Effects of exercise training on multiple sclerosis biomarkers of central nervous system and disease status: a systematic review of intervention studies

Background and purpose Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS) that can be tracked through biomarkers of disease status. We investigated the effects of exercise on MS biomarkers associated with CNS status including imaging, blood-brain barrier (BBB) function and neurotrophic factors. Methods We conducted open-dated searches of Scopus, Medline, EMBASE and the Cochrane Library. We included studies written in English describing interventions of exercise that measured one or more of the biomarkers associated with MS published up to October 2018. Results We located a total of 3012 citations through searches in electronic databases. Of these, 16 studies were eligible for review; six studies focused on magnetic resonance imaging (MRI) markers, nine studies focused on neurotrophic factors and three studies focused on BBB function markers. It is of note that two studies included both neurotrophic factor and BBB function markers and are therefore included across categories of biomarkers in this review. The existing evidence from MRI studies confirmed that exercise training can improve CNS integrity and function. There is evidence of a positive effect of exercise training on modulation of BBB permeability markers and brain-derived neurotrophic factor. Conclusions Exercise successfully improves MRI outcomes and peripheral biomarkers (i.e. brain-derived neurotrophic factor) in people with MS. This suggests that exercise can be recommended as an adjuvant therapy for MS treatment. This conclusion is tempered by some methodological limitations including small sample sizes and high drop-out rates in the reviewed studies.