Abstract

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 (VO2 max), and quality of life in people with MS (pwMS). 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 (24weeks of PAE followed by self-guided physical activity) and a waitlist (24weeks of habitual lifestyle followed by PAE) group. PAE comprised two supervised sessions per week; 30-60min, 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 36health survey; SF-36), and VO2 max were measured at baseline, 24weeks, and 48weeks. Eighty-six pwMS were enrolled. Following PAE between-group differences showed reductions in MFIStotal (-5.3 [95% CI: -10.9;0.4], point estimate >clinical relevance), MFISphysical subscore (-2.8 [-5.6;-0.1]), and MFISpsychosocial subscore (-0.9 [-1.6;-0.2]), and an increase in VO2 max (+3.5ml O2 /min/kg [2.0;5.1]). MSWS-12 (-5.9 [-11.9; 0.2]) and 6MWT (+14m [-5;33]) differences suggested potential small walking improvements. No changes observed in FSS, SSST, or SF-36. 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.

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