Structured exercise training for fatigue management in multiple sclerosis: an umbrella review of systematic reviews and meta-analyses.

Abstract

To synthesise evidence from systematic reviews and meta-analyses of randomised controlled trials on structured exercise training for fatigue in people with multiple sclerosis (MS), and to compare effects across exercise modalities and fatigue instruments. Web of Science, Cochrane Library, EBSCO, PubMed/MEDLINE, and Scopus were searched from inception to May 5, 2025. Systematic reviews, with or without meta-analysis, were eligible if they examined structured, multi-session exercise training interventions for fatigue among people with MS and included control conditions. Two reviewers independently performed the study selection and data extraction. The extracted data included review and participant characteristics, exercise modality, fatigue instrument, effect estimates, methodological quality, and FITT-VP descriptors. Standardised effects were expressed as Hedges' g using a random-effects umbrella meta-analytic framework. Heterogeneity, prediction intervals, and small-study effects were assessed when feasible. Evidence robustness was graded using the Ioannidis credibility classification. Thirty-five reviews/meta-analyses were included (5 systematic reviews and 30 meta-analyses). Across fatigue instruments, structured exercise training was associated with small-to-moderate reductions in self-reported fatigue (g range, -0.56 to -0.39). Cardiorespiratory exercise showed the most consistent evidence (Class I; g = -0.376; moderate heterogeneity). Resistance training showed a moderate pooled effect (Class II; g = -0.505; substantial heterogeneity). Other modalities were supported by limited and/or inconsistent evidence, predominantly Class IV. Review-level reporting of key FITT-VP elements was incomplete, and overlap analyses indicated moderate-to-very high redundancy within several modality clusters. Structured exercise training is associated with reductions in self-reported fatigue in MS. Cardiorespiratory exercise provides the most consistent review-level evidence, whereas resistance training shows a moderate pooled effect but greater heterogeneity. Aquatic, mind-body, neuromotor, and technology-mediated interventions are supported by limited or low-certainty evidence and should be considered complementary or hypothesis-generating. Substantial heterogeneity, incomplete exercise-dose reporting, and high overlap across reviews constrain definitive modality-specific prescriptions.