A randomized study to evaluate the effect of exercise on fatigue in people with relapsing-remitting multiple sclerosis treated with fingolimod.

BACKGROUND: Fatigue is a major symptom of multiple sclerosis (MS) in patients, and it has been shown to improve with physical exercise. Although fingolimod might lessen fatigue, it is unclear how patients treated with fingolimod react to physical activity regarding fatigue. OBJECTIVE: This study evaluated the effect of an exercise intervention on fatigue in relapsing-remitting MS patients receiving fingolimod. METHODS: People with MS (PwMS) were randomized to either a structured internet-based exercise program (e-training) or no e-training intervention. The primary endpoint was the change in the Modified Fatigue Impact Scale (mFIS) after six months. RESULTS: The primary analysis showed no statistically significant difference between groups in the mFIS change. Subgroup analyses revealed a beneficial effect of physical exercise for PwMS with low aerobic capacity and with low aerobic capacity plus more severe fatigue. The incidence of adverse events was similar in both groups. No cardiovascular events were reported. The majority of PwMS were relapse free. CONCLUSION: Physical exercise benefits on fatigue may depend on the physical capacity of the patient and requires individualized training. Consistent with previous studies, these results suggest that physical exercise generally does not impose a risk and that this holds true also for patients receiving fingolimod.Trial registration: ClinicalTrials.gov, NCT01490840.

Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.

BACKGROUND: Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. OBJECTIVE: To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial. METHODS: Patients with progressive MS and moderate disability (Expanded Disability Status Scale (EDSS) of 4-6) were randomized to one of three exercise interventions (arm ergometry, rowing, bicycle ergometry) for 8-10 weeks or a waitlist control group. We analyzed the drop-out rate as a measure of feasibility. The primary endpoint of the study was aerobic fitness. Secondary endpoints were walking ability, cognitive function as measured by a neuropsychological test battery, depression and fatigue. RESULTS: A total of 42 patients completed the trial (10.6% drop-out rate). Significant improvements were seen in aerobic fitness. In addition, exercise improved walking ability, depressive symptoms, fatigue and several domains of cognitive function. CONCLUSION: This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS. Larger exercise studies are needed to confirm the effect on cognition. TRIAL REGISTRATION: ISRCTN (trial number 76467492) http://isrctn.org.

[Multiple sclerosis and physical activity: an historical perspective]. / Multiple Sklerose und körperliche Aktivität : Eine historische Betrachtung.

Uncertainties concerning the pathology of multiple sclerosis have in the past led to numerous theories about the cause and therapy of the disease. In the last 40 years technological progress and the use of scientific research methods have contributed to a considerably enlarged body of medical and scientific knowledge, a process that has not yet come to an end. The attitude towards physical activity has also changed tremendously over time. There was a paradigm shift from the fear of triggering and aggravating the disease towards therapeutic benefits of physical activity and exercise. The first evidence for beneficial effects of exercise on symptoms and the course of the disease originated in the 1960s; however, a growing scientific interest in the topic was not recognizable until the 1990s when the number of exercise studies finally started to increase. Nowadays, the positive effects of physical activity and exercise are well established; nevertheless, high-quality research reports are still lacking. As a consequence there are still many unresolved questions concerning specific training effects and recommendations.

Behavioral interventions in multiple sclerosis: a biopsychosocial perspective.

Managing uncertainty is a major challenge associated with the diagnosis of multiple sclerosis (MS). In addition to physical symptoms, neuropsychiatric symptoms are highly prevalent in this disease. Depression in particular is more common in MS than in other chronic diseases. While substantial achievements have been made in the therapy of MS and an increasing number of immunomodulatory treatments are now available, the long-term benefits of these are still a matter of debate. Importantly, while the approved therapies show good efficacy on inflammatory lesions and relapse rate, and may slow certain aspects of disease progression, improvements in function have rarely been reported. On the other hand, behavioral interventions have recently been shown to significantly improve fatigue and depression as well as motor function. In addition, recent evidence suggests that group education or face-to-face behavioral interventions may decrease inflammatory disease activity (such as relapse rate or lesion formation measured by MRI). Therefore, behavioral interventions not only ameliorate symptoms but may have the potential to modify the disease process itself.

Physical activity in multiple sclerosis: a comparative study of vitamin D, brain-derived neurotrophic factor and regulatory T cell populations.

BACKGROUND: Previous studies suggest beneficial effects of exercise in multiple sclerosis (MS). However, knowledge on the effects of physical activity on the immune system is limited. OBJECTIVE: To assess potential relationships between cardiorespiratory fitness, cognitive function, and immune parameters in physically active and inactive MS patients. METHODS: We identified 83 patients with relapsing-remitting disease, an unrestricted walking range, and stable interferon-ß treatment from our data base. Based on the subjective report of physical activity, the lower/inactive (n = 21) and upper/active quartiles (n = 21) of patients were selected. We assessed the frequency of T cells, B cells, NK cells, monocytes and regulatory T cell populations by flow cytometry, measured brain-derived neurotrophic factor and vitamin D serum levels by ELISA, and conducted spiroergometry and transcranial sonography. RESULTS: Physical activity and cardiorespiratory fitness were not associated with brain-derived neurotrophic factor, frequency of T regulatory cells or any other immune cell subpopulation. However, we found a positive correlation of vitamin D serum levels with cardiorespiratory fitness. CONCLUSION: Overall, we found no negative effect of physical activity on the immune system. The association between vitamin D and cardiorespiratory fitness most likely reflects longer hours of sunlight exposure in active patients, suggesting a desirable 'side- effect' of physical activity.

Multiple sclerosis relapses are not associated with exercise.

Since multiple sclerosis (MS) often affects physically active young individuals, it is important to know if exercise can result in increased disease activity. Therefore we used a self-report questionnaire to examine the relationship of different levels of sports activity and relapses in 632 patients with MS. In order to analyse whether subjective recall might have biased the results, we performed, in a subgroup of our sample, an objective assessment of clinical data and physical fitness parameters. We were unable to find any association between sports activity and clinical relapses in either of the two analyses. The group with highest activity even shows the lowermost mean values, standard deviations and range concerning the number of relapses. Our data suggest that physical activity has no significant influence on clinical disease activity.

[Multiple sclerosis and exercise : effects of physical activity on the immune system]. / Multiple Sklerose und Sport : Auswirkungen körperlicher Aktivität auf das Immunsystem.

Multiple sclerosis is a chronic inflammatory CNS disease which accounts for functional impairment and lasting disability in young adults. Current studies demonstrate that physical activity in patients with MS counteracts depression and fatigue and may improve quality of life. Interventional studies have described a reduction of the functional impairment in MS patients. This report presents information on the effects of physical activity on the immune system and the release of neurotrophic factors, and highlights current data on a potential immunomodulatory effect of exercise in multiple sclerosis.