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.

Background: Many different walking capacity test formats are being used. It is unclear whether walking speed, obtained from short tests, and walking distance, obtained from long tests, provide different clinical information. Objectives: To determine the differential effect of various short and long walk test formats on gait velocity, and the actual relationship between walking speed and walking distance in multiple sclerosis (MS) patients with diverse ambulation status. Methods: A cross-sectional multicentre study design was applied. Ambulatory MS patients (Expanded Disability Status Scale (EDSS) 0–6.5; n = 189) were tested at 11 sites. Short tests consisted of the Timed 25-Foot Walk (static start, fastest speed) and 10-Metre Walk Test (dynamic start, usual and fastest speed). Long tests consisted of the 2- and 6-Minute Walk Tests (fastest speed). Subjects were divided into mild (EDSS 0–4; n = 99) or moderate (EDSS 4.5–6.5; n = 79) disability subgroups. Results: In both subgroups, the start protocol, instructed pace and length of test led to significantly different gait velocities. Fastest walking speed and 6-Minute walking distance showed the strongest correlation ( R² = 0.78 in mild and R² = 0.81 in moderate MS; p < 0.01). Short tests’ relative estimation errors for 6-Minute walking distance were 8–12% in mildly and 15–16% in moderately affected subjects. Based on the 2-Minute Walk Test, estimation errors significantly reduced to approximately 5% in both subgroups. Conclusions: A single short test format at fastest speed accurately describes an MS patient’s general walking capacity. For intervention studies, a long test is to be considered. We propose the Timed 25-Foot Walk and 2-Minute Walk Test as standards. Further research on responsiveness is needed.

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 (DWI_6-1) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify participants into 4 subgroups: (1) DWI_6-1[≥5%], (2) DWI_6-1[5%; –5%], (3) DWI_6-1[–5%; > –15%], and (4) DWI_6-1[≤−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 DWI_6-1 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 (DWI_6-1[≤−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 DWI_6-1 ( 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.

Purpose The aim of this study was to compare the effect of four different programmes on spiroergometric, spirometric and clinical parameters in multiple sclerosis (MS) patients. Methods One hundred and twelve MS patients were divided into four groups. The first group underwent neurophysiologically based physiotherapy, the second aerobic training, the third combined therapy (neurophysiologically based physiotherapy and aerobic training) and the fourth did not change any habits. Seventeen patients did not finish the study. Patients were examined on impairment (Expanded Disability Status Scale), disability (Barthel Index), handicap (Environment Status Scale), quality of life (Multiple Sclerosis Quality of Life), fatigue (Modified Fatigue Impact Scale), depression (Beck Depression Inventory Score), respiratory function (spirometric parameters on spirometry) and physical fitness (spiroergometric parameters on a bicycle ergometer). Results The patients who participated in one of our training programmes showed a significant improvement of the examined parameters in comparison to those who did not change their present habits. Each of the four training programmes had a different impact on the parameters, which means that each of them had a different effect. The neurophysiologically based physiotherapy had the greatest impact on impairment, and the aerobic training on spirometric and spiroergometric parameters. All methods (the neurophysiologically based physiotherapy, the aerobic training and the combined programme) had an impact on fatigue.

Objective To determine responsiveness of functional mobility measures, and provide reference values for clinically meaningful improvements, according to disability level, in persons with multiple sclerosis (pwMS) in response to physical rehabilitation. Methods Thirteen mobility measures (clinician- and patient-reported) were assessed before and after rehabilitation in 191 pwMS from 17 international centers (European and United States). Combined anchor- and distribution-based methods were used. A global rating of change scale, from patients9 and therapists9 perspective, served as external criteria when determining the area under the receiver operating characteristic curve (AUC), the minimally important change (MIC), and the smallest real change (SRC). Patients were stratified into 2 subgroups based on disability level (Expanded Disability Status Scale score ≤4 [n = 72], >4 [n = 119]). Results The Multiple Sclerosis Walking Scale–12, physical subscale of the Multiple Sclerosis Impact Scale–29 (especially for the mildly disabled pwMS), Rivermead Mobility Index, and 5-repetition sit-to-stand test (especially for the moderately to severely disabled pwMS) were the most sensitive measures in detecting improvements in mobility. Findings were determined once the AUC (95% confidence interval) was above 0.5, MIC was greater than SRC, and results were comparable from the patient and therapist perspective. Conclusions Responsiveness, clinically meaningful improvement, and real changes of frequently used mobility measures were calculated, showing great heterogeneity, and were dependent on disability level in pwMS.