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Comorbidities of Myalgic Encephalomyelitis
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== Research findings == Recent research has focused on the possible relationships between EDS, POTS, and MCAS. In particular, these disorders were associated in a sample of 25 families. {| class="wikitable" !Findings ![[ME/CFS]] ![[Postural orthostatic tachycardia syndrome|POTS]] !MCAS ![[Fibromyalgia]] ![[hEDS]] |- |'''[[Central nervous system]]''' | | | | | |- |[[Ventricular lactate]] |increased<ref name=":53">{{Cite journal | last = Mathew|first = Sanjay J. | last2 = Mao | first2 = Xiangling | last3 = Keegan | first3 = Kathryn A. | last4 = Levine | first4 = Susan M. | 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. | 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>{{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. | last8 = Mathew | first8 = Sanjay J. | last9 = Shungu | first9 = Dikoma C. | 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>{{Cite journal | last = Shungu|first = Dikoma C. | 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. | author-link8 = 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>{{Cite journal | last = Natelson | first = Benjamin H. | 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. | 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> | | | | |- |Neuroinflammmation | | | | | |- |Grey matter | | | | | |- |White matter | | | | | |- |[[Intracranial hypertension]] |Present in a subset<ref>{{Cite journal | last = Higgins | first = Nicholas | authorlink = Nicholas Higgins | last2 = Pickard | first2 = John | authorlink2 = John Pickard | last3 = Lever | first3 = Andrew | author-link3 = Andrew Lever | author-link4 = | author-link5 = | date = 2013-11-21 | title = Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study | url = http://journals.sagepub.com/doi/10.1177/2042533313507920 | journal = JRSM Short Reports|language=en|volume=4 | issue = 12 | pages = 204253331350792|doi=10.1177/2042533313507920|issn=2042-5333|quote=|via=}}</ref> | | | | |- |'''[[Autonomic nervous system]]''' | | | | | |- |[[Small fiber peripheral neuropathy]] | |37.5%<ref>{{Cite journal | last = Gibbons | first = Christopher H. | last2 = Bonyhay | first2 = Istvan | last3 = Benson | first3 = Adam | last4 = Wang | first4 = Ningshan | last5 = Freeman | first5 = Roy | date = 2013-12-27 | title = Structural and Functional Small Fiber Abnormalities in the Neuropathic Postural Tachycardia Syndrome | url =https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084716 | journal = PLoS ONE|language=en|volume=8 | issue = 12| pages = e84716|doi=10.1371/journal.pone.0084716|issn=1932-6203|pmc=3874039|pmid=24386408}}</ref> | |30-50%<ref>{{Cite journal | title = Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia | url = https://www.sciencedirect.com/science/article/pii/S0304395913002947 | journal = PAIN® | date = 2013-11-01|issn=0304-3959 | pages = 2310–2316|volume=154 | issue = 11|doi=10.1016/j.pain.2013.06.001|language=en}}</ref><ref>{{Cite journal | title = Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia | url = https://www.sciencedirect.com/science/article/pii/S0304395913002947 | journal = PAIN® | date = 2013-11-01|issn=0304-3959 | pages = 2310–2316|volume=154 | issue = 11|doi=10.1016/j.pain.2013.06.001|language=en}}</ref><ref>{{Cite journal | title = Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients |url =https://link.springer.com/article/10.1007/s10067-014-2850-5 | journal = Clinical Rheumatology | date = 2014-12-24|issn=0770-3198|pmc=4348533|pmid=25535201 | pages = 413–417|volume=34 | issue = 3|doi=10.1007/s10067-014-2850-5|language=en | first = ToddD. | last = Levine | first2 = David S. | last2 = Saperstein}}</ref> |100%<ref>{{Cite journal | last = Cazzato|first = Daniele | last2 = Castori | first2 = Marco | last3 = Lombardi | first3 = Raffaella | last4 = Caravello | first4 = Francesca | last5 = Bella | first5 = Eleonora Dalla | last6 = Petrucci | first6 = Antonio | last7 = Grammatico | first7 = Paola | last8 = Dordoni | first8 = Chiara | last9 = Colombi | first9 = Marina | date = 2016-06-15 | title = Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes |url =http://n.neurology.org/content/early/2016/06/15/WNL.0000000000002847 | journal = Neurology|language=en | pages = 10.1212/WNL.0000000000002847|doi=10.1212/WNL.0000000000002847|issn=0028-3878|pmid=27306637}}</ref> |- |Incidence of [[Postural orthostatic tachycardia syndrome|POTS]] |11-70% |100% | | | |- |Incidence of [[Neurally mediated hypotension|NMH]] | | | | | |- |Incidence of OI |57%<ref>{{Cite journal | date = 2002-04-01 | title = Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance | url =https://www.sciencedirect.com/science/article/pii/S0022347602157878 | journal = The Journal of Pediatrics|language=en|volume=140 | issue = 4 | pages = 412–417|doi=10.1067/mpd.2002.122725|issn=0022-3476}}</ref> | | | | |- |'''Musculoskeletal system''' | | | | | |- |mitochondria |[[mitochondrion|mitochondrial]] 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" /> | | | | |- |creatine | * 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]]) | | | | |- |'''Cell & metabolism''' | | | | | |- |[[Lipid raft]] |decreased [[Sphingolipid|sphingolipids]] and [[Glycosphingolipid|glycosphingolipids]], building blocks of lipid rafts.<ref>{{Cite journal | last = Naviaux | first = Robert K. | 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> |autoimmunoreactive [[IgG]]s to lipid raft proteins in the heart.<ref>{{Cite journal | date = 2013-07-01 | title = Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome | url =https://www.sciencedirect.com/science/article/pii/S1931524413000753 | journal = Translational Research|language=en|volume=162 | issue = 1 | pages = 34–44|doi=10.1016/j.trsl.2013.03.002|issn=1931-5244}}</ref> | | | |- |'''Immune system''' | | | | | |- |[[Acetylcholine]] receptor autoantibodies |29% |24% | | | |- |Other autoantibodies |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> [[antibodies]] | | | | |- |mast cells |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> | | | | |- |natural killer cells |[[Natural killer cell]] function is reduced<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><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=06 | issue = 04|doi=10.4172/2155-9899.1000348|issn=2155-9899}}</ref> | | | | |- |'''Cardiovascular system''' | | | | | |- |[[Preload failure]] |Yes |Yes | | | |- |[[Low blood volume]] |Yes |Yes | | |Yes |- | | | | | | |- |'''Gastrointestinal system''' | | | | | |- | | | | | | |- |'''Genetics''' | | | | | |- |''[[TPSAB1]]'' |Unknown |Mutation found in a sample of 35 families<ref name=":1">{{Cite journal | last = Lyons | first = Jonathan J. | last2 = Yu | first2 = Xiaomin | last3 = Hughes | first3 = Jason D. | last4 = Le | first4 = Quang T. | last5 = Jamil | first5 = Ali | last6 = Bai | first6 = Yun | last7 = Ho | first7 = Nancy | last8 = Zhao | first8 = Ming | last9 = Liu | first9 = Yihui | date = Dec 2016 | title = Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number |url =https://www.ncbi.nlm.nih.gov/pubmed/27749843 | journal = Nature Genetics|volume=48 | issue = 12 | pages = 1564–1569|doi=10.1038/ng.3696|issn=1546-1718|pmc=5397297|pmid=27749843}}</ref> |Mutation found in a sample of 35 families<ref name=":1" /> |Unknown |Mutation found in a sample of 35 families<ref name=":1" /> |}
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