Abstract
BACKGROUND: Changes in handgrip strength have recently been adapted as clinical biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) under the assumption of a disease-specific peripheral neuromuscular dysfunction. However, some have proposed that strength impairments in ME/CFS are better explained by alterations in higher-order motor control. In serial measurements, exertion can been assessed through analysis of variation, since maximal voluntary contractions exhibit lower coefficients of variation (CV) than submaximal contractions. METHODS: Serial handgrip strength measurements of 105 ME/CFS patients and 66 healthy controls from a previously published biomarker validation study are analyzed post hoc regarding their CV. CV is separately compared in a subsample of participant with normal indexes of fatigability. RESULTS: Compared to healthy controls, patients had significantly higher CV, largely over the conservative 15% cutoff associated with submaximal exertion. In the subsample of study participants, whose within-session fatigability was within normal bounds, CV was still significantly higher in female patients; the difference in male patients was not statistically significant (p = 0.06). CONCLUSIONS: This analysis suggests that loss of grip strength is likely compounded by alterations in higher-order motor control, challenging its utility as a biomarker of peripheral dysfunction. Functional weakness is discussed within a framework that sees motor fatigue as a result of reduced implicit self-efficacy acquired in the context of chronic dyshomoeostasis and disability.