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research-article2014
MSJ0010.1177/1352458514521309Multiple Sclerosis JournalEditorial
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 treat-
ment options for patients left behind by the disease-
modifying 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 accord-
ing 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 (VO2-
peak). 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 col-
leagues 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 dif-
ferent aerobic exercise modalities were applied and found
feasible and potentially beneficial, providing evidence-
based choices both for progressive MS patients and thera-
pists 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
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Multiple Sclerosis Journal
2014, Vol. 20(3) 269­–270
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DOI: 10.1177/1352458514521309
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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 dysfunc-
tion can affect up to three-quarters of patients with second-
ary progressive MS and half of all patients with primary
progressive MS, and the deficits cast a wide shadow imped-
ing the ability to work, maintain relationships, pursue lei-
sure 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 devel-
opments.8 Enter exercise, an intervention that is both com-
plied 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 induc-
ing 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, repli-
cation is needed and sample sizes need to increase
270 Multiple Sclerosis Journal 20(3)
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 tenta-
tively that there is some plasticity in a central nervous sys-
tem 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 cardio-
vascular 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 attain-
able 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.
Downloaded from msj.sagepub.com by guest on April 3, 2015
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 multi-
ple 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 long-
term results of PASAT and SDMT scores in relation to neu-
ropsychological 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
1Department of Psychiatry, Sunnybrook Health Sciences
Centre, Canada
2University of Toronto, Canada
3Department of Public Health, Section of Sport Science,
Aarhus University, Denmark
Corresponding author:
Anthony Feinstein, Department of Psychiatry, Sunnybrook
Health Sciences Centre, 2075 Bayview Ave., Toronto, ON
M4N 3M5, Canada.
Email: ant.feinstein@utoronto.ca