The benefits of exercise training in multiple sclerosis

Nature Reviews Neurology

Volumn 8, Issue 9, 2012, Pages 487-497

  Motl, Robert W ^a   Pilutti, Lara A ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; GAMMA INTERFERON; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 7; NERVE GROWTH FACTOR; NEUROTROPHIC FACTOR; SOMATOMEDIN C;

AEROBIC CAPACITY; BODY EQUILIBRIUM; CARDIOVASCULAR FUNCTION; CLINICAL EFFECTIVENESS; CYTOKINE PRODUCTION; DAILY LIFE ACTIVITY; DEPRESSION; DISEASE SEVERITY; EVIDENCE BASED MEDICINE; FATIGUE; GAIT; HUMAN; KINESIOTHERAPY; LEISURE; LIFESTYLE MODIFICATION; MENTAL CAPACITY; MENTAL FUNCTION; MOLECULAR PATHOLOGY; MOTOR PERFORMANCE; MULTIPLE SCLEROSIS; MUSCLE STRENGTH; NEUROANATOMY; NEUROMUSCULAR FUNCTION; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; QUALITY OF LIFE; RANGE OF MOTION; REVIEW; SENSORY FEEDBACK; THERAPY EFFECT;

CLINICAL TRIALS AS TOPIC; EXERCISE THERAPY; HUMANS; MULTIPLE SCLEROSIS; MUSCLE STRENGTH; PHYSICAL FITNESS; QUALITY OF LIFE;

EID: 84866132164     PISSN: 17594758     EISSN: 17594766     Source Type: Journal    
DOI: 10.1038/nrneurol.2012.136     Document Type: Review

References (119)

1. Frohman, E. M., Racke, M. K. & Raine, C. S. Multiple sclerosis - The plaque and its pathogenesis. N. Engl. J. Med. 354, 942-955 (2006).
2. Mayr, W. T. et al. Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985-2000. Neurology 61, 1373-1377 (2003).
3. Page, W. F., Kurtzke, J. F., Murphy, F. M. & Norman, J. E. Jr. Epidemiology of multiple sclerosis in U.S. veterans: V. Ancestry and the risk of multiple sclerosis. Ann. Neurol. 33, 632-639 (1993).
4. International Classification of Functioning, Disability and Health (ICF). World Health Organization [online], http://www.who.int/classifications/icf/en/ (2001).
5. Coenen, M. et al. The development of ICF Core Sets for multiple sclerosis: Results of the International Consensus Conference. J. Neurol. 258, 1477-1488 (2011).
6. Goldman, M. D., Marrie, R. A. & Cohen, J. A. Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls. Mult. Scler. 14, 383-390 (2008).
7. Larocca, N. G. Impact of walking impairment in multiple sclerosis: Perspectives of patients and care partners. Patient 4, 189-201 (2011).
8. Motl, R. W., McAuley, E. & Snook, E. M. Physical activity and multiple sclerosis: A meta-analysis. Mult. Scler. 11, 459-463 (2005).
9. Motl, R. W. Physical activity and irreversible disability in multiple sclerosis. Exerc. Sport Sci. Rev. 38, 186-191 (2010).
10. White, L. J. & Castellano, V. Exercise and brain health - implications for multiple sclerosis: Part 1 - neuronal growth factors. Sports Med. 38, 91-100 (2008).
11. Andreasen, A., Stenager, E. & Dalgas, U. The effect of exercise therapy on fatigue in multiple sclerosis. Mult. Scler. 17, 1041-1054 (2011).
12. Garrett, M. & Coote, S. Multiple sclerosis and exercise in people with minimal gait impairment - A review. Phys. Ther. Rev. 14, 169-180 (2009).
13. Motl, R. W., Goldman, M. D. & Benedict, R. H. Walking impairment in patients with multiple sclerosis: exercise training as a treatment option. Neuropsychiatr. Dis. Treat. 6, 767-774 (2010).
14. Rietberg, M. B., Brooks, D., Uitdehaag, B. M. & Kwakkel, G. Exercise therapy for multiple sclerosis. Cochrane Database of Systematic Reviews Issue 1. Art. No.:CD003980. http://dx.doi.org/10.1002/14651858.CD003980.pub2.
15. Dalgas, U., Stenager, E. & Ingemann-Hansen, T. Multiple sclerosis and physical exercise: Recommendations for the application of resistance, endurance- and combined training. Mult. Scler. 14, 35-53 (2008).
16. Asano, M., Dawes, D. J., Arafah, A., Moriello, C. & Mayo, N. E. What does a structured review of the effectiveness of exercise interventions for persons with multiple sclerosis tell us about the challenges of designing trials? Mult. Scler. 15, 412-421 (2009).
17. White, L. J. & Dressendorfer, R. H. Exercise and multiple sclerosis. Sports Med. 34, 1077-1100 (2004).
18. Brown, T. & Kraft, G. H. Exercise and rehabilitation for individuals with multiple sclerosis. Phys. Med. Rehabil. Clin. N. Am. 16, 513-555 (2006).
19. Ponichtera-Mulcare, J. A. Exercise and multiple sclerosis. Med. Sci. Sports Exerc. 25, 451-465 (1993).
20. Caspersen, C. J., Powell, K. E. & Christenson, G. M. Physical activity, exercise, and physical fitness: Definitions and distinctions for health-related research. Public Health Rep. 100, 126-131 (1985).
21. Petajan, J. H. & White, A. T. Recommendations for physical activity in patients with multiple sclerosis. Sports Med. 27, 179-191 (1999).
22. Dalgas, U., Ingemann-Hansen, T. & Stenager, E. Physical exercise and MS recommendations. Int. MS J. 16, 5-11 (2009).
23. Ginis, K. A. et al. The development of evidence-informed physical activity guidelines for adults with spinal cord injury. Spinal Cord 49, 1088-1096 (2011).
24. Brouwers, M. C. et al. AGREE II: Advancing guideline development, reporting and evaluation in health care. CMAJ 182, E839-E842 (2010).
25. Brouwers, M. C. et al. AGREE II: Advancing guideline development, reporting and evaluation in health care. J. Clin. Epidemiol. 63, 1308-1311 (2010).
26. Brouwers, M. C. et al. AGREE II: Advancing guideline development, reporting and evaluation in health care. Prev. Med. 51, 421-424 (2010).
27. Yong, V. W. Inflammation in neurological disorders: A help or a hindrance? Neuroscientist 16, 408-420 (2010).
28. Nicklas, B. J. & Brinkley, T. E. Exercise training as a treatment for chronic inflammation in the elderly. Exerc. Sport Sci. Rev. 37, 165-170 (2009).
29. Golzari, Z., Shabkhiz, F., Soudi, S., Kordi, M. R. & Hashemi, S. M. Combined exercise training reduces IFN-γ and IL 17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis. Int. Immunopharmacol. 10, 1415-1419 (2010).
30. Schulz, K. H. et al. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J. Neurol. Sci. 225, 11-18 (2004).
31. White, L. J., Castellano, V. & Mc Coy, S. C. Cytokine responses to resistance training in people with multiple sclerosis. J. Sports Sci. 24, 911-914 (2006).
32. Castellano, V., Patel, D. I. & White, L. J. Cytokine responses to acute and chronic exercise in multiple sclerosis. J. Appl. Physiol. 104, 1697-1702 (2008).
33. Cotman, C. W. & Engesser-Cesar, C. Exercise enhances and protects brain function. Exerc. Sport Sci. Rev. 30, 75-79 (2002).
34. Castellano, V. & White, L. J. Serum brain-derived neurotrophic factor response to aerobic exercise in multiple sclerosis. J. Neurol. Sci. 269, 85-91 (2008).
35. Prakash, R. S., Snook, E. M., Motl, R. W. & Kramer, A. F. Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis. Brain Res. 1341, 41-51 (2010).
36. Prakash, R. S., Patterson, B., Janssen, A., Abduljalil, A. & Boster, A. Physical activity associated with increased resting-state functional connectivity in multiple sclerosis. J. Int. Neuropsychol. Soc. 17, 986-997 (2011).
37. Rossi, S. et al. Exercise attenuates the clinical, synaptic and dendritic abnormalities of experimental autoimmune encephalomyelitis. Neurobiol. Dis. 36, 51-59 (2009).
38. Colcombe, S. J. et al. Aerobic exercise training increases brain volume in aging humans. J. Gerontol. A Biol. Sci. Med. Sci. 61, 1166-1170 (2006).
39. Colcombe, S. J. et al. Cardiovascular fitness, cortical plasticity, and aging. Proc. Natl Acad. Sci. USA 101, 3316-3321 (2004).
40. Colcombe, S. J. et al. Aerobic fitness reduces brain tissue loss in aging humans. J. Gerontol. A Biol. Sci. Med. Sci. 58, 176-180 (2003).
41. Erickson, K. I. et al. Exercise training increases size of hippocampus and improves memory. Proc. Natl Acad. Sci. USA 108, 3017-3022 (2011).
42. Erickson, K. I. et al. Training-induced plasticity in older adults: effects of training on hemispheric asymmetry. Neurobiol. Aging 28, 272-283 (2007).
43. Erickson, K. I. et al. Training-induced functional activation changes in dual-task processing: An fMRI study. Cereb. Cortex 17, 192-204 (2007).
44. Rao, S. M., Leo, G. J., Bernardin, L. & Unverzagt, F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 41, 685-691 (1991).
45. Benedict, R. H. et al. Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch. Neurol. 63, 1301-1306 (2006).
46. Calabrese, M. et al. Widespread cortical thinning characterizes patients with MS with mild cognitive impairment. Neurology 74, 321-328 (2010).
47. Benedict, R. H. et al. Frontal cortex atrophy predicts cognitive impairment in multiple sclerosis. J. Neuropsychiatry Clin. Neurosci. 14, 44-51 (2002).
48. Benedict, R. H. et al. Predicting quality of life in multiple sclerosis: Accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change. J. Neurol. Sci. 231, 29-34 (2005).
49. White, L. J. et al. Resistance training improves strength and functional capacity in persons with multiple sclerosis. Mult. Scler. 10, 668-674 (2004).
50. McCullagh, R., Fitzgerald, A. P., Murphy, R. P. & Cooke, G. Long-term benefits of exercising on quality of life and fatigue in multiple sclerosis patients with mild disability: A pilot study. Clin. Rehabil. 22, 206-214 (2008).
51. Oken, B. S. et al. Randomized controlled trial of yoga and exercise in multiple sclerosis. Neurology 62, 2058-2064 (2004).
52. Roehrs, T. G. & Karst, G. M. Effects of an aquatics exercise program on quality of life measures for individuals with progressive multiple sclerosis. J. Neurol. Phys. Ther. 28, 63-71 (2004).
53. Dalgas, U. et al. Fatigue, mood and quality of life improve in MS patients after progressive resistance training. Mult. Scler. 16, 480-490 (2010).
54. Konecný, L. et al. Combination of aerobic and resistance training in multiple sclerosis. Scr. Med. 83, 98-106 (2010).
55. Dettmers, C., Sulzmann, M., Ruchay-Plossl, A., Gutler, R. & Vieten, M. Endurance exercise improves walking distance in MS patients with fatigue. Acta Neurol. Scand. 120, 251-257 (2009).
56. Mostert, S. & Kesselring, J. Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Mult. Scler. 8, 161-168 (2002).
57. Newman, M. A. et al. Can aerobic treadmill training reduce the effort of walking and fatigue in people with multiple sclerosis: A pilot study. Mult. Scler. 13, 113-119 (2007).
58. Petajan, J. H. et al. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Ann. Neurol. 39, 432-441 (1996).
59. Cakt, B. D. et al. Cycling progressive resistance training for people with multiple sclerosis: A randomized controlled study. Am. J. Phys. Med. Rehabil. 89, 446-457 (2010).
60. Pilutti, L. A. et al. Effects of 12 weeks of supported treadmill training on functional ability and quality of life in progressive multiple sclerosis: A pilot study. Arch. Phys. Med. Rehabil. 92, 31-36 (2011).
61. Wier, L. M., Hatcher, M. S., Triche, E. W. & Lo, A. C. Effect of robot-assisted versus conventional body weight supported treadmill training on quality of life for people with multiple sclerosis. J. Rehabil. Res. Dev. 48, 483-492 (2011).
62. Freeman, J. & Allison, R. Group exercise classes in people with multiple sclerosis: A pilot study. Physiother. Res. Int. 9, 104-107 (2004).
63. Geddes, E. L., Costello, E., Raivel, K. & Wilson, R. The effects of a twelve-week home walking program on cardiovascular parameters and fatigue perception of individuals with multiple sclerosis: A pilot study. Cardiopulm. Phys. Ther. J. 20, 5-12 (2009).
64. Hayes, H. A., Gappmaier, E. & LaStayo, P. C. Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: A randomized controlled trial. J. Neurol. Phys. Ther. 35, 2-10 (2011).
65. Rampello, A. et al. Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: A randomized crossover controlled study. Phys. Ther. 87, 545-559 (2007).
66. Sabapathy, N. M., Minahan, C. L., Turner, G. T. & Broadley, S. A. Comparing endurance- and resistance-exercise training in people with multiple sclerosis: A randomized pilot study. Clin. Rehabil. 25, 14-24 (2011).
67. van den Berg, M. et al. Treadmill training for individuals with multiple sclerosis: A pilot randomised trial. J. Neurol. Neurosurg. Psychiatry. 77, 531-533 (2006).
68. Salem, Y. et al. Effects of an aquatic exercise program on functional mobility in individuals with multiple sclerosis. J. Aquatic Phys. Ther. 18, 22-32 (2010).
69. Velikonja, O., Curic, K., Ozura, A. & Jazbec, S. S. Influence of sports climbing and yoga on spasticity, cognitive function, mood and fatigue in patients with multiple sclerosis. Clin. Neurol. Neurosurg. 112, 597-601 (2010).
70. Fragoso, Y. D., Santana, D. L. B. & Pinto, R. C. The positive effects of a physical activity program for multiple sclerosis patients with fatigue. NeuroRehabilitation 23, 153-157 (2008).
71. Dodd, K. J. et al. Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: A randomized controlled trial. Mult. Scler. 17, 1362-1374 (2011).
72. Motl, R. W. & Gosney, J. L. Effect of exercise training on quality of life in multiple sclerosis: A meta-analysis. Mult. Scler. 14, 129-135 (2008).
73. Kjølhede, T., Vissing, K. & Dalgas, U. Multiple sclerosis and progressive resistance training: A systematic review. Mult. Scler. http://dx.doi.org/10.1177/1352458512437418.
74. Romberg, A., Virtanen, A. & Ruutiainen, J. Long-term exercise improves functional impairment but not quality of life in multiple sclerosis. J. Neurol. 252, 839-845 (2005).
75. Dalgas, U. et al. Resistance training improves muscle strength and functional capacity in multiple sclerosis. Neurology 73, 1478-1484 (2009).
76. Motl, R. W., Sandroff, B. M. & Benedict, R. H. Cognitive dysfunction and multiple sclerosis: Developing a rationale for considering the efficacy of exercise training. Mult. Scler. 17, 1034-1040 (2011).
77. Colcombe, S. & Kramer, A. F. Fitness effects on the cognitive function of older adults: A meta-analytic study. Psychol. Sci. 14, 125-130 (2003).
78. Motl, R. W., Gappmaier, E., Nelson, K. & Benedict, R. H. Physical activity and cognitive function in multiple sclerosis. J. Sport Exerc. Psychol. 33, 734-741 (2011).
79. Prakash, R. S. et al. Cardiorespiratory fitness: A predictor of cortical plasticity in multiple sclerosis. Neuroimage 34, 1238-1244 (2007).
80. McAuley, E., Kramer, A. F. & Colcombe, S. J. Cardiovascular fitness and neurocognitive function in older adults: A brief review. Brain Behav. Immun. 18, 214-220 (2004).
81. Motl, R. W. & Goldman, M. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis. Acta Neurol. Scand. 123, 98-104 (2011).
82. Pearson, O., Busse, M., van Deursen, R. & Wiles, C. Quantification of walking mobility in neurological disorders. QJM 97, 467-475 (2004).
83. Motl, R. W. & Fernhall, B. Accurate prediction of cardiorespiratory fitness using cycle ergometry in minimally disabled persons with relapsing-remitting multiple sclerosis. Arch. Phys. Med. Rehabil. 93, 490-495 (2012).
84. Kent-Braun, J. A. et al. Strength, skeletal muscle composition, and enzyme activity in multiple sclerosis. J. Appl. Physiol. 83, 1998-2004 (1997).
85. Givon, U., Zeilig, G. & Achiron, A. Gait analysis in multiple sclerosis: Characterization of temporal-spatial parameters using GAITRite functional ambulation system. Gait Posture 29, 138-142 (2009).
86. Sosnoff, J. J., Sandroff, B. M. & Motl, R. W. Quantifying gait abnormalities in persons with multiple sclerosis with minimal disability. Gait Posture 36, 154-156 (2012).
87. Broekmans, T. et al. Exploring the effects of a 20-week whole-body vibration training programme on leg muscle performance and function in persons with multiple sclerosis. J. Rehabil. Med. 42, 866-872 (2010).
88. de Souza-Teixeira, F. et al. Effects of resistance training in multiple sclerosis. Int. J. Sports Med. 30, 245-250 (2009).
89. Taylor, N. F., Dodd, K. J., Prasad, D. & Denisenko, S. Progressive resistance exercise for people with multiple sclerosis. Disabil. Rehabil. 28, 1119-1126 (2006).
90. DeBolt, L. S. & McCubbin, J. A. The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis. Arch. Phys. Med. Rehabil. 85, 290-297 (2004).
91. Romberg, A. et al. Effects of a 6 month exercise program on patients with multiple sclerosis: A randomized study. Neurology 63, 2034-2038 (2004).
92. Gehlsen, G. M., Grigsby, S. A. & Winant, D. M. Effects of an aquatic fitness program on the muscular strength and endurance of patients with multiple sclerosis. Phys. Ther. 64, 653-657 (1984).
93. Beer, S. et al. Robot-assisted gait training in multiple sclerosis: A pilot randomized trial. Mult. Scler. 14, 231-236 (2008).
94. Bjarnadottir, O. H., Konradsdottir, A. D., Reynisdottir, K. & Olafsson, E. Multiple sclerosis and brief moderate exercise. A randomised study. Mult. Scler. 13, 776-782 (2007).
95. Rodgers, M. M. et al. Gait characteristics of individuals with multiple sclerosis before and after a 6 month aerobic training program. J. Rehabil. Res. Dev. 36, 183-188 (1999).
96. Ponichtera-Mulcare, J. A., Mathews, T., Barrett, P. J. & Gupta, S. C. Change in aerobic fitness of patients with multiple sclerosis during a 6-month training program. Sports Med. Train. Rehabil. 7, 265-272 (1997).
97. Salem, Y. et al. Community-based group aquatic programme for individuals with multiple sclerosis: A pilot study. Disabil. Rehabil. 33, 720-728 (2011).
98. Conklyn, D. et al. A home-based walking program using rhythmic auditory stimulation improves gait performance in patients with multiple sclerosis: A pilot study. Neurorehabil. Neural Repair 24, 835-842 (2010).
99. Gutierrez, G. M. et al. Resistance training improves gait kinematics in persons with multiple sclerosis. Arch. Phys. Med. Rehabil. 86, 1824-1829 (2005).
100. Motl, R. W. et al. Combined training improves walking mobility in persons with significant disability from multiple sclerosis: A pilot study. J. Neurol. Phys. Ther. 36, 32-37 (2012).
101. Collett, J. et al. Exercise for multiple sclerosis: A single-blind randomized trial comparing three exercise intensities. Mult. Scler. 17, 594-603 (2011).
102. Kileff, J. & Ashburn, A. A pilot study of the effect of aerobic exercise on people with moderate disability multiple sclerosis. Clin. Rehabil. 19, 165-169 (2005).
103. Lo, A. C. & Triche, E. W. Improving gait in multiple sclerosis using robot-assisted, body weight supported treadmill training. Neurorehabil. Neural Repair 22, 661-671 (2008).
104. Freeman, J. A. et al. The effect of core stability training on balance and mobility in ambulant individuals with multiple sclerosis: A multi-centre series of single case studies. Mult. Scler. 16, 1377-1384 (2010).
105. Mutulay, F., Tekeoglu, A., Saip, S., Altintas, A. & Siva, A. Group exercise training approach to multiple sclerosis rehabilitation. Nobel Med. 4, 20-26 (2008).
106. Snook, E. M. & Motl, R. W. Effect of exercise training on walking mobility in multiple sclerosis: A meta-analysis. Neurorehabil. Neural Repair 23, 108-116 (2009).
107. Mitchell, A. J., Benito-Leon, J., Gonzalez, J. M. & Rivera-Navarro, J. Quality of life and its assessment in multiple sclerosis: Integrating physical and psychological components of wellbeing. Lancet Neurol. 4, 556-566 (2005).
108. Lobentanz, I. S. et al. Factors influencing quality of life in multiple sclerosis patients: Disability, depressive mood, fatigue and sleep quality. Acta Neurol. Scand. 110, 6-13 (2004).
109. Benito-Leon, J., Morales, J. M., Rivera-Navarro, J. & Mitchell, A. A review about the impact of multiple sclerosis on health-related quality of life. Disabil. Rehabil. 25, 1291-1303 (2003).
110. Rudick, R. A., Miller, D., Clough, J. D., Gragg, L. A. & Farmer, R. G. Quality of life in multiple sclerosis. Comparison with inflammatory bowel disease and rheumatoid arthritis. Arch. Neurol. 49, 1237-1242 (1992).
111. Sutherland, G., Andersen, M. B. & Stoove, M. A. Can aerobic exercise training affect health-related quality of life for people living with multiple sclerosis? J. Sport Exerc. Psychol. 23, 122-135 (2001).
112. Motl, R. W. & McAuley, E. Pathways between physical activity and quality of life in adults with multiple sclerosis. Health Psychol. 28, 682-689 (2009).
113. Motl, R. W., McAuley, E., Snook, E. M. & Gliottoni, R. C. Physical activity and quality of life in multiple sclerosis: Intermediary roles of disability, fatigue, mood, pain, self-efficacy and social support. Psychol. Health Med. 14, 111-124 (2009).
114. Patti, F. et al. Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients - A randomised controlled trial. J. Neurol. 250, 861-866 (2003).
115. Motl, R. W. & McAuley, E. Longitudinal analysis of physical activity and symptoms as predictors of change in functional limitations and disability in multiple sclerosis. Rehabil. Psychol. 54, 204-210 (2009).
116. Motl, R. W., Snook, E. M., McAuley, E., Scott, J. A. & Gliottoni, R. C. Are physical activity and symptoms correlates of functional limitations and disability in multiple sclerosis? Rehabil. Psychol. 52, 463-469 (2007).
117. Dalgas, U. et al. Muscle fiber size increases following resistance training in multiple sclerosis. Mult. Scler. 16, 1367-1376 (2010).
118. Confavreux, C. & Vukusic, S. Accumulation of irreversible disability in multiple sclerosis: from epidemiology to treatment. Clin. Neurol. Neurosurg. 108, 327-332 (2006).
119. Benito-León, J. Physical activity in multiple sclerosis: The missing prescription. Neuroepidemiology 36, 192-193 (2011).