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<0.01) improved in the exercise group. Conclusion: These findings
do not support a neuroprotective effect of PAE in terms of total brain
atrophy in people with MS. Oppositely, PAE-induced improvements in
cardiorespiratory fitness was accompanied by a potential neuroprotective
effect in terms of gray matter parenchymal fraction and a relapse rate of
zero. While these exploratory findings cautiously support PAE as a
potential adjunct disease-modifying treatment in MS, further
investigations are warranted. ClinicalTrials.gov identifier: NCT02661555
Level of evidence: This study provides level I evidence that 24 weeks of
high-intensity PAE did not elicit disease-modifying effects in PBVC in
people with MS. Exploratory analyses showed that PAE reduce relapse rate
and may preserve gray matter brain volume.