The Effects of Aerobic Exercise on the Recovery of Walking Ability and Neuroplasticity in People with Multiple Sclerosis: A Systematic Review of Animal and Clinical Studies

Abstract

Introduction Walking is of high priority for people with multiple sclerosis (PwMS). It remains unclear whether aerobic exercise can improve walking ability and upregulate neurotrophins. This review aims to consolidate evidence to develop optimal aerobic training parameters to enhance walking outcomes and neuroplasticity in PwMS. Methods Clinical studies examining aerobic exercise for ≥3 weeks, having outcomes on walking with or without neurotrophic markers, were included. Studies utilizing animal models of MS were included if they employed aerobic exercise with outcomes on neurological recovery and neurotrophins. From a total of 1783 articles, 12 clinical and 5 animal studies were included. Results Eleven clinical studies reported improvements in walking ability. Only two clinical studies evaluated both walking and neurotrophins, and neither found an increase in neurotrophins despite improvements in walking. Patients with significant walking impairments were underrepresented. Long-term follow-up revealed mixed results. Two animal studies reported a positive change in both neurological recovery and neurotrophins. Conclusion Aerobic exercise improves walking ability in PwMS. Gains are not consistently maintained at 2- to 9-month follow-up. Studies examining levels of neurotrophins are inconclusive, necessitating further research. Aerobic exercise enhances both neurological recovery and neurotrophins in animal studies when started 2 weeks before induction of MS.

Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders

“…Such cellular changes are sustained by molecular modifications involving neurotransmitters and neurotrophins, likely supporting neuroprotection. Indeed, motor training can stimulate neuroprotective mechanisms [179] and alleviate ataxic symptoms in both preclinical and clinical studies also at stages of overt ataxic pathology [180][181][182][183] and, in general terms, in other neurodegenerative disorders [184,185]. However, in cerebellar pathologies, the extent of exercise-dependent amelioration, as well as its endurance, is affected by factors such as disease severity and areas of neurodegeneration, and becomes more limited with the progression of the pathology [186][187][188].…”

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

“…There are multiple systematic reviews and meta‐analyses that support exercise training for symptomatic management and perhaps disease modification in MS . Regarding exercise training and MS biomarkers, we located a single systematic review that included both animals and humans ; the study only included two studies that assessed neurotrophic factors . We are unaware of other reviews regarding effects of exercise training on biomarkers of disease status in MS, yet such a review is important for the further understanding of effects of exercise training on biomarkers of disease status and progression.…”

Vigorous cool room treadmill training to improve walking ability in people with multiple sclerosis who use ambulatory assistive devices: a feasibility study

“…Aerobic exercise is an intervention that has both neuroprotective and anti-inflammatory benefits [96,97]. Evidence suggests that progressively intense, aerobic training performed 2 or 3 times per week for at least 8 to 9 weeks could improve walking ability as well as result in a trend towards an increase in resting BDNF levels in people with MS [12] and in other neurological disorders such as stroke [98]. Similarly, our participants with MS experienced statistically significant improvement in walking ability, and 6 out of 7 participants had an increase in resting levels of serum BDNF after training.…”

“…A systematic review of evidence suggested that aerobic training significantly altered peripheral levels of cytokines, interleukin (IL) 6, IL-10, interferon-gamma, and tumor necrosis factor-alpha [11]. Whether aerobic training has the potential to affect multiple underlying targets such as enhancing markers of neuroplasticity by upregulating neurotrophins and attenuating neural inflammation by altering levels of cytokines is not clear [12,13]. Since aerobic exercise performed on a treadmill also provides a high volume of task-specific practice, aerobic treadmill training has the potential to improve walking ability, fitness, and quality of life [12][13][14].…”

“…Our previous research showed that cooling the exercise environment to 16°C, mitigated exercise-induced losses in central drive among people with MS who reported having heat sensitivity [22]. Furthermore, there is a dearth of literature and rehabilitation options for individuals with higher levels of MS disability [12].…”