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Efficacy of High-Intensity Aerobic Exercise on Brain MRI Measures in Multiple Sclerosis
Martin Langeskov-Christensen1, Lars Grøndahl Hvid2, Mikkel Karl Emil Nygaard2
1From the Section for Sport Science, Department of Public Health (M.L.-C., L.G.H., U.D.), and Center of Functionally Integrative Neuroscience, Department of Clinical Medicine (M.K.E.N., S.F.E.), Aarhus University; MR Research Centre (S.R.) and Multiple Sclerosis Clinic, Department of Neurology (T.P.), Aarhus University Hospital; Brain and Nerve Diseases, Department of Neurology (H.B.J.), Lillebaelt Hospital, Kolding; Department of Regional Health Research (H.B.J.), Department of Neurobiology Research, Institute of Molecular Medicine (H.H.N.), BRIDGE-Brain Research-Inter-Disciplinary Guided Excellence, Department of Clinical Research (H.H.N.), and Department of Regional Health Research (E.S.), University of Southern Denmark, Odense; Department of Neurology (H.H.N.), Odense University Hospital; and MS-Clinic of Southern Jutland (Sønderborg, Kolding, Esbjerg), Department of Neurology (E.S.), Hospital of Southern Denmark, Sønderborg. mach@ph.au.dk.
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 patients with MS 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% confidence interval [CI] -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, 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 and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted.
Clinicaltrialsgov Identifier:
NCT02661555.
Classification 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 may reduce relapse rate.
