Advancements and Challenges in Exercise Training for Multiple Sclerosis: Comprehensive Review and Future Directions for Randomized Controlled Trials.

Exercise training represents a health behavior for the treatment and management of the multi-faceted manifestations of multiple sclerosis (MS). This paper provides a comprehensive overview of evidence from randomized controlled trials (RCTs) regarding benefits, safety, participation, and guidelines for exercise training in MS, based on systematic reviews and meta-analyses. The paper then provides our opinions based on extensive experience regarding challenges for improving and expanding future RCTs that will advance our understanding of exercise training in MS. The comprehensive review of evidence from RCTs indicates that exercise training yields substantial improvements in aerobic and muscle fitness, mobility, fatigue and depression, quality of life, and participation outcomes. There is a non-significant increase in the risk of adverse events or serious adverse events with exercise training compared with control conditions or healthy populations. Rates of adherence and compliance with exercise training (i.e., participation) approximate 80% and 70%, respectively. The current prescriptive guidelines suggest 2-3 days per week of aerobic and resistance exercise training as the minimal dose for safely benefiting from exercise training in MS. We propose 10 important topics as avenues for expanding the body of research and improving its scope for evidence-based practice in MS. Overall, the research on exercise training in MS is strong, but it can get stronger. The expansion and advancement of evidence are critical for moving exercise training into the clinical armamentarium of MS disease treatment and management.