Investigating the potential disease-modifying and neuroprotective efficacy of exercise therapy early in the disease course of multiple sclerosis: The Early Multiple Sclerosis Exercise Study (EMSES)

Abstract

Background: Potential supplemental disease-modifying and neuroprotective treatment strategies are warranted in multiple sclerosis (MS). Exercise is a promising non-pharmacological approach, and an uninvestigated ‘window of opportunity’ exists early in the disease course. Objective: To investigate the effect of early exercise on relapse rate, global brain atrophy and secondary magnetic resonance imaging (MRI) outcomes. Methods: This randomized controlled trial ( n = 84, disease duration <2 years) included 48 weeks of supervised aerobic exercise or control condition. Population-based control data (Danish MS Registry) was included ( n = 850, disease duration <2 years). Relapse rates were obtained from medical records, and patients underwent structural and diffusion-kurtosis MRI at baseline, 24 and 48 weeks. Results: No between-group differences were observed for primary outcomes, relapse rate (incidence-rate-ratio exercise relative to control: (0.49 (0.15; 1.66), p = 0.25) and global brain atrophy rate (−0.04 (−0.48; 0.40)%, p = 0.87), or secondary measures of lesion load. Aerobic fitness increased in favour of the exercise group. Microstructural integrity was higher in four of eight a priori defined motor-related tracts and nuclei in the exercise group compared with the control (thalamus, corticospinal tract, globus pallidus, cingulate gyrus) at 48 weeks. Conclusion: Early supervised aerobic exercise did not reduce relapse rate or global brain atrophy, but does positively affect the microstructural integrity of important motor-related tracts and nuclei.

The impact of aerobic and resistance training intensity on markers of neuroplasticity in health and disease

“…Motor outcomes included measures of upper and lower extremity muscle strength and power, maximal or peak oxygen uptake, metrics of cardiac function, various motor tests, reaction time, walking and balance performance, and gait properties (Supplement 2 The updated search in July 2022 identified no new eligible studies for inclusion in HYA, 9 studies in HOA (Cassilhas et al, 2022;Castells-Sanchez et al, 2022;DuBose et al, 2022;Frost et al, 2021;Pani et al, 2022aPani et al, , 2022bPani et al, , 2021Park, 2022;Tarumi et al, 2022), 2 studies in PwMS (Bahmani et al, 2022;Riemenschneider et al, 2022), 1 study in PwPD (Johansson et al, 2022), and 2 studies in PwST (Hsiao et al, 2022;Kufner et al, 2021).…”

Exercise Therapy in Early Multiple Sclerosis Improves Physical Function But Not Cognition: Secondary Analyses From a Randomized Controlled Trial

“…Data on disease-modifying and neuroprotective parameters (primary outcomes) has been published elsewhere. 11 Outcomes were assessed at baseline (T0), after 24 weeks (T24), and after 48 weeks (T48).…”

“…Data on disease-modifying and neuroprotective parameters (primary outcomes) has been published elsewhere. 11 A separate study protocol including full details on study design, recruitment and eligibility of patients, methodologies of applied outcomes, and statistical analysis has also been published elsewhere. 12 The study is approved by The Central Denmark Region Committees on Health Research Ethics (1-10-72-388-17) and registered at the Danish Data Protection Agency (2016-051-000001 (706)).…”

“…Primary analyses from this study-the Early Multiple Sclerosis Exercise Study (EMSES)-found a positive effect of supervised aerobic exercise early in the disease course of MS on the microstructural integrity of a priori defined motor-related tracts and nuclei, indicating that early exercise may have beneficial effects on physical function. 11 With these secondary analyses from the EMSES study we now aim to further investigate the efficacy of 48 weeks of supervised aerobic exercise on measures of disability progression (Multiple Sclerosis Functional Composite [MSFC]), physical function (walking capacity, hand dexterity, and aerobic fitness level), cognitive function (processing speed, attention, and memory), and patient reported outcome measures of disease and fatigue impact. We hypothesized that the general progression of disabilities would be lower, and specifically that measures of walking capacity and aerobic fitness level would increase in the group of patients receiving supervised aerobic exercise when compared to the control condition.…”

Protocol for an exploratory, randomised, single-blind clinical trial of aerobic exercise to promote remyelination in multiple sclerosis

“…2 Remyelination, however, improves conduction velocity and also provides neuroprotection across the axon; therefore, remyelination has the potential to be an effective long-term strategy to both improve and protect against future disability in people with MS (pwMS). 3 4 Numerous clinical trials demonstrate that aerobic exercise can improve physical fitness, fatigue, depression and walking mobility, 5 6 and may also reduce the rate of relapse and disease progression in MS. [7][8][9] Yet, the mechanisms underlying the effects of exercise/physical activity remains a high priority question for wellness research in MS. 10 In preclinical models of MS, aerobic exercise promotes remyelination, both alone and synergistically with pharmacotherapy. In a lysolecithin-induced demyelination study in mice, aerobic exercise was associated…”