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List of abnormal findings in chronic fatigue syndrome and myalgic encephalomyelitis
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[[Myalgic encephalomyelitis]]/[[chronic fatigue syndrome]] is a complex multi-system disease and biological abnormalities in patients have been found affecting multiple bodily systems. No single [[diagnostic biomarker|biomarker]]-based diagnostic test has been validated but patients have a range abnormal physical findings affecting multiple bodily systems.<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas | last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick | last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell | last7 = Staines | first7 = D | authorlink7 = Donald Staines | last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10 = Rosamund Vallings | last11 = Bateman | first11 = L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 = N | authorlink13 = Nicoletta Carlo-Stella | last14 = Chia | first14 = J | authorlink14 = John Chia | last15 = Darragh | first15 = A | authorlink15 = Austin Darragh | last16 = Gerken | first16 = A | authorlink16 = Anne Gerken | last17 = Jo | first17 = D | authorlink17 = Daehyun Jo | last18 = Lewis | first18 = DP | authorlink18 = Donald Lewis | last19 = Light | first19 = AR | authorlink19 = Alan Light | last20 = Light | first20 = KC | authorlink20 = Kathleen Light | last21 = Marshall-Gradisnik | first21 = S | authorlink21 = Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 = J | authorlink22 = John McLaren-Howard | last23 = Mena | first23 = I | authorlink23 = Ismael Mena | last24 = Miwa | first24 = K | authorlink24 = Kunihisa Miwa | last25 = Murovska | first25 = M | authorlink25= Modra Murovska | last26 = Stevens | first26 = SR | authorlink26 = Staci Stevens | title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012 | isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf }}</ref> The CDC states that diagnosing ME/CFS relies on a physical and psychiatric assessment, observations, medical history, clinical interview, and results from a mix of blood and urine tests.<ref name="CDC2020diagnosis">{{Cite web|url=https://www.cdc.gov/me-cfs/symptoms-diagnosis/diagnosis.html | title = Diagnosis of ME/CFS {{!}} Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | last = Centers of Disease Control|first = | authorlink = Centers for Disease Control and Prevention | date = 2019-05-15 | website = [[Centers for Disease Control and Prevention]]|language=en-us|archive-url=|archive-date=|url-status=|access-date=2020-09-26}}</ref> == Nervous system == ===Brain === {{Main article|Brain}} *Progressive brain changes<ref name="Shan2016"/> === Central nervous system === {{Main article |page_name =Central nervous system}} * increased [[Ventricular system|ventricular]] [[lactate]]<ref name="Mathew2009">{{Cite journal | last = Mathew|first = Sanjay J. | last2 = Mao | first2 = Xiangling | last3 = Keegan | first3 = Kathryn A. | last4 = Levine | first4 = Susan M. | authorlink4 = Susan Levine | last5 = Smith | first5 = Eric L.P. | last6 = Heier | first6 = Linda A. | last7 = Otcheretko | first7 = Viktor | last8 = Coplan | first8 = Jeremy D. | last9 = Shungu | first9 = Dikoma C. | authorlink9 = Dikoma Shungu | date = Apr 2009 | title = Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: anin vivo3.0 T1H MRS imaging study|url=https://onlinelibrary.wiley.com/doi/full/10.1002/nbm.1315|journal=NMR in Biomedicine|language=en|volume=22|issue=3|pages=251–258|doi=10.1002/nbm.1315|issn=0952-3480}}</ref><ref name="Murrough2010">{{Cite journal | last = Murrough|first = James W. | last2 = Mao | first2 = Xiangling | last3 = Collins | first3 = Katherine A. | last4 = Kelly | first4 = Chris | last5 = Andrade | first5 = Gizely | last6 = Nestadt | first6 = Paul | last7 = Levine | first7 = Susan M. | authorlink7 = Susan Levine | last8 = Mathew | first8 = Sanjay J. | last9 = Shungu | first9 = Dikoma C. | authorlink9 = Dikoma Shungu | date = Jul 2010 | title = Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder | url =https://www.ncbi.nlm.nih.gov/pubmed/20661876|journal=NMR in Biomedicine|volume=23|issue=6 | pages = 643–650|doi=10.1002/nbm.1512|issn=1099-1492|pmid=20661876}}</ref><ref name="Shungu2012">{{Cite journal | last = Shungu | first = Dikoma C. | authorlink1 = Dikoma Shungu | last2 = Weiduschat | first2 = Nora | last3 = Murrough | first3 = James W. | last4 = Mao | first4 = Xiangling | last5 = Pillemer | first5 = Sarah | last6 = Dyke | first6 = Jonathan P. | last7 = Medow | first7 = Marvin S. | last8 = Natelson | first8 = Benjamin H. | authorlink8 = Benjamin Natelson | last9 = Stewart | first9 = Julian M. | date = Sep 2012 | title = Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology|url=https://www.ncbi.nlm.nih.gov/pubmed/22281935|journal=NMR in biomedicine|volume=25|issue=9|pages=1073–1087|doi=10.1002/nbm.2772|issn=1099-1492|pmc=3896084|pmid=22281935}}</ref><ref name="Natelson2017">{{Cite journal | last = Natelson | first = Benjamin H. | authorlink1 = Benjamin Natelson | last2 = Vu | first2 = Diana | last3 = Coplan | first3 = Jeremy D. | last4 = Mao | first4 = Xiangling | last5 = Blate | first5 = Michelle | last6 = Kang | first6 = Guoxin | last7 = Soto | first7 = Eli | last8 = Kapusuz | first8 = Tolga | last9 = Shungu | first9 = Dikoma C. | authorlink9 = Dikoma Shungu | date = 2017-01-02 | title = Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2017.1280114?journalCode=rftg20|journal = Fatigue: Biomedicine, Health & Behavior |language=en|volume=5|issue=1|pages=15–20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=5754037|pmid=29308330}}</ref> * neuroinflammation<ref name="Nakatomi2014">{{Cite journal | last = Nakatomi|first = Yasuhito | last2 = Mizuno | first2 = Kei | last3 = Ishii | first3 = Akira | last4 = Wada | first4 = Yasuhiro | last5 = Tanaka | first5 = Masaaki | last6 = Tazawa | first6 = Shusaku | last7 = Onoe | first7 = Kayo | last8 = Fukuda | first8 = Sanae | last9 = Kawabe | first9 = Joji | date = 2014-06-01 | title = Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study|url=http://jnm.snmjournals.org/content/55/6/945|journal=Journal of Nuclear Medicine|language=en|volume=55|issue=6 | pages = 945–950|doi=10.2967/jnumed.113.131045|issn=0161-5505|pmid=24665088}}</ref><ref name="Zeineh2014">{{citation | last1 = Zeineh | first1 = Michael M | authorlink1 = Michael Zeineh | last2 = Kang | first2 = James | authorlink2 = James Kang | last3 = Atlas | first3 = Scott W | authorlink3 = Scott Atlas | last4 = Raman | first4 = Mira M | authorlink4 = Mira Raman | last5 = Reiss | first5 = Allan L | authorlink5 = Allan Reiss | last6 =Norris | first6 = Jane L | authorlink6 = Jane Norris | last7 =Valencia | first7 = Ian | authorlink7 = Ian Valencia | last8 =Montoya | first8 = Jose G | authorlink8 = Jose Montoya | title = Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome| journal = Radiology | volume = 274 | issue = 2| pages = 517–526 | date = 2014-10-29| doi = 10.1148/radiol.14141079| url = http://pubs.rsna.org/doi/abs/10.1148/radiol.14141079}}</ref><ref name="Mueller2019">{{Cite journal|url=https://link.springer.com/epdf/10.1007/s11682-018-0029-4 | title = Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy | last = Mueller | first = Christina | authorlink=Christina Mueller | last2 = Lin | first2 = Joanne C | authorlink2 = Joanne Lin | date = 2019 | doi=10.1007/s11682-018-0029-4|archive-url=|archive-date=|url-status=|access-date=2019-01-17 | authorlink3 = Sulaiman Sheriff | authorlink4 = Andrew Maudsley | authorlink5 = Jarred Younger | last3 = Sheriff | last4 = Maudsley | last5 = Younger | first3 = Sulaiman | first4 = Andrew A | first5 = Jarred W|volume=|issue=|pages= | page = |journal=Brain Imaging and Behavior}}</ref><ref name="RamsayAward20190117">{{Cite web|url=http://go.solvecfs.org/webmail/192652/97033877/74d435097e87231f24cffe4d9de93da8e3f71c0e077a67417eba10cbd269ccb1 | title = Brain Imaging and Behavior publication from Dr. Jarred Younger’s SMCI Ramsay pilot study supports involvement of neuroinflammation in ME/CFS|website=go.solvecfs.org|access-date=2019-01-17 | date = | last = | first = | authorlink = |archive-url=|archive-date=|url-status=}}</ref> * reduced [[Grey matter|grey]]<ref name="Puri2012">{{Cite journal | last = Puri|first = B K | last2 = Jakeman | first2 = P M | last3 = Agour | first3 = M | last4 = Gunatilake | first4 = K D R | last5 = Fernando | first5 = K A C | last6 = Gurusinghe | first6 = A I | last7 = Treasaden | first7 = I H | last8 = Waldman | first8 = A D | last9 = Gishen | first9 = P | date = Jul 2012 | title = Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel-based morphometry 3 T MRI study|url=https://www.birpublications.org/doi/full/10.1259/bjr/93889091|journal=The British Journal of Radiology|language=en|volume=85|issue=1015| pages = e270–e273|doi=10.1259/bjr/93889091|issn=0007-1285|pmc=3474083|pmid=22128128}}</ref> and [[white matter]]<ref name="Shan2016">{{Cite journal | last = Shan | first = Zack Y. | authorlink = Zack Shan | last2 = Kwiatek | first2 = Richard | last3 = Burnet | first3 = Richard | last4 = Del Fante | first4 = Peter | last5 = Staines | first5 = Donald R. | last6 = Marshall-Gradisnik | first6 = Sonya M. | last7 = Barnden | first7 = Leighton R. | date = 2016-04-28 | title = Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study|url=https://onlinelibrary.wiley.com/doi/full/10.1002/jmri.25283|journal=Journal of Magnetic Resonance Imaging|language=en|volume=44|issue=5|pages=1301–1311|doi=10.1002/jmri.25283|issn=1053-1807|pmc=5111735|pmid=27123773}}</ref><ref name="Puri2012" /> * [[Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy (2019) Mueller, et al|widespread metabolite abnormalities]]<ref name="Mueller2019"/> === Autonomic nervous system === {{Main article |page_name =Autonomic nervous system}} * Orthostatic intolerance<ref>Gerwin Morris, Michael Maes, see citations 12 through 27 in [http://www.biomedcentral.com/1741-7015/11/205 "Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics"] BMC Medicine, 17 September 2013</ref><ref>{{Cite journal | last = Miwa | first = K | date = Jul 2015 | title = Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle|url=https://www.ncbi.nlm.nih.gov/pubmed/24736946|journal=Heart and Vessels|volume=30|issue=4 | pages = 484–489|via=}}</ref> === Peripheral nervous system === {{Main article |page_name =Peripheral nervous system}} == Muscular system == {{Main article |page_name =Muscle}} *[[Mitochondrion|mitochondria]]l abnormalities found via [[muscle biopsy]] including: mitochondrial degeneration,<ref>{{Cite journal | last = Behan | first = W. M.H. | last2 = More | first2 = I.A.R. | last3 = Behan | first3 = P.O. | date = Dec 1991 | title = Mitochondrial abnormalities in the postviral fatigue syndrome|url=https://link.springer.com/article/10.1007/BF00294431|journal=Acta Neuropathologica|language=en|volume=83|issue=1 | pages = 61–65|doi=10.1007/bf00294431|issn=0001-6322}}</ref> deletions of mitochondrial DNA,<ref name=":0">{{Cite journal | date = 1996-04-19 | title = Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome|url=https://www.sciencedirect.com/science/article/abs/pii/0304394096125593|journal=Neuroscience Letters|language=en|volume=208|issue=2|pages=117–120|doi=10.1016/0304-3940(96)12559-3|issn=0304-3940}}</ref><ref>{{Cite journal | last = Zhang|first = C. | last2 = Baumer | first2 = A. | last3 = Mackay | first3 = I.R. | last4 = Linnane | first4 = A.W. | last5 = Nagley | first5 = P. | date = Apr 1995 | title = Unusual pattern of mitochondrial DNA deletions in skeletal muscle of an adult human with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/7633428|journal=Human Molecular Genetics|volume=4|issue=4 | pages = 751–754|issn=0964-6906|pmid=7633428}}</ref> the reduction of mitochondrial activity<ref name=":0" /> *Increased urinary [[creatine]] excretion during relapses<ref>{{Cite journal | last = Albrecht | first = Robert | date = March 21, 1964 | title = Epidemic Neuromyasthenia Outbreak in a Convent in New York State|url=https://www.ncbi.nlm.nih.gov/pubmed/14100144|journal=Journal of the American Medical Association|volume=187 | pages = 904-907|via=}}</ref> *Increased [[creatine kinase]] ([[postviral fatigue syndrome]]) *Persistence of [[enterovirus]]es in muscle tissue<ref name=":1">{{Cite journal | last = Gow|first = J.W. | last2 = Behan | first2 = W. M.H. | last3 = Simpson | first3 = K. | last4 = McGarry | first4 = F. | last5 = Keir | first5 = S. | last6 = Behan | first6 = P.O. | date = 1994-01-01 | title = Studies on Enterovirus in Patients with Chronic Fatigue Syndrome|url=https://academic.oup.com/cid/article-abstract/18/Supplement_1/S126/316946|journal=Clinical Infectious Diseases|language=en|volume=18|issue=Suppl 1|pages=S126–S129|doi=10.1093/clinids/18.Supplement_1.S126|issn=1537-6591}}</ref><ref name=":2">{{Cite journal | last = Cunningham|first = Louise | last2 = Bowles | first2 = N.E. | last3 = Lane | first3 = R. J.M. | last4 = Dubowitz | first4 = V. | last5 = Archard | first5 = L.C. | date = 1990 | title = Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA|url=http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-71-6-1399|journal=Journal of General Virology|volume=71|issue=6|pages=1399–1402|doi=10.1099/0022-1317-71-6-1399}}</ref><ref name=":3">{{Cite journal | last = Archard | first = LC | last2 = Bowles | first2 = NE | last3 = Behan | first3 = PO | last4 = Bell | first4 = EJ | last5 = Doyle | first5 = D | date = 1988-06-01 | title = Postviral Fatigue Syndrome: Persistence of Enterovirus RNA in Muscle and Elevated Creatine Kinase, Postviral Fatigue Syndrome: Persistence of Enterovirus RNA in Muscle and Elevated Creatine Kinase|url=https://doi.org/10.1177/014107688808100608|journal=Journal of the Royal Society of Medicine|language=en|volume=81|issue=6 | pages = 326–329|doi=10.1177/014107688808100608|issn=0141-0768|pmc=1291623|pmid=3404526}}</ref><ref name=":4">{{Cite journal | last = Gow|first = J.W. | last2 = Behan | first2 = W.M. | last3 = Clements | first3 = G.B. | last4 = Woodall | first4 = C. | last5 = Riding | first5 = M. | last6 = Behan | first6 = P.O. | date = 1991-03-23 | title = Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome.|url=https://www.bmj.com/content/302/6778/692|journal=BMJ|language=en|volume=302|issue=6778 | pages = 692–696|doi=10.1136/bmj.302.6778.692|issn=0959-8138|pmid=1850635}}</ref> *abnormalities of [[AMPK]] activation and glucose uptake in cultured skeletal muscle cells<ref name="BrownAE2015">{{Citation | last1 = Brown | first1 = Audrey E | authorlink1 = Audrey Brown | last2 = Jones | first2 = David E | authorlink2 = David Jones | last3 = Walker | first3 = Mark | authorlink3 = Mark Walker | last4 = Newton | first4 = Julia L | authorlink4 = Julia Newton | title = Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells | journal = PLoS One | volume = 10 | issue = 4 | date = 2 Apr 2015 | pmid = 25836975 | doi = 10.1371/journal.pone.0122982 | url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122982 }}</ref><ref name="Wellness20150420">{{citation | last1 = Dobberstein | first1 = Linda J. | authorlink1 = | title = Master Enzyme Switch Deactivated In Chronic Fatigue Syndrome and Fibromyalgia | journal = Wellness Resources | date = 20 Apr 2015 | url = http://www.wellnessresources.com/health/articles/master_enzyme_switch_deactivated_in_chronic_fatigue_syndrome_and_fibromyalg/ }}</ref> == Immune system == {{Main article |page_name =Immune system}} === Immune dysregulation === * [[Natural killer cell]] function is reduced<ref>{{Cite journal | title = Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology | date = Apr 2014|issn=1460-2377|pmid=24343819|pages=233–242|volume=26|issue=4|doi=10.1093/intimm/dxt068|first = Ekua Weba | last = Brenu | first2 = Teilah K. | last2 = Huth | first3 = Sharni L. | last3 = Hardcastle | first4 = Kirsty | last4 = Fuller | first5 = Manprit | last5 = Kaur | first6 = Samantha | last6 = Johnston | first7 = Sandra B. | last7 = Ramos | first8 = Don R. | last8 = Staines | first9 = Sonya M. | last9 = Marshall-Gradisnik}}</ref><ref>{{Cite journal | last = Victoria Scott | first = David Strayer | date = 2015 | title=Low NK Cell Activity in Chronic Fatigue Syndrome (CFS) and Relationship to Symptom Severity|url=https://www.omicsonline.org/open-access/low-nk-cell-activity-in-chronic-fatigue-syndrome-cfs-and-relationship-to-symptom-severity-2155-9899-1000348.php?aid=59415|journal=Journal of Clinical & Cellular Immunology|language=en|volume=6|issue=4|doi=10.4172/2155-9899.1000348|issn=2155-9899}}</ref> * [[Cytokine]] dysregulation<ref name="Montoya, 2017">{{citation | last1 = Montoya | first1 = Jose G. | authorlink1 = Jose Montoya | last2 = Holmes | first2 = Tyson H. | authorlink2 = | last3 = Anderson | first3 = Jill N. | authorlink3 = | last4 = Maecker | first4 = Holden T. | authorlink4 = | last5 = Rosenberg-Hasson | first5 = Yael | authorlink5 = | last6 = Valencia | first6 = Ian J. | authorlink6 = | last7 = Chu | first7 = Lily | authorlink7 = Lily Chu | last8 =Younger | first8 = Jarred W. | authorlink8 = Jarred Younger | last9 =Tato | first9 = Cristina M. | authorlink9 = | last10 = Davis | first10 = Mark M. | authorlink10 = Mark Davis | title = Cytokine signature associated with disease severity in chronic fatigue syndrome patients | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 34 | pages = E7150-E7158 | date = 2017 | pmid = | doi = 10.1073/pnas.1710519114 }}</ref><ref>[http://www.meaction.net/2015/12/07/study-finds-evidence-of-downregulated-immune-system-in-mecfs-patients Study finds evidence of downregulated immune system in ME/CFS patients - MEAction - Landi, et al.]</ref><ref>[http://microbediscovery.org/2017/04/04/new-research-discovers-evidence-of-atypical-classical-mecfs/ New Research Discovers Evidence of Atypical & Classical ME/CFS - The Microbe Discovery Project - Apr 4, 2017]</ref> * Elevated [[regulatory T cell]]s<ref>{{Cite journal | last = Brenu|first = Ekua Weba | last2 = Huth | first2 = Teilah K. | last3 = Hardcastle | first3 = Sharni L. | last4 = Fuller | first4 = Kirsty | last5 = Kaur | first5 = Manprit | last6 = Johnston | first6 = Samantha | last7 = Ramos | first7 = Sandra B. | last8 = Staines | first8 = Don R. | last9 = Marshall-Gradisnik | first9 = Sonya M. | date = Apr 2014 | title = Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis|url=http://www.ncbi.nlm.nih.gov/pubmed/24343819|journal=International Immunology|volume=26|issue=4|pages=233–242|doi=10.1093/intimm/dxt068|issn=1460-2377|pmid=24343819}}</ref> * increased [[mast cell]] populations<ref>{{Cite journal | last = Rönnberg|first = E | last2 = Calounova | first2 = G | last3 = Pejler | first3 = G | date = June 2017 | title = Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients|url=https://www.ncbi.nlm.nih.gov/pubmed/27362406|journal=Asian Pac J Allergy Immunol|volume=35|issue=2 | pages = 75-81|via=}}</ref> * elevated anti-cholinergic [[Muscarinic acetylcholine receptor|muscarinic]], Β-adrenergic,<ref>{{Cite journal | last = Loebel|first = Madlen | last2 = Grabowski | first2 = Patricia | last3 = Heidecke | first3 = Harald | last4 = Bauer | first4 = Sandra | last5 = Hanitsch | first5 = Leif G. | last6 = Wittke | first6 = Kirsten | last7 = Meisel | first7 = Christian | last8 = Reinke | first8 = Petra | last9 = Volk | first9 = Hans-Dieter | date = Feb 2016 | title = Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52 | pages = 32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref> [[phosphatidylinositol]]<ref>{{Cite journal | last = Maes | first = Michael | last2 = Mihaylova | first2 = Ivanka | last3 = Leunis | first3 = Jean-Claude | date = Dec 2007 | title = Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression | url =https://www.ncbi.nlm.nih.gov/pubmed/18063934|journal=Neuro Endocrinology Letters|volume=28|issue=6 | pages = 861–867|issn=0172-780X|pmid=18063934}}</ref> and [[serotonin]]<ref>{{Cite journal | last = Maes | first = Michael | last2 = Ringel | first2 = Karl | last3 = Kubera | first3 = Marta | last4 = Anderson | first4 = George | last5 = Morris | first5 = Gerwyn | last6 = Galecki | first6 = Piotr | last7 = Geffard | first7 = Michel | date = 2013-09-05 | title = In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation | url =https://www.ncbi.nlm.nih.gov/pubmed/23664637|journal=Journal of Affective Disorders|volume=150|issue=2|pages=223–230|doi=10.1016/j.jad.2013.03.029|issn=1573-2517|pmid=23664637}}</ref> autoantibodies * Reduced CD4+ function<ref name=":5">{{Cite journal|title=Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations|date=2020-03-02|url=https://pubmed.ncbi.nlm.nih.gov/31830003/|journal=The Journal of Clinical Investigation|volume=130|issue=3|pages=1491–1505|last=Mandarano|first=Alexandra H.|last2=Maya|first2=Jessica|last3=Giloteaux|first3=Ludovic|last4=Peterson|first4=Daniel L.|last5=Maynard|first5=Marco|last6=Gottschalk|first6=C. Gunnar|last7=Hanson|first7=Maureen R.|doi=10.1172/JCI132185|pmc=7269566|pmid=31830003|issn=1558-8238}}</ref> and reduced CD4+ count<ref name=":6">{{Cite journal|title=Study of immune alterations in patients with chronic fatigue syndrome with different etiologies|date=2004|url=https://pubmed.ncbi.nlm.nih.gov/15345193/|journal=International Journal of Immunopathology and Pharmacology|volume=17|issue=2 Suppl|pages=57–62|last=Racciatti|first=D.|last2=Dalessandro|first2=M.|last3=Delle Donne|first3=L.|last4=Falasca|first4=K.|last5=Zingariello|first5=P.|last6=Paganelli|first6=R.|last7=Pizzigallo|first7=E.|last8=Vecchiet|first8=J.|doi=10.1177/03946320040170S210|pmid=15345193|issn=0394-6320}}</ref> * Reduced CD8+ function<ref name=":5" /> and reduced CD8+ count<ref name=":6" /> * Lowered CD4+/CD8+ ratio<ref>{{Cite journal|title=Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers|date=2015-01-01|url=https://europepmc.org/article/med/26707044|journal=Neuro endocrinology letters|volume=36|issue=5|pages=439–446|last=Maes|first=Michael|last2=Bosmans|first2=Eugene|last3=Kubera|first3=Marta|pmid=26707044|issn=2354-4716}}</ref> === Chronic infection === * [[Enterovirus]]: Persistence of [[enterovirus]]es in muscle tissue;<ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /> brain;<ref name="McGarry19942">{{citation | last1 = McGarry | first1 = Frances | author-link1 = Frances McGarry | last2 = Gow | first2 = John | authorlink2 = John Gow | last3 = Behan | first3 = Peter O | authorlink3 = Peter O Behan | title = Enterovirus in the Chronic Fatigue Syndrome | journal = Annals of Internal Medicine | volume = 120 | issue = 11| pages = 972–973 | date = Jun 1, 1994 | doi = 10.7326/0003-4819-120-11-199406010-00020 | url = http://www.ncbi.nlm.nih.gov/pubmed/8172448 }}</ref> and gut;<ref name="ChiaJKS2016">{{Cite journal | last1 = Chia | first1 = JKS | authorlink1 = John Chia | last2 = Chia | first2 = AY | authorlink2 = Andrew Chia | title = Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach | journal = Journal of Clinical Pathology | volume = 61 | issue = 1| pages = 43–48 | date = Jan 1, 2008 | pmid = 17872383 | doi = 10.1136/jcp.2007.050054 | url = http://jcp.bmj.com/content/61/1/43 }}</ref> increased detection of viral [[RNA]] via PCR; increased [[:Category:Antibodies|antibodies]] * [[Herpesvirus]]{{citation needed}} == Lymphatic system == == Cardiovascular system == {{Main article|page_name =Cardiovascular system}}{{Main article|page_name =Cardiac problems in ME/CFS}} === Heart === * Smaller than normal [[left ventricle]] of the [[heart]],<ref name=":8">Miwa K., [http://www.ncbi.nlm.nih.gov/pubmed/24736946 "Cardiac dysfunction and orthostatic intolerance in patients with myalgic encephalomyelitis and a small left ventricle"] Heart Vessels, July 2015</ref><ref>Hollingsworth K.G [http://onlinelibrary.wiley.com/enhanced/doi/10.1111/j.1365-2796.2011.02429.x/ "Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging"] J Intern Med 2012; 271: 264–270.</ref><ref name="Olimulder, 2016">{{Cite journal | last1 = Olimulder | first1 = M.A.G.M. | authorlink1 = | last2 = Galjee | first2 = M.A. | authorlink2 = | last3 = Wagenaar | first3 = L.J. | authorlink3 = | last4 = van Es | first4 = J. | authorlink4 = | last5 = van der Palen | first5 = J. | authorlink5 = | last6 = Visser | first6 = F.C. | authorlink6 = | last7 =Vermeulen | first7 = R.C.W. | authorlink7 = | last8 = von Birgelen | first8 = C. | authorlink8 = | title = Chronic fatigue syndrome in women assessed with combined cardiac magnetic resonance imaging | journal = Netherlands Heart Journal | volume = 24 | pages = 709–716 | date = 2016 | url = https://link.springer.com/article/10.1007/s12471-016-0885-8 | doi = 10.1007/s12471-016-0885-8 }}</ref><ref>[http://openheart.bmj.com/content/3/1/e000381.long Reduced cardiac volumes in chronic fatigue syndrome associate with plasma volume but not length of disease: a cohort study]</ref> [[small heart syndrome]],<ref name=":8" /> and low [[Cardiovascular system|cardiac]] output.<ref>Miwa K., Fujita M., [http://www.ncbi.nlm.nih.gov/pubmed/19881233 "Cardiovascular dysfunction with low cardiac output due to a small heart in patients with chronic fatigue syndrome"] Intern Med, 2009;48(21):1849-54</ref> * Mean age of death from heart failure of [[chronic fatigue syndrome|CFS]] patients is 58.7 years as compared to 83.1 years for the general population.<ref>Jason LA, Corradi K, Gress S, Williams S, Torres-Harding S, [http://www.ncbi.nlm.nih.gov/pubmed/16844674 "Causes of death among patients with chronic fatigue syndrome"] Health Care Women Int., 27(7): 615-626. 2006</ref> === Circulation === * reduced blood flow to the [[Brain|brain,]]<ref name="Natelson, 2017">{{Cite journal | last1 = Natelson | first1 = Benjamin | authorlink1 = Benjamin Natelson | last2 = Mao | first2 = Xiangling | last3 = Stegner | first3 = Aaron J | last4 = Lange | first4 = Gudrun | authorlink4 = Gudrun Lange | last5 = Vu | first5 = Diana | last6 = Blate | first6 = Michelle | last7 = Kang | first7 = Guoxin | last8 = Soto | first8 = Eli | last9 = Kapusuz | first9 = Tolga | last10 = Shungu | first10 = Dikoma C | authorlink10 = Dikoma Shungu | title=Multimodal and simultaneous assessments of brain and spinal fluid abnormalities in chronic fatigue syndrome and the effects of psychiatric comorbidity | date = 2017 | journal=Journal of the Neurological Sciences|volume=375|issue= | page = 411-416|doi=10.1016/j.jns.2017.02.046|pmid=|quote=}}</ref><ref name=":32">{{Cite journal | last = Costa|first = D.C. | last2 = Tannock | first2 = C. | last3 = Brostoff | first3 = J. | date = Nov 1995 | title = Brainstem perfusion is impaired in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/8542261|journal=QJM: monthly journal of the Association of Physicians|volume=88|issue=11 | pages = 767–773|issn=1460-2725|pmid=8542261}}</ref><ref name=":10">{{Cite journal | last = Barnden | first = Leighton R. | last2 = Crouch | first2 = Benjamin | last3 = Kwiatek | first3 = Richard | last4 = Burnet | first4 = Richard | last5 = Mernone | first5 = Anacleto | last6 = Chryssidis | first6 = Steve | last7 = Scroop | first7 = Garry | last8 = Del Fante | first8 = Peter | date = 2011 | title = A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/nbm.1692|journal=NMR in Biomedicine|language=en|volume=24|issue=10|pages=1302–1312|doi=10.1002/nbm.1692|issn=1099-1492|pmc = 4369126|pmid=21560176}}</ref><ref>{{Cite journal | last = Biswal|first = Bharat | last2 = Kunwar | first2 = Pratap | last3 = Natelson | first3 = Benjamin H. | authorlink1 = Benjamin Natelson | date = 2011-02-15 | title = Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling | url =http://www.sciencedirect.com/science/article/pii/S0022510X10005666|journal=Journal of the Neurological Sciences|volume=301|issue=1 | pages = 9–11 |doi=10.1016/j.jns.2010.11.018|issn=0022-510X}}</ref><ref name=":11">{{Cite journal | last = Yoshiuchi|first = Kazuhiro | last2 = Farkas | first2 = Jeffrey | last3 = Natelson | first3 = Benjamin H. | authorlink3 = Benjamin Natelson | date = 2006 | title=Patients with chronic fatigue syndrome have reduced absolute cortical blood flow | url =https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1475-097X.2006.00649.x|journal=Clinical Physiology and Functional Imaging|language=en|volume=26|issue=2 | pages = 83–86|doi=10.1111/j.1475-097X.2006.00649.x|issn=1475-097X}}</ref><ref>{{Cite journal | last = Freedman | first = M. | last2 = Kirsh | first2 = J.C. | last3 = Gray | first3 = B. | last4 = Chung | first4 = D.G. | last5 = Abbey | first5 = S.E. | last6 = Salit | first6 = I.E. | last7 = Ichise | first7 = M. | date = Oct 1992 | title = Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome.|url=http://europepmc.org/abstract/med/1491843|journal=Nuclear medicine communications|volume=13|issue=10 | pages = 767–772|issn=0143-3636|pmid=1491843}}</ref><ref>{{Cite journal | last = Chao|first = C.C. | last2 = Hu | first2 = S. | last3 = Pheley | first3 = A.M. | last4 = Schenck | first4 = C.H. | last5 = Grammith | first5 = F.C. | last6 = Sirr | first6 = S.A. | last7 = Peterson | first7 = P.K. | date = 1994-03-01 | title = Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://cvi.asm.org/content/1/2/222|journal=Clinical and Diagnostic Laboratory Immunology|language=en|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref><ref>{{Cite journal | last = Lange | first = Gudrun | last2 = Wang | first2 = Samuel | last3 = DeLuca | first3 = John | last4 = Natelson | first4 = Benjamin H. | date = 1998-09-28 | title = Neuroimaging in chronic fatigue syndrome|url=http://www.sciencedirect.com/science/article/pii/S0002934398001752|journal=The American Journal of Medicine|volume=105|issue=3, Supplement 1 | pages = 50S–53S|doi=10.1016/S0002-9343(98)00175-2|issn=0002-9343}}</ref> even in the absence of [[Postural orthostatic tachycardia syndrome|POTS]]/[[Neurally mediated hypotension|NMH]]<ref>{{Citation | title = CMRC Conference 2017 day 1- Prof Dr Frans Visser |url =https://www.youtube.com/watch?v=IWRA23D_MUg|language=en|access-date=2019-09-03}}</ref> * reduced blood flow to the heart<ref>{{Cite journal | last = Patrick Neary|first = J. | last2 = Roberts | first2 = Andy D.W. | last3 = Leavins | first3 = Nina | last4 = Harrison | first4 = Michael F. | last5 = Croll | first5 = James C. | last6 = Sexsmith | first6 = James R. | date = Nov 2008 | title = Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1475-097X.2008.00822.x|journal=Clinical Physiology and Functional Imaging|volume=28|issue=6 | pages = 364–372|doi=10.1111/j.1475-097x.2008.00822.x|issn=1475-0961}}</ref><ref>{{Cite journal | last = Peterson | first = PK | last2 = Sirr | first2 = SA | last3 = Grammith | first3 = FC | last4 = Schenck | first4 = CH | last5 = Pheley | first5 = AM | last6 = Hu | first6 = S | last7 = Chao | first7 = C C | date = Mar 1994 | title = Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC368231/|journal=Clinical and Diagnostic Laboratory Immunology|volume=1|issue=2|pages=222–226|issn=1071-412X|pmid=7496949}}</ref> *peripheral endothelial dysfunction, which is an established risk factor for cardiovascular disease<ref name="endothelial2020">{{Cite journal | last = Scherbakov|first = Nadja | authorlink = | last2 = Szklarski | first2 = Marvin | author-link2 = | last3 = Hartwig | first3 = Jelka | author-link3 = | last4 = Sotzny | first4 = Franziska | author-link4 = Franziska Sotzny | last5 = Lorenz | first5 = Sebastian | author-link5 = | last6 = Meyer | first6 = Antje | authorlink6 = Antje Meyer | last7 = Grabowski | first7 = Patricia | last8 = Doehner | first8 = Wolfram | last9 = Scheibenbogen | first9 = Carmen | authorlink9 = Carmen Scheibenbogen | date = 2020 | title=Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/ehf2.12633|journal=ESC Heart Failure|language=en|volume=7|issue=3|pages=1064–1071|doi=10.1002/ehf2.12633|issn=2055-5822|pmc = 7261521|pmid=32154656|access-date=|quote=|via=}}</ref> === Blood vessels === === Blood === {{Main article|Brain}} * reduced [[blood]] volume<ref>{{Cite journal | last = Hurwitz|first = BE | last2 = Coryell | first2 = VT | last3 = Parker | first3 = M | last4 = Martin | first4 = P | last5 = LaPerriere .... | first5 = A | last6 = Bilsker | first6 = MS | date = | title = Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function | url =http://www.clinsci.org/content/118/2/125|journal=Clinical Science|volume=118|issue=2|pages=125-135|via=}}</ref><ref>{{Cite journal | last = Streeten | first = DHP | last2 = Bell | first2 = D | date = 1998 | title=Circulating Blood Volume in Chronic Fatigue Syndrome|url=https://www.tandfonline.com/doi/abs/10.1300/J092v04n01_02|journal=Journal of Chronic Fatigue Syndrome|volume=4 | pages = 3-11|via=}}</ref> * abnormally shaped of [[Red blood cell|red blood cells]]<ref name="Simpson1989">{{Citation | last1 = Simpson | first1 = LO | authorlink1 = Leslie Simpson | title = Nondiscocytic erythrocytes in myalgic encephalomyelitis | journal = The New Zealand Medical Journal | volume = 102 | issue = 864 | pages = 126-127 | date = 1989 | pmid = 2927808 | doi = }}</ref><ref>{{Cite journal | last = Richards | first = RS | last2 = Wang | first2 = L | last3 = Jelinek | first3 = H | date = Jan 2007 | title = Erythrocyte oxidative damage in chronic fatigue syndrome|url=https://www.sciencedirect.com/science/article/pii/S0188440906002992|journal=Archives of Medical Research|volume=38|issue=1 | pages = 94-98|via=}}</ref> * reduced oxygen uptake in [[hemoglobin]]<ref>{{Cite journal | last = Miller | first = Ruth R | last2 = Reid | first2 = W Darlene | last3 = Mattman | first3 = Andre | last4 = Yamabayashi | first4 = Cristiane | last5 = Steiner | first5 = Theodore | last6 = Parker | first6 = Shoshana | last7 = Gardy | first7 = Jennifer | last8 = Tang | first8 = Patrick | last9 = Patrick | first9 = David M | date = 2015-05-20 | title = Submaximal exercise testing with near-infrared spectroscopy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients compared to healthy controls: a case–control study|url=http://doi.org/10.1186/s12967-015-0527-8|journal=Journal of Translational Medicine|language=en|volume=13|issue=1|doi=10.1186/s12967-015-0527-8|issn=1479-5876|pmc=4438583|pmid=25990639}}</ref> == Digestive system == === Gastrointestinal tract === {{Main article |page_name = Gastrointestinal tract}} * lower levels of [[Bifidobacteria]], [[Escherichia coli]] and higher levels of [[aerobic bacteria]],<ref>{{Cite journal | title = Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value|url=http://www.medical-hypotheses.com/article/S0306-9877(03)00096-3/abstract|journal=Medical Hypotheses | date = Jun 2003|issn=0306-9877 | pages = 915–923|volume=60|issue=6|doi=10.1016/S0306-9877(03)00096-3|language=English|first = Alan C | last = Logan | first2 = A | last2 = Venket Rao | first3 = Dinaz | last3 = Irani}}</ref> in particular [[Enterococcus]] and [[Streptococcus]] species<ref>{{Cite journal | title = Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome|url=http://www.ncbi.nlm.nih.gov/pubmed/19567398|journal=In Vivo (Athens, Greece) | date = Jul 2009|issn=0258-851X|pmid=19567398 | pages = 621–628|volume=23|issue=4|first = John R. | last = Sheedy | first2 = Richard E.H. | last2 = Wettenhall | first3 = Denis | last3 = Scanlon | first4 = Paul R. | last4 = Gooley | first5 = Donald P. | last5 = Lewis | first6 = Neil | last6 = McGregor | first7 = David I. | last7 = Stapleton | first8 = Henry L. | last8 = Butt | first9 = Kenny L. | last9 = DE Meirleir}}</ref> * higher levels of enterococcus bacteria in CFS patients were associated with more severe neurological and cognitive dysfunction<ref>https://getinfo.de/en/search/id/BLCP%3ACN055885616/%60Bacterial-Colonosis-in-Patients-with-Persistent/</ref> * Significantly increased proportions of Firmicutes<ref>{{Cite journal | title = High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients|url=https://www.sciencedirect.com/science/article/pii/S1075996413000929|journal=Anaerobe | date = 2013-08-01|issn=1075-9964 | pages = 50–56|volume=22|doi=10.1016/j.anaerobe.2013.06.002|language=en}}</ref><ref name=":7">{{Cite journal | last = Giloteaux | first = Ludovic | last2 = Goodrich | first2 = Julia K. | last3 = Walters | first3 = William A. | last4 = Levine | first4 = Susan M. | author-link4 = Susan Levine | last5 = Ley | first5 = Ruth E. | last6 = Hanson | first6 = Maureen R. | date = 2016-06-23 | title = Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918027/|journal=Microbiome|volume=4|doi=10.1186/s40168-016-0171-4|issn=2049-2618|pmc=4918027|pmid=27338587}}</ref> and Bacteroides<ref name=":7" /> * CFS patients may suffer from [[small intestinal bacterial overgrowth]] (SIBO) at high rates<ref name="Pimentel2000">{{Citation | last1 = Pimentel | first1 = M | authorlink1 = Mark Pimentel | last2 = Hallegua | first2 = D | authorlink2 = David Hallegua | last3 = Chow | first3 = EJ | authorlink3 = Evelyn Chow | last4 = Wallace | first4 = D | authorlink4 = Daniel Wallace | last5 = Bonorris | first5 = G | authorlink5 = George Bonorris | last6 = Lin | first6 = HC | authorlink6 = Henry Lin | title = Eradication of small intestinal bacterial overgrowth decreases symptoms in chronic fatigue syndrome: A double blind, randomized study | journal = Gastroenterology | volume = 118 | issue = 4| pages = 414 | date = 1 Apr 2000 | doi = 10.1016/S0016-5085(00)83765-8 | url = http://www.gastrojournal.org/article/S0016508500837658/abstract }}</ref> * Higher levels of serum [[Immunoglobulin A|IgA]] and [[Immunoglobulin M|IgM]] against [[lipopolysaccharide]]s (LPS), a major component of the outer membrane of [[gram-negative bacteria]], indicating translocation.<ref>{{Cite journal | last = Maes | first = Michael | last2 = Mihaylova | first2 = Ivana | last3 = Leunis | first3 = Jean-Claude | date = 2007-04-01 | title = Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): Indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut–intestinal permeability|url=http://www.sciencedirect.com/science/article/pii/S0165032706003557|journal=Journal of Affective Disorders|language=en|volume=99|issue=1|pages=237–240|doi=10.1016/j.jad.2006.08.021|issn=0165-0327}}</ref> Serum [[Immunoglobulin A|IgA]] was significantly correlated to the severity of illness. === Liver === * Reduced [[liver]] volume<ref>{{Cite journal | title = Liver volume is lower and associates with resting and dynamic blood pressure variability in chronic fatigue syndrome|url=https://www.tandfonline.com/doi/abs/10.1080/21641846.2018.1488525|journal=Fatigue: Biomedicine, Health & Behavior | date = 2018-06-18|issn=2164-1846|pages=141–152|volume=6|issue=3|doi=10.1080/21641846.2018.1488525|language=en | first = Pawel | last = Zalewski | first2 = Andreas | last2 = Finkelmeyer | first3 = James | last3 = Frith | first4 = Laura | last4 = Maclachlan | first5 = Andrew | last5 = Blamire | first6 = Julia L. | last6 = Newton}}</ref> == Nutrition == * low red blood cell [[magnesium]]<ref name="cfs_and_blood_mg">{{Citation | last1 = I.M. | first1 = Cox | authorlink1 = | last2 = M.J. | first2 = Campbell | authorlink2 = | last3 = D. |first3 = Dowson | authorlink3 = | title = Red blood cell magnesium and chronic fatigue syndrome | journal = The Lancet | year = 1991 | pmid = 1672392 | doi = 10.1016/0140-6736(91)91371-Z }}</ref> * low serum [[carnitine]]<ref>{{Cite journal | last = Plioplys | first = A.V. | last2 = Plioplys | first2 = S. | date = 1995 | title = Serum levels of carnitine in chronic fatigue syndrome: clinical correlates|url=https://www.ncbi.nlm.nih.gov/pubmed/8544970|journal=Neuropsychobiology|volume=32|issue=3|pages=132–138|doi=10.1159/000119226|issn=0302-282X|pmid=8544970}}</ref><ref>{{Citation| issn = 1058-4838| volume = 18 | issue =Suppl 1| pages = 62-67| last1 = Kuratsune | first1 = H. | last2 = Yamaguti | first2 = K. | last3 = Takahashi | first3 = M. | last4 = Misaki | first4 = H. | last5 = Tagawa | first5 = S. | last6 = Kitani | first6 = T.| title = Acylcarnitine deficiency in chronic fatigue syndrome| journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = January 1994 | pmid = 8148455}}</ref><ref>{{Citation| doi = 10.1111/j.1468-1331.1995.tb00151.x| issn = 1351-5101| volume = 2 | issue = 5| pages = 425–428| last1 = Majeed | first1 = T. | last2 = de Simone | first2 = C. | last3 = Famularo | first3 = G. | last4 = Marcellini | first4 = S. | last5 = Behan | first5 = P.O. | title = Abnormalities of carnitine metabolism in chronic fatigue syndrome| journal = European Journal of Neurology | date = November 1995 | pmid = 24283722}}</ref> == Metabolism == * Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review<ref>{{Cite journal | last = Tomas | first = Cara | last2 = Newton | first2 = Julia | date = 2018-06-19 | title = Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review | url =https://portlandpress.com/biochemsoctrans/article-abstract/46/3/547/67402/Metabolic-abnormalities-in-chronic-fatigue?redirectedFrom=fulltext|journal=Biochemical Society Transactions|language=en|volume=46|issue=3 | pages = 547–553|doi=10.1042/BST20170503|issn=0300-5127}}</ref> * Analysis of peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction, supporting a model of deficient ATP production in ME/CFS.<ref name="Sweetman2020">{{Cite journal | last = Sweetman | first = Eiren | authorlink = | last2 = Kleffmann | first2 = Torsten | authorlink2 = | last3 = Edgar | first3 = Christina | authorlink3 = | last4 = de Lange | first4 = Michel | authorlink4 = | last5 = Vallings | first5 = Rosamund | authorlink5 = Rosamund Vallings | last6 = Tate | first6 = Warren | authorlink6 = Warren Tate | date = 2020-09-24 | title = A SWATH-MS analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction | url =https://doi.org/10.1186/s12967-020-02533-3|journal=Journal of Translational Medicine|volume=18|issue=1 | pages = 365|doi=10.1186/s12967-020-02533-3|issn=1479-5876|pmc = 7512220|pmid=|access-date=|quote=|via=}}</ref> === Cellular respiration === * abnormalities in [[cellular respiration]] including a reduction in [[glycolysis]],<ref>{{Cite journal | last = Armstrong | first = Christopher W. | last2 = McGregor | first2 = Neil R. | last3 = Lewis | first3 = Donald P. | last4 = Butt | first4 = Henry L. | last5 = Gooley | first5 = Paul R. | date = 2015-05-30 | title = Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients|url=https://link.springer.com/article/10.1007/s11306-015-0816-5 | journal=Metabolomics|language=en | volume=11 | issue=6 | pages=1626–1639 | doi=10.1007/s11306-015-0816-5 | issn=1573-3882}}</ref> including impaired [[pyruvate dehydrogenase]]<ref>{{Cite journal | last = Fluge | first = Øystein | last2 = Mella | first2 = Olav | last3 = Bruland | first3 = Ove | last4 = Risa | first4 = Kristin | last5 = Dyrstad | first5 = Sissel E. | last6 = Alme | first6 = Kine | last7 = Rekeland | first7 = Ingrid G. | last8 = Sapkota | first8 = Dipak | last9 = Røsland | first9 = Gro V. | date = 2016-12-22 | title = Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/28018972 | journal=JCI insight|volume=1 | issue=21 | pages = e89376 | doi=10.1172/jci.insight.89376 | issn=2379-3708 | pmc=5161229 | pmid=28018972}}</ref> * increased [[lactic acid]]<ref name="Plioplys1995">{{cite journal | last1 = Plioplys | first1 = AV | authorlink1 = | last2 = Plioplys | first2 = S | authorlink2 = | title = Serum levels of carnitine in chronic fatigue syndrome: clinical correlates | journal = Neuropsychobiology | date = 1995 | volume = 32 | issue = 3 | pages = 132-8 | pmid = 8544970 | url = http://www.ncbi.nlm.nih.gov/pubmed/8544970 }}</ref><ref name="LaneRJ1998">{{cite journal | last1 = Lane | first1 = RJ | authorlink1 = | last2 = Barrett | first2 = MC | authorlink2 = Michael Barrett | last3 = Taylor | first3 = DJ | authorlink3 = Doris Taylor | last4 = Kemp | first4 = GJ | authorlink4 = Graham Kemp | last5 = Lodi | first5 = R | authorlink5 = Raffaele Lodi | title = Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle | journal = Neuromuscul Disord | volume = 8 | issue = 3-4 | pages = 204-9 | date = May 1998 | pmid = 9631403 | url = http://www.ncbi.nlm.nih.gov/pubmed/9631403 }}</ref><ref name="JonesDE2010">{{cite journal | last1 = Jones | first1 = David EJ | authorlink1 = | last2 = Hollingsworth | first2 = Kieren G | authorlink2 = Kieren Hollingsworth | last3 = Taylor | first3 = Renee R | authorlink3 = Renee Taylor | last4 = Blamire | first4 = Andrew M | authorlink4 = Andrew Blamire | last5 = Newton | first5 = Julia L | authorlink5 = Julia Newton | title = Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome | journal = J Intern Med | volume = 267 | issue = 4 | pages = 394-401 | date = Apr 2010 | pmid = 20433583 | doi = 10.1111/j.1365-2796.2009.02160.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2009.02160.x/abstract }}</ref><ref name="LengertN2015">{{cite journal | last1 = Lengert | first1 = Nicor | authorlink1 = Nicor Lengert | last2 = Drossel | first2 = Barbara | authorlink2 = Barbara Drossel | title = In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome | journal = Biophysical Chemistry | volume = 202 | pages = 21–31 | date = Jul 2015 | pmid = 25899994 | doi = 10.1016/j.bpc.2015.03.009 | url = http://www.sciencedirect.com/science/article/pii/S0301462215000630 }}</ref><ref name="Mathew2009"/> * reduction in metabolites reflecting a slowed metabolism<ref>{{Cite journal | last = Naviaux | first = Robert K. | authorlink1 = Robert Naviaux | last2 = Naviaux | first2 = Jane C. | last3 = Li | first3 = Kefeng | last4 = Bright | first4 = A. Taylor | last5 = Alaynick | first5 = William A. | last6 = Wang | first6 = Lin | last7 = Baxter | first7 = Asha | last8 = Nathan | first8 = Neil | last9 = Anderson | first9 = Wayne | date = 2016-09-13 | title = Metabolic features of chronic fatigue syndrome|url=http://www.pnas.org/content/113/37/E5472 | journal=Proceedings of the National Academy of Sciences|language=en | volume=113 | issue=37 | pages = E5472–E5480 | doi=10.1073/pnas.1607571113 | issn=0027-8424 | pmid=27573827}}</ref> *analysis of peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction, supporting a model...that would suggest an elevation of oxidative stress.<ref name="Sweetman2020" /> === Exercise === * reduced pain threshold<ref name="Whiteside, 2004">{{Cite journal | last1 = Whiteside | first1 = Alan | authorlink1 = | last2 = Hansen | first2 = Stig | authorlink2 = | last3 = Chaudhuri | first3 = Abhijit | authorlink3 = Abhijit Chaudhuri | title = Exercise lowers pain threshold in chronic fatigue syndrome | journal = Pain | volume = 109 | issue = 3 | pages = 497-499 | date = 2004 | pmid = 15157711 | doi = 10.1016/j.pain.2004.02.029 }}</ref> * translocation of bacteria<ref name="ShuklaS2015">{{cite journal | last1 = Shukla | first1 = Sanjay K | authorlink1 = Sanjay Shukla | last2 = Cook | first2 = Dane | authorlink2 = Dane Cook | last3 = Meyer | first3 = Jacob | authorlink3 = Jacob Meyer | last4 = Vernon | first4 = Suzanne D | authorlink4 = Suzanne Vernon | last5 = Le | first5 = Thao | authorlink5 = Thao Le | last6 = Clevidence | first6 = Derek | authorlink6 = Derek Clevidence | last7 = Robertson | first7 = Charles E | authorlink7 = Charles Robertson | last8 =Schrodi | first8 = Steven J | authorlink8 = Steven Schrodi | last9 = Yale | first9 = Steven | authorlink9 = Steven Yale | last10 = Frank | first10 = Daniel N | authorlink10 = Daniel Frank | title = Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | journal = PLoS ONE | date = Dec 18, 2015 | pmid = 26683192 | doi = 10.1371/journal.pone.0145453 | url = http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145453 }}</ref> * loss of capacity to recover from acidosis on repeat exercise<ref name="JonesDE2012">{{cite journal | last1 = Jones | first1 = David EJ | authorlink1 = David Jones | last2 = Hollingsworth | first2 = Kieren G | authorlink2 = Kieren Hollingsworth | last3 = Jakovljevic | first3 = Djordje G | authorlink3 = Djordje Jakovljevic | last4 = Fattakhova | first4 = Gulnar | authorlink4 = Gulnar Fattakhova | last5 = Pairman | first5 = Jessie | authorlink5 = Jessie Pairman | last6 = Blamire | first6 = Andrew M | authorlink6 = Andrew Blamire | last7 =Trenell | first7 = Michael I | authorlink7 = Michael Trenell | last8 = Newton | first8 = Julia L | authorlink8 = Julia Newton | title = Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome | journal = Eur J Clin Invest | volume = 42 | issue = 2 | pages = 186-94 | date = 12 Jul 2011 | pmid = 21749371 | doi = 10.1111/j.1365-2362.2011.02567.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2011.02567.x/abstract }}</ref> * increased expression of sensory, adrenergic and immune genes following [[muscle]] exertion<ref name="LightAR2009">{{cite journal | last1 = Light | first1 = Alan R | authorlink1 = Alan Light | last2 = White | first2 = Andrea T | authorlink2 = | last3 = Hughen | first3 = Ronald W | authorlink3 = | last4 = Light | first4 = Kathleen C | authorlink4 = Kathleen Light | title = Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects | journal = J Pain | volume = 10 | issue = 10 | pages = 1099-112 | date = Jul 31, 2009 | pmid = 19647494 | doi = 10.1016/j.jpain.2009.06.003 | url = http://www.jpain.org/article/S1526-5900(09)00574-4/abstract }}</ref><ref name="LightAR2011">{{citation | last1 = Light | first1 = Alan R | authorlink1 = Alan Light | last2 = Bateman | first2 = Lucinda| authorlink2 = Lucinda Bateman | last3 = Jo | first3 = D | authorlink3 = Daehyun Jo | last4 = Hughen | first4 = Ronald W | authorlink4 = Ronald Hughen | last5 = Vanhaitsma | first5 = TA | authorlink5 = Timothy VanHaitsma | last6 = White | first6 = Andrea T | authorlink6 = Andrea White | last7 =Light | first7 = Kathleen C | authorlink7 = Kathleen Light | title = Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome | journal = J Intern Med | volume = 271 | issue = 1 | pages = 64-81 | date = Jul 13, 2011 | pmid = 21615807 | doi = 10.1111/j.1365-2796.2011.02405.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02405.x/abstract }}</ref><ref name="WhiteAT2012">{{citation | last1 = White | first1 = Andrea T | authorlink1 = Andrea White | last2 = Light | first2 = Alan R | authorlink2 = 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 | title = Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls | journal = Psychosom Med | volume = 74 | issue = 1 | pages = 46-54 | date = Dec 30, 2011 | pmid = 22210239 | doi = 10.1097/PSY.0b013e31824152ed | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/ }}</ref> * decreased [[oxygen]] utilization<ref>{{Cite journal | last = Vermeulen | first = Ruud CW | authorlink = Ruud Vermeulen | last2 = Vermeulen van Eck | first2 = Ineke WG| date = 2014 | title = Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome|url=https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-12-20|journal=Journal of Translational Medicine|language=en|volume=12|issue=1|pages=20|doi=10.1186/1479-5876-12-20|issn=1479-5876|pmc=3903040|pmid=24456560}}</ref> [[File:Abnormal findings in CFS ME.png|thumb|center|alt=Abnormal findings in Chronic fatigue syndrome and myalgic encephalomyelitis. There is no single biomarker, but tests have found differences in blood flow to the brain, hand grip strength, metabolite and mitochondria abnormalities, reduced heart output, white and red blood cell differences, reduced blood volume, differences in gut bacteria, neuroinflammation, abnormal responses to exercise, and other abnormalities.]] == See also == * [[Myalgic encephalomyelitis]] * [[List of systematic reviews about ME/CFS]] * [[:Category:Abnormal findings|Abnormal findings (images)]] == Learn more == * [https://www.mdpi.com/2075-4418/9/2/41 Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (2019)] - original research article * [http://www.meaction.net/wp-content/uploads/2015/05/ME2FCFS-RESEARCH-SUMMARY-Jamie-Seltzer.pdf #MEAction ME/CFS Research Summary] ==References== {{Reflist}} [[Category:Signs and symptoms]] [[Category:Lists]]
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