Lara A. Pilutti

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

OBJECTIVE To conduct a systematic review of evidence surrounding the effects of exercise training on physical fitness, mobility, fatigue, and health-related quality of life in adults with multiple sclerosis (MS). DATA SOURCES The databases included EMBASE, 1980 to 2011 (wk 12); Ovid MEDLINE and Ovid OLDMEDLINE, 1947 to March (wk 3) 2011; PsycINFO, 1967 to March (wk 4) 2011; CINAHL all-inclusive; SPORTDiscus all-inclusive; Cochrane Library all-inclusive; and Physiotherapy Evidence Database all-inclusive. STUDY SELECTION The review was limited to English-language studies (published before December 2011) of people with MS that evaluated the effects of exercise training on outcomes of physical fitness, mobility, fatigue, and/or health-related quality of life. DATA EXTRACTION One research assistant extracted data and rated study quality. A second research assistant verified the extraction and quality assessment. DATA SYNTHESIS From the 4362 studies identified, 54 studies were included in the review. The extracted data were analyzed using a descriptive approach. There was strong evidence that exercise performed 2 times per week at a moderate intensity increases aerobic capacity and muscular strength. The evidence was not consistent regarding the effects of exercise training on other outcomes. CONCLUSIONS Among those with mild to moderate disability from MS, there is sufficient evidence that exercise training is effective for improving both aerobic capacity and muscular strength. Exercise may improve mobility, fatigue, and health-related quality of life.

The benefits of exercise training in multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination and neurodegeneration within the CNS. This damage of CNS structures leads to deficits of body functions, which, in turn, affect patient activities, such as walking, and participation. The pathogenesis and resulting consequences of MS have been described as concepts within the International Classification of Functioning, Disability and Health (ICF) model—an international standard to describe and measure health and disability. Evidence suggests that exercise training in people with MS has the potential to target and improve many of the components outlined in the ICF model. Although the body of research examining the effects of exercise training on depression, cognition and participatory outcomes is not sufficiently developed, some preliminary evidence is promising. Exercise training is proposed to affect inflammation, neurodegeneration, and CNS structures, but current evidence is limited. In this Review, we discuss evidence from clinical trials that suggests beneficial effects of exercise training on muscle strength, aerobic capacity and walking performance, and on fatigue, gait, balance and quality of life. Issues with current studies and areas of future research are highlighted.

Effects of exercise training on fatigue in multiple sclerosis: a meta-analysis.

Objective To provide a quantitative synthesis of randomized controlled trials examining the effect of exercise training on symptomatic fatigue in persons with multiple sclerosis (MS). Methods Electronic databases (Web of Science, PubMed, PsycInfo, and Google Scholar) were searched for articles published between 1960 and October 2012 by using the key words “fatigue,” OR “tiredness,” OR “energy,” OR “mood,” OR “lassitude,” AND “exercise,” OR “physical activity,” OR “rehabilitation,” OR “fitness” WITH “multiple sclerosis.” The initial search resulted in 311 articles, of which 74 were reviewed in detail and 17 met the inclusion criteria and provided enough data to compute effect sizes (ESs; Cohen d). The meta-analysis was conducted using a meta-analysis software program, and a random-effects model was used to calculate the overall ES, expressed as Hedge g. Results The weighted mean ES from 17 randomized controlled trials with 568 participants with MS was 0.45 (standard error = 0.12, 95% confidence interval = 0.22–0.68, z = 3.88, p ⩽ .001). The weighted mean ES was slightly heterogeneous (Q = 29.9, df = 16, p = .019). Conclusions The cumulative evidence supports that exercise training is associated with a significant small reduction in fatigue among persons with MS.

Development of Evidence-Informed Physical Activity Guidelines for Adults With Multiple Sclerosis

Most adults with multiple sclerosis (MS) are physically inactive. Physical activity guidelines are an important tool for exercise prescription, promotion, and monitoring. This article describes the application of international standards for guideline development in the creation of evidence-based physical activity guidelines for people with MS. The development process was informed by the Appraisal of Guidelines Research and Evaluation II instrument. The evidence base for the guidelines consisted of a systematic review of research examining the effects of exercise on fitness, fatigue, mobility, and health-related quality of life among people with MS. A multidisciplinary consensus panel deliberated the evidence and generated the guidelines and a preamble. Expert and stakeholder reviews of the materials led to refinement of the wording of both components of the guidelines. The resulting guidelines state that to achieve important fitness benefits, adults with MS who have mild to moderate disability need at least 30 minutes of moderate intensity aerobic activity 2 times per week and strength training exercises for major muscle groups 2 times per week. Meeting these guidelines may also reduce fatigue, improve mobility, and enhance elements of health-related quality of life. People with MS and health professionals are encouraged to adopt these rigorously developed guidelines.

The safety of exercise training in multiple sclerosis: A systematic review

There are many reviews documenting the benefits of exercise training among persons with multiple sclerosis (MS). To date, we are unaware of a review that summarizes the risks of relapse and other adverse events (AEs) associated with exercise training, yet this is critical for informing decisions and recommendations regarding the safety of this behavior. We conducted a systematic review of relapse and other AEs reported in randomized controlled trials (RCTs) of exercise training in MS. We searched electronic databases for RCTs of exercise training in MS. We calculated the rate of relapse and AEs, and the relative risk of relapse and AEs for exercise training versus control. Twenty-six studies were reviewed that included 1295 participants. We determined that the rate of relapse was 6.3% and 4.6% for control and exercise, respectively. The rate of AEs was 1.2% and 2.0% for control and exercise, respectively. The relative risk of relapse for exercise training was 0.73, whereas the relative risk of AE for exercise training was 1.67. Exercise training was not associated with an increased risk of relapse, and risk of AEs was not higher than in healthy populations. This evidence should alleviate uncertainty regarding the safety of exercise training in MS.

Randomized controlled trial of a behavioral intervention targeting symptoms and physical activity in multiple sclerosis

Background: Exercise training is beneficial, but most persons with multiple sclerosis (MS) are sedentary and physically inactive. This has prompted a new focus on the promotion of lifestyle physical activity in MS. We previously designed, tested, and refined a behavioral intervention delivered through the Internet that successfully increased lifestyle physical activity in MS, but have not evaluated the effects on secondary symptomatic and health-related quality of life (HRQOL) outcomes. Objective: We conducted a 6-month randomized controlled trial (RCT) that examined the efficacy of an Internet-delivered, behavioral intervention for improving outcomes of fatigue, depression, anxiety, pain, sleep quality, and HRQOL in 82 ambulatory persons with MS. The secondary aim was to replicate previous results regarding change in free-living physical activity. Results: There was a significant and positive effect of the intervention on fatigue severity (p=.001, ηρ2=.15) and its physical impact (p=.008, ηρ2=.09), depression (p=.006, ηρ2=.10), and anxiety (p=.006, ηρ2=.10). There were non-significant improvements in pain (p=.08, ηρ2=.04), sleep quality (p=.06, ηρ2=.05), and physical HRQOL (p=.06, ηρ2=.05). We replicated our previous results by demonstrating an increase in self-reported physical activity (p=.001, ηρ2=.13). Conclusions: Our results support behavioral interventions targeting lifestyle physical activity as an alternative approach for managing symptoms in MS.

Exercise training improves depressive symptoms in people with multiple sclerosis: Results of a meta-analysis

OBJECTIVE There is a high prevalence, yet under-treatment of depressive disorder and symptoms by conventional therapy in people with multiple sclerosis (MS). We conducted a meta-analysis examining the overall effect of exercise training on depressive symptoms in MS. METHODS We searched PubMed for randomized controlled trials (RCT) of exercise training and depression as an outcome in samples with MS. There were 13 RCTs that met inclusion criteria and yielded data for effect size (ES) generation (Cohens d). An overall ES was calculated using a random effects model and expressed as Hedges g. RESULTS The weighted mean ES was small, but statistically significant (Hedges g=0.36, SE=0.09, 95% CI=0.18-0.54, z=3.92, p<.001) indicating the exercise training resulted in an improvement in depressive symptoms compared to control. The overall effect was not heterogeneous (Q=16.46, df=12, p=0.17, I2=27.08); and post-hoc, exploratory analyses only identified depression symptom scale as a potential moderator variable (p=0.04). CONCLUSION The cumulative evidence indicates that exercise training can yield a small, yet statistically significant and reliable reduction in depressive symptoms for people with MS.

Effects of 12 Weeks of Supported Treadmill Training on Functional Ability and Quality of Life in Progressive Multiple Sclerosis: A Pilot Study

OBJECTIVE To examine the effects of body-weight supported treadmill training (BWSTT) on functional ability and quality of life in patients with progressive multiple sclerosis (MS) of high disability. DESIGN Before-after trial. SETTING Exercise rehabilitation research center. PARTICIPANTS Patients with progressive MS (N=6; 5 primary progressive, 1 secondary progressive) with high disability (mean±SD expanded disability status scale, [EDSS]=6.9±1.07). All participants completed the trial. INTERVENTIONS Subjects completed 36 sessions of BWSTT (30-min sessions, 3×wk) over 12 weeks. MAIN OUTCOME MEASURES Outcome measures included functional ability assessed by EDSS and Multiple Sclerosis Functional Composite (MSFC). Quality of life and fatigue were assessed by the MS Quality of Life-54 (MSQoL-54) and the Modified Fatigue Impact Scale (MFIS), respectively. All tests were administered at baseline and after 12 weeks of training. RESULTS All participants progressively improved training intensity; treadmill walking speed increased (34%; P<.001), and percent body weight support was reduced (42%; P<.001). A significant improvement in both physical (P=.02) and mental (P=.01) subscales of the MSQoL-54 was found. Fatigue was nonsignificantly reduced by 31% (P=.22); however, a large effect size (ES) was noted (ES=-.93). Functional ability remained stable with nonsignificant improvements in MSFC (P=.35; ES=.23) and EDSS (P=.36; ES=-.08) scores. CONCLUSIONS Twelve weeks of BWSTT produces beneficial effects on quality of life and potentially reduces fatigue in patients with primary progressive MS of high disability level. Larger trials will be required to confirm these findings and to evaluate further the effects of BWSTT in progressive MS.

Psychometric properties of the Fatigue Severity Scale and the Modified Fatigue Impact Scale

OBJECTIVE Fatigue is one of the most common, debilitating and life altering symptoms experienced by those with multiple sclerosis (MS) and has become the focus of therapeutic interventions and clinical rehabilitation. There is limited evidence regarding the psychometric properties and clinical relevance of fatigue outcomes for interpreting the effectiveness of intervention and rehabilitation strategies. This study determined the reliability, precision and clinically important change of the uni-dimensional Fatigue Severity Scale (FSS) and the multi-dimensional Modified Fatigue Impact Scale (MFIS). METHODS The FSS and MFIS along with physical, psychological and cognitive clinical outcomes were administered to a sample of 82 persons with MS in a clinical research setting on two time points, separated by six months. Intraclass correlation coefficient (ICC) analyses established reliability; standard error of measurement (SEM) and coefficient of variation (CV) determined precision; minimal detectable change (MDC) defined clinically important change. RESULTS Participants varied in type of MS and disability status, with 77% of participants classified as having substantial fatigue, based on the criteria of a mean FSS score ≥4. The MFIS (ICC=0.863) and the FSS (ICC=0.751) had acceptable reliability over six months. Precision was reasonable for both scales (based on SEM and CV estimates) but better for the FSS. MDC estimates were established and were lower for the FSS. CONCLUSION Reliability of the FSS and MFIS falls within acceptable ranges, and precision and clinically important change estimates provide guidelines for interpreting change in scores from these outcomes in clinical research of intervention and rehabilitation approaches for managing fatigue.

The reliability, precision and clinically meaningful change of walking assessments in multiple sclerosis

Background: Assessing walking impairment in those with multiple sclerosis (MS) is common, however little is known about the reliability, precision and clinically important change of walking outcomes. Objective: The purpose of this study was to determine the reliability, precision and clinically important change of the Timed 25-Foot Walk (T25FW), Six-Minute Walk (6MW), Multiple Sclerosis Walking Scale-12 (MSWS-12) and accelerometry. Methods: Data were collected from 82 persons with MS at two time points, six months apart. Analyses were undertaken for the whole sample and stratified based on disability level and usage of walking aids. Intraclass correlation coefficient (ICC) analyses established reliability: standard error of measurement (SEM) and coefficient of variation (CV) determined precision; and minimal detectable change (MDC) defined clinically important change. Results: All outcome measures were reliable with precision and MDC varying between measures in the whole sample: T25FW: ICC=0.991; SEM=1 s; CV=6.2%; MDC=2.7 s (36%), 6MW: ICC=0.959; SEM=32 m; CV=6.2%; MDC=88 m (20%), MSWS-12: ICC=0.927; SEM=8; CV=27%; MDC=22 (53%), accelerometry counts/day: ICC=0.883; SEM=28450; CV=17%; MDC=78860 (52%), accelerometry steps/day: ICC=0.907; SEM=726; CV=16%; MDC=2011 (45%). Variation in these estimates was seen based on disability level and walking aid. Conclusion: The reliability of these outcomes is good and falls within acceptable ranges. Precision and clinically important change estimates provide guidelines for interpreting these outcomes in clinical and research settings.