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

Archives of Physical Medicine and Rehabilitation

Volumn 94, Issue 9, 2013, Pages 1800-1828.e3

  Latimer Cheung, Amy E ^a   Pilutti, Lara A ^b,c   Hicks, Audrey L ^b   Martin Ginis, Kathleen A ^b   Fenuta, Alyssa M ^b   MacKibbon, K Ann ^b   Motl, Robert W ^c  

^a QUEEN S UNIVERSITY   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

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

Author keywords

Exercise; Guideline; Multiple sclerosis; Physical fitness; Rehabilitation

Indexed keywords

AEROBIC CAPACITY; AEROBIC EXERCISE; AQUATIC EXERCISE; BICYCLE ERGOMETER; CLIMBING; DAILY LIFE ACTIVITY; DISABILITY SEVERITY; DISEASE COURSE; EXERCISE; EXPANDED DISABILITY STATUS SCALE; FATIGUE; FATIGUE IMPACT SCALE; FATIGUE SEVERITY SCALE; FITNESS; FUNCTIONAL ELECTRICAL STIMULATION; HUMAN; LEG EXERCISE; MOBILIZATION; MULTIPLE SCLEROSIS; MUSCLE STRENGTH; OXYGEN CONSUMPTION; PHYSICAL CAPACITY; PHYSIOTHERAPY; PLYOMETRICS; PRACTICE GUIDELINE; PROFILE OF MOOD STATES; QUALITY CONTROL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; RESISTANCE TRAINING; REVIEW; STRETCHING EXERCISE; SYSTEMATIC REVIEW; TREADMILL; WALKING; YOGA;

EID: 84882887739     PISSN: 00039993     EISSN: 1532821X     Source Type: Journal    
DOI: 10.1016/j.apmr.2013.04.020     Document Type: Review

References (110)

1. C.A. Beck, L.M. Metz, L.W. Svenson, and S.B. Patten Regional variation of multiple sclerosis prevalence in Canada Mult Scler 11 2005 516 519
2. The Canadian Burden of Illness Study Group. Burden of illness of multiple sclerosis. Part II: quality of life. The Canadian Burden of Illness Study Group Can J Neurol Sci 25 1998 31 38
3. J. Benito-Leon, J.M. Morales, J. Rivera-Navarro, and A. Mitchell A review about the impact of multiple sclerosis on health-related quality of life Disabil Rehabil 25 2003 1291 1303
4. R.W. Motl, and E. McAuley Symptom cluster and quality of life: preliminary evidence in multiple sclerosis J Neurosci Nurs 42 2010 212 216
5. Multiple Sclerosis International Federation. Global economic impact of multiple sclerosis. Availible at: http://www.msif.org/includes/documents/cm- docs/2011/g/global-economic-impact-of-ms.pdf?f=1. Accessed July 3, 2012.
6. R.W. Motl, P.A. Arnett, M.M. Smith, F.H. Barwick, B. Ahlstrom, and E.J. Stover Worsening of symptoms is associated with lower physical activity levels in individuals with multiple sclerosis Mult Scler 14 2008 140 142
7. R.W. Motl Physical activity and irreversible disability in multiple sclerosis Exerc Sport Sci Rev 38 2010 186 191
8. R.W. Motl, M. Weikert, Y. Suh, and D. Dlugonski Symptom cluster and physical activity in relapsing-remitting multiple sclerosis Res Nurs Health 33 2010 398 412
9. R. Marrie, R. Horwitz, G. Cutter, T. Tyry, D. Campagnolo, and T. Vollmer High frequency of adverse health behaviors in multiple sclerosis Mult Scler 15 2009 105 113
10. H. Beckerman, V. de Groot, M.A. Scholten, J.C.E. Kempen, and G.J. Lankhorst Physical activity behavior of people with multiple sclerosis: understanding how they can become more physically active Phys Ther 90 2010 1001 1013
11. R.W. Motl, E. McAuley, and E.M. Snook Physical activity and multiple sclerosis: a meta-analysis Mult Scler 11 2005 459 463
12. A.K. Stuifbergen, and G.J. Roberts Health promotion practices of women with multiple sclerosis Arch Phys Med Rehabil 78 12 Suppl 5 1997 S3 S9
13. B.M. Sandroff, D. Dlugonski, M. Weikert, Y. Suh, S. Balantrapu, and R.W. Motl Physical activity and multiple sclerosis: new insights regarding inactivity Acta Neurol Scand 126 2012 256 262
14. M.W. Nortvedt, T. Riise, and J.G. Maeland Multiple sclerosis and lifestyle factors: the Hordaland Health Study Neurol Sci 26 2005 334 339
15. U. Dalgas, T. Ingemann-Hansen, and E. Stenager Physical exercise and MS recommendations Int MS J 16 2009 5 11
16. American College of Sports Medicine ACSM's resources for clinical exercise physiology. Musculoskeletal, neuromuscular, neoplastic, immunologic, and hematologic conditions 2nd ed. 2010 Wolters Kluwer Baltimore
17. M.S. Tremblay, and W.L. Haskell From science to physical activity guidelines 2012 Human Kinetics Champaign
18. M.C. Brouwers, M.E. Kho, and G.P. Browman Development of the AGREE II, part 1: performance, usefulness and areas for improvement CMAJ 182 2010 1045 1052
19. C. Bouchard, S.N. Blair, and W.L. Haskell Why study physical activity and health? C. Bouchard, R.J. Shephard, T. Stephens, Physical activity and health 2nd ed. 2012 Human Kinetics Champaign 3 20
20. R.W. Motl, and J.L. Gosney Effect of exercise training on quality of life in multiple sclerosis: a meta-analysis Mult Scler 14 2008 129 135
21. E.M. Snook, and R.W. Motl Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis Neurorehabil Neural Repair 23 2009 108 116
22. U. Dalgas, E. Stenager, and T. Ingemann-Hansen Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training Mult Scler 14 2008 35 53
23. A.P. Verhagen, H.C. de Vet, and R.A. de Bie The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus J Clin Epidemiol 51 1998 1235 1241
24. L. Valent, A. Dallmeijerx, H. Houdijk, E. Talsma, and L. van der Woude The effects of upper body exercise on the physical capacity of people with a spinal cord injury: a systematic review Clin Rehabil 21 2007 315 330
25. S.H. Downs, and N. Black The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions J Epidemiol Community Health 52 1998 377 384
26. Eng JJ, Teasell RW, Miller W, et al. The Spinal Cord Injury Rehabilitation Evidence (SCIRE) 2010. Available at: http://www.scireproject.com. Accessed May 9, 2012.
27. W. McArdle, F. Katch, and V. Katch Exercise physiology energy, nutrition, and human performance 2001 Lippincott Williams & Wilkins Baltimore
28. B.F. Koseoglu, N.K.O. Gokkaya, U. Ergun, L. Inan, and E. Yesiltepe Cardiopulmonary and metabolic functions, aerobic capacity, fatigue and quality of life in patients with multiple sclerosis Acta Neurol Scand 114 2006 261 267
29. R.S. Prakash, E.M. Snook, R.W. Motl, and A.F. Kramer Aerobic fitness is associated with gray matter volume and white matter integrity in multiple sclerosis Brain Res 1341 2010 41 51
30. J.N. Slawta, J.A. McCubbin, A.R. Wilcox, S.D. Fox, D.J. Nalle, and G. Anderson Coronary heart disease risk between active and inactive women with multiple sclerosis Med Sci Sports Exerc 34 2002 905 912
31. J.H. Petajan, E. Gappmaier, A.T. White, M.K. Spencer, L. Mino, and R.W. Hicks Impact of aerobic training on fitness and quality of life in multiple sclerosis Ann Neurol 39 1996 432 441
32. L.S. DeBolt, and J.A. McCubbin The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis Arch Phys Med Rehabil 85 2004 290 297
33. O.H. Bjarnadottir, A.D. Konradsdottir, K. Reynisdottir, and E. Olafsson Multiple sclerosis and brief moderate exercise. A randomised study Mult Scler 13 2007 776 782
34. V. Castellano, D.I. Patel, and L.J. White Cytokine responses to acute and chronic exercise in multiple sclerosis J Appl Physiol 104 2008 1697 1702
35. Z. Golzari, F. Shabkhiz, S. Soudi, M.R. Kordi, and S.M. Hashemi Combined exercise training reduces IFN-gamma and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis Int Immunopharmacol 10 2010 1415 1419
36. S. Mostert, and J. Kesselring 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 2002 161 168
37. A. Rampello, M. Franceschini, and M. Piepoli Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study Phys Ther 87 2007 545 555
38. M.M. Rodgers, J.A. Mulcare, D.L. King, T. Mathews, S.C. Gupta, and R.M. Glaser Gait characteristics of individuals with multiple sclerosis before and after a 6-month aerobic training program J Rehabil Res Dev 36 1999 183 188
39. K.H. Schulz, S.M. Gold, and J. Witte Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis J Neurol Sci 225 2004 11 18
40. J. Ponichtera-Mulcare, T. Mathews, P. Barrett, and S. Gupta Change in aerobic fitness of patients with multiple sclerosis during a 6-month training program Sports Med Train Rehabil 7 1997 265 272
41. B.D. Cakt, B. Nacir, and H. Genc Cycling progressive resistance training for people with multiple sclerosis: a randomized controlled study Am J Phys Med Rehabil 89 2010 446 457
42. L. Konecny, P. Pospisil, and P. Vank Combination of aerobic and resistant training in multiple sclerosis Scr Med (Brno) 83 2010 98 106
43. T. Kjolhede, K. Vissing, and U. Dalgas Multiple sclerosis and progressive resistance training: a systematic review Mult Scler 18 2012 1215 1228
44. M.C. Mojtahedi, P. Boblick, J.H. Rimmer, J.L. Rowland, R.A. Jones, and C.L. Braunschweig Environmental barriers to and availability of healthy foods for people with mobility disabilities living in urban and suburban neighborhoods Arch Phys Med Rehabil 89 2008 2174 2179
45. L.H. Steffensen, S.I. Mellgren, and M.T. Kampman Predictors and prevalence of low bone mineral density in fully ambulatory persons with multiple sclerosis J Neurol 257 2010 410 418
46. T. Broekmans, M. Roelants, and P. Feys Effects of long-term resistance training and simultaneous electro-stimulation on muscle strength and functional mobility in multiple sclerosis Mult Scler J 17 2011 468 477
47. U. Dalgas, E. Stenager, and J. Jakobsen Resistance training improves muscle strength and functional capacity in multiple sclerosis Neurology 73 2009 1478 1484
48. U. Dalgas, E. Stenager, and J. Jakobsen Fatigue, mood and quality of life improve in MS patients after progressive resistance training Mult Scler 16 2010 480 490
49. L. Harvey, A.D. Smith, and R. Jones The effect of weighted leg raises on quadriceps strength, EMG parameters and functional activities in people with multiple sclerosis Physiotherapy 85 1999 154 161
50. A. Romberg, A. Virtanen, and J. Ruutiainen Effects of a 6-month exercise program on patients with multiple sclerosis: a randomized study Neurology 63 2004 2034 2038
51. F. de Souza-Teixeira, S. Castilla, C. Ayan, D. Garcia-Lopez, J. Gonzalez-Gallego, and J.A. de Paz Effects of resistance training in multiple sclerosis Int J Sports Med 30 2009 245 250
52. M.S. Fimland, J. Helgerud, M. Gruber, G. Leivseth, and J. Hoff Enhanced neural drive after maximal strength training in multiple sclerosis patients Eur J Appl Physiol 110 2010 435 443
53. C.A. Perez, V.M. Sanchez, F.D.S. Teixeira, and J.A.D. Fernandez Effects of a resistance training program in multiple sclerosis Spanish patients: a pilot study J Sport Rehabil 16 2007 143 153
54. N.F. Taylor, K.J. Dodd, D. Prasad, and S. Denisenko Progressive resistance exercise for people with multiple sclerosis Disabil Rehabil 28 2006 1119 1126
55. L.J. White, S.C. McCoy, V. Castellano, M.A. Ferguson, W. Hou, and R.H. Dressendorfer Effect of resistance training on risk of coronary artery disease in women with multiple sclerosis Scand J Clin Lab Invest 66 2006 351 355
56. H.A. Hayes, E. Gappmaier, and P.C. LaStayo 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 2011 2 10
57. S. Beer, B. Aschbacher, D. Manoglou, E. Gamper, J. Kool, and J. Kesselring Robot-assisted gait training in multiple sclerosis: a pilot randomized trial Mult Scler 14 2008 231 236
58. G.M. Gehlsen, S.A. Grigsby, and D.M. Winant Effects of an aquatic fitness program on the muscular strength and endurance of patients with multiple-sclerosis Phys Ther 64 1984 653 657
59. Y.J. Chang, M.J. Hsu, S.M. Chen, C.H. Lin, and A.M. Wong Decreased central fatigue in multiple sclerosis patients after 8 weeks of surface functional electrical stimulation J Rehabil Res Dev 48 2011 555 564
60. J.A. Kent-Braun, K.R. Sharma, R.G. Miller, and M.W. Weiner Effects of electrically stimulated exercise training on muscle function in multiple sclerosis J Neurol Rehabil 10 1996 143 151
61. J. Szecsi, C. Schlick, M. Schiller, W. Pollmann, N. Koenig, and A. Straube Functional electrical stimulation-assisted cycling of patients with multiple sclerosis: biomechanical and functional outcome - a pilot study J Rehabil Med 41 2009 674 680
62. N.G. LaRocca Impact of walking impairment in multiple sclerosis: perspectives of patients and care partners Patient 4 2011 189 201
63. M.D. Goldman, R.W. Motl, and R.A. Rudick Possible clinical outcome measures for clinical trials in patients with multiple sclerosis. Therapeutic advances in neurological disorders Ther Adv Neurol Disord 3 2010 229 239
64. R.W. Motl, M.D. Goldman, and R.H.B. Benedict Walking impairment in patients with multiple sclerosis: exercise training as a treatment option Neuropsychiatr Dis Treat 6 2010 767 774
65. C. Dettmers, M. Sulzmann, A. Ruchay-Plossl, R. Gutler, and M. Vieten Endurance exercise improves walking distance in MS patients with fatigue Acta Neurol Scand 120 2009 251 257
66. E.L. Geddes, E. Costello, K. Raivel, and R. Wilson 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 2009 5 12
67. M. van den Berg, H. Dawes, and D.T. Wade Treadmill training for individuals with multiple sclerosis: a pilot randomised trial J Neurol Neurosurg Psychiatry 77 2006 531 533
68. J. Collett, H. Dawes, and A. Meaney Exercise for multiple sclerosis: a single-blind randomized trial comparing three exercise intensities Mult Scler 17 2011 594 603
69. J. Kileff, and A. Ashburn A pilot study of the effect of aerobic exercise on people with moderate disability multiple sclerosis Clin Rehabil 19 2005 165 169
70. N.M. Sabapathy, C.L. Minahan, G.T. Turner, and S.A. Broadley Comparing endurance- and resistance-exercise training in people with multiple sclerosis: a randomized pilot study Clin Rehabil 25 2011 14 24
71. J. Freeman, and R. Allison Group exercise classes in people with multiple sclerosis: a pilot study Physiother Res Int 9 2004 104 107
72. A.C. Lo, and E.W. Triche Improving gait in multiple sclerosis using robot-assisted, body weight supported treadmill training Neurorehabil Neural Repair 22 2008 661 671
73. D. Conklyn, D. Stough, E. Novak, S. Paczak, K. Chemali, and F. Bethoux A home-based walking program using rhythmic auditory stimulation improves gait performance in patients with multiple sclerosis: a pilot study Neurorehabil Neural Repair 24 2010 835 842
74. L.J. White, S.C. McCoy, and V. Castellano Resistance training improves strength and functional capacity in persons with multiple sclerosis Mult Scler 10 2004 668 674
75. F.K. Mutluay, A. Tekeoglu, S. Saip, A. Altintas, and A. Siva Group exercise training approach to multiple sclerosis rehabilitation Nobel Medicus 4 2008 20 26
76. L.A. Pilutti, D.A. Lelli, and J.E. Paulseth 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 2011 31 36
77. Y. Salem, A. Scott, and V. Belobravka Effects of an aquatic exercise program on functional mobility in individuals with multiple sclerosis: a community-based study J Aquat Phys Ther 18 2010 22 32
78. Y. Salem, A.H. Scott, and H. Karpatkin Community-based group aquatic programme for individuals with multiple sclerosis: a pilot study Disabil Rehabil 33 2011 720 728
79. J.A. Freeman, M. Gear, and A. Pauli 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 2010 1377 1384
80. L. Krupp Fatigue in multiple sclerosis: a guide to diagnosis and management 2004 Demos Medical New York
81. B.S. Oken, S. Kishiyama, and D. Zajdel Randomized controlled trial of yoga and exercise in multiple sclerosis Neurology 62 2004 2058 2064
82. Y.D. Fragoso, D.L.B. Santana, and R.C. Pinto The positive effects of a physical activity program for multiple sclerosis patients with fatigue NeuroRehabilitation 23 2008 153 157
83. R. McCullagh, A.P. Fitzgerald, R.P. Murphy, and G. Cooke Long-term benefits of exercising on quality of life and fatigue in multiple sclerosis patients with mild disability: a pilot study Clin Rehabil 22 2008 206 214
84. G. Sutherland, M.B. Andersen, and M.A. Stoove Can aerobic exercise training affect health-related quality of life for people with multiple sclerosis? J Sport Exerc Psychol 23 2001 122 135
85. T.G. Roehrs, and G.M. Karst Effects of an aquatics exercise program on quality of life measures for individuals with progressive multiple sclerosis J Neurol Phys Ther 28 2004 63 71
86. O. Velikonja, K. Curic, A. Ozura, and S.S. Jazbec Influence of sports climbing and yoga on spasticity, cognitive function, mood and fatigue in patients with multiple sclerosis Clin Neurol Neurosurg 112 2010 597 601
87. L.M. Wier, M.S. Hatcher, E.W. Triche, and A.C. Lo 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 2011 483 492
88. A.J. Mitchell, J. Benito-Leon, J.M. Gonzalez, and J. Rivera-Navarro Quality of life and its assessment in multiple sclerosis: integrating physical and psychological components of wellbeing Lancet Neurol 4 2005 556 566
89. J. Benito-Leon, J.M. Morales, and J. Rivera-Navarro Health-related quality of life and its relationship to cognitive and emotional functioning in multiple sclerosis patients Eur J Neurol 9 2002 497 502
90. R.W. Motl, E. McAuley, E.M. Snook, and R.C. Gliottoni 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 2009 111 124
91. E. McAuley, R.W. Motl, and K.S. Morris Enhancing physical activity adherence and well-being in multiple sclerosis: a randomised controlled trial Mult Scler 13 2007 652 659
92. A. Romberg, A. Virtanen, and J. Ruutiainen Long-term exercise improves functional impairment but not quality of life in multiple sclerosis J Neurol 252 2005 839 845
93. Latimer-Cheung AE, Martin Ginis, KA Hicks AL, et al. The development of evidence-informed physical activity guidelines for adults with multiple sclerosis. Arch Phys Med Rehabil; in press.
94. M.D.D. Weikert, S. Balantrapu, and R.W. Motl Most common types of physical activity self-selected by people with multiple sclerosis Int J MS Care 13 2011 16 20
95. J. Surakka, A. Romberg, and J. Ruutiainen Effects of aerobic and strength exercise on motor fatigue in men and women with multiple sclerosis: a randomized controlled trial Clin Rehabil 18 2004 737 746
96. U. Dalgas, E. Stenager, J. Jakobsen, T. Petersen, K. Overgaard, and T. Ingemann-Hansen Muscle fiber size increases following resistance training in multiple sclerosis Mult Scler 16 2010 1367 1376
97. M. Asano, D. Dawes, A. Arafah, C. Moriello, and N. Mayo 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 2008 412 421
98. D. Cadavid, Y.Q. Tang, and G. O'Neill Responsiveness of the Expanded Disability Status Scale (EDSS) to disease progression and therapeutic intervention in progressive forms of multiple sclerosis Rev Neurol 51 2010 321 329
99. J. Hobart, J. Freeman, and A. Thompson Kurtzke scales revisited: the application of psychometric methods to clinical intuition Brain 123 2000 1027 1040
100. R.W. Motl, B.M. Sandroff, and R.H.B. Benedict Cognitive dysfunction and multiple sclerosis: developing a rationale for considering the efficacy of exercise training Mult Scler 17 2011 1034 1040
101. K.J. Dodd, N.F. Taylor, N. Shields, D. Prasad, E. McDonald, and A. Gillon 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 Multi Scler 17 2011 1362 1374
102. A. Doring, C.F. Pfueller, F. Paul, and J. Dorr Exercise in multiple sclerosis - an integral component of disease management EPMA J 3 2011 2
103. K. Jackson, K. Edginton-Bigelow, C. Bowsheir, M. Weston, and E. Grant Feasibility and effects of a group kickboxing program for individuals with multiple sclerosis: a pilot report J Bodyw Mov Ther 16 2012 7 13
104. M. Kargarfard, M. Etemadifar, P. Baker, M. Mehrabi, and R. Hayatbakhsh Effect of aquatic exercise training on fatigue and health-related quality of life in patients with multiple sclerosis Arch Phys Med Rehabil 93 2012 1701 1708
105. Y.C. Learmonth, L. Paul, L. Miller, P. Mattison, and A.K. McFadyen The effects of a 12-week leisure centre-based, group exercise intervention for people moderately affected with multiple sclerosis: a randomized controlled pilot study Clin Rehabil 26 2012 579 593
106. R.W. Motl, D.C. Smith, J. Elliott, M. Weikert, D. Dlugonski, and J.J. Sosnoff Combined training improves walking mobility in persons with significant disability from multiple sclerosis: a pilot study J Neurol Phys Ther 36 2012 32 37
107. R.W. Motl, and L.A. Pilutti The benefits of exercise training in multiple sclerosis Nat Rev Neurol 8 2012 487 497
108. R.W. Motl, E. McAuley, D. Wynn, B. Sandroff, and Y. Suh Physical activity, self-efficacy, and health-related quality of life in persons with multiple sclerosis: analysis of associations between individual-level changes over one year Qual Life Res 22 2013 253 261
109. U. Dalgas, and E. Stenager Exercise and disease progression in multiple sclerosis: can exercise slow down the progression of multiple sclerosis? Ther Adv Neurol Disord 5 2012 81 95
110. A.K. Andreasen, E. Stenager, and U. Dalgas The effect of exercise therapy on fatigue in multiple sclerosis Mult Scler 17 2011 1041 1054