Ilse Baert

Responsiveness and Clinically Meaningful Improvement, According to Disability Level, of Five Walking Measures After Rehabilitation in Multiple Sclerosis A European Multicenter Study

Background. Evaluation of treatment effects on walking requires appropriate and responsive outcome measures. Objectives. To determine responsiveness of 5 walking measures and provide reference values for clinically meaningful improvements, according to disability level, in persons with multiple sclerosis (pwMS). Methods. Walking tests were measured pre- and postrehabilitation in 290 pwMS from 17 European centers. Combined anchor- and distribution-based methods determined responsiveness of objective short and long walking capacity tests (Timed 25-Foot Walk [T25FW] and 2- and 6-Minute Walk Tests [2MWT and 6MWT] and of the patient-reported Multiple Sclerosis Walking Scale–12 [MSWS-12]). A global rating of change scale, from patients’ and therapists’ perspective, was used as external criteria to determine the area under the receiver operating characteristic curve (AUC), minimally important change (MIC), and smallest real change (SRC). Patients were stratified into disability subgroups (Expanded Disability Status Scale score ≤4 [n = 98], >4 [n = 186]). Results. MSWS-12, 2MWT, and 6MWT were more responsive (AUC 0.64-0.73) than T25FW (0.50-0.63), especially in moderate to severely disabled pwMS. Clinically meaningful changes (MICs) from patient and therapist perspective were −10.4 and −11.4 for MSWS-12 (P < .01), 9.6 m and 6.8 m for 2MWT (P < .05), and 21.6 m (P < .05) and 9.1 m (P = .3) for 6MWT. In subgroups, MIC was significant from patient perspective for 2MWT (10.8 m) and from therapist perspective for MSWS-12 (−10.7) in mildly disabled pwMS. In moderate to severely disabled pwMS, MIC was significant for MSWS-12 (−14.1 and −11.9). Conclusions. Long walking tests and patient-reported MSWS-12 were more appropriate than short walking tests in detecting clinically meaningful improvement after physical rehabilitation, particularly the MSWS-12 for moderate to severely disabled pwMS.

Upper Limb Assessment in Multiple Sclerosis: A Systematic Review of Outcome Measures and their Psychometric Properties

OBJECTIVE To provide an overview of applied upper limb outcome measures in multiple sclerosis (MS) according to the International Classification of Functioning, Disability and Health (ICF) levels and to review their psychometric properties in MS. DATA SOURCES PubMed and Web of Knowledge. STUDY SELECTION Articles published until June 2013 were selected when written in English, published in the last 25 years, peer reviewed, including >5 persons with MS, and including standardized clinical upper limb outcome measures. Included articles were screened based on title/abstract and full text by 2 independent reviewers. In case of doubt, feedback from a third independent reviewer was obtained. Additionally, references lists were checked for relevant articles. Of the articles, 109 met the selection criteria and were included for data extraction. DATA EXTRACTION All reported clinical upper limb outcome measures were extracted from the included studies and classified according to the ICF levels by 2 independent reviewers. In addition, available psychometric properties (reliability, validity, responsiveness) in MS were summarized and discussed. DATA SYNTHESIS A diversity of outcome measures assessing impairments on the body functions and structures level (n=33), upper limb capacity (n=11), and performance (n=8) on the activity level were extracted from 109 articles. Hand grip strength and the nine-hole peg test (NHPT) were the most frequently used outcome measures. However, multiple outcome measures are necessary to encapsulate the multidimensional character of the upper limb function. The psychometric properties were insufficiently documented for most of the outcome measures, except for the NHPT. CONCLUSIONS The results of this review may help with the selection of appropriate outcome measures and may guide future research regarding the psychometric properties in MS.

Within-day variability on short and long walking tests in persons with multiple sclerosis

OBJECTIVE To compare within-day variability of short (10 m walking test at usual and fastest speed; 10MWT) and long (2 and 6-minute walking test; 2MWT/6MWT) tests in persons with multiple sclerosis. DESIGN Observational study. SETTING MS rehabilitation and research centers in Europe and US within RIMS (European network for best practice and research in MS rehabilitation). SUBJECTS Ambulatory persons with MS (Expanded Disability Status Scale 0-6.5). INTERVENTION Subjects of different centers performed walking tests at 3 time points during a single day. MAIN MEASURES 10MWT, 2MWT and 6MWT at fastest speed and 10MWT at usual speed. Ninety-five percent limits of agreement were computed using a random effects model with individual pwMS as random effect. Following this model, retest scores are with 95% certainty within these limits of baseline scores. RESULTS In 102 subjects, within-day variability was constant in absolute units for the 10MWT, 2MWT and 6MWT at fastest speed (+/-0.26, 0.16 and 0.15m/s respectively, corresponding to +/-19.2m and +/-54 m for the 2MWT and 6MWT) independent on the severity of ambulatory dysfunction. This implies a greater relative variability with increasing disability level, often above 20% depending on the applied test. The relative within-day variability of the 10MWT at usual speed was +/-31% independent of ambulatory function. CONCLUSIONS Absolute values of within-day variability on walking tests at fastest speed were independent of disability level and greater with short compared to long walking tests. Relative within-day variability remained overall constant when measured at usual speed.

Prevalence of Walking-Related Motor Fatigue in Persons With Multiple Sclerosis Decline in Walking Distance Induced by the 6-Minute Walk Test

Objective. To investigate the individual occurrence of walking-related motor fatigue in persons with multiple sclerosis (PwMS), according to disability level and disease phenotype. Study design. This was a cross-sectional, multinational study. Participants. They were 208 PwMS from 11 centers with Expanded Disability Status Scale (EDSS) scores up to 6.5. Methods. The percentage change in distance walked (distance walked index, DWI) was calculated between minute 6 and 1 (DWI6-1) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify participants into 4 subgroups: (1) DWI6-1[≥5%], (2) DWI6-1[5%; –5%], (3) DWI6-1[–5%; > –15%], and (4) DWI6-1[≤−15%]. The latter group was labeled as having walking-related motor fatigue. PwMS were stratified into 5 subgroups based on the EDSS (0-2.5, 3-4, 4.5-5.5, 6, 6.5) and 3 subgroups based on MS phenotype (relapsing remitting [RR], primary progressive [PP], and secondary progressive [SP]). Results. The DWI6-1 was ≥5% in 16 PwMS (7.7%), between 5% and −5% in 70 PwMS (33.6%), between −5% and −15% in 58 PwMS (24%), and ≤−15% in 64 PwMS (30.8%). The prevalence of walking-related motor fatigue (DWI6-1[≤−15%]) was significantly higher among the progressive phenotype (PP = 50% and SP = 39%; RR = 15.6%) and PwMS with higher disability level (EDSS 4.5-5.5 = 48.3%, 6 = 46.3% and 6.5 = 51.5%, compared with EDSS 0-2.5 = 7.8% and 3-4 = 16.7%; P < .05). Stepwise multiple regression analysis indicated that EDSS, but not MS phenotype, explained a significant part of the variance in DWI6-1 (R2 = 0.086; P < .001). Conclusion. More than one-third of PwMS showed walking-related motor fatigue during the 6MWT, with its prevalence greatest in more disabled persons (up to 51%) and in those with progressive MS phenotype (up to 50%). Identification of walking-related motor fatigue may lead to better-tailored interventions.

Effects of an 1-day education program on physical functioning, activity and quality of life in community living persons with multiple sclerosis.

BACKGROUND Persons with MS (pwMS) in the community show reduced physical activity while studies demonstrated beneficial effects of exercise therapy in supervised settings. OBJECTIVE This study investigated, in pwMS living in the community, the effects of a 1-day education program about exercises and sports, on physical activity behavior and related outcome measures as self-efficacy, perceived walking ability, fatigue, perceived impact of MS and quality of life. METHODS PwMS attended an education day with theoretical and practical sessions that was organized by the Flemish MS Society and professional exercise experts. Forty-two participants immediately completed questionnaires as well as after three and six months. Overall disability and physical activity level were measured using PDSS (patient determined disease steps) and PASIPD (Physical Activity Scale for Individuals with Physical Disabilities) respectively. Other outcomes were the ESES, MSWS-12, MFIS, MSIS-29 and SF-36. Analyses of variance were performed in groups distinguished by self-reported disability level (PDDS ≤1; n = 24 and PDSS >1; n = 18). RESULTS Groups differed significantly for perceived walking ability (PDDS,MSWS-12) and physical related-domains of MSIS-29 and SF-36, but not PASIPD. A trend towards significant group*time interaction effect was found for the PASIPD indicating, at 3 and 6 months, increased physical activity in the subgroup PDDS ≤1. For the MSIS-29, a significant time effect was found with reduced impact being largest for the more disabled group at 6 months. No changes were found in other outcome measures. CONCLUSION An one-day education program had, depending on perceived disability level, some long-standing effects on physical activity and perceived impact of MS.

Performed and perceived walking ability in relation to the Expanded Disability Status Scale in persons with multiple sclerosis

BACKGROUND The severity of walking impairment in persons with multiple sclerosis (pwMS) at different levels on the expanded disability status scale (EDSS) is unclear. Furthermore, it is unclear if the EDSS is differently related to performed- and perceived walking capacity tests. AIMS To quantify walking impairment and perceived impact of MS on walking according to EDSS scores and to examine the relations between these parameters in pwMS. METHODS EDSS was collected by neurologists and walking was assessed by the timed 25ft walk test (T25FWT), two minute walk test (2MWT), six minute walk test (6MWT) and the 12-item MS walking scale (MSWS-12) in 474 PwMS with mild (EDSS 1-4: n=200) to moderate (EDSS 4.5-6.5: n=274) MS. Magnitude of walking impairment was calculated and related to EDSS. RESULTS Compared to predicted values in healthy controls, walking speed was reduced by 41.5±25.8% in the 6MWT for the total MS group and by 21.8±20.2% and 55.8±19.1% in the mild and moderate MS subgroups, respectively. The EDSS score showed the strongest relationship to the 2MWT and the 6MWT in the total MS group (r=-0.76, p<0.0001), to the MSWS-12 score in the mild MS group (r=0.56, p<0.0001), and to the 2MWT in the moderate MS group (r=-0.50, p<0.0001). CONCLUSION In pwMS (EDSS scores 1-6.5), walking speed is on average reduced by ~40% when compared to predicted values in healthy controls, and impairments are already present at early disease stages, suggesting early initiation of rehabilitation. The 2MWT and 6MWT show the strongest relationship to EDSS, but the MSWS-12 identify impairments more gradually at low EDSS scores.

Physical therapy in multiple sclerosis differs across Europe: Information regarding an ongoing study:

The survey is supported by a grant from RIMS, an educational grant from Novartis Pharma AG, 260045/SVV/2014 and PRVOUK P34.

Feasibility of an International Multiple Sclerosis Rehabilitation Data Repository: Perceived Challenges and Motivators for Sharing Data

Background Multiple sclerosis (MS) rehabilitation evidence is limited due to methodological factors, which may be addressed by a data repository. We describe the perceived challenges of, motivators for, interest in participating in, and key features of an international MS rehabilitation data repository. Methods A multimethod sequential investigation was performed with the results of two focus groups, using nominal group technique, and study aims informing the development of an online questionnaire. Percentage agreement and key quotations illustrated questionnaire findings. Subgroup comparisons were made between clinicians and researchers and between participants in North America and Europe. Results Rehabilitation professionals from 25 countries participated (focus groups: n = 21; questionnaire: n = 166). The top ten challenges (C) and motivators (M) identified by the focus groups were database control/management (C); ethical/legal concerns (C); data quality (C); time, effort, and cost (C); best practice (M); uniformity (C); sustainability (C); deeper analysis (M); collaboration (M); and identifying research needs (M). Percentage agreement with questionnaire statements regarding challenges to, motivators for, interest in, and key features of a successful repository was at least 80%, 85%, 72%, and 83%, respectively, across each group of statements. Questionnaire subgroup analysis revealed a few differences (P < .05), including that clinicians more strongly identified with improving best practice as a motivator. Conclusions Findings support clinician and researcher interest in and potential for success of an international MS rehabilitation data repository if prioritized challenges and motivators are addressed and key features are included.

Need for differentiation of real and clinical important change in research on responsiveness of walking outcome measures in multiple sclerosis

Knowledge of the psychometric properties of outcome measures is of great importance when selecting for clinical practice or research. Responsiveness is particularly important for the correct interpretation of change scores in intervention trials regardless of the intervention type (e.g. drug or rehabilitation). MSJ has recently published two papers that examined the responsiveness of walking and mobility outcome measures in persons with multiple sclerosis, followed for 6 months1 and 2 years,2 respectively. Statistical analyses on responsiveness data are typically divided into distribution and anchor-based methods, the latter comparing the change scores of the outcome measures in relation to external indicators of important change. Indicators can, for instance, be self-reported change of patients and/or clinicians or can include an objective measure such as change in Expanded Disability Status Scale (EDSS). The paper of Learmonth et al. (2013) aims to measure clinically meaningful change in addition to reliability and precision in persons with various degrees of disability.1 However, the statistical outcomes they report are the standard error of measurement (SEM) and minimal detectable change (MDC; limits of change with 95% certainty), both values of measurement error based on the distribution of the sample. As the authors state, a change above these values is considered a real change surpassing the measurement error, but we do not know whether this change is clinically important. The paper of Learmonth et al. does not include an anchor-based method during the 6 months of observation, and therefore, no clinical meaningful change was established. In fact, relative and absolute reliability was shown. Also, test–retest reliability measures were applied over a 6 month observational period, which is unusual when purely investigating test performance variance over sessions. One would expect that part of the sample would experience progression and/or relapses, increasing noise in reliability measures, but the study reported no change in the SR-EDSS.3 In conclusion, the results from the study of Learmonth et al. (2013) are valuable for documentation of the measurement error of the walking measures, but the MDC values are inappropriately advocated as clinical meaningful change.

Is the impact of fatigue related to walking capacity and perceived ability in persons with multiple sclerosis? A multicenter study

BACKGROUND The relationship between fatigue impact and walking capacity and perceived ability in patients with multiple sclerosis (MS) is inconclusive in the existing literature. A better understanding might guide new treatment avenues for fatigue and/or walking capacity in patients with MS. OBJECTIVE To investigate the relationship between the subjective impact of fatigue and objective walking capacity as well as subjective walking ability in MS patients. METHODS A cross-sectional multicenter study design was applied. Ambulatory MS patients (n = 189, age: 47.6 ± 10.5 years; gender: 115/74 women/men; Expanded Disability Status Scale (EDSS): 4.1 ± 1.8 [range: 0-6.5]) were tested at 11 sites. Objective tests of walking capacity included short walking tests (Timed 25-Foot Walk (T25FW), 10-Metre Walk Test (10mWT) at usual and fastest speed and the timed up and go (TUG)), and long walking tests (2- and 6-Minute Walk Tests (MWT). Subjective walking ability was tested applying the Multiple Sclerosis Walking Scale-12 (MSWS-12). Fatigue impact was measured by the self-reported modified fatigue impact scale (MFIS) consisting of a total score (MFIStotal) and three subscales (MFISphysical, MFIScognitive and MFISpsychosocial). Uni- and multivariate regression analysis were performed to evaluate the relation between walking and fatigue impact. RESULTS MFIStotal was negatively related with long (6MWT, r = -0.14, p = 0.05) and short composite (TUG, r = -0.22, p = 0.003) walking measures. MFISphysical showed a significant albeit weak relationship to walking speed in all walking capacity tests (r = -0.22 to -0.33, p < .0001), which persisted in the multivariate linear regression analysis. Subjective walking ability (MSWS-12) was related to MFIStotal (r = 0.49, p < 0.0001), as well as to all other subscales of MFIS (r = 0.24-0.63, p < 0.001), showing stronger relationships than objective measures of walking. CONCLUSIONS The physical impact of fatigue is weakly related to objective walking capacity, while general, physical, cognitive and psychosocial fatigue impact are weakly to moderately related to subjective walking ability, when analysed in a large heterogeneous sample of MS patients.