Rehabilitation to Improve Gaze and Postural Stability in People With Multiple Sclerosis: A Randomized Clinical Trial.

BACKGROUND: People with multiple sclerosis (PwMS) frequently experience dizziness and imbalance that may be caused by central vestibular system dysfunction. Vestibular rehabilitation may offer an approach for improving dysfunction in these people. OBJECTIVE: To test the efficacy of a gaze and postural stability (GPS) retraining intervention compared to a strength and endurance (SAE) intervention in PwMS. METHODS: About 41 PwMS, with complaints of dizziness or history of falls, were randomized to either the GPS or SAE groups. Following randomization participants completed 6-weeks of 3×/week progressive training, delivered one-on-one by a provider. Following intervention, testing was performed at the primary (6-weeks) and secondary time point (10-weeks). A restricted maximum likelihood estimation mixed effects model was used to examine changes in the primary outcome of the Dizziness Handicap Inventory (DHI) between the 2 groups at the primary and secondary time point. Similar models were used to explore secondary outcomes between groups at both timepoints. RESULTS: Thirty-five people completed the study (17 GPS; 18 SAE). The change in the DHI at the primary time point was not statistically different between the GPS and SAE groups (mean difference = 2.33 [95% CI -9.18, 12.85]). However, both groups demonstrated significant improvement from baseline to 6-weeks (GPS -8.73; SAE -7.31). Similar results were observed for secondary outcomes and at the secondary timepoint. CONCLUSIONS: In this sample of PwMS with complaints of dizziness or imbalance, 6-weeks of GPS training did not result in significantly greater improvements in dizziness handicap or balance compared to 6-weeks of SAE training.

Test-Retest Reliability and Response Stability of Gaze Stabilization, Postural Sway, and Dynamic Balance Tests in Persons with Multiple Sclerosis and Controls.

BACKGROUND: Psychometric properties of tests that assess the angular vestibulo-ocular reflex (aVOR) and vestibulospinal reflex function are currently unknown. This study investigated the test-retest reliability and response stability of gaze stabilization, postural sway, and dynamic balance measures in persons with multiple sclerosis (MS) and controls. METHODS: Nineteen adults with MS and 14 controls performed passive horizontal head impulses, quiet standing, and dynamic balance tests on two separate occasions. Gaze stabilization measures included aVOR gain, number of compensatory saccades (CSs) per head rotation, CS latency, and gaze position error. Postural sway included sway amplitude and total sway path. Dynamic balance measure included the Functional Gait Assessment. Intraclass correlation coefficient, standard error of measurement (SEM, SEM%), and minimal detectable difference at 95% confidence level were calculated. RESULTS: Test-retest reliability for aVOR gain, CSs per head rotation, and gaze position error was moderate and for each postural sway and dynamic balance measure was good. Low error (SEM, SEM%) for aVOR gain, CS latency, postural sway, and dynamic balance variables and low minimal detectable difference values for aVOR gain and Functional Gait Assessment scores were seen, suggestive of acceptable response stability. CONCLUSIONS: These results support the utility of some of the gaze and postural measures for examination and treatment efficacy purposes in people with MS.

Rehabilitation to improve gaze and postural stability in people with multiple sclerosis: study protocol for a prospective randomized clinical trial.

BACKGROUND: The use of vestibular rehabilitation principles in the management of gaze and postural stability impairments in people with multiple sclerosis (PwMS) has shown promise in pilot work completed in our lab and in a recently published randomized clinical trial (RCT). However, further work is needed to fully quantify the gaze and postural impairments present in people with multiple sclerosis and how they respond to rehabilitation. METHODS/DESIGN: The study is a single blind RCT designed to examine the benefit of a gaze and postural stability (GPS) intervention program compared to a standard of care (SOC) rehabilitation program in dizzy and balance impaired PwMS. Outcomes will be collected across the domains of body structure and function, activity, and participation as classified by the World Health Organization International Classification of Functioning, Disability, and Health (ICF). Our primary outcomes are the Dizziness Handicap Inventory (DHI) and the Functional Gait Assessment (FGA). Secondary outcomes include other measures of gaze and postural stability, fatigue, and functional mobility. Participants who are interested and eligible for enrollment will be consented prior to completing a baseline assessment. Following the baseline assessment each participant will be randomized to either the GPS or SOC intervention group and will complete a 6 week treatment period. During the treatment period, both groups will participate in guided exercise 3x/week. Following the treatment period participants will be asked to return for a post-treatment evaluation and again for a follow-up assessment 1 month later. We anticipate enrolling 50 participants. DISCUSSION: This study will be an innovative RCT that will utilize gaze and postural stability metrics to assess the efficacy of vestibular rehabilitation in PwMS. It will build on previous work by examining measures across the ICF and improve the current evidence base for treating PwMS. TRIAL REGISTRATION: ClinicalTrials.gov, May 29th 2018, NCT03521557 .

Gaze Stability, Dynamic Balance and Participation Deficits in People with Multiple Sclerosis at Fall-Risk.

Despite the common complaints of dizziness and demyelination of afferent or efferent pathways to and from the vestibular nuclei which may adversely affect the angular vestibulo-ocular reflex (aVOR) and vestibulo-spinal function in persons with multiple sclerosis (PwMS), few studies have examined gaze and dynamic balance function in PwMS. (1) Determine the differences in gaze stability, dynamic balance and participation measures between PwMS and controls, (2) Examine the relationships between gaze stability, dynamic balance and participation. Nineteen ambulatory PwMS at fall-risk and 14 age-matched controls were recruited. Outcomes included (1) gaze stability (angular aVOR gain [ratio of eye to head velocity]; number of compensatory saccades [CS] per head rotation; CS latency; gaze position error; coefficient of variation [CV] of aVOR gain), (2) dynamic balance (functional gait assessment, FGA; four square step test), and (c) participation (dizziness handicap inventory; activities-specific balance confidence scale). Separate independent t-tests and Pearson's correlations were calculated. PwMS were age = 53 ± 11.7 years and had 4.2 ± 3.3 falls/year. PwMS demonstrated significant (P < 0.05) impairments in gaze stability, dynamic balance and participation measures compared to controls. CV of aVOR gain and CS latency were significantly correlated with FGA. Deficits and correlations across a spectrum of disability measures highlight the relevance of gaze and dynamic balance assessment in PwMS. Anat Rec, 301:1852-1860, 2018. © 2018 Wiley Periodicals, Inc.

Anaplerotic therapy in propionic acidemia.

BACKGROUND: Propionic acidemia is a rare metabolic disorder caused by a deficiency of propionyl- CoA carboxylase, the enzyme converting propionyl-CoA to methylmalonyl-CoA that subsequently enters the citric acid cycle as succinyl-CoA. Patients with propionic acidemia cannot metabolize propionic acid, which combines with oxaloacetate to form methylcitric acid. This, with the defective supply of succinyl-CoA, may lead to a deficiency in citric acid cycle intermediates. PURPOSE: The objective of this study was to determine whether supplements with glutamine (400mg/kg per day), citrate (7.5mEq/kg per day), or ornithine α-ketoglutarate (400mg/kg per day) (anaplerotic agents that could fill up the citric acid cycle) would affect plasma levels of glutamine and ammonia, the urinary excretion of Krebs cycle intermediates, and the clinical outcome in 3 patients with propionic acidemia. METHODS: Each supplement was administered daily for four weeks with a two week washout period between supplements. The supplement that produced the most favorable changes was supplemented for 30 weeks following the initial study period and then for a 2 year extension. RESULTS: The urinary excretion of the Krebs cycle intermediates, α-ketoglutarate, succinate, and fumarate increased significantly compared to baseline during citrate supplementation, but not with the other two supplements. For this reason, citrate supplements were continued in the second part of the study. The urinary excretion of methylcitric acid and 3-hydroxypropionic acid did not change with any intervention. No significant changes in ammonia or glutamine levels were observed with any supplement. However, supplementation with any anaplerotic agents normalized the physiological buffering of ammonia by glutamate, with plasma glutamate and alanine levels significantly increasing, rather than decreasing with increasing ammonia levels. No significant side effects were observed with any therapy and safety labs (blood counts, chemistry and thyroid profile) remained unchanged. Motor and cognitive development was severely delayed before the trial and did not change significantly with therapy. Hospitalizations per year did not change during the trial period, but decreased significantly (p<0.05) in the 2years following the study (when citrate was continued) compared to the 2years before and during the study. CONCLUSIONS: These results indicate that citrate entered the Krebs cycle providing successful anaplerotic therapy by increasing levels of the downstream intermediates of the Krebs cycle: α-ketoglutarate, succinate and fumarate. Citrate supplements were safe and might have contributed to reduce hospitalizations in patients with propionic acidemia.

Associations Between Fatigue and Disability, Functional Mobility, Depression, and Quality of Life in People with Multiple Sclerosis.

BACKGROUND: Fatigue is a common symptom in people with multiple sclerosis (MS), but its associations with disability, functional mobility, depression, and quality of life (QOL) remain unclear. We aimed to determine the associations between different levels of fatigue and disability, functional mobility, depression, and physical and mental QOL in people with MS. METHODS: Eighty-nine individuals with MS (mean [SD] disease duration = 13.6 [9.8] years, mean [SD] Expanded Disability Status Scale [EDSS] score = 5.3 [1.5]) and no concurrent relapses were retrospectively analyzed. Participants were divided into two groups based on five-item Modified Fatigue Impact Scale (MFIS-5) scores: group LF (n = 32, MFIS-5 score ≤10 [low levels of fatigue]) and group HF (n = 57, MFIS-5 score >10 [high levels of fatigue]). RESULTS: Sixty-four percent of the sample reported high levels of fatigue. Compared with group LF, group HF demonstrated significantly (P < .05) greater impairments in the Timed Up and Go test, Activities-specific Balance Confidence scale, and 12-item Multiple Sclerosis Walking Scale scores; depression; and QOL but not in the EDSS scores, which were not significantly different between groups. CONCLUSIONS: Fatigue was found to be a predominant symptom in the study participants. Individuals reporting higher levels of fatigue concomitantly exhibited greater impairments in functional mobility, depression, and physical and mental QOL. Disability was not found to be related to level of fatigue. These findings can be important for appropriate assessment and management of individuals with MS with fatigue.

Top 10 research questions related to physical activity and multiple sclerosis.

An estimated 2.5 million people worldwide are living with multiple sclerosis (MS), and this disease may be increasing in prevalence. MS is a disease of the central nervous system that is associated with heterogeneous symptoms and functional consequences, and the current first-line disease-modifying therapies often become ineffective later in the disease. There is increasing evidence for the benefits of physical activity (PA) in people with MS, but this population is generally physically inactive and sedentary. We proposed 10 research questions to guide future research on PA and MS: (1) Is PA an MS disease-modifying behavior? (2) What are the benefits of PA among people with MS? (3) What is the optimal PA prescription for people with MS? (4) What are the safety issues with PA in people with MS? (5) What characteristics of people with MS modify the benefits of PA? (6) What variables explain participation in PA among people with MS? (7) What are effective behavioral interventions for PA change in people with MS? (8) How do we translate PA research into clinical MS practice? (9) What is the role of sedentary behavior in people with MS? And (10) what is the optimal measurement of PA in people with MS? These questions are critical for informing our understanding of the short- and long-term consequences of PA in MS as well as for identifying approaches for promoting and sustaining PA in MS. Addressing these questions may greatly improve the lives of people with this chronic disease.

Resistance strength training exercise in children with spinal muscular atrophy.

INTRODUCTION: Preliminary evidence in adults with spinal muscular atrophy (SMA) and in SMA animal models suggests exercise has potential benefits in improving or stabilizing muscle strength and motor function. METHODS: We evaluated feasibility, safety, and effects on strength and motor function of a home-based, supervised progressive resistance strength training exercise program in children with SMA types II and III. Up to 14 bilateral proximal muscles were exercised 3 times weekly for 12 weeks. RESULTS: Nine children with SMA, aged 10.4 ± 3.8 years, completed the resistance training exercise program. Ninety percent of visits occurred per protocol. Training sessions were pain-free (99.8%), and no study-related adverse events occurred. Trends in improved strength and motor function were observed. CONCLUSIONS: A 12-week supervised, home-based, 3-day/week progressive resistance training exercise program is feasible, safe, and well tolerated in children with SMA. These findings can inform future studies of exercise in SMA.

Ataluren treatment of patients with nonsense mutation dystrophinopathy.

INTRODUCTION: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. METHODS: Randomized, double-blind, placebo-controlled study; males ≥ 5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. RESULTS: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. CONCLUSIONS: As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need.

Cardiorespiratory response to exercise on a large therapeutic roll.

PURPOSE: Large therapeutic rolls (LTR) and balls are popular rehabilitation tools and have also been advertised as cardiovascular training devices. The aim of this study was to determine if individuals of varying fitness levels would reach aerobic training levels by evidence-based standards as described in American College of Sports Medicine (ACSM) publications. METHODS: Fourteen volunteers performed a maximal exercise test and on subsequent days, two submaximal exercise tests on the LTR (LTR-A and -B). LTR-A consisted of four 5-minute stages of exercise at progressive intensity levels. LTR-B included 20 minutes of continuous exercise. Oxygen consumption (VO2) and heart rate (HR) during exercise on the LTR were compared with ACSM recommended standards. RESULTS: The average (range) peak intensity achieved during LTR-A was 66.8% (51.7-82.7%) of maximal VO2 reserve (VO2R) and 82.9% (70.7%-91.2%) of maximal heart rate (HRmax). During LTR-B, HR and VO2 of all participants was maintained at moderate exercise intensity and averaged 56% of VO2R and 78% of HRmax during the 20 minute exercise period. CONCLUSIONS: These findings suggest that individuals with a wide range of aerobic fitness are able to reach and maintain aerobic training levels with appropriate exercise on a large therapeutic roll or ball.

Utility of disease-specific measures and clinical balance tests in prediction of falls in persons with multiple sclerosis.

BACKGROUND AND PURPOSE: The sensory and motor deficits associated with multiple sclerosis (MS) contribute to falls with the majority of persons with MS falling at least once annually. To appropriately direct treatment, accurate fall prediction measures are needed. In this study of community-dwelling individuals with MS followed for 12 months, we sought to determine frequency of falls, utility of clinical balance tests to predict falls, and accuracy of participants' retrospective recall of fall events. METHODS: Independently ambulatory persons with MS underwent 5 clinical balance tests including Activities-specific Balance Confidence, Berg Balance Scale, Functional Reach, Timed Up and Go, and Dynamic Gait Index, and one disease-specific measure of disability (Expanded Disability Status Scale) and then were followed for 1 year. Participants were queried monthly by phone to determine the number of fall events that had occurred. Accuracy of fall prediction was determined by receiver operating characteristic curve analysis and comparison of balance test performance between fallers and nonfallers. RESULTS: Sixty-one percent of the 38 participants were classified as fallers at 12-month follow-up. Only the Berg Balance Scale, Dynamic Gait Index, and the Activities-specific Balance Confidence demonstrated clinically useful levels of accuracy. In addition, participants were generally poor in their accurate recall of fall events relative to their monthly fall reports. DISCUSSION AND CONCLUSIONS: The majority of participants fell during a 1-year prospective follow-up. Only 2 balance performance measures and 1 balance confidence measure accurately distinguished between fallers and nonfallers as well as possessed clinically useful levels of sensitivity and specificity. These results also emphasized the inaccuracy of retrospective fall history in an MS sample.

The 6-minute walk test and other clinical endpoints in duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study.

INTRODUCTION: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. METHODS: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate-determined energy expenditure index, and other exploratory endpoints. RESULTS: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. CONCLUSIONS: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression.

The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study.

INTRODUCTION: Duchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double-blind, placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6-minute walk test (6MWT) and other endpoints. METHODS: Evaluations performed every 6 weeks included the 6-minute walk distance (6MWD), timed function tests (TFTs), and quantitative strength using hand-held myometry. RESULTS: Baseline age (≥7 years), 6MWD, and selected TFT performance are strong predictors of decline in ambulation (Δ6MWD) and time to 10% worsening in 6MWD. A baseline 6MWD of <350 meters was associated with greater functional decline, and loss of ambulation was only seen in those with baseline 6MWD <325 meters. Only 1 of 42 (2.3%) subjects able to stand from supine lost ambulation. CONCLUSION: Findings confirm the clinical meaningfulness of the 6MWD as the most accepted primary clinical endpoint in ambulatory DMD trials.

LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy.

OBJECTIVE: Duchenne muscular dystrophy (DMD) displays a clinical range that is not fully explained by the primary DMD mutations. Ltbp4, encoding latent transforming growth factor-ß binding protein 4, was previously discovered in a genome-wide scan as a modifier of murine muscular dystrophy. We sought to determine whether LTBP4 genotype influenced DMD severity in a large patient cohort. METHODS: We analyzed nonsynonymous single nucleotide polymorphisms (SNPs) from human LTBP4 in 254 nonambulatory subjects with known DMD mutations. These SNPs, V194I, T787A, T820A, and T1140M, form the VTTT and IAAM LTBP4 haplotypes. RESULTS: Individuals homozygous for the IAAM LTBP4 haplotype remained ambulatory significantly longer than those heterozygous or homozygous for the VTTT haplotype. Glucocorticoid-treated patients who were IAAM homozygotes lost ambulation at 12.5 ± 3.3 years compared to 10.7 ± 2.1 years for treated VTTT heterozygotes or homozygotes. IAAM fibroblasts exposed to transforming growth factor (TGF) ß displayed reduced phospho-SMAD signaling compared to VTTT fibroblasts, consistent with LTBP4' role as a regulator of TGFß. INTERPRETATION: LTBP4 haplotype influences age at loss of ambulation, and should be considered in the management of DMD patients.

The Submaximal Clinical Exercise Tolerance Test (SXTT) to Establish Safe Exercise Prescription Parameters for Patients with Chronic Disease and Disability.

PURPOSE: To describe how to perform a Submaximal Clinical Exercise Tolerance Test (SXTT) as part of an exercise evaluation in the physical therapy clinic to determine an appropriate exercise prescription and to establish safety of exercise for physical therapy clients. SUMMARY OF KEY POINTS: Physical activity is crucial for general health maintenance. An exercise evaluation includes a comprehensive patient history, physical examination, exercise testing, and exercise prescription. The SXTT provides important clinical data that form the foundation for an effective and safe exercise prescription. Observations obtained during the exercise evaluation will identify at-risk patients who should undergo further medical evaluation before starting an exercise program. Two case examples of SXTTs administered to individuals with multiple sclerosis are presented to demonstrate the application of these principles. STATEMENT OF RECOMMENDATIONS: Due to their unique qualifications, physical therapists shall assume responsibility to design and monitor safe and effective physical activity programs for all clients and especially for individuals with chronic disease and disability. To ensure safety and efficacy of prescribed exercise interventions, physical therapists need to perform an appropriate exercise evaluation including exercise testing before starting their clients on an exercise program.

Physical activity and cognitive function in multiple sclerosis.

Cognitive impairment is prevalent, disabling, and poorly managed in persons with multiple sclerosis (MS). This cross-sectional study examined the associations among physical activity, cognitive processing speed, and learning and memory in 33 persons with MS who underwent neuropsychological assessments and wore a physical activity monitor for 7 days. Cognitive impairment was greatest in cognitive processing speed. Physical activity was significantly correlated with cognitive processing speed (pr = .35), but not learning and memory (pr = .20), after controlling for sex, age, and education. Researchers should examine exercise training and physical activity effects on cognitive performance, particularly processing speed, in MS.

Influence of spasticity on mobility and balance in persons with multiple sclerosis.

BACKGROUND AND PURPOSE: Spasticity is a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes that presumably affects mobility and balance. This investigation examined the hypothesis that persons with multiple sclerosis (MS) who have spasticity of the lower legs would have more impairment of mobility and balance compared to those without spasticity. METHODS: Participants were 34 ambulatory persons with a definite diagnosis of MS. The expanded disability status scale (EDSS) was used to characterize disability in the study sample. All participants underwent measurements of spasticity in the gastroc-soleus muscles of both legs (modified Ashworth scale), walking speed (timed 25-foot walk), mobility (Timed Up and Go), walking endurance (6-minute walk test), self-reported impact of MS on walking ability (Multiple Sclerosis Walking Scale-12), and balance (Berg Balance Test and Activities-specific Balance Confidence Scale). RESULTS: Fifteen participants had spasticity of the gastroc-soleus muscles based on modified Ashworth scale scores. The spasticity group had lower median EDSS scores indicating greater disability (P=0.03). Mobility and balance were significantly more impaired in the group with spasticity compared to the group without spasticity: timed 25-foot walk (P = 0.02, d = -0.74), Timed Up and Go (P = 0.01, d = -0.84), 6-minute walk test (P < 0.01, d = 1.03), Multiple Sclerosis Walking Scale-12 (P = 0.04, d = -0.76), Berg Balance Test (P = 0.02, d = -0.84) and Activities-specific Balance Confidence Scale (P = 0.04, d = -0.59). DISCUSSION AND CONCLUSION: Spasticity in the gastroc-soleus muscles appears to have negative effect on mobility and balance in persons with MS. The relationship between spasticity and disability in persons with MS requires further exploration.

The First Physical Therapy Summit on Global Health: implications and recommendations for the 21st century.

The First Physical Therapy Summit on Global Health was convened at the 2007 World Confederation for Physical Therapy (WCPT) Congress to vision practice in the 21st century and, in turn, entry-level education and research, as informed by epidemiological indicators, and consistent with evidence-based noninvasive interventions, the hallmark of physical therapy. The Summit and its findings were informed by WHO data and validated through national databases of the countries of the five WCPT regions. The health priorities based on mortality were examined in relation to proportions of physical therapists practicing in the areas of regional priorities and of the curricula in entry-level programs. As a validation check and to contextualize the findings, input from members of the 800 Summit participants was integrated and international consultants refined the recommendations. Lifestyle-related conditions (ischemic heart disease, smoking-related conditions, hypertension, stroke, cancer, and diabetes) were leading causes of premature death across regions. Contemporary definitions of physical therapy support that the profession has a leading role in preventing, reversing, as well as managing lifestyle-related conditions. The proportions of practitioners practicing primarily in these priority areas and of the entry-level curricula based on these priorities were low. The proportions of practitioners in priority areas and entry-level curricula devoted to lifestyle-related conditions warrant being better aligned with the prevalence of these conditions across regions in the 21st century. A focus on clinical competencies associated with effective health education and health behavior change formulates the basis for The Second Physical Therapy Summit on Global Health.

Effects of high-intensity resistance training on strength, mobility, balance, and fatigue in individuals with multiple sclerosis: a randomized controlled trial.

BACKGROUND AND PURPOSE: Resistance exercise via negative, eccentrically induced work (RENEW) has been shown to be associated with improvements in strength, mobility, and balance in multiple clinical populations. However, RENEW has not been reported for individuals with multiple sclerosis (MS). METHODS: Nineteen individuals with MS (8 men, 11 women; age mean = 49 ± 11 years; Expanded Disability Status Scale [EDSS] mean = 5.2 ± 0.9) were randomized into either standard exercise (STAND) or standard exercise and RENEW training (RENEW) for 3×/week for 12 weeks. Outcome measures were lower extremity strength (hip/knee flexion and extension, ankle plantar and dorsiflexion, and the sum of these individual values [sum strength]); Timed Up and Go (TUG), 10-m walk, self-selected pace (TMWSS) and maximal-pace (TMWMP), stair ascent (S-A) and descent (S-D) and 6-Minute Walk Test (6MWT), Berg Balance Scale (BBS), Fatigue Severity Scale (FSS). RESULTS: No significant time effects or interactions were observed for strength, TUG, TMWSS, TMWMP, or 6MWT. However, the mean difference in sum strength in the RENEW group was 38.60 (representing a 15% increase) compared to the sum strength observed in the STAND group with a mean difference of 5.58 (a 2% increase). A significant interaction was observed for S-A, S-D, and BBS as the STAND group improved whereas the RENEW group did not improve in these measures. DISCUSSION AND CONCLUSIONS: Contrary to results in other populations, the addition of eccentric training to standard exercises did not result in significantly greater lower extremity strength gains in this group of individuals with MS. Further this training was not as effective as standard exercise alone in improving balance or the ability to ascend and descend stairs. Following data collection, reassessment of required sample size indicates we were likely underpowered to detect strength differences between groups.

Ambulatory activity in individuals with multiple sclerosis.

BACKGROUND AND PURPOSE: Specific characteristics of physical activity limitations associated with multiple sclerosis (MS) remain unclear. Our purpose was to examine the impact of MS disability on physical activity behaviors involving ambulation. We also explored relationships among ambulatory activity parameters and clinical measures of gait, balance, and fatigue. METHODS: Twenty-one adults with MS participated: 11 without ambulatory limitation (Expanded Disability Status Scale [EDSS] score ≤ 4.5) and 10 with ambulatory limitation (EDSS score > 4.5). Participants wore a step activity monitor for up to 7 days. Daily values were calculated for parameters indicative of (1) overall activity, (2) upper limits of activity output, and (3) activity work-rest cycles. Clinical measures included Multiple Sclerosis Walking Scale, Timed 25-Foot Walk, Timed Up and Go test, 6-Minute Walk, Dynamic Gait Index, Berg Balance Scale, Activities-specific Balance Confidence Scale, and Modified Fatigue Impact Scale. Statistical analyses were conducted using nonparametric tests. RESULTS: Participants without limitation were more active, demonstrated higher upper limits of activity output, and had longer activity bouts than participants with limitation (P < 0.05). Only 1 participant averaged more than 100 steps per minute over a 30-minute period. Of the ambulatory activity parameters, daily step count was most strongly related to gait and balance measures. Of the clinical measures, EDSS and Multiple Sclerosis Walking Scale scores were most strongly related to daily step count. CONCLUSION: Individuals with MS are not necessarily sedentary, but few may achieve recommended daily physical activity levels. Ambulatory activity characteristics revealed new insights into physical activity limitations in MS. The study findings suggest that disability status should direct physical activity interventions.