Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review

Abstract

Background: Since the 1990s, neuroimaging has been utilised to study Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a debilitating illness with unknown aetiology. While brain abnormalities in ME/CFS have been identified, relatively little is known regarding which specific abnormalities are consistently observed across research groups and to what extent the observed abnormalities are reproducible. Method: To identify consistent and inconsistent neuroimaging observations in ME/CFS, this retrospective and systematic review searched for studies in which neuroimaging was used to investigate brain abnormalities in ME/CFS in Ovid MEDLINE, PubMed (NCBI), and Scopus from January 1988 to July 2018. A qualitative synthesis of observations was performed to identify brain abnormalities that were consistently and inconsistently reported. Results: 63 full-text articles were included in the synthesis of results from 291 identified papers. Additional brain area recruitment for cognitive tasks and abnormalities in the brain stem are frequent observations in 11 and 9 studies using different modalities from different research teams respectively. Also, sluggish blood oxygenation level-dependent (BOLD) signal responses to tasks, reduced serotonin transporters, and regional hypometabolism are consistent observations by more than two research teams. Single observations include abnormal brain tissue properties, regional metabolic abnormalities, and association of brain measures with ME/CFS symptoms. Reduced resting cerebral blood flow and volumetric brain changes are inconsistent observations across different studies. Conclusion: Neuroimaging studies of ME/CFS have frequently observed additional brain area recruitment during cognitive tasks and abnormalities in the brain stem. The frequent observation of additional brain area recruitment and consistent observation of sluggish fMRI signal response suggest abnormal neurovascular coupling in ME/CFS.

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

“…Indeed, the dorsal brainstem is packed with nuclei governing symptoms such as dysautonomia, sleep problems, nausea, pain, and sickness ( Figure 5 ). Several studies have reported functional and structural brainstem abnormalities in ME/CFS ( Barnden et al, 2019 ; VanElzakker et al, 2019 ; Shan et al, 2020 ), including one study demonstrating brainstem glial activation positively correlated with cognitive impairment ( Nakatomi et al, 2014 ).…”

Broken Connections: The Evidence for Neuroglial Failure in ME/CFS

“…Indeed, several teams have delineated the apparently inadequate communication in ME/CFS between the brainstem and upstream regions like the hypothalamus, hippocampus and prefrontal cortex -here again, the assumption of the brainstem as the tectonic epicenter may help explain the findings of widespread dysfunctions in other regulatory areas of the brain. 6,110 Question 2: With so many pathogenetic links clearly identified in ME/CFS research (including hypoperfusion, inflammation, abnormal adrenergic signaling etc.) -with which link could the pathogenetic chain in ME/CFS start?…”

“…13 Imaging studies in ME/CFS patients have shown multiple alterations in the prefrontal cortex, combined with neuroinflammation in the midbrain. 110,111 Experimental evidence suggests that the astroglial compartment is centrally involved in cognitive and memory dysfunctions. 112 Astrocytes seem to especially contribute to memory consolidation and seem to mediate the effects of vigilance and arousal on memory performance.…”

Myalgic encephalomyelitis - enigma at the medicine’s crossroads

“…One study recognized nine biochemical factors common to both male and female ME/CFS patients but not healthy controls with an apparent diagnostic accuracy of more than 90% [19] Neuroimaging in ME/CFS shows more diffuse activation patterns than controls on attention tests, sometimes structural abnormalitis in the brain stem with signs of inflammation,reduction in the serotonin 1A receptor binding, particularly in the hippocampus bilaterally, and reduced serotonin transporters density in the rostral anterior cingulate [23].…”