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

To investigate whether fatigue is an independent factor associated with mobility and the walking capacity in patients with PD. Forty-eight patients with PD (22 with fatigue) were tested for mobility and their walking capacity: Timed Up and Go (TUG), 10-Meter Walk Test (10MWT) at usual and fastest speed, and 6-Minute Walk Test (6MWT). Fatigue was measured with Parkinson's Fatigue Scale (PFS-16). Linear regression analysis was used to investigate if fatigue is an independent factor contributing to variance in mobility and walking capacity. There was a positive correlation between PFS-16 and TUG (rs=0.385; p=0.007). There was a negative correlation between PFS-16 and 10MWT at comfortable (r=-0.385; p=0.007) and fast speeds (r=-0.396; p=0.005), and 6MWT (r=-0.472; p=0.001). Linear regression analysis revealed that fatigue did not explain the variance of TUG and 10MWT. PFS-16, age and section III of UPDRS explained 49.6% (adjusted R2; p<0.001) variance in the 6MWT, and fatigue was the most significant predictor (F=-32.1; p=0.022). Fatigue is an independent factor contributing to the distance covered during 6MWT in patients with PD. Our results highlight the importance of recognition and management of this symptom.

Background: Published data demonstrate promising results for rehabilitation in patients with multiple sclerosis (MS), including telerehabilitation technologies. Given the travel limitations during the coronavirus disease 2019 (COVID-19), telerehabilitation may provide a viable alternative to in-person physiotherapy. Objective: To determine the efficacy of telerehabilitation in MS patients during COVID-19. Design/Methods: A total of 42 patients participated in the study of which 24 were followed up till the end of 6 weeks. The investigated group consisted of 15 females and 09 males; the mean age was 42 ± 10 years. The telerehabilitation was provided for a duration of 6 weeks at a frequency of three classes per week. The patients used either laptops or mobile phones for attending these sessions. The inclusion criteria were a 6-minute walk test (with or without assistance). Motor function was evaluated using the Timed Up and Go (TUG) test and the 30-Second Sit-to-Stand (30STS) test. Patients were required to fill out two questionnaires also: 12-item MS Walking Scale (MSWS) and Modified Fatigue Impact Scale (MFIS). All the patient assessments were made by an independent physiotherapist before and after the intervention. Results: There was a statistically significant improvement in motor performance and MFIS and 12-item MSWS. The following results were observed: statistically improved parameters of TUG, 30STS, 12-item MSWS and MFIS. Conclusions: Based on the findings, it is reasonable to infer that the use of telemedicine in the rehabilitation of MS patients is very promising.

This study aims to assess the effectiveness of pure cannabidiol (CBD) in reducing spasticity in multiple sclerosis (MS) patients with spasticity-related walking difficulties.49Forty-nine MS patients were randomly assigned to receive either CBD C2 oral drops (n = 24, initially 5 mg/day, increasing to 70 mg/day over 2 weeks, and 80 mg/day from the thirdweek to the fourth week) or a placebo (n = 25) at Ghaem Hospital, Mashhad, Iran. After one 1month of treatment, the timed 25-foot walk (T25-FW) test was conducted, and patientscompleted several questionnaires, including the Modified Fatigue Impact Scale (MFIS), MultipleSclerosis Walking Scale (MSWS-12), Urinary Frequency, Pittsburgh Sleep Quality Index(PSQI), Beck Depression Inventory (BDI-II), and EuroQoL (EQ-5D).The duration of the T25-FW test decreased in both groups, but the reduction was significantly greater in the intervention group (IG) compared to the placebo group (PG) (p = 0.031). Both groups experienced a reduction in maximum pain after 1month, with the IG showing a significantly higher decrease (p = 0.033). There was no significant difference in plasticity levels between the groups at baseline, 4, and 8weeks. Results indicate that CBD does not significantly reduce spasticity severity in MS patients. However, the T25-FW test results showed a notable reduction in test duration.

Predicting falls in multiple sclerosis: Do electrophysiological measures have a better predictive accuracy compared to clinical measures?

Balance deficits are considered a risk factor for falls in MS patients. Therefore, developing innovative approaches such as virtual reality (VR) to improve balance in MS is required. The aims of this study were to develop and evaluate feasibility and acceptability of VR scenarios that target balance in MS using a pilot trial. Participants were randomly allocated to either a VR training (i.e. intervention group) (n = 20) or a control group (n = 20). Intervention group received VR training for 6 weeks. Control group received home-based traditional balance exercises without the VR. Participants were assessed at baseline and follow-up on Berg Balance Scale (BBS), Timed Up and Go (TUG), the 10 Meter Walk Test (10-MWT), the 3 Minute Walk Distance (3-MWD), the Modified Fatigue Impact Scale (MFIS) Fall Efficacy Scale- International (FES-I) and the Short Form 36 (SF-36). Six VR scenarios weer developed. Sixteen participants in the intervention and 16 in the control group completed the study. Significant differences between the two groups were observed at on BBS, MFIS and several outcomes of the SF-36 survey (P < 0.05). Participants reported overall level of satisfaction with the developed VR scenarios. Findings demonstrated the feasibility and acceptability of a VR-based program in MS individuals. Our findings support the implementation of a larger trial of longer-term VR program.

Combining a supervised and home-based task-oriented circuit training improves walking endurance in patients with multiple sclerosis. The MS_TOCT randomized-controlled trial

To assess the clinical utility of 5 physical therapy (PT) outcome measures in quantifying functional changes in pediatric lower extremity chronic pain treated at a hospital-based interdisciplinary rehabilitation center. This was a cross-sectional study with retrospective review of 173 individuals, 8 to 18 years old, treated from June 2008 to 2013. The measures used were the Timed Up and Go, Timed Up and Down Stairs, Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, 6-minute walk test, and Lower Extremity Functional Scale. Participant performance was correlated with demographic characteristics, the Functional Disability Index, Multidimensional Anxiety Scale for Children, Child Depression Inventory, and Canadian Occupational Performance Measure. Scores from all 5 PT measures showed significant improvement following treatment. Functional Disability Index correlated to every PT measure except the 6-minute walk test. This study supports the clinical use of these PT measures to track functional progress after rehabilitative treatment of lower extremity chronic pain-related disability.

Prevalence and determinants of falls in persons with multiple sclerosis without a clinical disability

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.

Short-term impact of fampridine on motor and cognitive functions, mood and quality of life among multiple sclerosis patients

BackgroundWalking impairment is one of the most prevalent symptoms in people with multiple sclerosis (pwMS). In this study, we aimed to explore the usefulness of a simple walking test, the Timed 25 Foot Walk (T25FW), in detecting subtle differences in “fully ambulatory” pwMS compared to HC. MethodsWe therefore investigated retrospective data from a clinical real-life cohort of 650 pwMS. We first analyzed the amount of patients showing clinically relevant impairment in the T25FW (T25FW > 6 s) within different levels of disability according to the Expanded Disability Status Scale (EDSS). For detailed analysis in “fully ambulatory” pwMS, we formed four groups according to the respective levels of disability (EDSS 0, EDSS 1, EDSS 1.5–2, EDSS 2.5–3), and compared their walking speed to age- and sex-matched healthy controls (HC). ResultsIn our cohort, the number of patients showing clinically relevant slowing in the T25FW ranged from 15% in “fully ambulatory” patients (EDSS 0–3) to 69% in patients with moderate (EDSS 3.5–5.5) and 100% in patients with severe impairment (EDSS ≥6). Further analyses in “fully ambulatory” patients revealed that all EDSS-subgroups showed significant slowing compared to HC. The mean difference to walking speed of HC became gradually more pronounced from 0.15 m/s in asymptomatic patients (EDSS 0) to 0.5 m/s in patients with EDSS 2.5–3. ConclusionThese findings underline the ability of the T25FW to detect slowing even in patients with minimal disability. While the difference to HC was slightly below clinical relevance in asymptomatic patients (EDSS 0), slowing gradually worsened from EDSS 1 onwards and exceeded published thresholds for clinical meaningfulness.

Gait impairment is a prevalent and important difficulty for patients with multiple sclerosis (MS), a common neurological disorder. An easy to use tool to objectively evaluate gait in MS patients in a clinical setting can assist clinicians to perform an objective assessment. The overall objective of this study is to develop a framework to quantify gait abnormalities in MS patients using the Microsoft Kinect for the Windows sensor; an inexpensive, easy to use, portable camera. Specifically, we aim to evaluate its feasibility for utilization in a clinical setting, assess its reliability, evaluate the validity of gait indices obtained, and evaluate a novel set of gait indices based on the concept of dynamic time warping. In this study, ten ambulatory MS patients, and ten age and sex-matched normal controls were studied at one session in a clinical setting with gait assessment using a Kinect camera. The expanded disability status scale (EDSS) clinical ambulation score was calculated for the MS subjects, and patients completed the Multiple Sclerosis walking scale (MSWS). Based on this study, we established the potential feasibility of using a Microsoft Kinect camera in a clinical setting. Seven out of the eight gait indices obtained using the proposed method were reliable with intraclass correlation coefficients ranging from 0.61 to 0.99. All eight MS gait indices were significantly different from those of the controls (p-values less than 0.05). Finally, seven out of the eight MS gait indices were correlated with the objective and subjective gait measures (Pearson's correlation coefficients greater than 0.40). This study shows that the Kinect camera is an easy to use tool to assess gait in MS patients in a clinical setting.

Background: Multiple sclerosis (MS) patients often suffer from fatigue. Objective: We evaluated the relationship of obstructive sleep apnea (OSA) to fatigue and sleepiness in MS patients. Methods: Ambulatory MS patients without known sleep disorders and healthy controls underwent diagnostic polysomnography and a multiple sleep latency test (objective sleepiness measure). Fatigue was measured with the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI), and subjective sleepiness by Epworth Sleepiness Scale. Covariates included age, sex, body mass index, Expanded Disability Status Scale (EDSS), depression, pain, nocturia, restless legs syndrome, and medication. Results: OSA (apnea–hypopnea index ≥15) was found in 36 of 62 MS subjects and 15 of 32 controls. After adjusting for confounders, severe fatigue (FSS ≥5) and MFI-mental fatigue (>group median) were associated with OSA and respiratory-related arousals in MS, but not control subjects. Subjective and objective sleepiness were not related to OSA in either group. In a multivariate model, variables independently associated with severe fatigue in MS were severe OSA [OR 17.33, 95% CI 2.53–199.84], EDSS [OR 1.88, 95% CI 1.21–3.25], and immunomodulating treatment [OR 0.14, 95% CI 0.023–0.65]. Conclusions: OSA was frequent in MS and was associated with fatigue but not sleepiness, independent of MS-related disability and other covariates.

Sarcopenia in patients with multiple sclerosis

Based on PubMed and Embase searches, psychometric as well as descriptive data of T25FW, 6MWT, SSST, and MSWS-12 were extracted from studies evaluating persons with MS (pwMS). Descriptive data was also extracted from healthy controls (HC), if reported. Data was displayed as median [IQR]. A total of n=84 studies (N=36.929 pwMS, 64% females, age 49.6 [43;51] yrs; N=3.093 HC, 40.0 [37.5;47.5] yrs) were included. In pwMS, expanded disability status scale (EDSS) was 4.0 [3.0;4.8], patient determined disease scale (PDDS) 2.6 [2.0;3.0], time since diagnosis 11.6 [9.9;13.2] yrs, and MS-phenotypes (RR/SP/PP/unknown) were 68/19/10/3%. PwMS performed substantially worse than HC across all walking capacity outcomes. Weak to strong associations were found for construct validity (r=0.29-0.88, EDSS or PDDS and walking capacity or ability outcomes) and concurrent validity (r=0.16-0.88 between walking capacity and ability, r=0.73-0.95 between walking capacity outcomes). Ecological validity showed weak to moderate associations between daily steps and walking outcomes (r=0.42-0.68). Good to excellent test-retest, intrarater, and interrater reliability were reported across outcomes (ICC=0.71-1.00). Responsiveness was most frequently reported as the minimal-clinically-important-difference, minimal-detectable-change, or as the minimal-important-change (data not shown). Overall the T25FW, 6MWT, SSST, and MSWS-12 demonstrate moderate to excellent psychometric properties (i.e., valid, reliable, and responsive to changes), which make them clinically useful and applicable to research.