The Impact of Upper Extremity Rehabilitation on Fatigue in Individuals With Multiple Sclerosis: A Systematic Review

Background: Although numerous interventions have been investigated to alleviate fatigue in people with multiple sclerosis (PwMS), evidence regarding the effects of upper extremity rehabilitation on fatigue remains limited. Objective: The objective of this review was to evaluate and synthesize the available evidence on the effects of upper extremity rehabilitation interventions on fatigue in PwMS. Methods: This review was conducted in accordance with the PRISMA guidelines and was prospectively registered in the PROSPERO database. A systematic search of PubMed, Web of Science, and Scopus was performed up to August 2026. Studies were eligible if they investigated the effects of upper extremity rehabilitation interventions on fatigue in PwMS. The risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 (RoB 2), and the certainty of the evidence was appraised using the GRADE methodology. Results: Nine studies including 250 participants (136 intervention, 114 control) met the inclusion criteria. The included studies evaluated a range of technology-assisted, exercise-based, home-based, and task-oriented upper extremity rehabilitation approaches, with some interventions incorporating more than one therapeutic or technological component. Fatigue outcomes were measured using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Risk of bias was low in three randomized controlled trials, with some concerns in two and high in two; among the two crossover studies, one was rated as low risk and one as high risk. GRADE assessment showed low certainty of evidence for studies using the FSS and very low certainty for those using the MFIS, indicating an overall low certainty of the available evidence. Conclusions: The available evidence is insufficient to draw definitive conclusions regarding the effects of upper extremity rehabilitation on fatigue in PwMS. Further high-quality randomized controlled trials are required.