Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis

Objective: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS). Methods: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired MS patients aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle. Results: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% CI -0.27;0.51, p=0.55). In contrast, gray matter parenchymal fraction (+1.13 percentage points, 0.00;2.26, p=0.05; did not remain after Bonferroni correction), cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0;5.1, p<0.01), and annualized relapse rate (p