Multiple Sclerosis Walking Scale Research Articles

Responder rates to fampridine differ between clinical subgroups of MS patients and patient reported outcome influences treatment decision making

BackgroundFampridine is an effective treatment to improve ambulation for some multiple sclerosis (MS) patients. Remarkable discrepancies exist between responder rates in clinical trials and the proportion of patients continuing treatment in clinical practice. This may be related to clinical phenotypes of MS patients, and the influence of patient reported outcome (PRO) on treatment decision making. ObjectiveTo analyse responder rates to fampridine on ambulation and upper extremity function (UEF) and the influence on treatment decision making in different clinical subgroups in a real-world setting. MethodsMS patients with ambulatory impairment treated with fampridine were included. Patients were subdivided based on disease duration, clinical phenotype, Expanded Disability Status Scale (EDSS), baseline walking speed, and presence of UEF impairment. Ambulatory response was assessed with the Timed 25-Foot Walk (T25FW, responder defined as ≥20% improvement) and with the MS Walking Scale (MSWS, responder defined as ≥8 points improvement) as a PRO. For patients also reporting impaired UEF, the Arm Function in MS Questionnaire (AMSQ, responder defined as ≥15 improvement) was the PRO of choice. Decision on treatment continuation was based on improvement of T25FW, MSWS and the clinicians’ overall impression for improvement. ResultsIn total 344 patients were included of which 75.3% continued treatment. More patients with a relapsing clinical phenotype continued treatment vs patients with a progressive phenotype (83.6 vs 68.6%, p < 0.01).A positive linear trend was found between severity of walking disability, as determined by baseline walking speed, and T25FW response (p < 0.01), while there was an inverse linear association between walking disability and MSWS response (p = 0.03). However, the proportion of patients continuing treatment was similar between subgroups of baseline walking speed. Impaired UEF was reported by 183 (66.5%) patients, of which 64 (39.3%) were AMSQ responders. Patients responding on AMSQ compared to non-responders, were also more frequently MSWS responders (82.8 vs 65.3%, p = 0.02), while response on T25FW was similar, and continued treatment more often (85.9 vs 70.7%, p = 0.04). This suggests an influence of PRO on treatment decision making. ConclusionResponder rates and treatment continuation of fampridine differed between clinical subgroups of MS. PROs influenced treatment decision making of fampridine in clinical practice, particularly in patients with mild ambulatory impairment or those reporting UEF impairment. To some extent, these findings explain discrepancies found between clinical trials and clinical practice, and support the importance of subgroup analyses and incorporation of PROs in clinical trials. For clinical practice, using PROs to assess patients experience in conjunction with performance measures helps in treatment decision making.

Self-efficacy and walking performance across the lifespan among adults with multiple sclerosis.

Aim: We examined associations between self-efficacy and walking mobility across the lifespan in multiple sclerosis (MS). Methods: This study included 39 young, 44 middle-aged and 41 older adults with MS who completed the Six-Minute Walk (6MW), Timed 25-foot Walk (T25FW), MS Walking Scale-12 (MSWS-12) and MS Self-efficacy Scale. Results: Self-efficacy for function explained 45 and 48% of variance in MSWS-12 scores for young and older adults with MS, respectively; 13, 29 and 23% of variance in T25FW for young, middle-aged and older adults, respectively; and 28, 31 and 28% of variance in 6MW for young, middle-aged and older adults with MS, respectively. Conclusion: This study highlights self-efficacy as a target of in-walking mobility interventions across the lifespan in MS.

Examining the validity of the multiple-sclerosis walking scale-12 with Rasch analysis: Results from an Italian study

BackgroundThe Multiple Sclerosis Walking Scale (MSWS-12) has showed good psychometric properties in reports exploring its validity using Classical Test Theory methods. Findings from recent studies using Item Response Theory methods advance the idea that some aspects of the MSWS-12 does not fully comply with some requirements of sound measurement. Research questionThe present study investigated whether the measurement properties of the Italian version of the MSWS-12 met the assumptions of the Rasch model. MethodsSample consisted of 199 patients with a diagnosis of MS (50% female; Mean age (SD) = 48.15 (12.33)). Analyses were performed using both unidimensional and multidimensional Rasch modeling techniques. ResultsRating scale for items assessing need for support when walking, and ability to run, showed significant functioning problems. A revision of the rating scale improved the measurement properties of these items. Items assessing need for support showed signs of multidimensionality and differential item functioning when controlling for patients’ disease course and EDSS score. Additionally, included items did not appear to cover the full range of impairment as observed in the sample. SignificanceEmerging findings are consistent with those from previous studies in highlighting the need for a revision of the current content of the MSWS-12, and the inclusion of new items assessing impairment at the lower end of the disability continuum.

ECTRIMS 2019 – Late Breaking News Abstracts

Introduction: Evidence suggests Epstein-Barr virus (EBV) infection is associated with multiple sclerosis pathogenesis. In patients (pt) with progressive forms of MS (pMS), autologous EBV-specific T cells may prevent progression and improve symptoms (Pender, et al. JCI Insight. 2018). Objectives: To evaluate ATA188, an off-the-shelf, allogeneic, EBV-targeted T cell immunotherapy comprised of HLA-matched, in vitro-expanded, cytotoxic T lymphocytes in a first-in-human, multicenter, 2-part study in adults with pMS (NCT03283826). Preliminary data are reported. Methods: Eligible pt (age 18–< 66) are EBV-seropositive with pMS and an Expanded Disability Status Scale (EDSS) score of 3–7. Cohorts (cht) 1–4 (6–9 pt/cht) receive escalating doses of ATA188. 1° endpoints: safety and identification of the recommended phase 2 dose (RP2D) of ATA188. Efficacy criteria: EDSS, MS Impact Scale-29, Fatigue Severity Scale, and 12-Item MS Walking Scale scores; timed 25-foot walk; 9-hole Peg Test; and visual acuity. A responder (R) has sustained ⩾ minimal clinically significant (MCS) improvement from BL in 2 consecutive evaluations on ⩾2 efficacy criteria; a partial responder (PR) has ⩾ MCS improvement from baseline (BL) in any 1 evaluation on ⩾2 efficacy criteria; and a non-responder (NR) has ⩾ MCS decline from BL in any 1 evaluation on ⩾2 efficacy criteria (if both criteria are met, pt is NR). Plasma inflammatory biomarkers (IL-2, IL-1β, TNF-α, IL-6) are monitored throughout treatment. Results: As of 27 May 2019, 19 pt (53% male; median age, 56 years) have enrolled (6 in each of cht 1–3; 1 in cht 4) and received ⩾1 dose of ATA188. Treatment-emergent AEs (TEAE) occurred in 63% (12/19) pt and treatment-related AEs (TRAE) in 37% (7/19) pt; 1 pt (cht 2) had a grade ⩾ 3 TEAE, and 1 (cht 4) had a serious TRAE. No dose-limiting toxicities or fatal TEAE have been reported. Efficacy data are available for cht 1 and 2: cht 1, 1 R, 1 PR, and 4 NR at 6 months and 1 R, 0 PR, and 1 NR at 12 months; cht 2, 2 R, 4 PR, and 0 NR at 6 months. On measures of disability, 3/6 showed improvement and 3/6 showed decline in cht 1; 4/6 showed improvement and 1/6 showed decline in cht 2. Inflammatory cytokines remained at or near baseline. Conclusion: Preliminary data indicate ATA188 is well tolerated and improves efficacy measures in adults with pMS, even at lower doses. These results support continuing part 1 to identify RP2D for part 2, (randomized, double-blind, placebo-controlled portion).

Wearable inertial sensors provide reliable biomarkers of disease severity in multiple sclerosis: A systematic review and meta-analysis.

Gait impairment is a hallmark of multiple sclerosis (MS). InertiaLocoGraphy, the quantification of gait with inertial measurement units (IMUs), has been found useful to detect early changes in gait in MS. Still, the potential use of IMUs as a reliable biomarker of disease severity in MS remains unknown. This systematic review and meta-analysis of observational studies aimed to describe IMU protocols used to assess gait in MS patients and calculate the effect sizes of IMU features associated with disease severity scale measures. We searched MEDLINE, Cochrane Central, EMBASE and grey literature to identify articles published before May 2, 2018 that measured gait in MS patients by using IMUs and correlated IMU parameters with disease severity scale measures. We excluded from the meta-analysis articles that did not provide enough data to evaluate the association between IMU parameters and disease severity scale measures. The study was registered with the International Prospective Register of Systematic Reviews on May 2, 2018 (Registration: CRD42018092651) and the protocol was published in Systematic Reviews on January 8, 2019. We included 36 articles in the systematic review and pooled 12 for the meta-analysis. The risk of bias was moderate, with only 2 articles (none included in the meta-analysis) showing a bias score<50%. Among protocols tested, 2 were predominant (the Timed Up and Go test and 6-min walk test). Speed, step length and step time with IMUs were significantly correlated with the Expanded Disability Status Scale (EDSS) score, and speed and step length were significantly correlated with the Multiple Sclerosis Walking Scale-12 score. IMU measurement has the potential to increase the sensitivity of clinical and performance tests to identify evolution in gait alteration in MS. Kinematic parameters easily accessible with IMUs, such as speed, step length and step duration, can help follow up disease severity in MS individuals with low to medium EDSS score (1.0-4.5).

The use of brain stimulation in the rehabilitation of walking disability in patients with multiple sclerosis: A randomized double-blind clinical trial study

Background: Transcranial direct current stimulation (tDCS) of the primary motor cortex of the lower limb has been exploited in the treatment of patients with stroke and spastic lower limb paresis. We examined this stimulation efficacy in the treatment of multiple sclerosis (MS)-related walking disability. Methods: In a single-center randomized double-blind clinical trial study, 13 patients with MS and walking disability and Expanded Disability Status Scale (EDSS) score of 3 to 6 were randomized to the real and sham stimulation groups. In the real tDCS stimulation, 7 patients received anodal 2.5 mA stimulation at 1 cm anterior to the Cz point for 30-minute daily sessions in 7 consecutive days. The other group received sham stimulation with the same protocol. The primary outcome of the trial was change in the Timed 25-Foot Walk (T25-FW) from before to after the stimulation. We also assessed the Multiple Sclerosis Walking Scale-12 (MSWS-12). We employed linear mixed effects model to examine the efficacy of tDCS stimulation on changing the outcomes. Results: On average, patients who received real tDCS stimulation walked faster after 7 sessions of stimulation [Estimate = -2.7, standard error (SE) = 1.3, P = 0.049], while walking speed of sham stimulation recipients did not change. For every session of stimulation, recipients of real tDCS stimulation spent 2.7 seconds less for walking the 25 feet. Real tDCS stimulation was not effective in improving MSWS-12 scores. Conclusion: tDCS stimulation of the lower limb motor cortex speeded up patients with MS in walking, but without improvement in patients' mobility in daily activities.

Group-based, individualized, comprehensive core stability and balance intervention provides immediate and long-term improvements in walking in individuals with multiple sclerosis: A randomized controlled trial.

Walking impairments are common in individuals with multiple sclerosis. Trunk control is a prerequisite for walking; however, knowledge regarding whether core stability and balance training influence walking is limited. This study aimed to investigate the immediate and long-term effects of a group-based, individualized, comprehensive core stability and balance intervention (GroupCoreDIST) compared with those of standard care on walking. This assessor-blinded, prospective randomized controlled trial included 80 participants (Expanded Disability Status Scale scores 1-6.5) randomly allocated to GroupCoreDIST, conducted in groups of three for 60min three times per week for 6weeks (18 sessions) or standard care (n=40/40). One participant attended no posttests, leaving 79 subjects for intention-to-treat analysis. The assessments were performed at baseline and at Weeks 7, 18, and 30. Outcomes included the 2-min walk test (2MWT), 10-m walk test-preferred/fast/slow speed (10MWT), Multiple Sclerosis Walking Scale-12 (MSWS-12), Patient Global Impression of Change-walking (PGIC-walking), Rivermead Visual Gait Assessment (RVGA), and ActiGraphsWgt3X-BT activity monitors (ActiGraph). The statistical analyses included repeated-measures mixed models performed in IBM SPSS Version 24. There were no significant between-group differences in the outcome measurements at baseline. The mean differences between groups were significant at all follow-up time points in favour of GroupCoreDIST for the 2MWT, 16.7m at 7weeks (95% CI [8.15, 25.25], 15.08m at 18weeks (95% CI [6.39, 23.77]) and 16.38m at 30weeks (95% CI [7.65, 25.12]; and the PGIC-walking, 0.89 points at 7weeks (95% CI [1.34, 0.45]), 0.97 points at 18weeks (95% CI [1.42, 0.52]), and 0.93 points at 30weeks (95% CI [1.39, 0.48]; all p≤.001). The 10MWT-fast speed and the MSWS-12 showed significant between-group differences at 7 and 18weeks and the RVGA at 7weeks. No between-group differences were found regarding activity level (ActiGraph) or the 10MWT-preferred or slow speed. Compared with standard care, GroupCoreDIST significantly improved walking immediately after the intervention for up to 24weeks of follow-up.

A self-management programme to reduce falls and improve safe mobility in people with secondary progressive MS: the BRiMS feasibility RCT.

Balance, mobility impairments and falls are common problems for people with multiple sclerosis (MS). Our ongoing research has led to the development of Balance Right in MS (BRiMS), a 13-week home- and group-based exercise and education programme intended to improve balance and encourage safer mobility. This feasibility trial aimed to obtain the necessary data and operational experience to finalise the planning of a future definitive multicentre randomised controlled trial. Randomised controlled feasibility trial. Participants were block randomised 1 : 1. Researcher-blinded assessments were scheduled at baseline and at 15 and 27 weeks post randomisation. As is appropriate in a feasibility trial, statistical analyses were descriptive rather than involving formal/inferential comparisons. The qualitative elements utilised template analysis as the chosen analytical framework. Four sites across the UK. Eligibility criteria included having a diagnosis of secondary progressive MS, an Expanded Disability Status Scale (EDSS) score of between ≥ 4.0 and ≤ 7.0 points and a self-report of two or more falls in the preceding 6 months. Intervention - manualised 13-week education and exercise programme (BRiMS) plus usual care. Comparator - usual care alone. Trial feasibility, proposed outcomes for the definitive trial (including impact of MS, mobility, quality of life and falls), feasibility of the BRiMS programme (via process evaluation) and economic data. A total of 56 participants (mean age 59.7 years, standard deviation 9.7 years; 66% female; median EDSS score of 6.0 points, interquartile range 6.0-6.5 points) were recruited in 5 months; 30 were block randomised to the intervention group. The demographic and clinical data were broadly comparable at baseline; however, the intervention group scored worse on the majority of baseline outcome measures. Eleven participants (19.6%) withdrew or were lost to follow-up. Worsening of MS-related symptoms unrelated to the trial was the most common reason (n = 5) for withdrawal. Potential primary and secondary outcomes and economic data had completion rates of > 98% for all those assessed. However, the overall return rate for the patient-reported falls diary was 62%. After adjusting for baseline score, the differences between the groups (intervention compared with usual care) at week 27 for the potential primary outcomes were MS Walking Scale (12-item) version 2 -7.7 [95% confidence interval (CI) -17.2 to 1.8], MS Impact Scale (29-item) version 2 (MSIS-29vs2) physical 0.6 (95% CI -7.8 to 9) and MSIS-29vs2 psychological -0.4 (95% CI -9.9 to 9) (negative score indicates improvement). After the removal of one outlier, a total of 715 falls were self-reported over the 27-week trial period, with substantial variation between individuals (range 0-93 falls). Of these 715 falls, 101 (14%) were reported as injurious. Qualitative feedback indicated that trial processes and participant burden were acceptable, and participants highlighted physical and behavioural changes that they perceived to result from undertaking BRiMS. Engagement varied, influenced by a range of condition- and context-related factors. Suggestions to improve the utility and accessibility of BRiMS were highlighted. The results suggest that the trial procedures are feasible and acceptable, and retention, programme engagement and outcome completion rates were sufficient to satisfy the a priori progression criteria. Challenges were experienced in some areas of data collection, such as completion of daily diaries. Further development of BRiMS is required to address logistical issues and enhance user-satisfaction and adherence. Following this, a definitive trial to assess the clinical effectiveness and cost-effectiveness of the BRiMS intervention is warranted. Current Controlled Trials ISRCTN13587999. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 27. See the NIHR Journals Library website for further project information.

Why patients with multiple sclerosis perceive improvement of gait during treatment with natalizumab?

Gait impairment is one of the common manifestations of multiple sclerosis (MS) and contributes to a loss of quality of life. Natalizumab, an anti-α4 integrin monoclonal antibody, has been shown to have an effect in treatment of MS, reducing relapses and inflammatory lesions. Aim of our study was to assess how patients perceive gait impairment over the first year of treatment with natalizumab and what is the objective correlate of this change. This is an open-label prospective observational study. Subjective gait evaluation was measured by Multiple Sclerosis Walking Scale-12 (MSWS-12). Objective gait assessment included Timed 25-Foot Walk Test (T25FW) and spatiotemporal parameters of gait measured by a GAITRite instrument during a self-selected speed of walking (normal walk) and a fast speed of walking (fast walk). We analysed data of 50 patients with a relapsing-remitting form of MS, median EDSS 3.5 (range 1.5-5). MSWS-12 score significantly decreased between the baseline and month 12 of treatment (p < 0.001). Walking velocity and step length were significantly improved in Normal walk tests (p < 0.001). During the Fast walk tests, a step length and a double support time of the gait cycle were significantly improved (p = 0.001). Change in MSWS-12 score confirmed the clinically significant improvement of gait in patients with MS treated with natalizumab for 1 year. The analysis of spatiotemporal gait parameters has shown a significant improvement in self-selected gait velocity and step length.

The clinical- and cost-effectiveness of functional electrical stimulation and ankle-foot orthoses for foot drop in Multiple Sclerosis: a multicentre randomized trial

Objective: To compare the clinical- and cost-effectiveness of ankle-foot orthoses (AFOs) and functional electrical stimulation (FES) over 12 months in people with Multiple Sclerosis with foot drop. Design: Multicentre, powered, non-blinded, randomized trial. Setting: Seven Multiple Sclerosis outpatient centres across Scotland. Subjects: Eighty-five treatment-naïve people with Multiple Sclerosis with persistent (>three months) foot drop. Interventions: Participants randomized to receive a custom-made, AFO (n = 43) or FES device (n = 42). Outcome measures: Assessed at 0, 3, 6 and 12 months; 5-minute self-selected walk test (primary), Timed 25 Foot Walk, oxygen cost of walking, Multiple Sclerosis Impact Scale-29, Multiple Sclerosis Walking Scale-12, Modified Fatigue Impact Scale, Euroqol five-dimension five-level questionnaire, Activities-specific Balance and Confidence Scale, Psychological Impact of Assistive Devices Score, and equipment and National Health Service staff time costs of interventions. Results: Groups were similar for age (AFO, 51.4 (11.2); FES, 50.4(10.4) years) and baseline walking speed (AFO, 0.62 (0.21); FES 0.73 (0.27) m/s). In all, 38% dropped out by 12 months (AFO, n = 21; FES, n = 11). Both groups walked faster at 12 months with device (P < 0.001; AFO, 0.73 (0.24); FES, 0.79 (0.24) m/s) but no difference between groups. Significantly higher Psychological Impact of Assistive Devices Scores were found for FES for Competence (P = 0.016; AFO, 0.85(1.05); FES, 1.53(1.05)), Adaptability (P = 0.001; AFO, 0.38(0.97); FES 1.53 (0.98)) and Self-Esteem (P = 0.006; AFO, 0.45 (0.67); FES 1 (0.68)). Effects were comparable for other measures. FES may offer value for money alternative to usual care. Conclusion: AFOs and FES have comparable effects on walking performance and patient-reported outcomes; however, high drop-outs introduces uncertainty.

Searching for the “Active Ingredients” in Physical Rehabilitation Programs Across Europe, Necessary to Improve Mobility in People With Multiple Sclerosis: A Multicenter Study

Background. Physical rehabilitation programs can lead to improvements in mobility in people with multiple sclerosis (PwMS). Objective. To identify which rehabilitation program elements are employed in real life and how they might affect mobility improvement in PwMS. Methods. Participants were divided into improved and nonimproved mobility groups based on changes observed in the Multiple Sclerosis Walking Scale–12 following multimodal physical rehabilitation programs. Analyses were performed at group and subgroup (mild and moderate-severe disability) levels. Rehabilitation program elements included setting, number of weeks, number of sessions, total duration, therapy format (individual, group, autonomous), therapy goals, and therapeutic approaches. Results. The study comprised 279 PwMS from 17 European centers. PwMS in the improved group received more sessions of individual therapy in both subgroups. In the mildly disabled group, 60.9% of the improved received resistance training, whereas, 68.5% of the nonimproved received self-stretching. In the moderately-severely disabled group, 31.4% of the improved, received aerobic training, while 50.4% of the nonimproved received passive mobilization/stretching. Conclusions. We believe that our findings are an important step in opening the black-box of physical rehabilitation, imparting guidance, and assisting future research in defining characteristics of effective physical rehabilitation.

Association of Continuous Assessment of Step Count by Remote Monitoring With Disability Progression Among Adults With Multiple Sclerosis

ImportanceDisability measures in multiple sclerosis (MS) fail to capture potentially important variability in walking behavior. More sensitive and ecologically valid outcome measures are needed to advance MS research.ObjectivesTo assess continuous step count activity remotely among individuals with MS for 1 year and determine how average daily step count is associated with other measures of MS disability.Design, Setting, and ParticipantsIn a prospective longitudinal observational cohort study, 95 adults with relapsing or progressive MS who were able to walk more than 2 minutes with or without an assistive device were recruited between June 15, 2015, and August 8, 2016, and remotely monitored in their natural environment for 1 year. Patients were excluded if they had a clinical relapse within 30 days or comorbidity contributing to ambulatory impairment. Longitudinal analysis was performed from October 2017 to March 2018. Revised analysis was performed in December 2018.InterventionActivity monitoring of step count using a wrist-worn accelerometer.Main Outcomes and MeasuresAverage daily step count compared with in-clinic assessments and patient-reported outcomes.ResultsOf the 95 participants recruited (59 women and 36 men; mean [SD] age, 49.6 [13.6] years [range, 22.0-74.0 years]), 35 (37%) had progressive MS, and the median baseline Expanded Disability Status Scale score was 4.0 (range, 0-6.5). At 1 year, 79 participants completed follow-up (83% retention). There was a modest reduction in accelerometer use during the 1 year of the study. A decreasing average daily step count during the study was associated with worsening of clinic-based outcomes (Timed 25-Foot Walk, β = −13.09; P < .001; Timed-Up-and-Go, β = −9.25; P < .001) and patient-reported outcomes (12-item Multiple Sclerosis Walking Scale, β = −17.96; P < .001). A decreasing average daily step count occurred even when the Expanded Disability Status Scale score remained stable, and 12 of 25 participants (48%) with a significant decrease in average daily step count during the study did not have a reduction on other standard clinic-based metrics. Participants with a baseline average daily step count below 4766 (cohort median) had higher odds of clinically meaningful disability (Expanded Disability Status Scale score) worsening at 1 year, adjusting for age, sex, and disease duration (odds ratio, 4.01; 95% CI, 1.17-13.78; P = .03).Conclusions and RelevanceContinuous remote activity monitoring of individuals with MS for 1 year appears to be feasible. In this study, a decreasing average daily step count during a 1-year period was associated with worsening of standard ambulatory measures but could also occur even when traditional disability measures remained stable. These results appear to support the prospect of using the average daily step count as a sensitive longitudinal outcome measure in MS and as a clinically relevant metric for targeted intervention.

Value of gait analysis for measuring disease severity using inertial sensors in patients with multiple sclerosis: protocol for a systematic review and meta-analysis

BackgroundGait impairment is a hallmark of multiple sclerosis (MS) which significantly endangers the quality of life of the individual. Inertial measurement units (IMUs) are small, light wearable sensors that can be used in routine neurological practice. InertiaLocoGraphy (ILG), the quantification of gait with IMUs, has proven useful to detect early changes in MS undetectable with standard stopwatch-timed measures. Still, whether such markers are useful for evaluating the severity of the disease remains unknown. Therefore, the correlation between ILG and disease progression would be worth exploring.MethodsWe will search MEDLINE via PubMed, Cochrane, and EMBASE electronic databases to identify articles published before May 2, 2018 that measure gait using IMUs in MS patients. In addition, grey literature will be searched. Inclusion criteria will be adults with a clinical diagnosis of MS and gait measured by using inertial sensors. We will exclude from the meta-analysis articles that do not provide sufficient data for evaluating the correlations between ILG parameters and disease severity as measured by at least one of the six following tests: the Expanded Disability Status Scale (EDSS), the Multiple Sclerosis Walking Scale-12 (MSWS), the Multiple Sclerosis Severity Score (MSSS), the Multiple Sclerosis Impact Scale (MSIS-29), the Multiple Sclerosis Functional Composite (MSFC), and the Timed 25-ft Walk Test (T25FW). Extracted data from included articles will be presented descriptively, and effect sizes will be computed based on the recommendations from the Cochrane Collaboration handbook and RevMan software.DiscussionIdentifying changes in disease state throughout the course of MS is essential for optimal care. Current clinical and performance tests allow for identifying advanced gait alteration but lack sensitivity to detect subtle gait change. IMUs can be easily used in clinical practice to quantify gait in MS patients. Nevertheless, whether these outcomes are clinically relevant is uncertain because no study has evaluated their correlation with disease severity across different settings. This systematic review and meta-analysis would bring insight into the potential of this outcome as a marker of disease evolution.Systematic review registrationThis review was registered with the International Prospective Register of Systematic Reviews on May 2, 2018 (Registration: CRD42018092651). Both the search strategy and study protocol are available at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=92651.

The Expanded Disability Status Scale scoring in patients with multiple sclerosis

Gait disturbance is a major symptom in patients with multiple sclerosis. The Expanded Disability Status Scale (EDSS) was first used in clinical trials of multiple sclerosis for the assessment of disability, however it has become more and more widely used in clinical practice as well. Nowadays its use is essential in application of the new diagnostic criteria, the new clinical form classification and in monitoring the efficacy of therapies. EDSS is based on a standardised neurological examination, but focuses on those symptoms that are frequent in multiple sclerosis. Based on the examination it assesses seven functional systems: visual, brainstem, pyramidal, cerebellar, sensory, bowel-bladder and cerebral functions. EDSS scores can be determined based on the scores given in the functional systems and on testing the walking distance. In newer versions the "Ambulation score" has been added. This chapter clarifies the scores based on the maximal walking distance and the need for a walking aid to walk this distance. The Neurostatus/EDSS training method improves the reproducibility of the standardised neurological examination that forms the basis of the EDSS scoring. Of the tests assessing walking, the Timed-25 Foot Walk Test and the self-administered 12-Item Multiple Sclerosis Walking Scale are suitable for routine evaluation of walking performance. An increase of more than 20% in the Timed-25 Foot Walk may be considered a significant change in gait.

Evaluation of the Multiple Sclerosis Spasticity Scale 88: A Short Report.

Background:The Multiple Sclerosis Spasticity Scale 88 (MSSS-88) is designed to capture the patient experience and impact of spasticity, but there is limited evaluation against clinician-rated measures of spasticity.Objective:To evaluate the convergent validity and responsiveness of the MSSS-88.Design:Longitudinal study.Setting:University Laboratory.Subjects:Thirty-four people with multiple sclerosis.Methods:People with multiple sclerosis (MS; n = 34) completed the self-reported 12-item Multiple Sclerosis Walking Scale, Multiple Sclerosis Spasticity Scale, Barthel Index alongside the clinician-rated Ashworth Scale, and a laboratory-based measure of ankle spasticity. Spasticity measure responsiveness was evaluated in 20 participants at two time points, an average of 8.75 ± 3.8 months apart.Results:In people with MS (mean age 55.1 ± 8.1 years; Expanded Disability Scale range 4.5-7.0), spasticity symptom specific subscales of the MSSS-88 (stiffness and spasms) showed strong and significant correlations with the clinician-rated Ashworth Scale (r = 0.52-0.53; P < .01). Responsiveness of the MSSS-88 was comparable to a laboratory-based measure of ankle spasticity.Conclusions:Our findings lend additional support to the convergent validity of this measure.

Impact of Nutritional Intake on Function in People with Mild-to-Moderate Multiple Sclerosis.

We sought to assess the associations between nutrition and ambulation, daily activity, quality of life (QOL), and fatigue in individuals with mild-to-moderate disability with multiple sclerosis (MS). This cross-sectional pilot study included 20 ambulatory adult volunteers with MS (14 women and 6 men; mean ± SD age, 57.9 ± 10.2 years; mean ± SD Expanded Disability Status Scale score = 4.1 ± 1.8). Primary outcome variables included dietary assessment and the 6-Minute Walk Test (6MWT). Secondary measures included the Timed 25-Foot Walk test, Timed Up and Go test, daily activity, and three self-report questionnaires: the 12-item Multiple Sclerosis Walking Scale, the 36-item Short Form Health Survey (SF-36), and the Modified Fatigue Impact Scale. Significant correlations were seen between the percentage of diet comprising fats and the 6MWT (r = 0.51, P = .02) and the physical functioning component of the SF-36 (r = 0.47, P = .03). The percentage of carbohydrates was significantly correlated with the 6MWT (r = -0.43, P = .05), daily activity (r = -0.59, P = .005), and the physical functioning component of the SF-36 (r = -0.47, P = .03). Cholesterol, folate, iron, and magnesium were significantly positively correlated with the physical functioning component of the SF-36 and the 6MWT. These findings indicate better ambulation, daily function, and QOL with increased fat intake, decreased carbohydrate intake, and increased intake of the micronutrients cholesterol, folate, iron, and magnesium in people with mild-to-moderate MS. This pilot study highlights the potential impact of diet on function and QOL in MS.

Associations between activity and participation in adults with multiple sclerosis: a cross sectional study

ObjectivesThe aim of this study was to determine the association between walking ability in a clinical setting (activity capacity), walking ability in a person’s daily environment (activity capability) and walking performance in daily life (activity performance), and the contribution of each activity construct to participation among people with multiple sclerosis (MS). DesignCross-sectional study. SettingFive MS therapy centres in England. ParticipantsFifty-two adults (13 males) with MS who were independently ambulatory with or without a walking aid (mean (SD) age 55.4 (9.1) year). InterventionsNo intervention. Main outcome measuresActivity capacity, capability, and performance were assessed using the Six Minute Walk Test (6MWT), Twelve Item MS Walking Scale (MSWS-12), and steps/day measured using a pedometer worn for 6 days, respectively. Participation was assessed using the Impact on Participation and Autonomy questionnaire (IPA). ResultsDistance walked on the 6MWT was associated with MSWS-12 score (β=−0.56, 95% CI −0.87 to −0.22) and steps/day (β=129.49, 95% CI 48.48 to 207.57). MSWS-12 score was also associated with step count (β=−87.35, 95% CI −172.29 to −15.71). 6MWT distance was associated with the autonomy indoors subscale of the IPA (β=−0.02, 95% CI −0.04 to −0.01). No other activity measure was associated with participation. ConclusionsFindings suggest that while activity capacity, capability and performance are related, activity is a poor predictor of participation. The strength of associations between constructs of activity, and activity and participation, however, are often small with wide confidence intervals, indicating that there is considerable uncertainty associated with effect estimates.

Predicting responsiveness to fampridine in gait-impaired patients with multiple sclerosis.

Fampridine leads to significant improvements in walking in many people with multiple sclerosis (PwMS). However, a relevant proportion of PwMS does not respond to fampridine and predictors of initial drug responsiveness are unknown. Drug response to prolonged-release (PR)-fampridine was assessed in 55 PwMS using the timed 25-foot walk (T25FW), 6-min walk test (6MWT) and 12-item multiple sclerosis walking scale as outcome parameters. Patients were treated with PR-fampridine and placebo for 6weeks each in a randomized, double-blind, placebo-controlled trial with crossover design (NCT01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed the drug responses of 32 patients treated with PR-fampridine over 3years to identify potential predictors of long-term drug responsiveness. Severity of walking disability was positively correlated with enhanced responses to PR-fampridine. The strongest single predictor of drug responsiveness was poor 6MWT performance at baseline, which was positively correlated with enhanced drug response in the 6MWT (R=-0.541; P<0.001). A multivariable logistic regression model including 6MWT and T25FW baseline performances predicted PR-fampridine responder status with an accuracy of 85.5% (specificity, 90.0%; sensitivity, 73.3%), with a threshold of 211m in the 6MWT best separating responders from non-responders. Enhanced drug responsiveness after 3years correlated with decline in walking endurance during this period (R=-0.634; P=0.001). Initial walking impairment is a good predictor of therapeutic responsiveness to PR-fampridine. Valid predictors of patients' responsiveness to PR-fampridine are essential for patient stratification and optimization of multiple slcerosis treatment.

Naturally occurring change in Multiple Sclerosis Walking Scale-12 scores over time in multiple sclerosis.

This study examined the trajectory and pattern of naturally occurring change in perceived walking impairment over a 30-month period in relapsing-remitting multiple sclerosis (RRMS). Two hundred and sixty-nine persons with RRMS completed the 12-item Multiple Sclerosis Walking Scale (MSWS-12) every 6months over a 30-month period. Data were analyzed using latent growth curve modeling and latent class growth curve modeling. Latent growth curve modeling demonstrated that a linear trajectory adequately described the group-level pattern of change in MSWS-12 scores over time. Latent class growth curve modeling supported a three-class model for describing the heterogeneity of changes in MSWS-12 scores over time. Walking impairment does change over time in RRMS, and this can be described by three patterns of change trajectories that differed based on initial status of walking impairment.

Objective and subjective measures of dalfampridine efficacy in clinical practice.

BackgroundMultiple sclerosis affects mobility in over 80% of patients. Dalfampridine is the only approved treatment for walking impairment in multiple sclerosis. We assessed dalfampridine utilization in our practice and investigated response using timed 25 foot walk (T25FW) improvement and a patient-reported ambulation inventory.MethodsChart review identified patients with multiple sclerosis for whom dalfampridine was prescribed. T25FW data were extracted from medical records. Participants completed a dalfampridine-specific version of the multiple sclerosis walking scale (dMSWS-12) to assess the qualitative impact of dalfampridine on ambulation. We evaluated two responder categories: liberally defined as any improvement in T25FW; and over 20% T25FW improvement.ResultsThe dMSWS-12 questionnaire was completed by 39 patients. Eighteen patients (46%) did not show any T25FW improvement. Of the 21 patients (54%) with T25FW improvement, four patients (11%) showed improvement greater than 20%. Analysis of dMSWS-12 scores showed a median score of 40 (range 12–60). Eleven patients (28%) showed no improvement (dMSWS-12 score ≤36). In contrast to objective T25FW improvement (54%), 28 patients (72%) reported improvement in walking ability (dMSWS-12 score ≥37).ConclusionOur results suggest that T25FW alone might not be sufficient for response characterization and that adding patient-reported measures may further elucidate the therapeutic response.