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Abstract
Objective This systematic review aims to synthesise and evaluate structural MRI (sMRI) and functional MRI (fMRI) studies in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).
Methods We systematically searched Medline and Ovid and included articles from 1991 (date of Oxford diagnostic criteria for CFS/ME) to first April 2019. Studies were selected by predefined inclusion and exclusion criteria. Two reviewers independently reviewed the titles and abstracts to determine articles for inclusion, full text and quality assessment for risk of bias.
Results sMRI studies report differences in CFS/ME brain anatomy in grey and white matter volume, ventricular enlargement and hyperintensities. Three studies report no neuroanatomical differences between CFS/ME and healthy controls. Task-based fMRI investigated working memory, attention, reward and motivation, sensory information processing and emotional conflict. The most consistent finding was CFS/ME exhibited increased activations and recruited additional brain regions. Tasks with increasing load or complexity produced decreased activation in task-specific brain regions.
Conclusions There were insufficient data to define a unique neural profile or biomarker of CFS/ME. This may be due to inconsistencies in finding neuroanatomical differences in CFS/ME and the variety of different tasks employed by fMRI studies. But there are also limitations with neuroimaging. All brain region specific volumetric differences in CFS/ME were derived from voxel-based statistics that are biased towards group differences that are highly localised in space. fMRI studies demonstrated both increases and decreases in activation patterns in CFS/ME, this may be related to task demand. However, fMRI signal cannot differentiate between neural excitation and inhibition or function-specific neural processing. Many studies have small sample sizes and did not control for the heterogeneity of this clinical population. We suggest that with robust study design, subgrouping and larger sample sizes, future neuroimaging studies could potentially lead to a breakthrough in our understanding of the disease.
- chronic fatigue Syndrome
- myalgic encephalopathy
- magnetic resonance imaging
- functional MRI
- CFS/ME
- structural MRI
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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Footnotes
Contributors BA created systematic review protocol, conducted online literature search, reviewed and selected articles for inclusion, conducted full-text review of all articles, data extraction, synthesis and quality assessment, and wrote this manuscript. CL reviewed search articles, read full texts of articles for inclusion and edited this manuscript. EC conceived the systematic review topic, and reviewed and edited the protocol. She also reviewed and edited this manuscript. NJT reviewed and edited the protocol, read full-text articles included in the systematic review for quality assessment, reviewed and edited data extraction and synthesis. and reviewed and edited the manuscript for submission.
Funding BA is supported by the Saudi Ministry of Health PhD Scholarship at the University of Bristol.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.