Exercise Training and Multiple Sclerosis

NeurologyLiveNovember 2021
Volume 4
Issue 6

In line with the push for more comprehensive care, literature suggests that patients with multiple sclerosis benefit from physical therapy interventions to help manage disease symptoms.

ROBERT W. MOTL, PHD Professor of Kinesiology and Nutrition, College of Applied Health Sciences, University of Illinois Chicago

Robert W. Motl, PhD

MULTIPLE SCLEROSIS (MS), an immune-mediated disease of the central nervous system (CNS) with secondary neurodegenerative processes in its pathogenesis, has a prevalence approaching 1 million adults in the United States.1,2 MS is clinically characterized by relapses, lesions in the CNS, and progression of neurological disability. Those clinical expressions are brought about by periods of inflammatory demyelination and transection of axons as well as neurodegeneration involving loss of trophic support of neurons. The disease pathogenesis and resulting damage are expressed as dysfunction, such as walking and cognitive impairment, and in symptoms, such as fatigue and depression, that compromise quality of life (QOL) and full participation.

There has been a steadily increasing body of research on the outcomes of exercise training among individuals with MS.3 Exercise training is defined as planned, structured, and repetitive physical activity undertaken over periods of time with the objective of improving outcomes such as fitness, function, symptoms, and QOL. This paper provides an overview of exercise training and its outcomes, safety, and prescription in MS, and serves as an overview and reference for investigators and clinicians interested in the benefits, safety, and prescription of exercise training in MS.

Scope of Exercise Benefits in MS

Consistent evidence exists for the benefits of exercise training in individuals with MS.4,5 One recent review provided a quantitative synthesis of 20 randomized controlled trials (RCTs) and reported that exercise training improved muscular and cardiorespiratory fitness in patients with MS.6 Other meta-analytic reviews have reported that exercise training has been associated with improvements in symptomatic fatigue, depression, pain, and cognition.7-10 Some meta-analyses have reported beneficial effects of exercise training on balance and walking function in patients with the disease.11,12 An older meta-analysis has reported beneficial effects of exercise training interventions on QOL outcomes among patients.13

Importantly, one group of investigators provided a literature review on the topic of exercise as a disease-modifying therapy by first identifying metrics for evaluating disease modification and progression in MS (ie, relapse rate, neurological disability and its progression, brain lesion volume, and neuro-performance outcomes of walking and cognition), and then reviewing evidence for exercise as a disease-modifying therapy (DMT).14 The evidence indicated that exercise was associated with reduced relapse rate, neurological disability and progression, and lesion volume, and further yielded improved neuro-performance, particularly walking outcomes. Of note, one review of 26 RCTs that included 1295 participants with MS reported relapse rates of 4.6% and 6.3% for exercise and control conditions, respectively; those rates yielded a relative risk of relapse for exercise training of 0.73 compared with control conditions (ie, 27% reduction in relapse rate for exercise training).15

Overall, we can classify the evidence regarding exercise training effects on outcomes in MS using the International Classification of Functioning, Disability, and Health (ICF) model (FIGURE).16 The existing evidence demonstrated a pattern of smaller effects of exercise on outcomes when moving from body structure and function through activity performance. This is logical, as body structure and function represent more proximal outcomes associated with adaptations as a result of exercise itself, whereas activity performance (ie, participation) is a more distal outcome that is likely not the direct result of exercise training. This is consistent with models of exercise and physical activity effects on QOL in aging.17 There is obviously a need for considerable work in the areas of disease pathogenesis, activities, and participation within the ICF framework for providing a complete picture of exercise in MS.

FIGURE. ICF Model of Exercise for MS (Click to enlarge)

FIGURE. ICF Model of Exercise for MS (Click to enlarge)

Safety of Exercise in MS

The safety profile of exercise has been described in a recent review of exercise in individuals with MS,15 and this is critical for informing decisions and recommendations regarding its safety. To that end, the systematic review focused on adverse events (AEs) reported in RCTs of exercise training in MS. The investigators searched electronic databases for RCTs of exercise training in MS; they calculated the rate of AEs, and the relative risk of AEs for exercise training versus control. Twenty-six studies were reviewed that included 1295 participants. The rate of AEs was 1.2% and 2.0% for control and exercise, respectively. The relative risk of AEs for exercise training was 1.67, and the risk of AEs was no different when compared with evidence from the general population of adults who participate in exercise. The most common AEs involved musculoskeletal issues (eg, low back and joint pain) associated with resistance exercise training. This evidence should reduce uncertainty regarding the safety profile of exercise training in MS, and there are current efforts for updating the safety profile of exercise training in MS based on research published over the past 10 years.18

Prescription of Exercise in MS

Two primary resources on the prescription of exercise in people with MS have recently been summarized by the National Multiple Sclerosis Society.19-21 One set of guidelines was developed based on a systematic literature review of exercise training interventions in MS.4,20 The resulting guidelines suggest that patients with MS who have mild or moderate disability should engage in at least 30 minutes of moderate-intensity aerobic activity 2 times per week and strength training exercises for major muscle groups 2 times per week. The aerobic and resistance exercise training can be performed on the same day, but should be separated by 24 hours (ie, not performed on consecutive days). This prescription should yield fitness benefits and possibly reduce fatigue, improve mobility, and improve components of health-related QOL. Importantly, these guidelines have not been formally tested, and require evaluation before broad application, particularly among those who have advanced disability with MS.

The other set of guidelines was developed through a scoping review of existing resources on exercise prescriptions in individuals with MS, stroke, and Parkinson disease (PD) to provide resources that are uniformly recognizable by health care practitioners and patients with these diseases.19 This paper, in particular, synthesized resources that reported aerobic and resistance training guidelines for patients with MS, stroke, and PD. Regarding MS, the systematic search yielded 10 eligible resources from electronic databases and textbooks or websites of major organizations. Data were extracted (exercise frequency, intensity, time, and type) and synthesized into recommendations per disease. Exercise guidelines for MS consistently recommended 2 to 3 days per week of aerobic training (per session, 10-30 minutes at moderate intensity) and 2 to 3 days per week of resistance training (maximum per session, 1-3 sets of between 8-15 repetitions). The frequency ranges between 2 to 3 days per week and should generally start with 2 days and progress toward 3 days per week over time. The duration of the exercise bouts ranges between 10 and 30 minutes and should gradually progress from 10 to 30 minutes over time. The intensity should be moderate and range between 11 to 13 on the 20-point rating of perceived exertion scale, or between 40% and 60% peak oxygen consumption or peak heart rate. The overall progression should start with increases in either duration or frequency. Progression in intensity should be based on the tolerability of the individual with MS, only after duration and frequency are well tolerated. This harmonizing of exercise guidelines provides a prescriptive basis for health care providers, exercise professionals, and those living with MS regarding disease-specific exercise programming. Importantly, these guidelines still require verification for benefits and safety before their broad application, particularly among those with advanced MS disability.


Overall, there is increasing evidence for the role of exercise in managing the MS disease pathophysiology, functions, and symptoms and for optimizing QOL and participation outcomes. Further, evidence exists for the safety and prescription of exercise in MS. Nevertheless, there are exciting opportunities for research on exercise and neuroplasticity in MS, as well as a need for developing a strong knowledge base regarding exercise training in patients with advanced stages of the disease. Such research will provide a comprehensive knowledge base for the promotion of exercise by health care providers as an approach for managing MS itself and the many consequences of this disease.22

1. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247-269. doi:10.1146/annurev.neuro.30.051606.094313
2. Wallin MT, Culpepper WJ, Campbell JD, et al; US Multiple Sclerosis Prevalence Workgroup. The prevalence of MS in the United States: a population-based estimate using health claims data. Neurology. 2019;92(10):e1029-e1040. doi:10.1212/WNL.0000000000007035
3. Dalgas U, Hvid LG, Kwakkel G, et al. Moving exercise research in multiple sclerosis forward (the MoXFo initiative): developing consensus statements for research. Mult Scler. 2020;26(11):1303-1308. doi:10.1177/1352458520910360
4. Latimer-Cheung AE, Pilutti LA, Hicks AL, et al. Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development. Arch Phys Med Rehabil. 2013;94(9):1800-1828.e3. doi:10.1016/j.apmr.2013.04.020
5. Motl RW, Sandroff BM, Kwakkel G, et al. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017;16(10):848-856. doi:10.1016/S1474-4422(17)30281-8
6. Platta ME, Ensari I, Motl RW, Pilutti LA. Effect of exercise training on fitness in multiple sclerosis: a meta-analysis. Arch Phys Med Rehabil. 2016;97(9):1564-1572. doi:10.1016/j.apmr.2016.01.023
7. Pilutti LA, Greenlee TA, Motl RW, Nickrent MS, Petruzzello SJ. Effects of exercise training on fatigue in multiple sclerosis: a meta-analysis. Psychosom Med. 2013;75(6):575-580. doi:10.1097/PSY.0b013e31829b452
8. Ensari I, Motl RW, Pilutti LA. Exercise training improves depressive symptoms in people with multiple sclerosis: results of a meta-analysis. J Psychosom Res. 2014;76(6):465-471. doi:10.1016/j.jpsychores.2014.03.014
9. Demaneuf T, Aitken Z, Karahalios A, et al. Effectiveness of exercise intervention for pain reduction in people with multiple sclerosis: a systematic review and meta-analysis of randomzied controled trials. Arch Phys Med Rehabil. 2019;100(1):128-139. doi:10.1016/j.apmr.2018.08.178
10. Sandroff BM, Motl RW, Scudder MR, DeLuca J. Systematic, evidence-based review of exercise, physical activity, and physical fitness effects on cognition in persons with multiple sclerosis. Neuropsychol Rev. 2016;26(3):271-294. doi:10.1007/s11065-016-9324-2
11. Paltamaa J, Sjögren T, Peurala SH, Heinonen A. Effects of physiotherapy interventions on balance in multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials. J Rehabil Med. 2012;44(10):811-823. doi:10.2340/16501977-1047
12. Pearson M, Dieberg G, Smart N. Exercise as a therapy for improvement of walking ability in adults with multiple sclerosis: a meta-analysis. Arch Phys Med Rehabil. 2015;96(7):1339-1348.e7. doi:10.1016/j.apmr.2015.02.011
13. Motl RW, Gosney JL. Effect of exercise training on quality of life in multiple sclerosis: a meta-analysis. Mult Scler. 2008;14(1):129-135. doi:10.1177/1352458507080464
14. Motl RW, Pilutti LA. Is physical exercise a multiple sclerosis disease modifying treatment? Expert Rev Neurother. 2016;16(8):951-960. doi:10.1080/14737175.2016.1193008
15. Pilutti LA, Platta ME, Motl RW, Latimer-Cheung AE. The safety of exercise training in multiple sclerosis: a systematic review. J Neurol Sci. 2014;343(1-2):3-7. doi:10.1016/j.jns.2014.05.016
16. Motl RW, Pilutti LA. The benefits of exercise training in multiple sclerosis. Nat Rev Neurol. 2012;8(9):487-497. doi:10.1038/nrneurol.2012.136
17. Stewart AL, King AC. Evaluating the efficacy of physical activity for influencing quality-of-life outcomes in older adults. Ann Behav Med. 1991;13(3):108-116. doi:10.1093/abm/13.3.108
18. Learmonth YC, Pilutti LA, Herring MP, Motl RW, Chan B, Metse AP. Safety of exercise training in multiple sclerosis: a protocol for an updared systematic review and meta-analysis. Syst Rev. 2021;10(1):208. doi:10.1186/s13643-021-01751-0
19. Latimer-Cheung AE, Martin Ginis KA, Hicks AL, et al. Development of evidence-informed physical activity guidelines for adults with multiple sclerosis. Arch Phys Med Rehabil. 2013;94(9):1829-1836.e7. doi:10.1016/j.apmr.2013.05.015
20. Kim Y, Lai B, Mehta T, et al. Exercise training guidelines for multiple sclerosis, stroke, and Parkinson disease: rapid review and synthesis. Am J Phys Med Rehabil. 2019;98(7):613-621. doi:10.1097/PHM.0000000000001174
21. Kalb R, Brown TR, Coote S, et al. Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course. Mult Scler. 2020;26(12):1459-1469. doi:10.1177/1352458520915629
22. Motl RW, Barstow EA, Blaylock S, Richardson E, Learmonth YC, Fifolt M. Promotion of exercise in multiple sclerosis through health care providers. Exerc Sport Sci Rev. 2018;46(2):105-111. doi:10.1249/JES.0000000000000140
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