Ellen Jensen

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.

Validity and variability of the 5-repetition sit-to-stand test in patients with multiple sclerosis

Purpose: To investigate; (i) the relationship between the 5STS-test and lower extremity muscle strength and balance, and (ii) the variability of the 5STS-test in multiple sclerosis (MS) patients. Method: 22 MS patients were divided into two groups (Group A and Group B) who completed one 5STS familiarization test session and two testing sessions. In Group A, session 1 also included assessment of lower extremity muscle strength. Session 2 and 3 involved completion of two 5STS-tests and assessment of balance. In Group B, session 2 and 3 involved completion of two rounds of two 5STS-tests separated by a 30 min break. Results: Significant correlations were found between the 5STS-test and isometric and isokinetic knee flexor and extensor muscle strength of the most affected leg (R = −0.60 to −0.77), and between the 5STS-test and balance performance (R = 0.69). Intra-assessor day-to-day variability, intra-assessor test-retest variability and intra-assessor variability within test were 25.5, 22.3, and 23.1%, respectively. Inter-assessor variability within test and inter-assessor variability were 23.4 and 5.9%, respectively. Conclusions: The 5STS-test is related to lower extremity muscle strength and to balance performance in MS patients. For interventional purposes, a change of >25% can be regarded as a real change. Implications for Rehabilitation The 5STS-test is a valid measure of lower extremity muscle strength of the most affected leg in patients with MS. For interventional purposes, a change of more than 25% can be regarded as a real change. Familiarization to the 5STS-test has to be performed to achieve reliable results.

Heat sensitive persons with multiple sclerosis are more tolerant to resistance exercise than to endurance exercise

Background: Heat sensitivity (HS) is reported by 58% of all persons with multiple sclerosis (MS), causing symptom exacerbation possibly limiting exercise participation. Objective: The purpose of this study was to test the hypotheses that (a) a relationship between exercise-induced changes in core–temperature (Ctemp) and changes in symptom intensity exists, and (b) that resistance exercise (RE), as a consequence of a minor increase in core temperature, will induce a lesser worsening of symptoms than endurance exercise (EE) in HS persons with MS. Methods: On two separate days, 16 HS persons with MS randomly completed a session of RE and EE, or EE and RE, respectively. Testing was conducted pre, post and one hour after exercise and consisted of Visual Analogue Scale (VAS) scoring (fatigue, spasticity, pain, strength, walking and balance), the 5-time sit-to-stand (5STS), the Multiple Sclerosis Functional Composite (MSFC) and Body Sway. Composite scores describing average subjective symptom intensity (SI) and total number of symptoms (SN) were calculated from VAS scores. Results: Ctemp (0.9±0.4°C vs 0.3±0.1°C, p<0.001), SI (1.7±1.9 cm vs 0.6±1.5 cm, p<0.05) and SN (1.6±1.9 vs 0.6±2.1, p<0.05) increased significantly more during EE than RE. Changes in Ctemp correlated to changes in SI (r=0.50, p<0.01). No differences were observed in 5STS, MSFC and Body Sway scores after EE when compared to RE. Conclusion: An exercise-induced increase in Ctemp is associated with increased number and severity of perceived symptoms in HS persons with MS. Based on these findings it is expected that HS persons with MS do tolerate RE better than EE.

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.

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.