Drop-out, adherence, and compliance in randomized controlled trials of exercise training in multiple sclerosis: Short report.

We documented reporting and rates of drop-out, adherence, and compliance from 40 randomized controlled trials (RCTs) included in our meta-analysis on safety of exercise training (ET) in MS. We adopted definitions and metrics of adherence and compliance provided by the MoXFo adherence group. Drop-out was reported in 100% of the RCTs and approximated 10% for intervention and control conditions. Adherence and compliance were reported in approximately 50% and 10% of the RCTs, respectively, and approximated 80% and 70%, respectively. Standardized metrics for reporting adherence and compliance are important in future RCTs for understanding the impact on outcomes and translation of research evidence into practice.

Randomized Controlled Trial of the Behavioral Intervention for Physical Activity in Multiple Sclerosis Project: Response Heterogeneity and Predictors of Change.

BACKGROUND: We reported that a social cognitive theory-based (SCT), Internet-delivered behavioral intervention increased device-measured minutes/day of moderate-to-vigorous physical activity (MVPA) over a 6-month period among persons with multiple sclerosis (MS). This paper examined the pattern and predictors of heterogeneity in change for MVPA. Based on previous research, we hypothesized that mild MS disability, fewer MS symptoms, lower baseline MVPA, and positive SCT characteristics (e.g., high exercise self-efficacy) would be associated with greater change in MVPA. METHOD: Persons with MS (N = 318) were randomized into behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions that were administered via Internet websites and supported with behavioral coaching. Demographic, clinical, symptom, behavioral, and SCT data were from before the 6-month period of delivering the conditions, and MVPA data were from before and after the 6-month period. We examined heterogeneity based on waterfall plots, box plots, and the Levene statistic. We identified predictors of MVPA change using bivariate correlation and multiple, linear regression analyses per condition. RESULTS: The Levene statistic indicated statistically significant heterogeneity of variances for MVPA change between conditions (p = .003), and the waterfall plots and box plots indicated greater heterogeneity in MVPA change for the behavioral intervention. MVPA change score was correlated with baseline MVPA (r = - .33 and r = - .34, p = .0004 and p = .0001) in both conditions and walking impairment (r = - .188, p = .047) and race (r = .233, p = .014) in the behavioral intervention condition. The regression analysis indicated that baseline MVPA (Standardized B = - .449, p = .000002), self-reported walking impairment (Standardized B = - .310, p = .0008), and race (Standardized B = .215, p = .012) explained 25.6% of variance in MVPA change for the behavioral intervention condition. CONCLUSION: We provide evidence for walking impairment, baseline MVPA, and race as predictors of the heterogeneity in the pattern of MVPA change with a behavioral intervention.

Arterial stiffness in persons with multiple sclerosis and controls: Does aerobic fitness account for group differences?

Vascular function is worse in multiple sclerosis (MS) than healthy controls perhaps based on differences in aerobic fitness. We compared carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx75) between MS and controls while accounting for aerobic fitness. Aerobic fitness was measured as peak oxygen consumption on a recumbent stepper. cfPWV and AIx75 were measured using applanation tonometry. Persons with MS demonstrated lower aerobic fitness and higher cfPWV, but no difference in AIx75 compared with controls. The difference in cfPWV remained statistically significant after controlling for aerobic fitness, suggesting that arterial stiffness might reflect underlying pathophysiology processes of MS.

Primary results of a phase-III, randomized controlled trial of the Behavioral Intervention for increasing Physical Activity in Multiple Sclerosis project.

BACKGROUND: We undertook a phase-III, randomized controlled trial (RCT) that examined the effectiveness of a behavioral intervention based on social cognitive theory (SCT) and delivered through the Internet using e-learning approaches for immediate and sustained increases in physical activity among persons with multiple sclerosis (MS). METHOD: The study followed a parallel group RCT design. Persons with MS (N = 318) were randomized into either behavioral intervention (n = 159) or attention/social contact control (n = 159) conditions. The conditions were administered over a 6-month period by persons who were uninvolved in screening, recruitment, random assignment, and outcome assessment. There was a 6-month follow-up period without access of conditions. We collected outcome data every 6 months over the 12-month period. The primary outcome was device-measured minutes/day of moderate-to-vigorous physical activity (MVPA). The data analysis involved a modified intent-to-treat approach (i.e. those who received the allocated conditions) using a linear mixed model. RESULTS: There was a significant group by time interaction on the primary outcome of device-measured minutes/day of MVPA (p < 0.005). MVPA was increased immediately after the 6-month period in the behavioral intervention compared with control, and this difference was sustained over the 6-month follow-up. CONCLUSION: This study provides evidence for the effectiveness of a widely scalable approach for increasing MVPA in persons with MS.

The MoXFo initiative - study design: Considerations related to study design and methodology in exercise research for people with multiple sclerosis.

BACKGROUND: Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleiotropic effects, but continued progression of the field requires better future designs and methodologies. OBJECTIVES: This paper outlines the work of the 'Study design and methodology' group of the MoXFo (moving exercise research forward) initiative, and addresses critical aspects and future directions when defining the research question of interest, and subsequently, designing the study and exercise intervention in MS patients. METHODS: The work is based on the formation of an international expert panel formed within the MoXFo initiative. We provide a structured and concise synthesis of exercise-specific MS research challenges and considerations when designing randomized controlled trials (RCTs). RESULTS: Challenges and considerations are presented using the Patient population, Intervention, Comparator, Outcomes, Timing, Setting (PICOTS) framework, thereby forming a new and specific MS exercise PICOTS framework. CONCLUSION: We propose that researchers should carefully consider and align all elements of this MS exercise PICOTS framework when developing future research questions and study designs, ultimately improving the quality of new exercise studies in people with MS.

The MoxFo initiative - outcomes: Outcome measures in studies of exercise training in multiple sclerosis; scoping review of reviews and classification according to the ICF framework.

BACKGROUND: The number of published studies of exercise training in multiple sclerosis (MS) has grown exponentially with increasing numbers of outcomes capturing exercise effects. This has complicated the selection of relevant indicators and interpretation of intervention effects. OBJECTIVES: The Outcomes subgroup of the MoXFo initiative aimed to (1) identify outcome measures and biomarkers in studies of exercise training in MS; (2) systematically map retrieved outcomes to International Classification of Functioning, Disability and Health (ICF) categories; (3) identify gaps where relevant ICF categories have been omitted. METHODS: Electronic databases and registers were searched from 2010 to July 2020 to identify systematic reviews or meta-analyses of controlled trials of exercise training on any outcome in MS. Retrieved outcomes/biomarkers were mapped to the corresponding ICF category. RESULTS: Eighty-one review articles reporting 235 different outcomes were included. The outcomes corresponded to 15 chapters and 45 categories within the ICF. Outcomes mapped primarily to body function (30 categories) and activities and participation (9 categories) components. Few outcomes mapped to body structures (2 categories) or environmental factors (1 category). CONCLUSION: This sets the stage to develop a resource for researchers/clinicians that will aid in the selection of appropriate outcomes/biomarkers when examining exercise effects in MS.

Safety of exercise training in multiple sclerosis: An updated systematic review and meta-analysis.

BACKGROUND: A review of the safety profile of exercise training in multiple sclerosis (MS) has not been conducted since 2013. OBJECTIVE: We undertook a systematic review and meta-analysis of randomised controlled trials (RCTs) of exercise training published since 2013 and quantified estimated population risks of clinical relapse, adverse events (AE) and serious adverse event (SAE). METHODS: Articles reporting safety outcomes from comparisons of exercise training with non-exercise among persons with MS were identified. The risk of bias was established from study's internal validity assessed using Physiotherapy Evidence Database (PEDro). Rates and estimated mean population relative risks (RRs; 95% confidence interval (CI)) of safety outcomes were calculated, and random-effects meta-analysis estimated the mean RR. RESULTS: Forty-six interventions from 40 RCTs (N = 1780) yielded 46, 40 and 39 effects for relapse, AE, adverse effects and SAE, respectively. The mean population RRs ((95% CI), p-value) for relapse, AE and SAE were 0.95 ((0.61, 1.48), p = 0.82), 1.40 ((0.90, 2.19), p = 0.14) and 1.05 ((0.62, 1.80), p = 0.85), respectively. No significant heterogeneity is observed for any outcome. CONCLUSION: In studies that reported safety outcomes, there was no higher risk of relapse, AE, adverse effects or SAE for exercise training than the comparator. Exercise training may be promoted as safe and beneficial to persons with MS.

Towards conceptual convergence: A systematic review of psychological resilience in family caregivers of persons living with chronic neurological conditions.

BACKGROUND: The demand for family caregiving in persons with chronic neurological conditions (CNCs) is increasing. Psychological resilience may empower and protect caregivers in their role. Thus, a synthesis of resilience evidence within this specific population is warranted. AIM: In this systematic review we aimed to: (1) examine the origins and conceptualizations of resilience; (2) summarize current resilience measurement tools; and (3) synthesize correlates, predictors and outcomes of resilience in family caregivers of persons with CNCs. DESIGN: We sourced English articles published up to July 2020 across five databases using search terms involving CNCs, family caregivers and resilience. RESULTS: A total of 50 studies were retained. Nearly half (44%) of the studies used trait-based resilience definitions, while about one third (36%) used process-based definitions. Twelve different resilience scales were used, revealing mostly moderate to high-resilience levels. Findings confirmed that resilience is related to multiple indicators of healthy functioning (e.g., quality of life, social support, positive coping), as it buffers against negative outcomes of burden and distress. Discordance relating to the interaction between resilience and demographic, sociocultural and environmental factors was apparent. CONCLUSIONS: Incongruity remains with respect to how resilience is defined and assessed, despite consistent definitional concepts of healthy adaptation and equilibrium. The array of implications of resilience for well-being confirms the potential for resilience to be leveraged within caregiver health promotion initiatives via policy and practice. PATIENT OR PUBLIC CONTRIBUTION: The findings may inform future recommendations for researchers and practitioners to develop high-quality resilience-building interventions and programmes to better mobilize and support this vulnerable group.

Do subcortical gray matter volumes and aerobic capacity account for cognitive-motor coupling in multiple sclerosis?

BACKGROUND: There is evidence of cognitive-motor coupling in multiple sclerosis (MS) such that the slowing of cognitive processing speed correlates with the worsening of walking speed and endurance. OBJECTIVE: The current study first established the presence of cognitive-motor coupling and second examined the possibility that volumes of subcortical gray matter (SGM) structures and aerobic capacity might explain the coupling of cognitive and motor functions in persons with MS. METHODS: We included data from 62 persons with clinically definite MS who underwent assessments of cognitive processing speed, walking performance, and aerobic capacity, and completed magnetic resonance imaging (MRI) within 7 days of the aforementioned assessments. RESULTS: The strong correlations between cognitive processing speed and walking performance were attenuated in magnitude and not statistically significant when controlling for aerobic capacity alone and aerobic capacity and SGM volumes together. The associations between cognitive processing speed and walking performance remained statistically significant when controlling for SGM volumes alone. CONCLUSION: Aerobic capacity may be an important target for neurorehabilitation-based approaches for managing co-occurring cognitive and motor dysfunction in MS.

Exercise and lifestyle physical activity recommendations for people with multiple sclerosis throughout the disease course.

OBJECTIVES: To provide clinicians who treat multiple sclerosis (MS) patients with evidence-based or expert opinion-based recommendations for promoting exercise and lifestyle physical activity across disability levels. METHODS: The National MS Society ("Society") convened clinical and research experts in the fields of MS, exercise, rehabilitation, and physical activity to (1) reach consensus on optimal exercise and lifestyle physical activity recommendations for individuals with MS at disability levels 0-9.0 on the Expanded Disability Status Scale (EDSS) and (2) identify and address barriers/facilitators for participation. RECOMMENDATIONS: Based on current evidence and expert opinion, the Society makes the following recommendations, endorsed by the Consortium of Multiple Sclerosis Centers:Healthcare providers should endorse and promote the benefits/safety of exercise and lifestyle physical activity for every person with MS.Early evaluation by a physical or occupational therapist or exercise or sport scientist, experienced in MS (hereafter referred to as "specialists"), is recommended to establish an individualized exercise and/or lifestyle physical activity plan.Taking into account comorbidities and symptom fluctuations, healthcare providers should encourage ⩾150 min/week of exercise and/or ⩾150 min/week of lifestyle physical activity.Progress toward these targets should be gradual, based on the person's abilities, preferences, and safety.If disability increases and exercise/physical activity becomes more challenging, referrals to specialists are essential to ensure safe and appropriate prescriptions.When physical mobility is very limited, exercise should be facilitated by a trained assistant.

Moving exercise research in multiple sclerosis forward (the MoXFo initiative): Developing consensus statements for research.

Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and accelerate discovery, a new international partnership of MS-related experts in exercise has emerged with the goal of advancing the research agenda. As a first step, the expert panel met in May 2018 and identified the most urgent areas for moving the field forward, and discussed the framework for such a process. This led to identification of five themes, namely "Definitions and terminology," "Study methodology," "Reporting and outcomes," "Adherence to exercise," and "Mechanisms of action." Based on the identified themes, five expert groups have been formed, that will further (a) outline the challenges per theme and (b) provide recommendations for moving forward. We aim to involve and collaborate with people with MS/MS organizations (e.g. Multiple Sclerosis International Federation (MSIF) and European Multiple Sclerosis Platform (EMSP)) in all of these five themes. The generation of this thematic framework with multi-expert perspectives can bolster the quality and scope of exercise studies in MS that may ultimately improve the daily lives of people with MS.

Sedentary behaviour in people with multiple sclerosis: Is it time to stand up against MS?

Historically, people with multiple sclerosis (MS) have been considered sedentary, although the actual scientific study of sedentary behaviour in MS did not originate until 2011. Sedentary behaviour, which is conceptually distinct from physical inactivity, is defined as any waking activity characterised by an energy expenditure ⩽ 1.5 metabolic equivalents and in a sitting or reclining posture. In the general population, the volume of sitting time is associated with increased risks of morbidity and mortality, independent of physical activity, and has been suggested to carry a greater risk of mortality than smoking behaviour. There are many symptoms of MS (e.g. mobility disability and fatigue) that could increase the prevalence of sedentary behaviour, and sedentary behaviour may have considerable implications for the development of comorbid conditions prevalent in MS. This review provides a summary of the rates, correlates, consequences and interventions attempting to reduce sedentary behaviour in MS. We provide a research agenda that guides future research on sedentary behaviour in MS. This paper provides a clarion call that it is time to 'stand up against MS'.

Body Mass Index Underestimates Adiposity in Persons With Multiple Sclerosis.

OBJECTIVES: To examine the relation between body mass index (BMI) and adiposity assessed by dual-energy x-ray absorptiometry in persons with multiple sclerosis (MS) and non-MS controls as well as to determine the accuracy of standard and alternate BMI thresholds for obesity. DESIGN: Cross-sectional. SETTING: University research laboratory. PARTICIPANTS: The sample included persons with MS (n=235) and controls (n=53) (N=288). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Main outcome measures included BMI, whole body soft tissue composition (ie, percent body fat [%BF], fat mass, and lean soft tissue mass), bone mineral content, and bone mineral density. RESULTS: We observed significant strong associations between BMI and sex-specific %BF in persons with MS and non-MS controls, and BMI explained ∼40% of the variance in %BF in both MS and control samples. Receiver operating characteristic curve analyses indicated that the standard BMI threshold for obesity (ie, 30kg/m(2)) had excellent specificity (93%-100%) but poor sensitivity (37%-44%) in persons with MS and non-MS controls. The BMI threshold that best identified %BF-defined obesity was 24.7kg/m(2) in the MS sample and 25.1kg/m(2) in the control sample. CONCLUSIONS: We determined a strong association between BMI and adiposity; however, the current BMI threshold for classifying obesity underestimates true adiposity in persons with MS. A similar relation was observed between BMI and obesity in non-MS controls. The non-MS sample included primarily middle-aged women, and similar BMI-%BF misclassifications have been reported in these samples.

Effect of Exercise Training on Fitness in Multiple Sclerosis: A Meta-Analysis.

OBJECTIVE: To provide a quantitative synthesis of randomized controlled trials (RCTs) examining the effect of exercise training on muscular and cardiorespiratory fitness in persons with multiple sclerosis (MS). DATA SOURCES: Three electronic databases, PubMed, Google Scholar, and Web of Science, were searched for all relevant articles published up until October 2014. STUDY SELECTION: Keywords included exercise or aerobic or strength or resistance training or cardiorespiratory and multiple sclerosis. Trials examining the effect of exercise training on muscular and/or cardiorespiratory fitness parameters were included. DATA EXTRACTION: The initial search yielded 1501 articles; of these, 62 were reviewed in detail, and 20 RCTs met the inclusion criteria and provided enough data to compute effect sizes (ESs) (Cohen d). The meta-analyses was conducted using a random effects model to compute the overall or mean ES per fitness parameter. DATA SYNTHESIS: The mean ES was .27 (SE=.05; 95% confidence interval [CI], .17-.38; z=5.05; P<.001) for muscular fitness outcomes and .47 (SE=.09; 95% CI, .30-.65; z=5.4; P<.001) for cardiorespiratory fitness outcomes. The weighted mean ES was not heterogeneous for muscular (Q13=11.09, P=.60, I(2)=.00) or cardiorespiratory (Q9=7.83, P=.55, I(2)=.00) fitness outcomes. CONCLUSIONS: The cumulative evidence supports that exercise training is associated with changes in muscular (small in magnitude) and cardiorespiratory (moderate in magnitude) fitness outcomes in persons with MS. Such an indication of magnitude is important for clinical research and practice by providing an evidence-based estimate of the actual benefit that exercise training confers on physiological fitness.

Physical Fitness Assessment Across the Disability Spectrum in Persons With Multiple Sclerosis: A Comparison of Testing Modalities.

BACKGROUND AND PURPOSE: Appropriate assessment of physical fitness (ie, aerobic capacity and muscular strength) is necessary for the design and evaluation of exercise training in multiple sclerosis (MS). However, this is challenging in persons with substantial disability, because of physical inaccessibility and insensitivity of certain exercise testing modalities. This study compared different methods of measuring cardiorespiratory (arm ergometer vs recumbent stepper) and muscular (hand-held dynamometry vs computerized dynamometry) fitness across the MS disability spectrum. Associations between physical fitness and other measures that represented all domains of the International Classification of Functioning, Disability and Health (ICF) were also examined. METHODS: Sixty-four participants with MS completed 2 symptom-limited cardiorespiratory fitness and muscular strength tests. We also assessed disability, cognition, fatigue, walking speed and endurance, health-related quality of life, and activities of daily living. RESULTS: Across all levels of disability, peak aerobic capacity assessed by recumbent stepping was higher compared with arm ergometry (P < 0.001). Peak torque of the knee extensors and knee flexors was significantly higher assessed by computerized dynamometry compared with hand-held dynamometry (P < 0.001). Aerobic capacity and peak torque decreased as a function of increasing disability (P < 0.001). Significant, moderate to strong correlations were observed between the physical fitness measures and measures representing all domains of the ICF, irrespective of the fitness testing mode. DISCUSSION AND CONCLUSIONS: Overall, peak physical capacity was higher when assessed by recumbent stepping and computerized dynamometry. The assessment and prescription of exercise in MS should be based on these modalities to provide the most appropriate stimulus for exercise training adaptations. There continues to be an important association between physical fitness and other measures that represent all domains of the ICF, regardless of fitness assessment mode.Video Abstract available for additional insights from the authors (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/JNPT/A109).

Impairment and disability in persons with MS: do functional performance or functional limitations matter?

Persons with multiple sclerosis (MS) often demonstrate impairment in cardiorespiratory and musculoskeletal systems that may be associated with functional performance, functional limitations, and disability limitations. This study examined such relationships in persons with MS using Nagi's disablement model and its subsequent conceptual modifications. The sample included 63 persons with MS (75% relapsing-remitting MS, median EDSS = 4.0, and mean MS duration = 13.1 years) who underwent measurements of aerobic fitness and muscular strength (i.e. impairment), functional performance, functional limitations, and disability limitations. The data were primarily examined using path analysis in Mplus 7.0. Our final model provided an excellent fit for the data (χ² = 0.67, df = 3, p = 0.88, SRMR = 0.01, and CFI = 1.00). The final model indicated that aerobic fitness and muscular strength were indirectly associated with disability limitations in persons with MS through a pathway that included functional limitations (indirect path coefficients of 0.29 and 0.20, respectively), but not functional performance. Aerobic fitness and muscular strength may be the important targets of exercise training interventions for improving perceived functional limitations and disability limitations in persons with MS.

Internet-delivered lifestyle physical activity intervention improves body composition in multiple sclerosis: preliminary evidence from a randomized controlled trial.

OBJECTIVE: To examine the efficacy of a physical activity behavioral intervention for improving outcomes of body composition in persons with multiple sclerosis (MS). DESIGN: Secondary analysis of data from a randomized controlled trial. SETTING: University research laboratory. PARTICIPANTS: Ambulatory persons with MS (N=82). INTERVENTION: A 6-month, internet-delivered physical activity behavioral intervention designed to increase lifestyle physical activity, primarily walking. The behavioral intervention was based on principles of social cognitive theory. MAIN OUTCOME MEASURES: Whole-body bone mineral content (BMC), bone mineral density (BMD), and soft tissue composition, using dual-energy x-ray absorptiometry. RESULTS: There were no significant differences between conditions posttrial on body composition outcomes using the adjusted critical value (P<.008). There was a significant effect of the intervention on whole-body BMC (P=.04, ω(2)<.001) and BMD (P=.01, ω(2)=.003) using the unadjusted critical value (P<.05). The effect of the intervention on percent body fat (P=.09, ω(2)=.001) and whole-body fat mass (P=.05, ω(2)=.003) approached significance using unadjusted criteria. There was not a significant effect on whole-body lean soft tissue (P=.28, ω(2)<.001) or body mass index (P=.86, ω(2)<.001). CONCLUSIONS: Our results provide preliminary evidence that an internet-delivered lifestyle physical activity intervention might improve bone health and body composition in MS. Such findings are important considering that physical activity is a modifiable behavior with the potential to confer long-term benefits for the prevention and management of fracture risk and comorbidities among those with MS.

Cognitive motor interference during walking in multiple sclerosis using an alternate-letter alphabet task.

OBJECTIVE: To examine cognitive motor interference (CMI) during walking using a simple, standardized, and well-refined alphabet dual-task (DT) paradigm in individuals with multiple sclerosis (MS) in whom cognitive and walking impairment often co-occur. DESIGN: A single time point, cross-sectional study. SETTING: A university clinical laboratory. PARTICIPANTS: Individuals with MS (N=61; mean age ± SD, 50.8±9.3 y) performed 4 walking trials over a 4.6-m walkway to determine gait parameters. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait parameters were assessed over 4 walking trials. The first 2 walks involved the single task (ST) of walking only; the second 2 walks involved participants performing the DT of reciting alternate letters of the alphabet while walking. The gait parameters recorded during the ST and DT walks were used to compute a dual-task cost (DTC) of walking (% change in gait parameter between ST and DT walks) as a metric of CMI. RESULTS: Our multivariate analysis with univariate follow-ups indicated CMI during walking based on slower velocity (ηp(2)=.59; F=84.6; P<.001) and cadence (ηp(2)=.46; F=51.6; P<.001), shorter step length (ηp(2)=.38; F=36; P<.001), and increased step time (ηp(2)=.34; F=31; P<.001) and double-support time (ηp(2)=.31; F=27.3; P<.001) in DT versus ST conditions. The DTC of walking for the gait parameters was not correlated with clinical (disability, disease duration) and demographic (eg, education, age) factors (all |r|≤.240). CONCLUSIONS: The alphabet DT paradigm is easily administered and well refined. We highlight its ability and acceptability to determine CMI during walking in people with MS, independent of disease status.

Validity of minimal clinically important difference values for the multiple sclerosis walking scale-12?

BACKGROUND AND OBJECTIVE: Minimal clinically important difference (MCID) values of 4 and 6 points have been proposed for interpreting meaningful change in Multiple Sclerosis Walking Scale-12 (MSWS-12) scores. This study examined the validity of those MCID values based on capturing corresponding changes in other walking outcomes in persons with multiple sclerosis (MS). METHODS: On 2 occasions separated by 6 months, 82 persons with MS completed the MSWS-12, timed 25-ft walk (T25FW), 6-min walk (6MW), and gait analysis, and then wore an accelerometer over a 7-day period. We generated change scores for the MSWS-12 and formed groups of stable, worsened, and improved perceived walking based on both 4- and 6-point changes. The groups were compared for corresponding changes in other walking measures over time using mixed-model ANOVAs. RESULTS: The mixed-model ANOVAs did not identify statistically significant group-by-time interactions on the T25FW (p = 0.98 and p = 0.67), the 6MW (p = 0.89 and p = 0.72), gait (p = 0.54 and p = 0.21), or accelerometry (p = 0.40 and p = 0.68) for MCID values of 4- or 6-point changes in MSWS-12 scores. CONCLUSIONS: We did not confirm that MCID values of 4 and 6 points for the MSWS-12 correspond with changes in performance, gait, and free-living assessments of walking in MS.