Exercise Therapy Has Positive Effect on Multiple Sclerosis-Related Fatigue

Researchers sought to determine if physical exercise has a positive effect on multiple sclerosis fatigue and which type of exercise has the largest effect on fatigue, also based on disease severity.

Exercise is an effective therapeutic strategy for fatigue in patients with multiple sclerosis (MS), and combined exercise is the most effective modality for physical and total fatigue, according to a review study published in the Archives of Physical Medicine and Rehabilitation.

Among patients with MS, fatigue is one of the most common and disabling symptoms, affecting up to 80% of this population. The cause of fatigue is complex and can make it challenging to manage, especially finding interventions that can effectively reduce fatigue in patients with MS. However, regular exercise has been suggested as a nonpharmacologic intervention that has a positive effect on MS-related fatigue.

The objective of the current study was to assess whether physical exercise has a positive effect on reducing total and physical fatigue in patients with MS, determine which exercise yields the greatest effect, and predict the type of exercise with the largest effect on fatigue based on disease severity.

Researchers conducted a network meta-analysis (NMA) by searching MEDLINE, Embase, SPORTDiscus, Physiotherapy Evidence Database, Cochrane Library, and Web of Science through February 2021 for relevant terms related to MS, clinical trials, exercise, and fatigue.

A total of 58 randomized controlled trials (RCT) with 2644 participants were included in the analysis. The exercise interventions included were aerobic, resistance, aerobic with resistance, balance, combined exercise, body weight support, mind-body exercises (yoga or Pilates), and a control group.

The Grading of Recommendations, Assessment, Development, and Evaluation was used for assessing the quality of the evidence. The surface under the cumulative ranking (SUCRA) was estimated for each intervention, and the main summary measure was the standardized difference in means.

The researchers found that all estimates supported exercise as being effective for total and physical fatigue. Combined exercise and resistance training had the highest effect size (ES) for pairwise comparisons vs control participants (range, –0.74 and –1.24). The NMA showed that combined exercise (–1.51; 95% CI, –2.01 to –1.01) and resistance training (–1.15; 95% CI, –1.81 to –0.49) had the highest effects for physical and total fatigue, respectively, compared with the control group.

Regarding physical fatigue, combined exercise (86.3%) and body weight support (85.4%) had the highest SUCRA. For total fatigue, resistance training (83.9%) and combined exercise (77.9%) had the highest SUCRA.

Analyses according to disease severity were conducted only for the mild and moderate levels. Regarding physical fatigue with mild disease severity level, the highest statistically significant ES was –1.05 (95% CI, –1.42 to –0.67) for combined exercise vs the control group. For total fatigue with mild severity, combined exercise vs the control group had an ES of –0.50 (95% CI, –0.80 to –0.20), and mind-body vs the control group had an ES of –0.80 (95% CI, –1.36 to –0.23). Regarding total fatigue for moderate severity, resistance training and combined exercise vs the control group had an ES of –0.52 (95% CI, –1.02 to –0.02) and –0.58 (95% CI, –0.89 to –0.28), respectively.

Among several study limitations, the researchers were unable to consider the intensity of exercise owing to the lack of data for most exercise modalities. Also, the study does not provide any recommendation about the appropriateness of each type of exercise according to disease duration because recent innovative therapies such as gene therapy may have affected disease progression. Furthermore, grouping of interventions was necessary given the limited number of studies in some exercise categories.

“Our results are based on evidence based on RCTs and represent the most comprehensive research effort to synthesize the best available evidence on the type of exercise that is most effective to improve fatigue in this population,” the researchers concluded.


Torres-Costoso A, Martínez-Vizcaíno V, Reina-Gutiérrez S, et al. Effect of exercise on fatigue in multiple sclerosis: a network meta-analysis comparing different types of exercise. Arch Phys Med Rehabil. Published online September 10, 2021. doi: 10.1016/j.apmr.2021.08.008