12-item Multiple Sclerosis Walking Scale Research Articles

Efficacy of dalfampridine in neuromyelitis optica spectrum disorder: A pilot study.

To assess the efficacy of dalfampridine in patients with neuromyelitis optica spectrum disorder. We included 15 consecutive patients, who were started on a treatment of dalfampridine 10 mg twice daily for 2 weeks. Efficacy assessment was based on walking ability improvement using Timed-25-Foot Walk and 12-item Multiple Sclerosis Walking Scale tests. The mean Timed-25-Foot Walk score was reduced from 14.8 (±2.4) to 11.3 (±1.9) seconds (p = 0.01). The mean score on the 12-item Multiple Sclerosis Walking Scale was reduced from 41.2 (±3.5) to 31.4 (±3.2) (p = 0.004). Dalfampridine seems to be useful for symptomatic treatment of walking impairment in neuromyelitis optica spectrum disorder.

Do depressive and anxiety symptoms influence the construct validity of Multiple Sclerosis Walking Scale-12 scores?

Walking dysfunction, depression, and anxiety are prevalent, burdensome, and interrelated outcomes in persons with multiple sclerosis (MS). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a common patient-reported outcome (PRO) of walking dysfunction in research and practice involving MS, but the construct validity of its scores might be influenced by symptoms of depression and anxiety. This study examined if symptoms of depression and anxiety influenced the construct validity of MSWS-12 scores. The sample included 189 participants with MS who completed the MSWS-12, Hospital Anxiety and Depression Scale (HADS-Depression subscale [HADS-D] and HADS-Anxiety subscale [HADS-A]), 6-minute walk (6MW), and timed 25-foot walk (T25FW). We conducted bivariate correlation analysis to examine the associations between MSWS-12 scores and both the 6MW and T25FW, while controlling for HADS-D and HADS-A scores. MSWS-12 scores were significantly correlated with the 6MW (r = -.752), T25FW (r = .694), HADS-D (r = .405), and HADS-A (r = .235). The correlations between MSWS-12 and 6MW (pr = -.725) and T25FW (pr = .685) did not change when controlling for HADS-D and HADS-A scores. The correlations between MSWS-12 and 6MW (r = -.708 and r = -.726) and T25FW (r = .687 and r = .748) were strong in subsamples with elevated HADS-D and HADS-A scores. Our results strengthen the validity evidence for MSWS-12 scores as a PRO of walking dysfunction in MS, including among those with symptoms of depression and anxiety. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sedentary behaviour and related factors in people with multiple sclerosis

BackgroundSedentary behaviour is a major problem in persons with multiple sclerosis (pwMS). However, little is known about the related factors of sedentary behaviour in MS. Our study aimed to examine the association between sedentary behaviour and physical activity level, fear of falling, and fatigue. MethodDemographic and clinical data have been recorded. Sedentary behaviour was assessed with the Marshall Sitting Questionnaire, physical activity level was evaluated with the Godin Leisure Time Exercise Questionnaire, fear of falling was evaluated with the Fall Efficacy Scale International, and fatigue was evaluated with the modified fatigue impact scale (MFIS). The Timed 25-Foot Walk, 6-Minute Walk Test, Timed Up and Go Test, and 12-Item Multiple Sclerosis Walking Scale were also used to assess walking and perceived walking disability. ResultsWe recruited 71 pwMS [49 were female (69 %), mean age:38.08 years, median EDSS:1.5]. The mean daily sitting time was 593.54 min (∼10 h). No significant correlation was found between sitting times and demographics, leisure time physical activity, fear of falling, walking, perceived walking disability, and neurological disability level (p > 0.05). Logistic regression analysis indicated that being male increased the risk of sedentary behaviour by 3.08 times, being employed increased the risk of sitting by 4.65 times, and each point increase in MFIS scores resulted in a 1.03-fold elevation in the odds of prolonged sitting. ConclusionThe fact that pwMS, even with a mild disability spend almost 10 h sitting highlights the significance of sedentary behaviour in this population. Developing strategies to address modifiable factors, such as fatigue, may be effective in reducing sedentary behaviour.

Feasibility of Low-Load Resistance Training Using Blood Flow Restriction for People With Advanced Multiple Sclerosis: A Prospective Cohort Study.

The objective of this study was to determine the feasibility of low-load resistance training with blood flow restriction (BFR) for people with advanced disability due to multiple sclerosis (MS). In this prospective cohort study, 14 participants with MS (Expanded Disability Status Scale [EDSS] score = 6.0 to 7.0; mean age = 55.4 [SD = 6.2] years; 71% women) were asked to perform 3 lower extremity resistance exercises (leg press, calf press, and hip abduction) bilaterally twice weekly for 8weeks using BFR. Feasibility criteria were as follows: enrollment of 20 participants, ≥80% retention and adherence, ≥90% satisfaction, and no serious adverse events related to the intervention. Other outcomes included knee extensor, ankle plantar flexor, and hip abductor muscle strength, 30-Second Sit-to-Stand Test, Berg Balance Scale, Timed 25-Foot Walk Test, 12-Item MS Walking Scale, Modified Fatigue Impact Scale, Patient-Specific Functional Scale, and daily step count. Sixteen participants consented, and 14 completed the intervention, with 93% adherence overall. All participants were satisfied with the intervention. A minor hip muscle strain was the only intervention-related adverse event. There were muscle strength improvements on the more-involved (16%-28%) and less-involved (12%-19%) sides. There were also changes in the 30-Second Sit-to-Stand Test (1.9 repetitions; 95% CI = 1.0 to 2.8), Berg Balance Scale (5.3 points; 95% CI = 3.2 to 7.4), Timed 25-Foot Walk Test (-3.3seconds; 95% CI = -7.9 to 1.3), Modified Fatigue Impact Scale (-8.8 points; 95% CI = -16.5 to -1.1), 12-Item MS Walking Scale (-3.6 points; 95% CI = -11.5 to 4.4), Patient-Specific Functional Scale (2.9 points; 95% CI = 1.9 to 3.8), and daily step count (333 steps; 95% CI = -191 to 857). Low-load resistance training using BFR in people with MS and EDSS scores of 6.0 to 7.0 appears feasible, and subsequent investigation into its efficacy is warranted. Although efficacy data are needed, combining BFR with low-load resistance training may be a viable alternative for people who have MS and who do not tolerate conventional moderate- to high-intensity training because of more severe symptoms, such as fatigue and weakness. Low-load strength training with BFR was feasible in people who have advanced disability due to MS. Using BFR may provide an alternative for people with MS who do not tolerate higher intensity training due to more severe symptoms, such as fatigue and weakness.

Comparison of physical performance, gait, balance, falls efficacy, and step reaction time in individuals with multiple sclerosis

ObjectiveThe study aimed to investigate the physical performance, gait, balance, falls efficacy, and step reaction time in individuals with MS. MethodsA total of 60 individuals (30 individuals with MS and 30 age and sex-matched healthy controls) were enrolled. Individuals’ physical performance was evaluated with the Timed Up and Go Test (TUG) and Five-Times-Sit-to-Stand Test (FTSTS). Activities-specific Balance Confidence (ABC) Scale, 12-item Multiple Sclerosis Walking Scale (MSWS-12v2) and Falls Efficacy Scale International (FES-I) were used to assess the balance, gait and fall efficacy of the participants. Individuals' step reaction time (SRT) was calculated with video-based software. The time between the step command and the first contact of the foot with the ground in the first step was recorded. ResultsThe mean age of the individuals with MS and the control group was 38.5 ± 9.4 years and 33.9 ± 11.7 years, respectively. Significant differences existed between the groups in SRT, FES-I, ABC, and FTSTS (p < 0.05). There was no significant correlation between SRT with any other parameter (p > 0.05). TUG was moderately correlated with MSWS-12 and FES-I (r1 =0.426, r2 =0.495, p < 0.05). Besides, there was a moderate correlation between ABC with TUG and FTSTS (r1 =−0.605, r2 =−0.468, p < 0.05). A high degree correlation was found between MSWS-12 with FES-I and ABC (r1 =0.843, r2 =−0.834, p < 0.05). ConclusionIndividuals with MS have decreased SRTs. However, this condition was not found to be related to physical performance. Further studies should focus on the association of SRT with cognitive and psychosocial parameters.

A case series in individuals with multiple sclerosis using direct current electrical stimulation to inhibit spasticity and improve functional outcomes.

Multiple sclerosis (MS) has a high incidence of debilitating spasticity. Central Nervous System (CNS) intrafusal settings have an impact on spasticity level. Mechanoreceptors of the Peripheral Nervous System (PNS) communicate monosynaptically with the central nervous system (CNS). This case series assesses feasibility of multimodal treatment of individuals with MS using a direct current electrical stimulation (DC) to influence mechanoreceptors. Seven MS diagnosed participants with Expanded Disability Status Scale (EDSS) = 6.0-8.0 completed 18 visits over 6 weeks of using DC combined with neuromuscular reeducation. Design included pre-, post- outcome measures of EDSS, 12-item MS Walking Scale (MSWS-12), Range of Motion (ROM), Manual Muscle Testing (MMT), Modified Ashworth Test (MAT), Timed 25-Foot walk (T25WT), Timed Up and Go (TUG) and the Multiple Sclerosis Impact Scale-29 (MSIS-29). 125 out of a possible 126 visits were completed, demonstrating a high level of tolerance. Individual results included trends towards improvement in spasticity and agonists. This case series design of seven heterogenous subjects with MS is a low sample size for statistical analysis and should be considered a pilot. The study demonstrates a high level of feasibility and possible correlations to consider. Further research is warranted.

Association of Daily Physical Activity with Cervical Spinal Cord Areas in Multiple Sclerosis (S27.009)

Association of Daily Physical Activity with Cervical Spinal Cord Areas in Multiple Sclerosis (S27.009)

Reliability, Validity, and Responsiveness of the Patient-Specific Functional Scale for Measuring Mobility-Related Goals in People With Multiple Sclerosis.

This study's purpose was to investigate the reliability, validity, and responsiveness of the Patient-Specific Functional Scale (PSFS) for measuring mobility-related goals in people with multiple sclerosis (MS). Data from 32 participants with MS who underwent 8 to 10 weeks of rehabilitation were analyzed (Expanded Disability Status Scale scores 1.0-7.0). For the PSFS, participants identified 3 mobility-related areas where they had difficulty and rated them at baseline, 10 to 14 days later (before starting intervention), and immediately after intervention. Test-retest reliability and response stability of the PSFS were calculated using the intraclass correlation coefficient (ICC 2,1 ) and minimal detectable change (MDC 95 ), respectively. Concurrent validity of the PSFS was determined with the 12-item Multiple Sclerosis Walking Scale (MSWS-12) and the Timed 25-Foot Walk Test (T25FW). PSFS responsiveness was determined using Cohen's d , and minimal clinically important difference (MCID) was calculated based on patient-reported improvements on a Global Rating of Change (GRoC) scale. The PSFS total score demonstrated moderate reliability (ICC 2,1 = 0.70, 95% CI: 0.46 to 0.84) and the MDC was 2.1 points. At baseline, the PSFS was fairly and significantly correlated with the MSWS-12 ( r = -0.46, P = 0.008) but not with the T25FW. Changes in the PSFS were moderately and significantly correlated with the GRoC scale (ρ = 0.63, P < 0.001), but not with MSWS-12 or T25FW changes. The PSFS was responsive ( d = 1.7), and the MCID was 2.5 points or more to identify patient-perceived improvements based on the GRoC scale (sensitivity = 0.85, specificity = 0.76). This study supports the use of the PSFS as an outcome measure in people with MS to assess mobility-related goals.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A423 ).

Validity of the 30-Second Sit-to-Stand test as a measure of lower extremity function in persons with multiple sclerosis: Preliminary evidence.

The 30-Second Sit-To-Stand (30SSTS) is a quick, inexpensive, safe, and widely used clinical measure of lower extremity function. To date, there is limited evidence regarding the use of 30SSTS in multiple sclerosis (MS). The purpose of this study was to examine the construct validity of the 30SSTS test in persons with MS compared with non-MS healthy controls. Twenty ambulatory persons with MS and twenty age- and sex-matched healthy controls completed the 30SSTS, Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), Six-Minute Walk (6MW), and Godin Leisure-Time Exercise Questionnaire (GLTEQ). Persons with MS also completed the Patient Determined Disease Steps (PDDS) and 12-item MS Walking Scale (MSWS-12). Persons with MS had significantly worse performance on the TUG (mean difference [95% confidence interval]=1.4 [0.5, 2.3] sec) and 6MW (-259.2 [-450.8, -67.6] ft), but not on the 30SSTS (-1.6 [-1.5, 4.6] reps) and T25FW (-0.59 [-0.1, 1.2] ft/sec) compared with controls. There were significant moderate-to-strong correlations between the 30SSTS with T25FW, TUG, and 6MW scores in persons with MS (r=0.48, -0.65 and 0.61, respectively), whereas the 30SSTS was only significantly associated with 6MW scores (r=0.43) in controls. The 30SSTS was negatively associated with MS-related walking disability assessed by the PDDS and MSWS-12 (rs=-0.52 and -0.64, respectively), but was not significantly associated with the GLTEQ in MS and controls (r=0.30 and 0.17, respectively). This study provides initial support for the construct validity of the 30SSTS as a measure of lower extremity function in persons with MS. Our findings warrant the inclusion of the 30SSTS as a feasible and valid measure of physical function in clinical research and practice involving persons with MS.

Psychometric assessment of the Persian version of the patient determined disease steps scale in patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

Background: The purpose of this study was to evaluate the validity and reliability of the Persian version of Patient Determined Disease Steps (PDDS) in both patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Methods: One hundred and forty-five patients were enrolled between May and September 2020 by consecutive sampling. Participants were asked to complete timed 25-foot walk (T25FW), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and Multiple Sclerosis Quality of Life-54 (MSQOL-54). Patients also completed Timed Up and Go (TUG) and six-minute walk (6MW) tests. Construct validity was assessed by calculating correlation between PDDS and ambulatory and demographic items. The intra-class correlation coefficient (ICC) was used to evaluate reliability. Results: One hundred and eleven patients with MS and 34 with NMOSD with disease duration of 7.6 ± 5.8 years were enrolled. Twenty-seven percent were men and mean Expanded Disability Status Scale (EDSS) was 1.8 ± 1.8. There was a significant positive correlation between EDSS and PDSS (rho = 0.64, P < 0.001) which was evident in MS subgroups and NMOSD [secondary progressive MS (SPMS): rho = 0.64, P < 0.001; relapsing-remitting MS (RRMS): rho = 0.47, P < 0.001; NMOSD: rho = 0.52, P = 0.001]. PDDS had also significant positive correlation with TUG, T25FW, and MSWS-12. PDDS had also significant negative correlation with 6MW test. PDDS had weak correlation with demographic variables. The ICC was calculated as 0.99 for PDDS. Conclusion: The Persian version of PDDS provides valid and reliable instrument to assess MS/NMOSD-related disability.

Anterior horn atrophy in the cervical spinal cord: A new biomarker in progressive multiple sclerosis

Background: Spinal cord (SC) gray and white matter pathology plays a central role in multiple sclerosis (MS). Objective: We aimed to investigate the extent, pattern, and clinical relevance of SC gray and white matter atrophy in vivo. Methods: 39 relapsing–remitting patients (RRMS), 40 progressive MS patients (PMS), and 24 healthy controls (HC) were imaged at 3T using the averaged magnetization inversion recovery acquisitions sequence. Total and lesional cervical gray and white matter, and posterior (SCPH) and anterior horn (SCAH) areas were automatically quantified. Clinical assessment included the expanded disability status scale, timed 25-foot walk test, nine-hole peg test, and the 12-item MS walking scale. Results: PMS patients had significantly reduced cervical SCAH — but not SCPH — areas compared with HC and RRMS (both p < 0.001). In RRMS and PMS, the cervical SCAH areas increased significantly less in the region of cervical SC enlargement compared with HC (all p < 0.001). This reduction was more pronounced in PMS compared with RRMS (both p < 0.001). In PMS, a lower cervical SCAH area was the most important magnetic resonance imaging (MRI)-variable for higher disability scores. Conclusion: MS patients show clinically relevant cervical SCAH atrophy, which is more pronounced in PMS and at the level of cervical SC enlargement.

Objective and subjective measures of daily physical activity in persons with Multiple Sclerosis beginning a rehabilitation regime: A cross-sectional study

IntroductionFatigue, and balance and gait disorders can impact on physical activity (PA) levels in persons with Multiple Sclerosis (pwMS). To date, several studies have examined PA in pwMS during daily life, but little is known about PA levels in pwMS during a rehabilitation period. The present study investigated PA levels (daily steps, light physical activity (LPA), and moderate-vigorous physical activity (MVPA)) in inpatient and outpatients with MS during their rehabilitation period and described the relationship between objectively measured PA and levels of disability, quality of life, fatigue, and self-efficacy. MethodsIn this exploratory cross-sectional study, we examined 40 pwMS during their inpatient or outpatient rehabilitation regime. Participants included in the study (N = 34) wore a Fitbit Versa tracker for one week recording daily steps, minutes of LPA, and minutes of MVPA (primary outcomes). They underwent a clinical assessment of physical activity levels (Godin Leisure-Time Exercise Questionnaire(GLTEQ)), fatigue (Fatigue Severity Scale(FSS)), walking ability (10 Meter Walk Test(10MWT), 2-Min Walk Test(2MWT), 12-item Multiple Sclerosis Walking scale(MSWS-12)), quality of life (12-Item Short Form Survey (SF-12)), and self-efficacy (Self-Efficacy in Multiple Sclerosis scale (SEMS)) (secondary outcomes).Multiple linear regressions (MLR) models were used to test whether the demographic difference between the two groups influenced the estimation of objective variables measured by Fitbit. Finally, correlations between objectively measured physical activity and subjective clinical scales were estimated with Spearman correlations. ResultsOur sample consisted of 21 females and 13 males with a mean (interquartile range) age of 52 (20) years and an Expanded Disability Status scale(EDSS) score of 6.0 (1.50) points; baseline characteristics of inpatients (N = 18) and outpatients (N = 16) differed statistically only in EDSS levels (p-value = 0.008) and use of assistive devices (p=0.007). The whole sample performed (mean±standard deviation) 3969±2190 steps per day, with no significant difference between inpatients (3318±1515) and outpatients (4660±2606). No statistical difference was found between the groups in LPA (p-value=0.064). A significant difference in MVPA (p-value < 0.001) was found between inpatients and outpatients, 1.52±3.98 and 14.69±11.56 min per day, respectively. Significant correlations were found between FSS and MVPA both in the whole sample (r(32)= -0.62, p < 0.001) and in the outpatients group (r(14) = -0.66, p = 0.005), and between 10MWT and daily steps (whole sample:(r(32) = 0.48, p = 0.005), outpatients:(r(14)= -0.51, p = 0.05)). ConclusionsPwMS in our study overall engaged in reduced and less intense levels of daily PA with respect to the guidelines with inpatients performing almost no vigorous activities. Considering the importance of PA in improving physical and mental well-being, clinicians and researchers should develope strategies to increase daily PA of PwMS during their rehabilitation programs and daily life.

Detection of Fall Risk in Multiple Sclerosis by Gait Analysis-An Innovative Approach Using Feature Selection Ensemble and Machine Learning Algorithms.

One of the common causes of falls in people with Multiple Sclerosis (pwMS) is walking impairment. Therefore, assessment of gait is of importance in MS. Gait analysis and fall detection can take place in the clinical context using a wide variety of available methods. However, combining these methods while using machine learning algorithms for detecting falls has not been performed. Our objective was to determine the most relevant method for determining fall risk by analyzing eleven different gait data sets with machine learning algorithms. In addition, we examined the most important features of fall detection. A new feature selection ensemble (FS-Ensemble) and four classification models (Gaussian Naive Bayes, Decision Tree, k-Nearest Neighbor, Support Vector Machine) were used. The FS-Ensemble consisted of four filter methods: Chi-square test, information gain, Minimum Redundancy Maximum Relevance and RelieF. Various thresholds (50%, 25% and 10%) and combination methods (Union, Union 2, Union 3 and Intersection) were examined. Patient-reported outcomes using specialized walking questionnaires such as the 12-item Multiple Sclerosis Walking Scale (MSWS-12) and the Early Mobility Impairment Questionnaire (EMIQ) achieved the best performances with an F1 score of 0.54 for detecting falls. A combination of selected features of MSWS-12 and EMIQ, including the estimation of walking, running and stair climbing ability, the subjective effort as well as necessary concentration and walking fluency during walking, the frequency of stumbling and the indication of avoidance of social activity achieved the best recall of 75%. The Gaussian Naive Bayes was the best classification model for detecting falls with almost all data sets. FS-Ensemble improved the classification models and is an appropriate technique for reducing data sets with a large number of features. Future research on other risk factors, such as fear of falling, could provide further insights.

No association between body composition and walking outcomes in multiple sclerosis

BackgroundOne major concern of excess body weight is diminished physical function. The excess body weight associated with obesity can bring about challenges for physical function, particularly walking performance, among persons living with the consequences of a chronic, neurological disease. There is evidence that persons with multiple sclerosis (MS) have significantly reduced walking performance compared with controls; however, the relationship between body composition and walking outcomes has not been well-defined in persons with MS. To that end, the study examined the associations between body composition metrics and a comprehensive battery of walking outcomes in persons with MS recruited across a wide distribution of body mass index. MethodsAmbulatory participants with MS (n=64) underwent an assessment of neurological disability status using the Expanded Disability Status Scale (EDSS) and body composition metrics (i.e., percent body fat, fat mass, lean mass, bone mineral content and density) using dual-energy x-ray absorptiometry. Participants then completed the Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 6-Minute Walk (6MW), and 12-Item Multiple Sclerosis Walking Scale (MSWS-12). We examined Spearman rank-order bivariate correlations among percent body fat, fat mass, lean mass, bone mineral content and density, T25FW, TUG, 6MW, MSWS-12, and EDSS. ResultsBody composition metrics were not significantly associated with T25FW (rs=-.11, .12), TUG (rs=-.04, .11), 6MW (rs=-.01, .20), and MSWS-12 (rs=-.16, .03). Of note, body composition metrics were not correlated with disability status based on EDSS (rs=-.11, .03). Body composition metrics were not associated with walking outcomes even after controlling for EDSS. ConclusionOur data indicated that worse body composition profiles are not necessarily associated with worse walking performance, greater perception of MS-related walking impairment, or more severe disability status in MS. Future research may consider examining other health-related or disease outcomes of overweight or obesity in MS. Overall, our findings suggest that optimization of body composition may not be a target of interventions for improving walking outcomes, and future research might explore other factors that influence lower physical function in MS.

Identifying different cognitive phenotypes and their relationship with disability in neuromyelitis optica spectrum disorder.

BackgroundThe existence, frequency, and features of cognitive impairment (CI) in patients with neuromyelitis optica spectrum disorder (NMOSD) are still debated. A precise classification and characterization of cognitive phenotypes in patients with NMOSD are lacking.MethodsA total of 66 patients with NMOSD and 22 healthy controls (HCs) underwent a neuropsychological assessment. Latent profile analysis (LPA) on cognitive test z scores was used to identify cognitive phenotypes, and ANOVA was used to define the clinical features of each phenotype. Univariate and multivariate analyses were used to explore the predictors of severe CI, and a corresponding nomogram was created to visualize the predictive model.ResultsLPA results suggested four distinct meaningful cognitive phenotypes in NMOSD: preserved cognition (n = 20, 30.3%), mild-attention (n = 21, 31.8%), mild-multidomain (n = 18, 27.3%), and severe-multidomain (n = 7, 10.6%). Patients with the last three phenotypes were perceived to have CI, which accounts for 67.6% of patients with NMOSD. Patients with NMOSD and worse cognitive function were older (p < 0.001) and had lower educational levels (p < 0.001), later clinical onset (p = 0.01), worse Expanded Disability Status Scale scores (p = 0.001), and poorer lower-limb motor function (Timed 25-Foot Walk, p = 0.029; 12-item Multiple Sclerosis Walking Scale [MSWS-12], p < 0.001). Deterioration of Nine-Hole Peg Test (odds ratio, OR: 1.115 [1, 1.243], p = 0.05) and MSWS-12 (OR: 1.069 [1.003, 1.139], p = 0.04) were the independent risk factors for severe cognitive dysfunction. Finally, a nomogram was built based on the entire cohort and the above factors to serve as a useful tool for clinicians to evaluate the risk of severe cognitive dysfunction.ConclusionsWe introduced a classification scheme for CI and highlighted that the deterioration of upper- and lower-limb motor disability potentially predicts cognitive phenotypes in NMOSD.

Evaluation of neurotrophic factor secreting mesenchymal stem cells in progressive multiple sclerosis

Background: Autologous mesenchymal stem cell neurotrophic factor–secreting cells (NurOwn®) have the potential to modify underlying disease mechanisms in progressive multiple sclerosis (PMS). Objective: This open-label phase II study was conducted to evaluate safety/efficacy of three intrathecal cell treatments. Methods: Eighteen participants with non-relapsing PMS were treated. The primary endpoint was safety. Secondary endpoints included: cerebrospinal fluid (CSF) biomarkers; timed 25-foot walk speed, nine-hole peg test (9-HPT), low-contrast letter acuity, symbol digit modalities test, and 12-item multiple sclerosis (MS) walking scale. Seventeen participants received all treatments. Results: No deaths/adverse events related to worsening of MS, clinical/magnetic resonance imaging (MRI) evidence of disease activation, and clinically significant changes in safety lab results were reported. Two participants developed symptoms of low back and leg pain, consistent with a diagnosis of arachnoiditis, occurring in one of three intrathecal treatments in both participants. Nineteen percent of treated participants achieved pre-specified ⩾ 25% improvements in timed 25-foot walk speed/nine-HPT at 28 weeks compared to baseline, along with consistent efficacy signals for pre-specified response criteria across other secondary efficacy outcomes. CSF neuroprotective factors increased, and inflammatory biomarkers decreased after treatment, consistent with the proposed mechanism of action. Conclusion: Based on these encouraging preliminary findings, further confirmation in a randomized study is warranted.

Evaluation of functional outcome measures after fampridine treatment in patients with multiple sclerosis - An interventional follow-up study

ObjectiveThe purpose of this interventional study on participants with multiple sclerosis (MS) with walking disability was to evaluate changes in functional hand and walking measurements after fampridine treatment, after stratifying by the Expanded Disability Status Scale (EDSS). We furthermore wanted to investigate different functional measurements to evaluate their ability to detect responders to fampridine with a clinically relevant improvement. MethodsPatients were recruited from the MS Clinic at Odense University Hospital and were classified into two disability groups based on their EDSS score (moderate EDSS (EDSSMod) 4.5–5.5 [n = 19] and severe EDSS (EDSSSev) 6.0–7.0 [n = 14]). At baseline (visit 1) they completed the Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Nine Hold Peg Test (9HPT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and the Six Spot Step Test (SSST). Participants were given 10 mg twice daily fampridine for 14 days before retested (visit 2). For each measurement, cut-off values were used to define responders with a clinically relevant improvement to treatment. The measurements were evaluated separately and in combination. ResultsOf the 33 participants, 25 (75.8%) were identified as having a clinically relevant improvement (CRI). For all patients combined (EDSSAll), all five measurements showed significant functional improvement after treatment. For the individual measurements, the highest participant response rates after 14 days of fampridine treatment were seen on the MSWS-12 (57.6%) and 2MWT (42.4%). The 2MWT also showed the largest performance improvement (18.5%) from visit 1 to visit 2. For patients with severe disability (EDSSSev), no significant improvement was seen after fampridine treatment on the T25FW, and most of the responders to T25FW had moderate disability (EDSSMod, 71.5%). Conversely for the SSST, most responders were EDSSSev (83.3%). No participants had a clinically relevant improvement on the 9HPT. The combination of T25FW, SSST, and MSWS-12 was less sensitive in distinguishing responders from non-responders, whereas the combination of 2MWT and MSWS-12 identified the same responders and could better distinguish fampridine responders from non-responders. ConclusionEDSS level did not influence the effect of fampridine treatment on functional hand and walking measures and the responsiveness of the measurements differed only a little between moderate and severe EDSS levels. The combination of self-reported walking capacity (MSWS-12) and walking endurance (2MWT) was better than T25FW, SSST, and MSWS-12 at detecting clinically meaningful improvement after fampridine treatment, which could prove useful in the clinical monitoring of walking disabilities in MS during fampridine treatment.

Making Every Step Count: Minute-by-Minute Characterization of Step Counts Augments Remote Activity Monitoring in People With Multiple Sclerosis.

BackgroundAmbulatory disability is common in people with multiple sclerosis (MS). Remote monitoring using average daily step count (STEPS) can assess physical activity (activity) and disability in MS. STEPS correlates with conventional metrics such as the expanded disability status scale (Expanded Disability Status Scale; EDSS), Timed-25 Foot walk (T25FW) and timed up and go (TUG). However, while STEPS as a summative measure characterizes the number of steps taken over a day, it does not reflect variability and intensity of activity.ObjectivesNovel analytical methods were developed to describe how individuals spends time in various activity levels (e.g., continuous low versus short bouts of high) and the proportion of time spent at each activity level.Methods94 people with MS spanning the range of ambulatory impairment (unaffected to requiring bilateral assistance) were recruited into FITriMS study and asked to wear a Fitbit continuously for 1-year. Parametric distributions were fit to minute-by-minute step data. Adjusted R2 values for regressions between distributional fit parameters and STEPS with EDSS, TUG, T25FW and the patient-reported 12-item MS Walking scale (MSWS-12) were calculated over the first 4-weeks, adjusting for sex, age and disease duration.ResultsDistributional fits determined that the best statistically-valid model across all subjects was a 3-compartment Gaussian Mixture Model (GMM) that characterizes the step behavior within 3 levels of activity: high, moderate and low. The correlation of GMM parameters for baseline step count measures with clinical assessments was improved when compared with STEPS (adjusted R2 values GMM vs. STEPS: TUG: 0.536 vs. 0.419, T25FW: 0.489 vs. 0.402, MSWS-12: 0.383 vs. 0.378, EDSS: 0.557 vs. 0.465). The GMM correlated more strongly (Kruskal-Wallis: p = 0.0001) than STEPS and gave further information not included in STEPS.ConclusionsIndividuals' step distributions follow a 3-compartment GMM that better correlates with clinic-based performance measures compared with STEPS. These data support the existence of high-moderate-low levels of activity. GMM provides an interpretable framework to better understand the association between different levels of activity and clinical metrics and allows further analysis of walking behavior that takes step distribution and proportion of time at three levels of intensity into account.

Validity and reliability of the 3-meter backward walk test in patients with multiple sclerosis

BackgroundThe 3-meter backward walk test (3MBWT) evaluates neuromuscular control, proprioception, protective reflexes, fall risk, and balance. This study aimed to examine the reliability, validity, and minimal detectable change (MDC) of the 3MBWT in patients with Multiple Sclerosis (pwMS). Methods40 pwMS (8 male, 32 female) were included in the study. The Intraclass Correlation Coefficient (ICC) was used for the reliability of the 3MBWT. MDC estimates were calculated using baseline data. The validity of the 3MBWT was evaluated by the correlation between The Timed Up and Go test (TUG), The 12-item Multiple Sclerosis Walking Scale (MSWS-12), The 2 Min Walk Test (2MWT), The Timed 25-Foot Walk Test (T25FW), and The Four Square Step Test (FSST) ResultsThe intra-rater (ICC 0.944-0.945) and inter-rater (ICC 0.932-0.935) reliability of the 3MBWT was determined to be excellent. MDC values for intra-rater were 1.13-1.30 sec, and MDC values for inter-rater were 1.10-1.24 sec. The correlation with 3MBWT, TUG, MSWS-12, and 2MWT was found to be statistically significant. ConclusionThe 3MBWT was found to be valid and reliable in pwMS. It is a short and easily applied test in outpatient and inpatient clinics without any need for equipment. According to the MDC results, small differences in pwMS can be adequately detected with 3MBWT. Therefore, it may be a clinically suitable test for detecting subtle changes in synergistic motor functions related to prorioception in relapsing or remitting periods. It, also may add some more information on to EDSS data for following the disease progression as well as treatment responses.

Intensive Circuit Class Therapy in Patients with Relapsing-Remitting Multiple Sclerosis.

ObjectiveLong-term physiotherapy is of considerable benefit to patients with multiple sclerosis (MS) who have motor dysfunction or gait impairment. The aim of this study was to determine the effectiveness of a 12-week intensive circuit class therapy for patients with MS, with a wider focus on fatigue and gait ability.MethodsA total of 46 patients with relapsing-remitting MS were divided randomly into 2 groups: 23 patients (mean Expanded Disability Status Scale (EDSS) 2.33 ± 0.74) participated in an intensive 12-week course of intensive circuit class therapy, and 23 patients (mean EDSS 2.04 ± 0.63) served as a control group. The EDSS, Timed Up and Go (TUG) test and Four-Stage Balance Test (FSBT) made up the physical testing part, supplemented by questionnaires such as the Modified Fatigue Impact Scale (MFIS), 12-Item Multiple Sclerosis Walking Scale (MSWS-12), Beck Depression Inventory (BDI) and 36-Item Short Form Survey (SF-36).ResultsSignificant improvements were found among intensive circuit class therapy-exercising patients in FSBT (p < 0.05), TUG test (p < 0.01), MFIS (p < 0.01), BDI (p < 0.05), MSWS-12 (p < 0.05) and the 3 subscales of SF-36 after 12 weeks of intensive circuit class therapy, while there were no significant changes in the control group.ConclusionIntensive circuit class therapy is an effective therapeutic approach for improving gait and balance problems in patients with MS. It has also proved to alleviate fatigue and symptoms of depression.LAY ABSTRACTGait impairment and fatigue are among the most common manifestations of multiple sclerosis (MS). In this study we aimed to test the effect of 12-week intensive circuit class therapy (ICT) on motor skills and fatigue in MS patients. Forty-six MS patients with mild to moderate disability were randomly assigned to those who underwent the ICT, or to the control group. The ICT patients exercised intensively one day per week on nine different stations with two experienced physiotherapists, the control group patients continued their routine daily exercise. Intensively exercising MS patients then improved significantly in the overall balance, gait and fatigue parameters, while there was no significant improvement in the control group. These findings indicate that ICT is an effective therapy for MS patients with gait, balance or fatigue problems.