Meeting Physical Activity Guidelines for Persons With Multiple Sclerosis Reduces Fatigue Severity and Impact: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Objective: Regular physical activity is a recommended behavioral goal for persons with multiple sclerosis. This review aimed to determine the effect of interventions that met physical activity guidelines for persons with multiple sclerosis on fatigue measures and to compare the magnitudes of the effect sizes for meeting these guidelines with the minimal clinically important differences for fatigue measures.

Methods: The search was conducted in PubMed, Embase, Web of Science, SPORTDiscus, Scopus, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO from inception to October 2024. Only randomized clinical trials that explicitly met physical activity guidelines and evaluated fatigue were included. Two independent reviewers screened articles for inclusion and evaluated the risk of bias of included trials using the Cochrane risk-of-bias tool for randomized trials. Findings were summarized, and a meta-analysis was conducted. Fatigue measures included the Fatigue Severity Scale, Fatigue Impact Scale, and modified Fatigue Impact Scale. The Grading of Recommendations, Assessment, Development and Evaluation was used to evaluate the quality of the evidence. The review protocol was preregistered in the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42023387305).

Results: Twenty-two randomized clinical trials with 920 participants were included in the review; 17 studies were included in the meta-analysis. Findings indicated that interventions meeting physical activity guidelines for at least 4 weeks significantly reduced fatigue severity (standardized mean difference = -1.46; 95% CI = -2.11 to -0.81) and fatigue impact measured with the modified Fatigue Impact Scale (mean difference = -11.88; 95% CI = -20.57 to -3.19) and Fatigue Impact Scale (mean difference = -21.08; 95% CI = -31.01 to -11.15). All findings were clinically relevant, with effect sizes exceeding the established minimal clinically important differences for the fatigue measures. Some methodological concerns were noted, and the evidence level ranged from very low to moderate.

Conclusions: Evidence suggests that engaging in physical activity for at least 150 minutes per week or 2 sessions of 10 to 30 minutes of moderate-intensity aerobic training plus 2 sessions of resistance training per week results in clinically significant reductions in fatigue severity and impact necessary to improve the quality of life of persons with multiple sclerosis.

Impact: Fatigue is a highly prevalent symptom associated with poor outcomes, including falls, activity restrictions, pain, cognitive problems, functional limitations, and mortality risk among persons with multiple sclerosis. Our study suggests that adhering to physical activity guidelines developed for persons with multiple sclerosis clinically reduces the severity and impact of fatigue. This regimen includes engaging in physical activity for at least 150 minutes per week or participating in 2 sessions of 10 to 30 minutes of moderate-intensity aerobic training plus 2 sessions of resistance training per week.