Efficacy of high-intensity aerobic exercise on common multiple sclerosis symptoms

Objectives: Fatigue and walking impairment are disabling symptoms of multiple sclerosis (MS). We investigated the effects of progressive aerobic exercise (PAE) on fatigue, walking, cardiorespiratory fitness (VO₂max), and quality of life in people with MS (pwMS). Materials & Methods: Randomized controlled trial (1:1 ratio, stratified by sex) with a 24-week crossover follow-up and intention-to-treat analysis. Allocation to an exercise (24 weeks of PAE followed by self-guided physical activity) and a waitlist (24 weeks of habitual lifestyle followed by PAE) group. PAE comprised two supervised sessions per week; 30–60 min, 65–95% of maximum heart rate. Fatigue impact (Modified Fatigue Impact Scale; MFIS) and severity (Fatigue Severity Scale; FSS), walking ability (12-item MS Walking Scale; MSWS-12) and capacity (Six-Minute Walk Test; 6MWT, Six Spot Step Test; SSST), quality of life (Short Form 36 health survey; SF-36), and VO₂max were measured at baseline, 24 weeks, and 48 weeks. Results: Eighty-six pwMS were enrolled. Following PAE between-group differences showed reductions in MFIS_total (−5.3 [95% CI: −10.9;0.4], point estimate >clinical relevance), MFIS_physical subscore (−2.8 [−5.6;-0.1]), and MFIS_psychosocial subscore (−0.9 [−1.6;-0.2]), and an increase in VO₂max (+3.5 ml O₂/min/kg [2.0;5.1]). MSWS-12 (−5.9 [−11.9; 0.2]) and 6MWT (+14 m [−5;33]) differences suggested potential small walking improvements. No changes observed in FSS, SSST, or SF-36. Conclusions: In a representative sample of pwMS, PAE induced a clinically relevant reduction in fatigue impact, whereas small and no effects were seen for walking and quality of life, respectively. The results need confirmation in a future trial due to the study limitations.