Background: The inflammatory and neurodegenerative component of the disease process of multiple sclerosis (MS) are closely intertwined and characterized by the accumulation of white matter lesions in the central nerve system and accelerated brain atrophy. The inflammation can nowadays efficiently be targeted with the currently available disease modyfying drugs, but the neurodegenerative process and efficient symptom management are harder to tackle. Along with new pharmaceutical approaches, non-pharmaceutical approaches to alleviate MS symptoms and decelerate the disease progression are being sought. Studies on ageing in healthy subjects and subjects wih dementia suggest that aerobic exercise may have a neuroprotective effect. There is insufficient knowledge about how aerobic exercise impacts the disease process of MS and how aerobic exercise, combined with pharmaceutical treatment, might have a role in the management of MS.
Objective: Our study objective was to examine the impact of aerobic exercise on neuroinflammation and neurodegeneration in persons with MS. Evidence of a favourable impact of aerobic exercise would serve as a base for further research, focused on finding strategies which would help alleviate and better control the disease process of multiple sclerosis and therefore improve their quality of life. Additionally, newly gained information could serve as proof and support for rehabilitation programs for persons with MS.
Patients and methods: An exploratory 12-week randomized control trial including an intervention group (n=14, 12 weeks of aerobic exercise twice weekly in duration of 60 minutes) and a control group (n=14, continuation of usual lifestyle). Primary outcomes were magnetic resonance imaging measures of inflammation (T2 and T1-gadolinium enhancing lesion count and volume) and neurodegeneration (whole brain, gray matter and brain structure volume change), while secondary outcomes included disability measures (Expanded Disability Status Scale), Timed 25-foot Walk Test, blood cytokine levels (interleukin-6, soluble interleukin-2 receptor, brain-derived neurotrophic factor), cognitive tests and patient-reported outcomes (fatigue, mood, quality of life).
Results: The effects od aerobic exercise on whole brain and grey matter atrophy were minor. The observed effect on volume (atrophy) in selected brain substructures was heterogeneous. Putaminal and posterior cingulate volumes decreased, parahippocampal gyrus volume increased, thalamuus and amygdala volume remained the same, and active lesion load and count decreased. However, apart from weak improvements in walking speed and brain-derived neurotrophic factor levels, there was no effect of aerobic exercise on other clinical, cognitive or patient-reported measures.
Conclusion: The results of our study provide new information on the impact of aerobic exercise in combination with pharmaceutical treatment with fingolimod on thedisease process of MS. The results suggest that aerobic exercise in persons with MS has a positive effect on the volume of some of the substructures of the brain (parahippocampal gyrus, thalamus and amygdala), possibly indicating a slowing of the neurodegenerative process in these regions. However, the observed effect of aerobic exercise on the selected brain substructures seems to be heterogeneous so a negative impact on the volume of putamen and posterior cingulate gyrus was observed, with unclear implications. While the total T2 lesion load remained stable, a slight decrease in active lesion volume and count have been observed, which could imply to an antiinflammatory effect of aerobic exercise in persons with MS. Apart from weak improvements in walking speed and brain-derived neurotrophic factor levels we have observed no meaningful impact of aerobic exercise on disability, cognitive function, fatigue, mood or quality of life of persons with MS. Several limitations, especially the small sample size and study length, preclude the generalization of our study findings to all persons with MS. However, our study provides an important foundation for further studies of longer duration and larger sample size with inclusion of other disease-modifying drugs to either confirm of refute there findings and further elucidate the role of aerobic exercise as an adjunctive treatment option in the management of patients with MS. Furthermore, this study provides novel information on the probable positive effect of aerobic exercise on the neurodegenerative and inflammatory process of MS, additionally supporting rehabilitation strategies for people with MS.
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