521309 research-article2014

MSJ0010.1177/1352458514521309Multiple Sclerosis JournalEditorial

MULTIPLE SCLEROSIS MSJ JOURNAL

Editorial

The benefits of exercise in progressive MS: some cautious optimism

The therapeutic landscape in progressive multiple sclerosis (MS) is bleak. The promise of disease-modifying drugs has not extended to this subgroup of patients, which has meant that treatment is confined to symptom management. Here too the challenges are considerable given the greater all-around morbidity that accompanies the transition to a progressive disease course coupled with a dearth of clinical trials focusing specifically on this subgroup of patients. Cognizant of these challenges, researchers and clinicians from seven countries have recently joined forces to form a Progressive MS Alliance with a multiplicity of aims, one of which is to advance treatment options for patients left behind by the diseasemodifying bandwagon.1 All of which makes the study by Briken et al. timely and important. The authors have shown that three different aerobic exercise modalities tailored according to a patient’s physical condition at baseline and undertaken two to three times a week over an eight- to 10-week period produced an array of benefits, including improved walking and cognition plus a reduction in fatigue and depression. Furthermore, a low drop-out rate suggests that patients were comfortable with the exercise intervention. The primary outcome of the study by Briken et al. is cardiorespiratory fitness in terms of the gold-standard measure of this, the peak oxygen consumption (VO2peak). The VO2-peak is an important health2 and physical performance marker3 known to be impaired in patients with MS.4 Moreover, a VO2-peak score below 20 ml/kg/ min has been shown to be the threshold for independent living in elderly people.5 Importantly, Briken and colleagues found a general beneficial effect of exercise on VO2-peak, and further that particularly bicycling induced the largest improvements. Also of note is that several different aerobic exercise modalities were applied and found feasible and potentially beneficial, providing evidencebased choices both for progressive MS patients and therapists when choosing aerobic exercise modalities for future rehabilitation programs. Walking distance covered during the 6-minute walk test improved following exercise. In the arm-ergometry and bicycling groups the improvement was most pronounced, and corresponded to ~63 m and ~56 m, respectively. These average changes are well above the threshold required for a change to be regarded as clinically relevant from a patient perspective for the 6-minute walk test of 22 m.6 Surprisingly, arm-ergometry improved walking distance, and the authors struggle to explain this improvement. However, the most

Multiple Sclerosis Journal 2014, Vol. 20(3) 269­–270 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1352458514521309 msj.sagepub.com

likely explanations seem to be improved core stability and/ or improved arm-swinging during walking. Of particular note is the observation that exercise may enhance certain aspects of cognition. Cognitive dysfunction can affect up to three-quarters of patients with secondary progressive MS and half of all patients with primary progressive MS, and the deficits cast a wide shadow impeding the ability to work, maintain relationships, pursue leisure activities and complete basic self-care tasks.7 There are as yet no effective pharmacological treatments, while the benefits of cognitive rehabilitation are still considered equivocal, notwithstanding some recent promising developments.8 Enter exercise, an intervention that is both complied with and relatively free of side effects, and the data indicate some notable gains in memory and attention. It is, however, surprising that no improvements were seen on the Symbol-Digit Modality Test, considered the most sensitive marker of information processing speed, the quintessential cognitive abnormality in MS.9 While this highlights the need for the data to be replicated, the findings do overlap broadly with those found in other disease groups and in healthy subjects, as the authors note, and where intriguing neuroimaging results enhance the validity of exercise as an effective treatment for cognitive dysfunction. Exercise also appears to boost mood, another aspect of behavior that is particularly vulnerable in the MS patient, for whom rates of depression exceed those found in most other neurological disorders and are three times those seen in the general population.10 Given that severe depression may further adversely affect cognition, if exercise does indeed enhance mood, it holds out the additional benefit of secondarily boosting cognition as well. Whether the same may hold true for fatigue is less certain. In a challenging disorder like progressive MS, it is all too easy to get carried away when a putative intervention that has been there all along, right under the noses of everyone, suddenly pops out to reveal itself as potentially effective, moreover for a multiplicity of symptoms and without inducing side effects. However, there are as yet many important unanswered questions. For example, can the benefits of exercise be enhanced and, just as importantly, maintained by other concomitant interventions, like cognitive behavior therapy for depression or psychostimulant medication, like methylphenidate for fatigue? And can exercise influence disease progression in progressive MS? Furthermore, replication is needed and sample sizes need to increase

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substantially. Nonetheless, the study by Birken et al. is the pilot showing us one way forward. Exercise will not be the panacea for a tough disease, but it has revealed albeit tentatively that there is some plasticity in a central nervous system afflicted by a progressive condition. That in turn holds out a bigger promise to patients looking for help and the clinicians, basic scientists and funding agencies working to provide it. Conflict of interest None declared.

References 1. Fox RJ, Thompson A, Baker D, et al. Setting a research agenda for progressive multiple sclerosis: The International Collaborative on Progressive MS. Mult Scler 2012;18: 1534–1540. 2. Kodama S, Saito K, Tanaka S, et al. Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: A meta-analysis. JAMA 2009; 301: 2024–2035. 3. Day JR, Rossiter HB, Coats EM, et al. The maximally attainable VO2 during exercise in humans: The peak vs. maximum issue. J Appl Physiol 2003; 95: 1901–1907. 4. Castellano V, Patel DI and White LJ. Cytokine responses to acute and chronic exercise in multiple sclerosis. J Appl Physiol 2008; 104: 1697–1702. 5. Cress ME and Meyer M. Maximal voluntary and functional performance levels needed for independence in adults aged 65 to 97 years. Phys Ther 2003; 83: 37–48.

6. Baert I, Freeman J, Smedal T, et al. Responsiveness and clinically meaningful improvement, according to disability level, of five walking measures after rehabilitation in multiple sclerosis: A European multi-center study. Neurorehabil Neural Repair (in press). 7. Rao SM, Leo GJ, Ellington L, et al. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology 1991; 41: 692–696. 8. Sumowski JF, Leavitt VM, Cohen A, et al. Retrieval practice is a robust memory aid for memory-impaired patients with MS. Mult Scler 2013; 19: 1943–1946. 9. Sonder JM, Burggraaff J, Knol DL, et al. Comparing longterm results of PASAT and SDMT scores in relation to neuropsychological testing in multiple sclerosis. Mult Scler. [Epub ahead of print 9; September 2013]. 10. Feinstein A. Multiple sclerosis and depression. Mult Scler 2011; 17: 1276–1281.

Anthony Feinstein1,2 and Ulrik Dalgas3 of Psychiatry, Sunnybrook Health Sciences Centre, Canada 2University of Toronto, Canada 3Department of Public Health, Section of Sport Science, Aarhus University, Denmark

1Department

Corresponding author: Anthony Feinstein, Department of Psychiatry, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Toronto, ON M4N 3M5, Canada. Email: [email protected]

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The benefits of exercise in progressive MS: some cautious optimism.

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