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

PLoS One. 2020 Apr 30;15(4):e0232475. doi: 10.1371/journal.pone.0232475. eCollection 2020.


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 and cognitive function. Secondary measures including symptom severity were also reported in most studies.

Conclusions: The results suggest widespread disruption of the autonomic nervous system network including morphological changes, white matter abnormalities and aberrations in functional connectivity. However, these findings are not consistent across studies and the origins of these anomalies remain unknown. Future studies are required confirm the potential neurological contribution to the pathology of ME/CFS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Autonomic Nervous System / diagnostic imaging
  • Autonomic Nervous System / physiopathology*
  • Cerebrovascular Circulation / physiology
  • Fatigue Syndrome, Chronic / diagnosis
  • Fatigue Syndrome, Chronic / physiopathology*
  • Gray Matter / diagnostic imaging
  • Gray Matter / physiopathology
  • Humans
  • Neuroimaging*
  • Severity of Illness Index
  • White Matter / diagnostic imaging
  • White Matter / physiopathology*

Grant support

This research was supported by the Stafford Fox Medical Research Foundation, the Mason Foundation, Mr. Douglas Stutt, Blake Beckett Foundation, Alison Hunter Memorial Foundation, the McCusker Charitable Foundation, Buxton Foundation, Mr and Mrs Stewart, Henty Community, Henty Lions Club and the Change for ME Charity. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.