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== Possible neurological biomarkers of ME == When the brain is going through challenges such as neuroinflammation or neurodegeneration, several chemicals become dysregulated. These changes are able to be recorded using a special function of magnetic resonance (MR) scanners. Because each chemical has a distinct molecular structure, the magnetic field formed by the scanner will bounce off of each chemical in unique ways. Β This allows the technician to measure the amounts of these chemicals in the brain. Several neurochemicals have been studied in relation to ME patients. Myo-inositol is thought to be involved in astrocyte function (Albrecht et al. 2016) and trended to be higher in ME patients compared to controls.<ref name=":5">{{Cite journal | last = Brooks | first = J.C. | last2 = Roberts | first2 = N. | last3 = Whitehouse | first3 = G. | last4 = Majeed | first4 = T. | date = Nov 2000 | title = Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/11144799|journal=The British Journal of Radiology|volume=73|issue=875|pages=1206β1208|doi=10.1259/bjr.73.875.11144799|issn=0007-1285|pmid=11144799}}</ref> N-acetylacetate (NAA) shows neuron density, which has been found in other neurological disorders<ref name=":2" /> and has been shown to be lower in ME patients,<ref name=":4" /><ref name=":5" /> but this was not found in all studies.<ref>{{Cite journal | last = Puri | first = B. K. | last2 = Counsell | first2 = S.J. | last3 = Zaman | first3 = R. | last4 = Main | first4 = J. | last5 = Collins | first5 = A.G. | last6 = Hajnal | first6 = J.V. | last7 = Davey | first7 = N.J. | date = Nov 2002 | title = Relative increase in choline in the occipital cortex in chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/12197861|journal=Acta Psychiatrica Scandinavica|volume=106|issue=3|pages=224β226|issn=0001-690X|pmid=12197861}}</ref><ref name=":6">{{Cite journal | last = Tomoda | first = A. | last2 = Miike | first2 = T. | last3 = Yamada | first3 = E. | last4 = Honda | first4 = H. | last5 = Moroi | first5 = T. | last6 = Ogawa | first6 = M. | last7 = Ohtani | first7 = Y. | last8 = Morishita | first8 = S. | date = Jan 2000 | title = Chronic fatigue syndrome in childhood | url =https://www.ncbi.nlm.nih.gov/pubmed/10761837|journal=Brain & Development|volume=22|issue=1 | pages = 60β64|issn=0387-7604|pmid=10761837}}</ref> [[Choline]] is linked to activation of glia, loss of energy and expression of macrophages in the brain<ref name=":2" /> and has been shown to change compared to controls.<ref name=":4" /><ref name=":5" /><ref name=":6" /> <ref>{{Cite journal | last = Puri | first = B.K. | last2 = Agour | first2 = M. | last3 = Gunatilake | first3 = K.D.R. | last4 = Fernando | first4 = K.A.C. | last5 = Gurusinghe | first5 = A.I. | last6 = Treasaden | first6 = I.H. | date = Nov 2009 | title = An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)|url=https://www.ncbi.nlm.nih.gov/pubmed/19906518|journal=Prostaglandins, Leukotrienes, and Essential Fatty Acids|volume=81|issue=5-6 | pages = 303β305 |doi=10.1016/j.plefa.2009.10.002|issn=1532-2823|pmid=19906518}}</ref> Lactate increases when more energy is being expended and has been shown to be higher than controls,<ref name=":7">{{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: an in vivo 3.0 T (1)H MRS imaging study|url=https://www.ncbi.nlm.nih.gov/pubmed/18942064|journal=NMR in biomedicine|volume=22|issue=3|pages=251β258|doi=10.1002/nbm.1315|issn=0952-3480|pmid=18942064}}</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. | 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=1073β1087|doi=10.1002/nbm.2772|issn=1099-1492|pmc=3896084|pmid=22281935}}</ref><ref name=":8">{{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 | title=Elevations of Ventricular Lactate Levels Occur in Both Chronic Fatigue Syndrome and Fibromyalgia|url=https://www.ncbi.nlm.nih.gov/pubmed/29308330|journal = Fatigue: Biomedicine, Health & Behavior |volume=5|issue=1|pages=15β20|doi=10.1080/21641846.2017.1280114|issn=2164-1846|pmc=5754037|pmid=29308330}}</ref><ref name=":9">{{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 = 643β650|doi=10.1002/nbm.1512|issn=1099-1492|pmid=20661876}}</ref> and significantly differs from lactate levels in people with psychological disorders.<ref name=":7" /><ref name=":9" /> Both ME patients and [[fibromyalgia]] patients were found to have similar levels of elevated lactate, so more tests would be needed to differentiate the two.<ref name=":8" /> Though contrasts were found between ME people and controls in many of these [[Diagnostic biomarker|biomarker]] studies, researchers are not sure what the changes mean specifically because the metabolites are used in multiple brain processes. Furthermore, the results shown by these papers has not been largely replicated. However, if repeated, these biomarkers could potentially become an objective measure for diagnosing ME.
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