Multiple Sclerosis Walking Scale Research Articles

A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis – An explorative study

ObjectiveTo compare baseline physical and cognitive performance, neurophysiological, and magnetic resonance imaging (MRI) outcomes and examinetheir interrelationship inparticipants with Multiple Sclerosis (MS), already established aseither responder or non-responder to Fampridine treatment, andto examine associationswiththe expanded disability status scale (EDSS) and 12-item MS walking scale (MSWS-12). MethodsBaseline data from an explorative longitudinal observational study were analyzed. Participants underwent the Timed 25-Foot Walk Test (T25FW), Six Spot Step Test (SSST), Nine-Hole Peg Test, Five Times Sit-to-Stand Test, Symbol Digit Modalities Test (SDMT), neurophysiological testing, including central motor conduction time (CMCT), peripheral motor conduction time (PMCT), motor evoked potential (MEP) amplitudesand electroneuronographyof the lower extremities, and brain MRI (brain volume, number and volume of T2-weighted lesions and lesion load normalized to brain volume). Results41 responders and 8 non-responders were examined. There were no intergroup differences inphysical performance, cognitive, neurophysiological, andMRI outcomes (p > 0.05).CMCT was associated withT25FW, SSST, EDSS, and MSWS-12,(p < 0.05). SDMT was associated with the number and volume of T2-weighted lesions, and lesion load normalized to brain volume (p < 0.05). ConclusionNo differences were identified between responders and non-responders to Fampridine treatment regarding physical and cognitive performance, neurophysiological or MRI outcomes. The results call for cautious interpretation and further large-scale studies are needed to expand ourunderstanding of underlying mechanisms discriminating Fampridine responders and non-responders.CMCT may be used as a marker of disability and walking impairment, while SDMT was associated with white matter lesions estimated by MRI.ClinicalTrials.gov identifier: NCT03401307.

Effects of Virtual Reality vs Conventional Balance Training on Balance and Falls in People With Multiple Sclerosis: A Randomized Controlled Trial

ObjectiveTo assess the efficacy of virtual reality (VR)-based vs conventional balance training on the improvement of balance and reduction of falls in people with multiple sclerosis (PwMS). DesignSingle-blinded, randomized, controlled trial. SettingMusculoskeletal Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences. ParticipantsPwMS (N=39), randomized into VR (n=19) and control (n=20) groups. InterventionThe VR group performed exergames using Kinect, while the control group accomplished conventional balance exercises. Both groups received 18 training sessions for 6 weeks. Main Outcome MeasuresLimits of stability, timed Up and Go (TUG) test, and 10-m walk tests with and without cognitive task and their dual-task costs (DTCs), Berg Balance Scale, Multiple Sclerosis Walking Scale-12, Fall Efficacy Scale-International, Activities-specific Balance Confidence Scale, and fall history were obtained pre- and post intervention and after a 3-month follow-up. ResultsAt both post intervention and follow-up, TUGcognitive and DTCs on the TUG were significantly lower and the 10-m walkcognitive was significantly higher in the VR group. At follow-up, reaction time and the number of falls demonstrated significant differences favoring the VR group, whereas the directional control revealed significant difference in favor of the control group (P<.05). The other outcomes showed no statistically significant difference at post intervention or follow-up. ConclusionsBoth the VR-based and conventional balance exercises improved balance and mobility in PwMS, while each acted better in improving certain aspects. VR-based training was more efficacious in enhancing cognitive-motor function and reducing falls, whereas conventional exercises led to better directional control. Further studies are needed to confirm the effectiveness of recruiting VR-based exercises in clinical settings.

Multiple Sclerosis Walking Scale-12 (MSWS-12) and its Relationship With Fatigue in People With Multiple Sclerosis

Background and Objectives: Walking disorder is one of the most important manifestations of multiple sclerosis (MS), and indicates the progression of the disease. Fatigue and walking are considered as key symptoms affecting the patient’s quality of life. Therefore, this study aimed to investigate the relationship between walking status and fatigue, in people with MS. Methods: A total number of 60 Iranian patients with MS completed the Persian version of the Multiple Sclerosis Walking Scale-12 (MSWS-12), the Modified Fatigue Impact Scale, and the Hospital Anxiety and Depression Scale. Data were analyzed using SPSS V. 20 software. The multivariate correlation and linear regression analyses were conducted to investigate the relationship between fatigue, anxiety, depression, demographic characteristics, and MSWS-12 scores. Results: Gait problems were observed in 46.7% of the study participants. Also, the MSWS-12 scores were significantly associated with fatigue severity (P=0.001), in these patients. Moreover, depression, cognitive status, anxiety, and gait status were the most important factors affecting fatigue. Conclusion: According to the present results, the presence of depression, cognitive problems, anxiety, and gait disorders are the most important factors affecting fatigue, in patients with MS.

Fatigue and fluctuations in physical and psychological wellbeing in people with multiple sclerosis: A longitudinal study

BackgroundFatigue is a highly prevalent and disabling symptom of multiple sclerosis (MS). The aetiology remains unclear, potentially resulting from neuroinflammatory or neurodegenerative processes, mood disturbance, MS symptoms including pain, poor sleep, physical decompensation or medication side effects. Cross-sectional associations have been reported between fatigue and markers of physical and psychological health in people with MS. The current study examined if fluctuations in markers of physical and psychological wellbeing were associated with between-person differences in fatigue in MS. MethodsLongitudinal data of up to 7 years was available of 3369 people with MS who were enrolled in the UK MS Register. Participants completed MS impact scale ratings and MS walking scales up to 4 times per year for up to 7 years. Fatigue was assessed at one time point using the Fatigue Severity Scale. Multilevel analyses were conducted to examine the degree of variance in the outcome measures accounted for by fatigue. ResultsFatigue was associated with fluctuations in depression, MS impact, and walking ability, and to a lesser extent with fluctuations in anxiety and perceived health status. Interference of fatigue in participation in social activities and work-related responsibilities and the physical effects of fatigue were most strongly related to MS-related outcomes. ConclusionGiven the strong associations between fatigue and many MS outcomes, fatigue management interventions are likely to impact on different aspects of physical and psychological wellbeing in MS.

Acceptability and outcomes of an individualized exergaming telePT program for veterans with multiple sclerosis: a pilot study

BackgroundPhysical rehabilitation services are an important component of treatment for persons with multiple sclerosis (PwMS) to improve and maintain physical mobility. However, PwMS often have significant barriers to outpatient physical therapy (PT) services including mobility deficits and lack of transportation. The integration of exercise gaming (exergaming) and telehealth into clinical PT practices may overcome these barriers. The overarching purpose of this pilot study was to evaluate the acceptability and effects of an individualized telePT intervention using exergaming.MethodsTen individuals with multiple sclerosis (MS) completed a 12-week exergaming (Jintronix®) telerehabilitation intervention. In order to measure the acceptability of the telerehabilitation intervention, adherence was measured through the tablet-based rehabilitation software and each participant completed a satisfaction questionnaire. Clinical outcome measures were assessed at baseline and post-intervention. To evaluate the efficacy of this intervention, the following measures of physical function and fatigue were included; the Short Physical Performance Battery (SPPB), 25-Foot Walk (25FW), Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Walking Scale-12 (MSWS), and the 2-Minute Walk Test (2MWT). Clinical outcomes were analyzed using the Sign test and Wilcoxon signed rank test. All other data were evaluated using descriptive statistics.ResultsAfter the intervention, participants demonstrated significant improvements in ambulation speed during the 25FW (p = 0.04) and ambulation distance during the 2MWT (p = 0.002). Statistically significant increases of SPPB total score (p = .04) and sub-scores were also found. Participants did not demonstrate significant changes in the MFIS (p = 0.31) or MSWS-12 (p = 0.06) after the intervention. Participants had a 58.3% adherence rate during the intervention and performed their exercise program an average of 2.5 times per week. All participants reported that they were either ‘satisfied or ‘very satisfied’ with their telerehabilitation experience, would use telerehabilitation again, and would recommend telerehabilitation to others.ConclusionThis individualized telerehabilitation intervention which integrates exergaming and clinical video teleconferencing is acceptable to patients and may offer a viable alternative to traditional PT for PwMS.Trial registrationNCT03655431, retrospectively registered on August 31st, 2018.

Improving our understanding of the most important items of the Multiple Sclerosis Walking Scale-12 indicating mobility dysfunction: Secondary results from a RIMS multicenter study

BackgroundThe 12-item Multiple Sclerosis Walking Scale (MSWS-12) is currently the most widely validated, patient-reported outcome measure assessing patients’ perception of the impact of multiple sclerosis (MS) on walking ability. To date, the majority of previous studies investigating the MSWS-12 have focused on the total score despite individual items being potentially informative. Therefore, our objective was to examine the associations between the individual items of the MSWS-12 and mobility and whether these associations depend on disability level. MethodsParticipants completed the MSWS-12, Two-Minute Walk Test (2MWT), Timed 25-Foot Walk (T25FW), Timed Up and Go Test (TUG) and the Four Square Step Test (FSST). Subsequently, they were divided into two groups according to their disability level, classified as either “mildly” or “moderately-severely” disabled. The correlation between individual items of the MSWS-12 and clinical measures of mobility were separately examined by Spearman's correlation coefficients; linear regression analyses were performed for each disability group, with/without adjusting for cognition, age and gender. Results242 people with MS (PwMS), 108 mildly and 134 moderately-severely disabled, were included. Stronger correlations between the MSWS-12 items and mobility tests were found in the mildly disabled compared to the moderately-severely disabled group. The linear regression analysis showed that in the mildly disabled, item 9 (use of support outdoors) explained 35.4%, 30.8%, and 23.7% of the variance related to the 2MWT, T25FW and TUG, respectively. As for the moderately-severely disabled, the linear regression analysis presented a model which included item 8 (use of support indoors), explaining 31.6%, 18.0%, 20.2% and 9.5% of the variance related to the 2MWT, T25FWT, TUG and FSST, respectively. ConclusionsItems 8 and 9 of the MSWS-12 focusing on the patient's use of walking support in and outdoors, provide a robust indicator of mobility capabilities for mildly and moderately-severely disabled PwMS.

Construct Validity of the Gait Assessment and Intervention Tool (GAIT) in People With Multiple Sclerosis.

In clinical practice, observational scales are the most common approach used to assess gait pattern in people with neurological disorders. The Gait Assessment and Intervention Tool (GAIT) is an observational gait scale, and it has proved to be the most comprehensive, homogeneous, and objective of all the observational gait scales studied in people with neurological conditions. To study the construct validity of the GAIT in people with multiple sclerosis (MS). An observational study was conducted. Multiple Sclerosis Foundation in Madrid (Spain). Thirty-five patients with MS were assessed. GAIT construct validity was assessed using the following scales: Rivermead Visual Gait Assessment (RVGA), Tinetti Gait Scale (TGS), 10-Meter Walking Test (10MWT), Timed Up&Go (TUG), Hauser Ambulatory Index (HAI), Multiple Sclerosis Walking Scale-12 (MSWS-12), Functional Gait Assessment (FGA), Modified Ashworth Scale (MAS), and Rivermead Mobility Index (RMI). A total of 35 subjects with MS were assessed. The correlations between the GAIT and the RVGA were excellent (r > .90) and moderate with TGS (values between -.62 and -.59). Correlations with HAI, FGA, MSWS-12, and RMI were moderate (with values between .57 and .67). Correlations were lower for the velocity scales TUG and MAS. The construct validity of the GAIT is high, as a measure of gait coordination in people with MS. Specifically, there was excellent correlation with the RVGA. There was a moderate correlation for the GAIT with measures of functional mobility, but a lesser correlation of the GAIT with measures restricted to temporal gait characteristics (speed measures) or measurements of impairments underlying gait patterns such as balance or muscle tone.

What are the relationships between trunk control, balance and walking in individuals with multiple sclerosis with minor to moderate disability?

Purpose This study aimed to identify relationships between trunk control, balance and walking in individuals with multiple sclerosis (MS) with minor to moderate disability to guide the content of interventions to optimise balance and walking. Methods and materials Correlation analysis of baseline data from a prospective randomised controlled study comprising 79 individuals with MS was conducted using the Expanded Disability Status Scale (EDSS) 1.0–6.5 (mean 2.36), Trunk Impairment Scale-Norwegian Version (TIS-modNV), Mini Balance Evaluation Systems Test (Mini-BESTest), 2-min walk test (2MWT), 10-m walk test (10MWT), MS Walking Scale-12 (MSWS-12), Rivermead Visual Gait Assessment (RVGA) and number of steps using ActiGraphsWgt3X-BT. Log-transformations of skewed variables were conducted and Pearson correlation coefficients were calculated. Results Strong correlations (r = 0.70–0.90) between the 2MWT and 10MWT, the 10MWT preferred speed and number of steps, and the Mini-BESTest and 2MWT and 10MWT were identified. Moderate relationships (r = 0.50–0.70) were detected between the TIS-modNV and Mini-BESTest, as well as the 2MWT, 10MWT and RVGA. Conclusions The strong relationships support the need to address several aspects of balance to improve walking, while the moderate associations suggest that dynamic trunk control should be considered addressed in interventions for individuals with minor to moderate disability to optimise balance and walking.

Effect of task-oriented circuit training on motor and cognitive performance in patients with multiple sclerosis: A single-blinded randomized controlled trial.

Exercise training has positive effects on motor and cognitive performance which deteriorates over time in patients with Multiple Sclerosis (MS). The effects of task-oriented circuit training (TOCT) on motor and cognitive performance in patients with MS are not yet clear. The aims of this study are to investigate the effects of TOCT on balance, walking, manual dexterity, cognitive performance, and to determine the extent to which patients are able to transfer changes in their performance to activities of daily living. Twenty patients with MS (EDSS: 2-5.5), were randomly assigned to two groups; the task-oriented circuit training group (TOCTG, n:10) and the control group (CG, n:10). The TOCTG received TOCT twice a week for six weeks while the CG performed the relaxation exercises at home. All patients were assessed by using Modified Sensory Organization Test, Berg Balance Scale, Activities-specific Balance Confidence, Timed Up and Go, Functional Gait Assessment, 12-item Multiple Sclerosis Walking Scale, Nine-Hole Peg Test, Brief Repeatable Battery of Neuropsychological Tests, Multiple Sclerosis Neuropsychological Questionnaire. Balance and walking performance were improved after TOCT (p < 0.05), whereas manual dexterity and cognitive performance except for verbal memory did not change significantly (p > 0.05). The CG showed no changes in any measurements (p > 0.05). TOCT is quite effective to improve balance and walking in patients with MS. However, further studies are needed to determine the effect of TOCT on cognitive performance.

A Head-to-Head Comparison of an Isometric and a Concentric Fatigability Protocol and the Association With Fatigue and Walking in Persons With Multiple Sclerosis

Background. Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (MS). Distinction is made between subjective perceptions of fatigue and objective measures of fatigability. Fatigability can be measured by different protocols. Yet no studies have compared isometric and concentric contraction protocols of the lower extremities head-to-head. Therefore, the purpose of the present study was to (1) compare 2 such protocols head-to-head and (2) to investigate the association between fatigability evoked by the 2 protocols and measures of fatigue and walking. Methods. A total of 45 patients with MS had their walking capacity measured objectively by the 6-minute walk test (6MWT) and subjectively by the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Fatigue was measured by the Modified Fatigue Impact Scale (MFIS) and fatigability by 2 knee extension protocols: sustained isometric and concentric. Results. The sustained isometric protocol induced a higher degree of fatigability than the concentric protocol (P < .01). Regression analyses revealed that sustained isometric fatigability was not associated with either measures of fatigue or walking (all r2 = 0.00; P = .85-.99), whereas the concentric protocol was significantly associated with fatigue (r2 = 0.20; P < .01), 6MWT (r2 = 0.09; P < .05), and MSWS-12 (r2 = 0.16; P < .01). Furthermore, after adjusting for maximal strength and sex, concentric fatigability remained a strong and significant predictor of fatigue (β = 0.49) and walking (6MWT: β = −0.26; MSWS: β = 0.37). Conclusion. This study provides the first evidence that a lower-extremity concentric fatigability protocol provides superior reflection of both fatigue and walking when compared with a sustained isometric protocol. We suggest that concentric protocols should be the focus of future studies investigating fatigability.

Randomized comparison of functional electric stimulation in posturally corrected position and motor program activating therapy: treating foot drop in people with multiple sclerosis

Functional electric stimulation (FES) is recommended for foot drop in multiple sclerosis, although little is known about its therapeutic effect. The aim of this study is to evaluate a therapeutic effect immediately and two months after program termination (persistent and delayed effect) of a new approach using FES in combination with correcting the patients' postural system. More specifically, we evaluate the effects of this approach on the patients' clinical functions and compared it with individual physiotherapy. Parallel randomized blind trial. Two-month-long treatments, functional electric stimulation in posturally corrected position (group 1) and neuroproprioceptive facilitation and inhibition physiotherapy called motor program activating therapy (group 2). Forty-four subjects with multiple sclerosis. Primary outcomes: gait (the 2-Minute Walk Test; Timed 25-Foot Walk test; Multiple Sclerosis Walking Scale-12) and balance (by e.g. Berg Balance Scale [BBS], the Activities-Specific Balance Confidence Scale [ABC], Timed Up-and-Go Test [TUG]). mobility, cognition, fatigue and subjects' perceptions (e.g. Multiple Sclerosis Impact Scale [MSIS], Euroqol-5 dimensions-5 levels [EQ-5D-5L]). Group 1 showed immediate therapeutic effect in BBS (P=0.008), ABC (P=0.04) and EQ-5D-5L (self-care, P=0.019, mobility P=0.005). The improvement in EQ-5D-5L persisted and in TUG-cognitive we documented a delayed effect (P=0.005). Group 2 showed an immediate improvement in BBS (P=0.025), MSIS (P=0.043) and several aspects of daily life (the effect on health today was significantly higher than in group 1, significant difference between groups P=0.038). FES in the posturally corrected position has an immediate therapeutic effect on balance and patients' perceptions comparable to motor program activating therapy, and higher persistent and even delayed therapeutic effect. The study results point to the importance of correcting the patients' posture when applying FES, the possibility to treat foot drop by individual physiotherapy and the activation of the patients' auto reparative processes.

Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT

BackgroundNeuroprotective drugs are needed to slow or prevent neurodegeneration and disability accrual in secondary progressive multiple sclerosis. Amiloride, fluoxetine and riluzole are repurposed drugs with potential neuroprotective effects.ObjectivesTo assess whether or not amiloride, fluoxetine and riluzole can reduce the rate of brain volume loss in people with secondary progressive multiple sclerosis over 96 weeks. The secondary objectives that were assessed were feasibility of a multiarm trial design approach, evaluation of anti-inflammatory effects, clinician- and patient-reported efficacy and three mechanistic substudies.DesignA multicentre, multiarm, randomised, double-blind, placebo-controlled, parallel-group Phase IIb trial with follow-up at 4, 8, 12, 24, 36, 48, 72 and 96 weeks. Patients, investigators (including magnetic resonance imaging analysts), and treating and independent assessing neurologists were blinded to the treatment allocation. The target sample size was 440 patients.SettingThirteen UK clinical neuroscience centres.ParticipantsParticipants were aged 25–65 years, had secondary progressive multiple sclerosis with evidence of disease progression independent of relapses in the previous 2 years, and had an Expanded Disability Status Scale score of 4.0–6.5. Patients were ineligible if they could not have a magnetic resonance imaging scan; had a relapse or steroids in the previous 3 months; or had epilepsy, depression, bipolar disorder, glaucoma, bleeding disorders or significant organ comorbidities. Exclusion criteria were concurrent disease-modified treatments, immunosuppressants or selective serotonin reuptake inhibitors.InterventionsParticipants received amiloride (5 mg), fluoxetine (20 mg), riluzole (50 mg) or placebo (randomised 1 : 1 : 1 : 1) twice daily.Main outcome measuresThe primary end point was magnetic resonance imaging-derived percentage brain volume change at 96 weeks. Secondary end points were new/enlarging T2 lesions, pseudoatrophy, and clinician- and patient-reported measures (including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Symbol Digit Modalities Test, low-contrast letter visual acuity, Multiple Sclerosis Impact Scale 29 items, version 2, Multiple Sclerosis Walking Scale, version 2, and questionnaires addressing pain and fatigue). The exploratory end points included measures of persistent new T1 hypointensities and grey matter volume changes. The substudies were advanced magnetic resonance imaging, optical coherence tomography and cerebrospinal fluid analyses.ResultsBetween December 2014 and June 2016, 445 patients were randomised (analysed) to amiloride [n = 111 (99)], fluoxetine [n = 111 (96)], riluzole [n = 111 (99)] or placebo [n = 112 (99)]. A total of 206 randomised patients consented to the advanced magnetic resonance imaging substudy, 260 consented to the optical coherence tomography substudy and 70 consented to the cerebrospinal fluid substudy. No significant difference was seen between the active drugs and placebo in percentage brain volume change at week 96 as follows (where negative values mean more atrophy than placebo): amiloride minus placebo 0.0% (Dunnett-adjusted 95% confidence interval –0.4% to 0.5%), fluoxetine minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.5% to 0.3%); riluzole minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.6% to 0.3%). There was good adherence to study drugs. The proportion of patients experiencing adverse events was similar in the treatment and placebo groups. There were no emergent safety issues.LimitationsThere was a lower than expected uptake in the cerebrospinal fluid substudy.ConclusionsA multiarm Phase II paradigm is efficient in determining which neuroprotective agents to take through to Phase III trials. Amiloride, fluoxetine and riluzole were not effective in reducing the brain atrophy rate in people with secondary progressive multiple sclerosis. Mechanistic pathobiological insight was gained.Future workTo use the information gained from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) to inform future trial design as new candidate agents are identified.Trial registrationCurrent Controlled Trials ISRCTN28440672, NCT01910259 and EudraCT 2012-005394-31.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full inEfficacy and Mechanism Evaluation; Vol. 7, No. 3. See the NIHR Journals Library website for further project information. This trial also received funding from the UK MS Society and the US National Multiple Sclerosis Society.

Detection of subtle gait disturbance and future fall risk in early multiple sclerosis.

To test the hypothesis that higher-challenge gait and balance tasks are more sensitive than traditional metrics to subtle patient-reported gait dysfunction and future fall risk in early multiple sclerosis (MS). Persons with early MS (n = 185; ≤5 years diagnosed) reported gait function (MS Walking Scale) and underwent traditional disability metrics (Expanded Disability Status Scale [EDSS], Timed 25 Foot Walk). Patients and healthy controls (n = 50) completed clinically feasible challenge tasks of gait endurance (2-Minute Walk Test), standing balance (NIH Toolbox), and dynamic balance (balance boards; tandem walk on 2 ten-foot boards of different widths, 4.5 and 1.5 in). MRI assessed global and regional brain volumes, total T2 lesion volume (T2LV), infratentorial T2LVs and counts, and cervical cord lesion counts. Falls, near falls, and fall-related injuries were assessed after 1 year. We examined links between all tasks and patient-reported gait, MRI markers, and fall data. Patients performed worse on higher challenge balance, but not gait, tasks compared with healthy controls. Worse patient-reported gait disturbance was associated with worse performance on all tasks, but only dynamic balance was sensitive to mild patient-reported gait difficulty. Balance tasks were more correlated with MRI metrics than were walking tasks or EDSS score. Thirty percent of patients reported either a fall or near fall after 1 year, with poor dynamic balance as the only task independently predicting falls. Balance plays a leading role in gait dysfunction early in MS. Clinically feasible higher-challenge balance tasks were most sensitive to patient-reported gait, MRI disease markers, and risk of future falls, highlighting potential to advance functional outcomes in clinical practice and trials.

Validation of the Korean Version of the 12-Item Multiple Sclerosis Walking Scale and Application to Neuromyelitis Optica Spectrum Disorder.

Background and PurposeGait problems are a primary complaint in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported measure assessing the impact of MS on the walking ability. We aimed to adapt and validate the Korean version of the MSWS-12 for the Korean population with MS and NMOSD.MethodsThirty-four MS and 35 NMOSD patients were recruited. The MSWS-12 questionnaire was translated into the Korean language and evaluated for its validity and reliability in these patients.ResultsThe MS and NMOSD patients had mean ages of 35.9 and 42.1 years, respectively, median disease durations of 5.6 and 7.2 years, median Expanded Disability Status Scale (EDSS) scores of 2.75 (range, 0–6.5) and 3.5 (range, 0–7.5), and median baseline MSWS-12 total scores of 25 [interquartile range (IQR), 2.60–53.65] and 25 (IQR, 7.29–50.00). The baseline MSWS-12 total score in the patients with MS showed strong correlations with scores for the EDSS, timed 25-foot walk (T25FW), Multiple Sclerosis Impact Scale-29 (MSIS-29) physical dimension, and 36-item Short-Form Health Survey (SF-36) physical component summary (PCS), with Spearman's correlation coefficients (ρ) of 0.922, 0.756, 0.933, and −0.874, respectively. In patients with NMOSD, the baseline MSWS-12 total score showed strong correlations with scores for the EDSS, MSIS-29 physical dimension, and SF-36 PCS (ρ=0.769, 0.910, and −0.852, respectively), and moderate correlations with scores for the T25FW and Fatigue Severity Scale-9 (ρ=0.597 and 0.630, respectively).ConclusionsThe Korean version of the MSWS-12 appears to be a valid and reliable scale that can be used for Korean patients with MS. The MSWS-12 can also be applied to patients with NMOSD.

Objective sensor-based gait measures reflect motor impairment in multiple sclerosis patients: Reliability and clinical validation of a wearable sensor device

BackgroundGait deficits are common in multiple sclerosis (MS) and contribute to disability but may not be easily detected in the early stages of the disease. ObjectivesWe investigated whether sensor-based gait analysis is able to detect gait impairments in patients with MS (PwMS). MethodsA foot-worn sensor-based gait analysis system was used in 102 PwMS and 22 healthy controls (HC) that were asked to perform the 25-foot walking test (25FWT) two times in a self-selected speed (25FWT_pref), followed by two times in a speed as fast as possible (25FWT_fast). The Multiple Sclerosis Walking Scale (MSWS-12) was used as a subjective measure of patient mobility. Patients were divided into EDSS and functional system subgroups. ResultsDatasets between two consecutive measurements (test-retest-reliability) were highly correlated in all analysed mean gait parameters (e.g. 25FWT_fast: stride length r = 0.955, gait speed r = 0.969) Subgroup analysis between HC and PwMS with lower (EDSS≤3.5) and higher (EDSS 4.0–7.0) disability showed significant differences in mean stride length, gait speed, toe off angle, stance time and swing time (e.g. stride length of EDSS subgroups 25FWT_fast p ≤ 0.001, 25FWT_pref p = 0.003). The differences between EDSS subgroups were more pronounced in fast than in self-selected gait speed (e.g. stride length 25FWT_fast 33.6 cm vs. 25FWT_pref 16.3 cm). Stride length (25FWT_fast) highly correlated to EDSS (r=-0.583) and MSWS-12 (r=-0.668). We observed significant differences between HC and PwMS with (FS 0–1) and without (FS≥2) pyramidal or cerebellar disability (e.g. gait speed of FS subgroups p ≤ 0.001). ConclusionSensor-based gait analysis objectively supports the clinical assessment of gait abnormalities even in the lower stages of MS, especially when walking with fast speed. Stride length and gait speed where identified as the most clinically relevant gait measures. Thus, it may be used to support the assessment of PwMS with gait impairment in the future, e.g. for more objective classification of disability. Its role in home-monitoring scenarios need to be evaluated in further studies.

Biofeedback Based Home Balance Training can Improve Balance but Not Gait in People with Multiple Sclerosis.

Background Impaired balance is common in people with multiple sclerosis (MS) and can be present even in those with a mild disability level. With increasing disability, gait, and balance impairment progress, and lead to increased risk of falls. In some recent studies, interactive commercial video games were used for improving balance, but their limitation is their lack of individual training parameter settings needed for rehabilitation purposes. The aim of this study was to evaluate the feasibility and effect of balance exercise in the home setting using the rehabilitation Homebalance® system. Methods A single-centre, controlled, single blind study with allocation to intervention group or to control group was utilised. Participants were assessed at baseline, after four weeks of home-based balance training, and follow-up after four weeks. The primary outcomes were the Berg Balance Test (BBT). The secondary outcome measures included the Mini-BESTest, Timed Up, and Go Test (part of Mini-BESTest), and spatio-temporal gait parameter evaluation using the GAITRite instrument. The patient reported outcomes (PRO) included the 12-Item MS Walking Scale, Activities-specific Balance Confidence Scale, and the Falls Efficacy Scale. Results A total of 39 people with Multiple Sclerosis (10 men) were enrolled into the study. The mean age of participants was 40.69 ± 10.2 years, with a mean disease duration 14.76 ± 9.1 years and mean disability level 3.8 ± 1.9 EDSS (EDSS range 1.5–7). Statistically significant improvements within the home exercise group were present for the BBT and the Mini-BESTest. This improvement was more significant in the subgroup with moderate and higher disability (EDSS 4.5–7). All other gait parameters and PRO did not show any improvement. Follow-up assessment after four weeks showed that the reached improvement persisted for a short time period after finishing the regular training regimen. Conclusion In comparison with no intervention, a short-term programme of home-based balance training using Homebalance® improved balance but not gait performance in a group of people with MS. It seems that home-based balance training tailored according to individual needs by a physiotherapist may be a future approach to consider for telerehabilitation of people with MS.

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).