark | authorlink8 = Hazel Dockrell | authorlink9 = Eleanor Riley}}</ref><ref name="Morris2013">{{Cite journal | last = Morris | first = Gerwyn | authorlink = Gerwyn Morris | last2 = Maes | first2 = Michael | authorlink2 = Michael Maes | date = Dec 2013 | title = Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics|url=http://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-205|journal=BMC Medicine|language=en|volume=11|issue=1|pages=205|doi=10.1186/1741-7015-11-205|issn=1741-7015|pmc=3847236|pmid=24229326|quote=|via=}}</ref><ref name="White2012">{{Cite journal | last = White | first = Andrea T. | authorlink = Andrea White | last2 = Light | first2 = Alan R. | author-link2 = Alan Light | last3 = Hughen | first3 = Ronald W. | authorlink3 = Ronald Hughen | last4 = VanHaitsma | first4 = Timothy A. | authorlink4 = Timothy VanHaitsma | last5 = Light | first5 = Kathleen C. | authorlink5 = Kathleen Light | date = Jan 2012 | title = Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/|journal=Psychosomatic Medicine|volume=74|issue=1 | pages = 46–54|doi=10.1097/PSY.0b013e31824152ed|issn=0033-3174|pmc=PMC3256093|pmid=22210239|quote=|via=}}</ref>


There are many similar features in multiple sclerosis and [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS), including: severe disabling [[fatigue]] that worsens after exercise; debilitating [[Autonomic nervous system|autonomic]] symptoms, including [[orthostatic intolerance]]; illness course may be relapsing-remitting or progressive; infections and psychosocial stress causing exacerbation; autoimmunity and [[auto-inflammatory]] processes; [[mitochondria dysfunction]]; and decreased cerebral blood flow, atrophy of some brain structures.<ref name="Morris2013" />
There are many similar features in multiple sclerosis and [[ME/CFS|myalgic encephalomyelitis/chronic fatigue syndrome]] (ME/CFS), including: severe disabling [[fatigue]] that worsens after exercise; debilitating [[Autonomic nervous system|autonomic]] symptoms, including [[orthostatic intolerance]]; illness course may be relapsing-remitting or progressive; infections and psychosocial stress causing exacerbation; autoimmunity and [[auto-inflammatory]] processes; [[mitochondria dysfunction]]; and decreased cerebral blood flow, atrophy of some brain structures.<ref name="Morris2013" />


In the [[United States]], the prevalence rate of [[chronic fatigue syndrome]] (CFS) is 0.42% of the population versus MS which has a rate of 0.09%.<ref name="Jason2010">{{Cite journal|title=Frequency and content analysis of chronic fatigue syndrome in medical text books|date=2010|url=https://pubmed.ncbi.nlm.nih.gov/21128580/|journal=Australian Journal of Primary Health|volume=16|issue=2|pages=174–178|last=Jason|first=Leonard A.|author-link=Leonard Jason|last2=Paavola|first2=Erin|author-link2=|last3=Porter|first3=Nicole|author-link3=|last4=Morello|first4=Morgan L.|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|doi=10.1071/py09023|pmc=3691015|pmid=21128580|access-date=|issn=1448-7527|quote=|via=}}</ref> Approximately 14% of MS patients meet the [[Fukuda criteria]] for CFS.<ref name="Gaber2014">{{Cite journal|title=Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide|date=2014|url=https://pubmed.ncbi.nlm.nih.gov/25238862/|journal=NeuroRehabilitation|volume=35|issue=3|pages=529–534|last=Gaber|first=Tarek A.-Z. K.|last2=Oo|first2=Wah Wah|last3=Ringrose|first3=Hollie|doi=10.3233/NRE-141146|pmid=25238862|issn=1878-6448}}</ref>
In the [[United States]], the prevalence rate of [[chronic fatigue syndrome]] (CFS) is 0.42% of the population versus MS which has a rate of 0.09%.<ref name="Jason2010">{{Cite journal | title = Frequency and content analysis of chronic fatigue syndrome in medical text books | date = 2010 | url=https://pubmed.ncbi.nlm.nih.gov/21128580/|journal=Australian Journal of Primary Health|volume=16|issue=2|pages=174–178 | last= Jason | first = Leonard A. | authorlink = Leonard Jason | last2 = Paavola | first2 = Erin | authorlink2 = | last3 = Porter | first3 = Nicole | authorlink3 = | last4 = Morello | first4 = Morgan L. | authorlink4 = |doi=10.1071/py09023|pmc=3691015|pmid=21128580|access-date=|issn=1448-7527|quote=|via=}}</ref> Approximately 14% of MS patients meet the [[Fukuda criteria]] for CFS.<ref name="Gaber2014">{{Cite journal | title = Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide | date = 2014 |url=https://pubmed.ncbi.nlm.nih.gov/25238862/|journal=NeuroRehabilitation|volume=35|issue=3 | pages = 529–534 | last = Gaber | first = Tarek A.-Z.K. | last2 = Oo | first2 = Wah Wah | last3 = Ringrose | first3 = Hollie|doi=10.3233/NRE-141146|pmid=25238862|issn=1878-6448}}</ref>


In 2017, a study examined whether network analysis of cytokine production differed between patients with CFS,  multiple sclerosis, and healthy controls. The study's model, using a select [[cytokine]] profile, showed that immunologic activation in CFS was significantly different from that found in the control and multiple sclerosis groups.<ref name="Sorenson, 2017" />
In 2017, a study examined whether network analysis of cytokine production differed between patients with CFS,  multiple sclerosis, and healthy controls. The study's model, using a select [[cytokine]] profile, showed that immunologic activation in CFS was significantly different from that found in the control and multiple sclerosis groups.<ref name="Sorenson, 2017" />
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A 2015 study found a markedly disturbed immune signature in the [[cerebrospinal fluid]] that is consistent with immune activation in the [[central nervous system]] (CNS), and autoimmunity.  The MS and ME/CFS groups had markedly different immune signatures, and the ME/CFS group had a greater degree of CNS [[immune activation]] than the MS group.<ref name="Hornig2016" />   
A 2015 study found a markedly disturbed immune signature in the [[cerebrospinal fluid]] that is consistent with immune activation in the [[central nervous system]] (CNS), and autoimmunity.  The MS and ME/CFS groups had markedly different immune signatures, and the ME/CFS group had a greater degree of CNS [[immune activation]] than the MS group.<ref name="Hornig2016" />   


In December 2016, [[Diana Ohanian|Ohanian]], et al, published a study identifying two key immune symptoms that physicians could use to differentiate [[myalgic encephalomyelitis]] (ME) and [[Chronic fatigue syndrome|CFS]] from MS: [[flu-like symptoms]] and [[Swollen lymph nodes|tender lymph nodes]]. Subjects included 106 people with MS and 354 people with [[ME]] or CFS who completed the [[DePaul Symptom Questionnaire]]. The data was analyzed using data mining techniques and machine learning that resulted in correctly categorizing MS and ME or CFS 81.2% of the time. The authors conclude that "because ME or CFS and MS have similar presentations recognizing the importance of immune dysfunction for ME or CFS might be important for healthcare providers."<ref name="Ohanian, 2016">{{Cite journal
In December 2016, [[Diana Ohanian|Ohanian]], et al, published a study identifying two key immune symptoms that physicians could use to differentiate [[myalgic encephalomyelitis]] (ME) and [[Chronic fatigue syndrome|CFS]] from MS: [[flu-like symptoms]] and [[Swollen lymph nodes|tender lymph nodes]]. Subjects included 106 people with MS and 354 people with [[myalgic encephalomyelitis|ME]] or CFS who completed the [[DePaul Symptom Questionnaire]]. The data was analyzed using data mining techniques and machine learning that resulted in correctly categorizing MS and ME or CFS 81.2% of the time. The authors conclude that "because ME or CFS and MS have similar presentations recognizing the importance of immune dysfunction for ME or CFS might be important for healthcare providers."<ref name="Ohanian, 2016">{{Cite journal | last1 = Ohanian | first1 = Diana | authorlink1 = Diana Ohanian | last2 = Brown | first2 = Abigail | authorlink2 = Abigail Brown | last3 = Sunnquist | first3 = Madison | authorlink3 = Madison Sunnquist | last4 = Furst | first4 = Jacob | authorlink4 = Jacob Furst | last5 = Nicholson | first5 = Laura | authorlink5 = Laura Nicholson | last6 = Klebek | first6 = Lauren | authorlink6 = Lauren Klebek | last7 = Jason | first7 = Leonard | authorlink7 = Leonard Jason | title = Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis | journal = EC Neurology | volume = 4.1 | issue = 2 | pages = 41-45 | date = 2016 | pmid = 28066845 | pmc = PMC5214344 | doi = | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214344/}}</ref>
| last1   = Ohanian           | first1 = Diana             | authorlink1 = Diana Ohanian
| last2   = Brown             | first2 = Abigail           | authorlink2 = Abigail Brown
| last3   = Sunnquist         | first3 = Madison           | authorlink3 = Madison Sunnquist
| last4   = Furst             | first4 = Jacob             | authorlink4 = Jacob Furst
| last5   = Nicholson         | first5 = Laura             | authorlink5 = Laura Nicholson
| last6   = Klebek           | first6 = Lauren           | authorlink6 = Lauren Klebek
| last7   = Jason             | first7 = Leonard           | authorlink7 = Leonard Jason
| title   = Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis
| journal = EC Neurology   | volume = 4.1   | issue = 2   | pages = 41-45
| date   = 2016 | pmid   = 28066845 | pmc = PMC5214344 | doi     =  
| url     = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214344/}}</ref>


=== Differences in symptoms between multiple sclerosis and ME/CFS ===
=== Differences in symptoms between multiple sclerosis and ME/CFS ===
Line 113: Line 72:
*2012, Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.<ref name="White2012" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/ (Full Text)]
*2012, Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.<ref name="White2012" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/ (Full Text)]
*2013, Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics<ref name="Morris2013" /> - [https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-205 (Full Text)]
*2013, Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics<ref name="Morris2013" /> - [https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-205 (Full Text)]
*2015, A Preliminary Comparative Assessment of the Role of CD8+ [[T cell|T Cell]]s in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis<ref name="Brenu2016">{{Cite journal
*2015, A Preliminary Comparative Assessment of the Role of CD8+ [[T cell|T Cell]]s in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis<ref name="Brenu2016">{{Cite journal | last1 = Brenu | first1 = EW | authorlink1 = Ekua Brenu | last2 = Broadley | first2 = S | authorlink2 = Simon Broadley | last3 = Nguyen | first3 = T | authorlink3 = Thao Nguyen | last4 = Johnston | first4 = S | authorlink4 = Samantha Johnston | last5 = Ramos | first5 = S | authorlink5 = Sandra Ramos | last6 = Staines | first6 = D | authorlink6 = Donald Staines | last7 = Marshall-Gradisnik | first7 = S | authorlink7 = Sonya Marshall-Gradisnik | title = A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis | journal = Journal of Immunology Research | volume = | pages = | date = 2016 | doi = 10.1155/2016/9064529 | url = https://pdfs.semanticscholar.org/bf21/36527480dcd18592aa0e60970c5f5b2400fb.pdf }}</ref> - [https://pdfs.semanticscholar.org/bf21/36527480dcd18592aa0e60970c5f5b2400fb.pdf (Full Text)]  
| last1   = Brenu               | first1 = EW       | authorlink1 = Ekua Brenu
*2015, A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients<ref name="Wong, 2015">{{Cite journal | last1 = Wong | first1 = Naomi | authorlink1 = Naomi Wong | last2 = Nguyen | first2 = Thao | authorlink2 = Thao Nguyen | last3 = Brenu | first3 = Ekua Weba  | authorlink3 = Ekua Brenu | last4 = Broadley | first4 = Simon | authorlink4 = Simon Broadley | last5 = Staines | first5 = Donald | authorlink5 = Donald Staines | last6 = Marshall-Gradisnik | first6 = Sonya | authorlink6 = Sonya Marshall-Gradisnik | title = A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients | journal = International Journal of Clinical Medicine | volume = 6 | issue = 10 | pages = 769-783 | date = 2015 | url = https://doi.org/10.4236%2Fijcm.2015.610103 | pmid = | doi = 10.4236/ijcm.2015.610103 }}</ref> - [http://file.scirp.org/Html/10-2101204_60764.htm (Full Text)]  
| last2   = Broadley           | first2 = S       | authorlink2 = Simon Broadley
| last3   = Nguyen             | first3 = T       | authorlink3 = Thao Nguyen
| last4   = Johnston           | first4 = S       | authorlink4 = Samantha Johnston
| last5   = Ramos               | first5 = S       | authorlink5 = Sandra Ramos
| last6   = Staines             | first6 = D       | authorlink6 = Donald Staines
| last7   = Marshall-Gradisnik | first7 = S       | authorlink7 = Sonya Marshall-Gradisnik
| title   = A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis | journal = Journal of Immunology Research | volume = | pages =  
| date   = 2016 | doi     = 10.1155/2016/9064529
| url     = https://pdfs.semanticscholar.org/bf21/36527480dcd18592aa0e60970c5f5b2400fb.pdf }}</ref> - [https://pdfs.semanticscholar.org/bf21/36527480dcd18592aa0e60970c5f5b2400fb.pdf (Full Text)]  
*2015, A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients<ref name="Wong, 2015">{{Cite journal  
| last1   = Wong               | first1 = Naomi     | authorlink1 = Naomi Wong
| last2   = Nguyen             | first2 = Thao       | authorlink2 = Thao Nguyen
| last3   = Brenu               | first3 = Ekua Weba  | authorlink3 = Ekua Brenu
| last4   = Broadley           | first4 = Simon     | authorlink4 = Simon Broadley
| last5   = Staines             | first5 = Donald     | authorlink5 = Donald Staines
| last6   = Marshall-Gradisnik | first6 = Sonya     | authorlink6 = Sonya Marshall-Gradisnik
| title   = A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients
| journal = International Journal of Clinical Medicine | volume = 6   | issue = 10   | pages = 769-783
| date   = 2015 | url = https://doi.org/10.4236%2Fijcm.2015.610103
| pmid   = | doi     = 10.4236/ijcm.2015.610103 }}</ref> - [http://file.scirp.org/Html/10-2101204_60764.htm (Full Text)]  
*2016, Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis<ref name="Ohanian, 2016" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214344/ (Full Text)]
*2016, Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis<ref name="Ohanian, 2016" /> - [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214344/ (Full Text)]
*2016, Pilot Study of [[Natural killer cell|Natural Killer Cell]]s in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis<ref name="HuthTK2016">{{Cite journal
*2016, Pilot Study of [[Natural killer cell|Natural Killer Cell]]s in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis<ref name="HuthTK2016">{{Cite journal | last1 = Huth | first1 = TK | authorlink1 = Teilah Huth | last2 = Brenu | first2 = EW | authorlink2 = Ekua Brenu | last3 = Ramos | first3 = S | authorlink3 = Sandra Ramos | last4 = Nguyen | first4 = T | authorlink4 = | last5 = Broadley | first5 = S | authorlink5 = | last6 = Staines | first6 = D | authorlink6 = Donald Staines | last7 = Marshall-Gradisnik | first7 = S | authorlink7 = Sonya Marshall-Gradisnik | title = Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis | journal = Scand J Immunol | date = Jan 2016 | volume = 83 | issue = 1 | pages = 44-51 | pmid = 26381393 | doi = 10.1111/sji.12388 | url = https://www.ncbi.nlm.nih.gov/pubmed/26381393 }}</ref> -  [https://www.ncbi.nlm.nih.gov/pubmed/26381393 (Abstract)]
| last1   = Huth                 | first1 = TK       | authorlink1 = Teilah Huth
*2016, [[Regulatory T cell|Regulatory T]], natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison<ref name="Ramos, 2016">{{Cite journal | last1 = Ramos | first1 = S | authorlink1 = Sandra Ramos | last2 = Brenu | first2 = E | authorlink2 = Ekua Brenu | last3 = Broadley | first3 = S | authorlink3 = | last4 = Kwiatek | first4 = R | authorlink4 = Richard Kwiatek | last5 = Ng | first5 = J | authorlink5 = | last6 =Nguyen | first6 = T | authorlink6 = | last7 = Freeman | first7 = S | authorlink7 = | last8 = Staines | first8 = D | authorlink8 = Donald Staines | last9 =Marshall-Gradisnik | first9 = S | authorlink9 = Sonya Marshall-Gradisnik | title = Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison | journal = Asian Pac J Allergy Immunol | volume = | issue = 34 | pages = 300-305 | date = March 20, 2016 | doi = 10.12932/AP0733 | url = http://apjai-journal.org/wp-content/uploads/2016/12/8RegulatoryTnaturalkillerAPJAIVol34No4December2016P300.pdf}}</ref> - [http://apjai-journal.org/wp-content/uploads/2016/12/8RegulatoryTnaturalkillerAPJAIVol34No4December2016P300.pdf (Full Text)]  
| last2   = Brenu               | first2 = EW       | authorlink2 = Ekua Brenu
*2016, [[Cytokine]] network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome<ref name="Hornig2016">{{Cite journal | last1 = Hornig | first1 = M | authorlink1 = Mady Hornig | last2 = Gottschalk | first2 = CG | authorlink2 = Gunnar Gottschalk | last3 = Peterson | first3 = DL | authorlink3 = Daniel Peterson | last4 = Knox | first4 = KK | authorlink4 = | last5 = Schultz | first5 = AF | authorlink5 = | last6 =Eddy | first6 = ML | authorlink6 = | last7 = Che | first7 = X | authorlink7 = | last8 = Lipkin | first8 = WI | authorlink8 = Ian Lipkin | title = Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome | journal = Molecular Psychiatry | issn = 1359-4184 | volume = 21 | issue = 2| pages = 261–269 | date = Feb 2016 | doi = 10.1038/mp.2015.29 | url = http://www.nature.com/doifinder/10.1038/mp.2015.29}}</ref> - [https://www.nature.com/articles/mp201529 (Abstract)]  
| last3   = Ramos               | first3 = S       | authorlink3 = Sandra Ramos
*2017, Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome<ref name="Jason, Ohanian, 2017">{{Cite journal | last1 = Jason | first1 = LA | authorlink1 = Leonard Jason | last2 = Ohanian | first2 = D | authorlink2 = Diana Ohanian | last3 = Brown | first3 = A | authorlink3 = Abigail Brown | last4 = Sunnquist | first4 = M | authorlink4 = Madison Sunnquist | last5 = McManimen | first5 = S | authorlink5 = Stephanie McManimen | last6 = Klebek | first6 = L | authorlink6 = | last7 = Fox | first7 = P | authorlink7 = Pamela Fox | last8 = Sorenson | first8 = M | authorlink8 = Matthew Sorenson | title = Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome| journal = Insights in Biomedicine | volume = 2 | issue =  2  | pages = | date = 2017 | url = https://doi.org/10.21767%2F2572-5610.100011 | doi = 10.21767/2572-5610.100011 }}</ref> - [http://biomedicine.imedpub.com/differentiating-multiple-sclerosis-from-myalgic-encephalomyelitis-and-chronic-fatigue-syndrome.pdf (Full Text)]
| last4   = Nguyen               | first4 = T       | authorlink4 =  
*2017, Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis<ref name="Sorenson, 2017">{{Cite journal | last1 = Sorenson | first1 = Matthew | authorlink1 = Matthew Sorenson | last2 = Furst | first2 = Jacob | authorlink2 = Jacob Furst | last3 = Mathews | first3 = Herbert | authorlink3 = Herbert Mathews | last4 = Jason | first4 = Leonard A. | authorlink4 = Leonard Jason | title = Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis | journal = Fatigue: Biomedicine, Health & Behavior | volume = 5 | issue = 3 | pages = 145-158 | date = 2017 | pmid = | doi = 10.1080/21641846.2017.1335237|url=https://doi.org/10.1080%2F21641846.2017.1335237|pmc=|quote=|access-date= | authorlink5 = |via=}}</ref> - [https://www.researchgate.net/publication/318094772_Dysregulation_of_cytokine_pathways_in_chronic_fatigue_syndrome_and_multiple_sclerosis_Dysregulation_of_cytokine_pathways_in_chronic_fatigue_syndrome_and_multiple_sclerosis (Abstract)]
| last5   = Broadley             | first5 = S       | authorlink5 =  
*2017, Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study<ref name="Polli, 2017">{{Cite journal | last1 = Polli | first1 = Andrea | authorlink1 = | last2 = Willekens | first2 = Barbara | authorlink2 = | last3 = Meeus | first3 = Mira| authorlink3 = Mira Meeus | last4 = Nijs | first4 = Jo | authorlink4 = Jo Nijs | last5 = Collin | first5 = Simon M. | authorlink5 = Simon Collin | last6 =Ickmans | first6 = Kelly | authorlink6 = Kelly Ickmans | title = Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study Observational Study | journal = Pain Physician | volume = 20 | issue =  4  | pages = E489-E497 | date = 2017 | pmid = 28535557 | url = http://www.painphysicianjournal.com/current/pdf?article=NDQxMQ%3D%3D&journal=105 }}</ref> - [http://www.painphysicianjournal.com/current/pdf?article=NDQxMQ%3D%3D&journal=105 (Full Text)]
| last6   = Staines             | first6 = D       | authorlink6 = Donald Staines
*2018, Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls<ref>{{Cite journal | last = Kingdon | first = Caroline C. | last2 = Bowman | first2 = Erinna W. | last3 = Curran | first3 = Hayley | last4 = Nacul | first4 = Luis | last5 = Lacerda | first5 = Eliana M. | date = 2018-12-01 | title = Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=2|issue=4|pages=381–392|doi=10.1007/s41669-018-0071-6|issn=2509-4254|pmc=|pmid=29536371|quote= | author-link = Caroline Kingdon | authorlink2 = Erinna Bowman | authorlink3 = Hayley Curran | authorlink4 = Luis Nacul | authorlink5 = Eliana Lacerda | via=}}</ref> - [https://link.springer.com/article/10.1007%2Fs41669-018-0071-6 (Full Text)]  
| last7   = Marshall-Gradisnik   | first7 = S       | authorlink7 = Sonya Marshall-Gradisnik
| title   = Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis
| journal = Scand J Immunol | date = Jan 2016 | volume = 83 | issue = 1 | pages = 44-51
| pmid   = 26381393 | doi = 10.1111/sji.12388
| url     = https://www.ncbi.nlm.nih.gov/pubmed/26381393
}}</ref> -  [https://www.ncbi.nlm.nih.gov/pubmed/26381393 (Abstract)]
*2016, [[Regulatory T cell|Regulatory T]], natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison<ref name="Ramos, 2016">{{Cite journal
| last1   = Ramos               | first1 = S       | authorlink1 = Sandra Ramos
| last2   = Brenu               | first2 = E       | authorlink2 = Ekua Brenu
| last3   = Broadley             | first3 = S       | authorlink3 =  
| last4   = Kwiatek             | first4 = R       | authorlink4 = Richard Kwiatek
| last5   = Ng                   | first5 = J       | authorlink5 =  
| last6   = Nguyen               | first6 = T       | authorlink6 =  
| last7   = Freeman             | first7 = S       | authorlink7 =  
| last8   = Staines             | first8 = D       | authorlink8 = Donald Staines
| last9   = Marshall-Gradisnik   | first9 = S       | authorlink9 = Sonya Marshall-Gradisnik
| title   = Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison
| journal = Asian Pac J Allergy Immunol   | volume = | issue = 34 | pages = 300-305
| date   = March 20, 2016  
| doi     = 10.12932/AP0733
| url     = http://apjai-journal.org/wp-content/uploads/2016/12/8RegulatoryTnaturalkillerAPJAIVol34No4December2016P300.pdf}}</ref> - [http://apjai-journal.org/wp-content/uploads/2016/12/8RegulatoryTnaturalkillerAPJAIVol34No4December2016P300.pdf (Full Text)]  
*2016, [[Cytokine]] network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome<ref name="Hornig2016">{{Cite journal
| last1   = Hornig           | first1 = M                 | authorlink1 = Mady Hornig
| last2   = Gottschalk       | first2 = CG                 | authorlink2 = Gunnar Gottschalk
| last3   = Peterson         | first3 = DL                 | authorlink3 = Daniel Peterson
| last4   = Knox             | first4 = KK                 | authorlink4 =  
| last5   = Schultz         | first5 = AF                 | authorlink5 =  
| last6   = Eddy             | first6 = ML                 | authorlink6 =  
| last7   = Che             | first7 = X                 | authorlink7 =  
| last8   = Lipkin           | first8 = WI                 | authorlink8 = Ian Lipkin
| title   = Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome | journal = Molecular Psychiatry | issn = 1359-4184 | volume = 21| issue = 2| pages = 261–269
| date   = Feb 2016 | doi     = 10.1038/mp.2015.29
| url     = http://www.nature.com/doifinder/10.1038/mp.2015.29}}</ref> - [https://www.nature.com/articles/mp201529 (Abstract)]  
*2017, Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome<ref name="Jason, Ohanian, 2017">{{Cite journal
| last1   = Jason             | first1 = LA             | authorlink1 = Leonard Jason
| last2   = Ohanian           | first2 = D             | authorlink2 = Diana Ohanian
| last3   = Brown             | first3 = A             | authorlink3 = Abigail Brown
| last4   = Sunnquist         | first4 = M             | authorlink4 = Madison Sunnquist
| last5   = McManimen         | first5 = S             | authorlink5 = Stephanie McManimen
| last6   = Klebek           | first6 = L             | authorlink6 =  
| last7   = Fox               | first7 = P             | authorlink7 = Pamela Fox
| last8   = Sorenson         | first8 = M             | authorlink8 = Matthew Sorenson  
| title   = Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome| journal = Insights in Biomedicine     | volume = 2   | issue =  2  | pages = | date   = 2017 | url = https://doi.org/10.21767%2F2572-5610.100011 | doi     = 10.21767/2572-5610.100011 }}</ref> - [http://biomedicine.imedpub.com/differentiating-multiple-sclerosis-from-myalgic-encephalomyelitis-and-chronic-fatigue-syndrome.pdf (Full Text)]
*2017, Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis<ref name="Sorenson, 2017">{{Cite journal
| last1   = Sorenson         | first1 = Matthew             | authorlink1 = Matthew Sorenson  
| last2   = Furst           | first2 = Jacob               | authorlink2 = Jacob Furst
| last3   = Mathews         | first3 = Herbert             | authorlink3 = Herbert Mathews
| last4   = Jason           | first4 = Leonard A.         | authorlink4 = Leonard Jason  
| title   = Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis
| journal = Fatigue: Biomedicine, Health & Behavior | volume = 5 | issue = 3 | pages = 145-158 | date   = 2017
| pmid   = | doi     = 10.1080/21641846.2017.1335237|url=https://doi.org/10.1080%2F21641846.2017.1335237|pmc=|quote=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|access-date=|author-link5=|author-link6=|via=}}</ref> - [https://www.researchgate.net/publication/318094772_Dysregulation_of_cytokine_pathways_in_chronic_fatigue_syndrome_and_multiple_sclerosis_Dysregulation_of_cytokine_pathways_in_chronic_fatigue_syndrome_and_multiple_sclerosis (Abstract)]
*2017, Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study<ref name="Polli, 2017">{{Cite journal | last1   = Polli                 | first1 = Andrea             | authorlink1 =  
| last2   = Willekens             | first2 = Barbara             | authorlink2 =  
| last3   = Meeus                 | first3 = Mira               | authorlink3 = Mira Meeus
| last4   = Nijs                 | first4 = Jo                 | authorlink4 = Jo Nijs  
| last5   = Collin               | first5 = Simon M.           | authorlink5 = Simon Collin
| last6   = Ickmans               | first6 = Kelly               | authorlink6 = Kelly Ickmans
| title   = Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study Observational Study
| journal = Pain Physician | volume = 20   | issue =  4  | pages = E489-E497
| date   = 2017 | pmid   = 28535557
| url     = http://www.painphysicianjournal.com/current/pdf?article=NDQxMQ%3D%3D&journal=105 }}</ref> - [http://www.painphysicianjournal.com/current/pdf?article=NDQxMQ%3D%3D&journal=105 (Full Text)]
*2018, Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls<ref>{{Cite journal|last=Kingdon|first=Caroline C.|last2=Bowman|first2=Erinna W.|last3=Curran|first3=Hayley|last4=Nacul|first4=Luis|last5=Lacerda|first5=Eliana M.|date=2018-12-01|title=Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls|url=https://doi.org/10.1007/s41669-018-0071-6|journal=PharmacoEconomics - Open|language=en|volume=2|issue=4|pages=381–392|doi=10.1007/s41669-018-0071-6|issn=2509-4254|pmc=|pmid=29536371|quote=|author-link=Caroline Kingdon|author-link2=Erinna Bowman|author-link3=Hayley Curran|author-link4=Luis Nacul|author-link5=Eliana Lacerda|via=}}</ref> - [https://link.springer.com/article/10.1007%2Fs41669-018-0071-6 (Full Text)]  


===Other studies===
===Other studies===
Line 213: Line 90:


==See also==
==See also==
*[[Myelin]]
*[[Rituximab]]
*[[Rituximab]]
*[[Ocrelizumab]]
*[[Ocrelizumab]]

Latest revision as of 00:31, December 31, 2023

Multiple sclerosis (MS) is a chronic, irreversible, autoimmune and neurological disease that affects the central nervous system, including the brain and spinal cord.[1][2] In multiple sclerosis the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. Specific symptoms can include double vision, blindness in one eye, muscle weakness, trouble with sensation, or trouble with coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent neurological problems often remain, especially as the disease advances.[citation needed]

Epidemiology[edit | edit source]

MS prevalence.png

Prevalence[edit | edit source]

An estimated 2.3 million people worldwide have multiple sclerosis.

Risk factors[edit | edit source]

  • Latitude, which may be a main cause of vitamin D deficiency

Gender differences[edit | edit source]

Over the last decades, the ratio of women to men with MS has increased markedly, representing a true increase in MS among women but not men.[3]

Disease mechanisms[edit | edit source]

Demyelination of the myelin sheath[edit | edit source]

In multiple sclerosis, the myelin sheath, which is the layers of myelin surrounding the nerves of the brain and spinal cord, is destroyed, disrupting the transmission of signals in the nerves.[4]

Epstein-Barr virus[edit | edit source]

In 2022, clear evidence was found of the role of Epstein-Barr virus infection in triggering multiple sclerosis,[5] the strength of the link was higher than that between smoking and lung cancer.[6]

The hypothesis that EBV causes MS has been investigated by our group and others for several years, but this is the first study providing compelling evidence of causality...This is a big step because it suggests that most MS cases could be prevented by stopping EBV infection, and that targeting EBV could lead to the discovery of a cure for MS.[7] — Alberto Ascherio, Harvard Chan School

Genes[edit | edit source]

Genetic factors have been recognized as important in multiple sclerosis, and may combine with certain environmental factors, such as smoking and vitamin D deficiency, as well as Epstein-Barr virus infection.[7]

Immune system[edit | edit source]

In 1997, it was discovered that B cell therapy (eg Rituximab) which reduces the number of B cells, can bring immediate improvement in MS symptoms. This treatment is more effective for the relapsing-remitting variant of MS, and less effective for the primary progressive variant.[8]

Microbiome[edit | edit source]

Specific changes in the gut microbiome might increase the risk of MS[9], and the risk might be reduced using probiotics, antibiotics, a combination, or a change of diet. An International Multiple Sclerosis Microbiome Study commenced in 2015.[8]

Treatments[edit | edit source]

Standard of care[edit | edit source]

Experimental treatments[edit | edit source]

Another discovery was that a commonly available and inexpensive antihistamine, can be used to induce remyelination of the nerve cells.[8]

Dietary tryptophan can help reduce brain inflammation and 'cognitive fog'.[10]

Comparison of Multiple Sclerosis and ME/CFS[edit | edit source]

Multiple sclerosis patients or samples are sometimes used for comparison with in ME/CFS in research studies, for instance at the UK ME/CFS biobank, and both are female predominant diseases of the central nervous system.[11][12][13]

There are many similar features in multiple sclerosis and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), including: severe disabling fatigue that worsens after exercise; debilitating autonomic symptoms, including orthostatic intolerance; illness course may be relapsing-remitting or progressive; infections and psychosocial stress causing exacerbation; autoimmunity and auto-inflammatory processes; mitochondria dysfunction; and decreased cerebral blood flow, atrophy of some brain structures.[12]

In the United States, the prevalence rate of chronic fatigue syndrome (CFS) is 0.42% of the population versus MS which has a rate of 0.09%.[14] Approximately 14% of MS patients meet the Fukuda criteria for CFS.[15]

In 2017, a study examined whether network analysis of cytokine production differed between patients with CFS, multiple sclerosis, and healthy controls. The study's model, using a select cytokine profile, showed that immunologic activation in CFS was significantly different from that found in the control and multiple sclerosis groups.[16]

A 2015 study found a markedly disturbed immune signature in the cerebrospinal fluid that is consistent with immune activation in the central nervous system (CNS), and autoimmunity. The MS and ME/CFS groups had markedly different immune signatures, and the ME/CFS group had a greater degree of CNS immune activation than the MS group.[17]

In December 2016, Ohanian, et al, published a study identifying two key immune symptoms that physicians could use to differentiate myalgic encephalomyelitis (ME) and CFS from MS: flu-like symptoms and tender lymph nodes. Subjects included 106 people with MS and 354 people with ME or CFS who completed the DePaul Symptom Questionnaire. The data was analyzed using data mining techniques and machine learning that resulted in correctly categorizing MS and ME or CFS 81.2% of the time. The authors conclude that "because ME or CFS and MS have similar presentations recognizing the importance of immune dysfunction for ME or CFS might be important for healthcare providers."[18]

Differences in symptoms between multiple sclerosis and ME/CFS[edit | edit source]

Ohanian et al. (2016) found that the following five symptoms were significantly more common in patients with ME/CFS compared to patients with multiple sclerosis, with mean scores reported as:

  1. Flu-like symptoms: reported in 51 in ME/CFS patients, and 17 inMS patients
  2. Tender lymph nodes: 37 in ME/CFS patients, 8% in MS patients
  3. Alcohol intolerance: 38 in ME/CFS patients, 9 in MS patients
  4. Inability to tolerate upright position (orthostatic intolerance): 51 in ME/CFS patients, 16 in MS patients
  5. post-exertional symptom exacerbation e.g., next-day soreness after non-strenuous activities: 75 in ME/CFS patients, 46 in MS patients

The presence of just two immune-related symptoms (tender lymph nodes and flu-like symptoms), which are optional symptoms in ME/CFS, was found to correctly classify around 80% of patients with ME/CFS, who did not have MS.[18]

Notable studies comparing ME/CFS and multiple sclerosis[edit | edit source]

  • 2012, Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.[13] - (Full Text)
  • 2013, Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics[12] - (Full Text)
  • 2015, A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis[19] - (Full Text)
  • 2015, A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients[20] - (Full Text)
  • 2016, Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis[18] - (Full Text)
  • 2016, Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis[21] - (Abstract)
  • 2016, Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison[22] - (Full Text)
  • 2016, Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome[17] - (Abstract)
  • 2017, Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome[23] - (Full Text)
  • 2017, Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis[16] - (Abstract)
  • 2017, Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study[24] - (Full Text)
  • 2018, Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls[25] - (Full Text)

Other studies[edit | edit source]

  • 2015, HIV and lower risk of multiple sclerosis: beginning to unravel a mystery using a record-linked database study - (Abstract)

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. Javalkar, Vijaykumar; McGee, Jeanie; Minagar, Alireza (2016). "Clinical Manifestations of Multiple Sclerosis: An Overview". Multiple Sclerosis: A Mechanistic View. Academic Press. pp. 1–12. doi:10.1016/b978-0-12-800763-1.00001-4. ISBN 9780128007631.
  2. "What is multiple sclerosis?". University College London Hospitals NHS trust. Retrieved April 17, 2019.
  3. Harbo, Hanne F.; Gold, Ralf; Tintoré, Mar (July 2013). "Sex and gender issues in multiple sclerosis". Therapeutic Advances in Neurological Disorders. 6 (4): 237–248. doi:10.1177/1756285613488434. ISSN 1756-2856. PMC 3707353. PMID 23858327.
  4. Levin, Michael C. (2023). "Overview of Demyelinating Disorders - Brain, Spinal Cord, and Nerve Disorders". MSD Manual Consumer Version. Retrieved December 30, 2023.
  5. Bjornevik, Kjetil; Cortese, Marianna; Healy, Brian C.; Kuhle, Jens; Mina, Michael J.; Leng, Yumei; Elledge, Stephen J.; Niebuhr, David W.; Scher, Ann I.; Munger, Kassandra L.; Ascherio, Alberto (January 21, 2022). "Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis". Science. doi:10.1126/science.abj8222.
  6. Denworth, Lydia (January 13, 2022). "Epstein-Barr Virus Found to Trigger Multiple Sclerosis". Scientific American. Retrieved January 15, 2022.
  7. 7.0 7.1 "Epstein-Barr virus may be leading cause of multiple sclerosis". Harvard T.H. Chan School of Public Health. January 13, 2022. Retrieved January 15, 2022.
  8. 8.0 8.1 8.2 Conway, Claire (April 25, 2016). "Wrapping Up Multiple Sclerosis". UC San Francisco News Center.
  9. "Gut bacteria regulate nerve fibre insulation". The Guardian - Science. April 5, 2016.
  10. Rothhammer, Veit; Mascanfroni, Ivan D; Bunse, Lukas; Takenaka, Maisa C; Kenison, Jessica E; Mayo, Lior; Chao, Chun-Cheih; Patel, Bonny; Yan, Raymond; Blain, Manon; Alvarez, Jorge I; Kébir, Hania; Anandasabapathy, Niroshana; Izquierdo, Guillermo; Jung, Steffen; Obholzer, Nikolaus; Pochet, Nathalie; Clish, Clary B; Prinz, Marco; Prat, Alexandre; Antel, Jack; Quintana, Francisco J (May 9, 2016). "Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor". Nature Medicine. doi:10.1038/nm.4106. ISSN 1078-8956.
  11. Lacerda, Eliana M.; Bowman, Erinna W.; Cliff, Jacqueline M.; Kingdon, Caroline C.; King, Elizabeth C.; Lee, Ji-Sook; Clark, Taane G.; Dockrell, Hazel M.; Riley, Eleanor M. (2017). "The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis". Open journal of bioresources. 4. doi:10.5334/ojb.28. ISSN 2056-5542. PMC 5482226. PMID 28649428.
  12. 12.0 12.1 12.2 Morris, Gerwyn; Maes, Michael (December 2013). "Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics". BMC Medicine. 11 (1): 205. doi:10.1186/1741-7015-11-205. ISSN 1741-7015. PMC 3847236. PMID 24229326.
  13. 13.0 13.1 White, Andrea T.; Light, Alan R.; Hughen, Ronald W.; VanHaitsma, Timothy A.; Light, Kathleen C. (January 2012). "Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls". Psychosomatic Medicine. 74 (1): 46–54. doi:10.1097/PSY.0b013e31824152ed. ISSN 0033-3174. PMC 3256093. PMID 22210239.
  14. Jason, Leonard A.; Paavola, Erin; Porter, Nicole; Morello, Morgan L. (2010). "Frequency and content analysis of chronic fatigue syndrome in medical text books". Australian Journal of Primary Health. 16 (2): 174–178. doi:10.1071/py09023. ISSN 1448-7527. PMC 3691015. PMID 21128580.
  15. Gaber, Tarek A.-Z.K.; Oo, Wah Wah; Ringrose, Hollie (2014). "Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide". NeuroRehabilitation. 35 (3): 529–534. doi:10.3233/NRE-141146. ISSN 1878-6448. PMID 25238862.
  16. 16.0 16.1 Sorenson, Matthew; Furst, Jacob; Mathews, Herbert; Jason, Leonard A. (2017). "Dysregulation of cytokine pathways in chronic fatigue syndrome and multiple sclerosis". Fatigue: Biomedicine, Health & Behavior. 5 (3): 145–158. doi:10.1080/21641846.2017.1335237.
  17. 17.0 17.1 Hornig, M; Gottschalk, CG; Peterson, DL; Knox, KK; Schultz, AF; Eddy, ML; Che, X; Lipkin, WI (February 2016). "Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome". Molecular Psychiatry. 21 (2): 261–269. doi:10.1038/mp.2015.29. ISSN 1359-4184.
  18. 18.0 18.1 18.2 Ohanian, Diana; Brown, Abigail; Sunnquist, Madison; Furst, Jacob; Nicholson, Laura; Klebek, Lauren; Jason, Leonard (2016). "Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis". EC Neurology. 4.1 (2): 41–45. PMC 5214344. PMID 28066845.
  19. Brenu, EW; Broadley, S; Nguyen, T; Johnston, S; Ramos, S; Staines, D; Marshall-Gradisnik, S (2016). "A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis" (PDF). Journal of Immunology Research. doi:10.1155/2016/9064529.
  20. Wong, Naomi; Nguyen, Thao; Brenu, Ekua Weba; Broadley, Simon; Staines, Donald; Marshall-Gradisnik, Sonya (2015). "A Comparison of Cytokine Profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis Patients". International Journal of Clinical Medicine. 6 (10): 769–783. doi:10.4236/ijcm.2015.610103.
  21. Huth, TK; Brenu, EW; Ramos, S; Nguyen, T; Broadley, S; Staines, D; Marshall-Gradisnik, S (January 2016). "Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis". Scand J Immunol. 83 (1): 44–51. doi:10.1111/sji.12388. PMID 26381393.
  22. Ramos, S; Brenu, E; Broadley, S; Kwiatek, R; Ng, J; Nguyen, T; Freeman, S; Staines, D; Marshall-Gradisnik, S (March 20, 2016). "Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison" (PDF). Asian Pac J Allergy Immunol (34): 300–305. doi:10.12932/AP0733.
  23. Jason, LA; Ohanian, D; Brown, A; Sunnquist, M; McManimen, S; Klebek, L; Fox, P; Sorenson, M (2017). "Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome". Insights in Biomedicine. 2 (2). doi:10.21767/2572-5610.100011.
  24. Polli, Andrea; Willekens, Barbara; Meeus, Mira; Nijs, Jo; Collin, Simon M.; Ickmans, Kelly (2017). "Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study Observational Study". Pain Physician. 20 (4): E489–E497. PMID 28535557.
  25. Kingdon, Caroline C.; Bowman, Erinna W.; Curran, Hayley; Nacul, Luis; Lacerda, Eliana M. (December 1, 2018). "Functional Status and Well-Being in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Compared with People with Multiple Sclerosis and Healthy Controls". PharmacoEconomics - Open. 2 (4): 381–392. doi:10.1007/s41669-018-0071-6. ISSN 2509-4254. PMID 29536371.