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Abstract
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.
Clinicaltrials.gov 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.
Glossary
- 6MWT=
- 6-Minute Walk Test;
- ARR=
- absolute risk reduction;
- BPF=
- brain parenchymal fraction;
- DKI=
- diffusion kurtosis imaging;
- DMT=
- disease-modifying treatment;
- EDSS=
- Expanded Disability Status Scale;
- FA=
- fractional anisotropy;
- FLAIR=
- fluid-attenuated inversion recovery;
- GM=
- gray matter;
- GMPF=
- gray matter parenchymal fraction;
- HRmax=
- maximum heart rate;
- KFA=
- kurtosis fractional anisotropy;
- MD=
- mean diffusivity;
- MKT=
- mean kurtosis tensor;
- MS=
- multiple sclerosis;
- MSIS=
- MS Impact Scale;
- NNT=
- number needed to treat;
- PAE=
- progressive aerobic exercise;
- PBVC=
- percentage brain volume change;
- PRT=
- progressive resistance training;
- pwMS=
- people with multiple sclerosis;
- RCT=
- randomized controlled trial;
- SIENA=
- structural imaging evaluation of normalized atrophy;
- sNfL=
- serum neurofilament light chain;
- WMPF=
- white matter parenchymal fraction
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received February 18, 2020.
- Accepted in final form August 11, 2020.
- © 2020 American Academy of Neurology
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