A systematic review of neurological impairments in myalgic encephalomyelitis/ chronic fatigue syndrome using neuroimaging techniques

Abstract

Background Myalgic encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a multi-system illness characterised by a diverse range of debilitating symptoms including autonomic and cognitive dysfunction. The pathomechanism remains elusive, however, neurological and cognitive aberrations are consistently described. This systematic review is the first to collect and appraise the literature related to the structural and functional neurological changes in ME/ CFS patients as measured by neuroimaging techniques and to investigate how these changes may influence onset, symptom presentation and severity of the illness. Methods A systematic search of databases Pubmed, Embase, MEDLINE (via EBSCOhost) and Web of Science (via Clarivate Analytics) was performed for articles dating between December 1994 and August 2019. Included publications report on neurological differences in ME/CFS patients compared with healthy controls identified using neuroimaging techniques such as magnetic resonance imaging, positron emission tomography and electroencephalography. Article selection was further refined based on specific inclusion and exclusion criteria. A quality assessment of included publications was completed using the Joanna Briggs Institute checklist. Results A total of 55 studies were included in this review. All papers assessed neurological or cognitive differences in adult ME/CFS patients compared with healthy controls using neuroimaging techniques. The outcomes from the articles include changes in gray and white matter volumes, cerebral blood flow, brain structure, sleep, EEG activity, functional connectivity

Glatiramer Acetate Treatment in Multiple Sclerosis-Associated Fatigue—Beneficial Effects on Self-Assessment Scales But Not on Molecular Markers

“…Suggestions are (i) immunological mechanisms such as overexpression of pro-inflammatory cytokines, (ii) metabolic dysregulation, (iii) diffuse axonal damage, (iv) fatigability due to reduced plasticity of the MS brain, or (v) neuropsychological influences [ 6 , 7 , 8 ]. Functional MRI studies revealed different areas of cortical activation in fatigued MS patients as compared to non-fatigued patients, indicating different functional patterns in both groups [ 9 , 10 ]. The question if biomolecules—and if yes, which ones—play crucial roles in the pathogenesis of MS fatigue is still unanswered [ 11 ].…”

Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology

“…Therefore, the identification of acceptable objective markers of ME/CFS which can be utilised in epidemiological research in Europe is of very high priority. On this question, differences between ME/CFS cases and controls have been observed in the brain (structure, function, and metabolites), cognitive function and sleep function [37][38][39]. Associations between the occurrence of ME/CFS clinical symptoms, HHV−6, HHV−7 and B19 infection/co-infection reactivation, and increased expression levels of TNF-α and IL6 [40] have been observed, as well as alterations in the levels of infection markers of B19V [41] and EBV [42].…”

Letter: future studies of high‐dose thiamine should consider whether its effects on fatigue are related to the inhibition of carbonic anhydrase isoenzymes. Authors' reply

“…A systematic review on CFS and cerebral blood flow found inconsistencies in the published results 5 . We have not identified studies showing that high‐dose thiamine can increase the cerebral blood flow in humans.…”

“…Elevated cerebral lactate levels in patients with CFS were reported in several studies 5 . High‐dose thiamine treatment has been shown to activate the pyruvate dehydrogenase complex, catalysing decarboxylation of pyruvate, and reduce lactate concentrations in patients with congenital lactic acidaemia 6 …”