Alon Kalron

Responsiveness and Clinically Meaningful Improvement, According to Disability Level, of Five Walking Measures After Rehabilitation in Multiple Sclerosis A European Multicenter Study

Background. Evaluation of treatment effects on walking requires appropriate and responsive outcome measures. Objectives. To determine responsiveness of 5 walking measures and provide reference values for clinically meaningful improvements, according to disability level, in persons with multiple sclerosis (pwMS). Methods. Walking tests were measured pre- and postrehabilitation in 290 pwMS from 17 European centers. Combined anchor- and distribution-based methods determined responsiveness of objective short and long walking capacity tests (Timed 25-Foot Walk [T25FW] and 2- and 6-Minute Walk Tests [2MWT and 6MWT] and of the patient-reported Multiple Sclerosis Walking Scale–12 [MSWS-12]). A global rating of change scale, from patients’ and therapists’ perspective, was used as external criteria to determine the area under the receiver operating characteristic curve (AUC), minimally important change (MIC), and smallest real change (SRC). Patients were stratified into disability subgroups (Expanded Disability Status Scale score ≤4 [n = 98], >4 [n = 186]). Results. MSWS-12, 2MWT, and 6MWT were more responsive (AUC 0.64-0.73) than T25FW (0.50-0.63), especially in moderate to severely disabled pwMS. Clinically meaningful changes (MICs) from patient and therapist perspective were −10.4 and −11.4 for MSWS-12 (P < .01), 9.6 m and 6.8 m for 2MWT (P < .05), and 21.6 m (P < .05) and 9.1 m (P = .3) for 6MWT. In subgroups, MIC was significant from patient perspective for 2MWT (10.8 m) and from therapist perspective for MSWS-12 (−10.7) in mildly disabled pwMS. In moderate to severely disabled pwMS, MIC was significant for MSWS-12 (−14.1 and −11.9). Conclusions. Long walking tests and patient-reported MSWS-12 were more appropriate than short walking tests in detecting clinically meaningful improvement after physical rehabilitation, particularly the MSWS-12 for moderate to severely disabled pwMS.

Muscular and Gait Abnormalities in Persons With Early Onset Multiple Sclerosis

Background and Purpose: Muscular and gait abnormalities are common complaints among persons with multiple sclerosis, even in the early stages of the disease. Our aim was to evaluate peak isometric strength, major lower limb muscle fatigue, and spatiotemporal gait parameters in persons with a first neurological event suggestive of multiple sclerosis, defined as a clinically isolated syndrome (CIS). Methods: Fifty-two individuals (36 women, 16 men) with CIS, aged 35.2 (SD = 7.2) with an Expanded Disability Status Scale score of 1.7 (SD = 1.3), participated in the study. Peak isometric torque and fatigue index were measured at the knee and ankle bilaterally as well spatiotemporal parameters of gait. Twenty-eight age- and gender-matched healthy subjects served as controls. Results: The CIS group demonstrated increased muscle fatigue, and greater ankle muscle torque asymmetries compared with the control group. The overall fatigue index scores intensified on an average of 40% in the CIS group (27% vs 19% in controls). Participants in the CIS group walked with a larger step length difference, longer step time difference, wider base of support, and prolonged double support period compared with the control group. Positive correlations were identified between double support period and some muscle parameters. Discussion and Conclusion: At this early stage of clinically isolated syndrome, evidence of a reduction in lower limb motor performance can already be identified. The possibility of early identification and potential for developing an intervention program that may alter treatment outcome warrants further exploration.

Effect of Alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study

Context: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS); however, there is no medication that has been approved specifically to treat MS-related fatigue. Objective: We aimed to evaluate the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue. Design, settings, participants: This was a randomized, double-blind, parallel group, placebo-controlled trial in patients with clinically definite MS by McDonald criteria conducted in a single university-affiliated medical center in Israel. Randomly selected patients from the Sheba MS Registry computerized database (N=600) were assessed using the self-report Fatigue Severity Scale (FSS). Patients with clinically meaningful fatigue (N=259) were further assessed for trial eligibility, and MS patients with significant fatigue (N=158; 61%, 118 females, mean age 41.1 ± 9.2 years and mean disease duration of 6.2 ± 5.5 years) were included in the study and randomized to receive treatment or placebo. Intervention: Alfacalcidol (1 mcg/d, N=80) or placebo (N=78) was administered for six consecutive months. Main outcome measure: The primary endpoint of the study was the change between Alfacalcidol and placebo-treated patients in the Fatigue Impact Scale (FIS) score; the cut-off point for improvement was defined as 30% decrease. All analyses followed the intention-to-treat principle and were performed for all participants based on the group they were randomly allocated regardless of whether or not they dropped out. Results: Alfacalcidol decreased the mean relative FIS score as compared with placebo (–41.6% vs. –27.4%, p=0.007, respectively). This advantage was further emphasized when the modified FIS (MFIS) relative change was calculated. Quality of Life (QoL) improved in Alfacalcidol-treated patients as compared with placebo in the RAYS psychological (p=0.033) and social (p=0.043) sub-scales. The Alfacalcidol-treated group had reduced number of relapses (p=0.006) and higher proportion of relapse-free patients (p=0.007). Reduction of relapses by Alfacalcidol became significant at 4 months of treatment, was sustained at 6 months and decayed 2 months after drug discontinuation. Alfacalcidol treatment was safe and no serious adverse events were recorded. Conclusion: Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in patients with MS.

Postural control, falls and fear of falling in people with multiple sclerosis without mobility aids

The purpose of the study was to determine the relationship between static postural control parameters to fear of falling and falling history in people with multiple sclerosis (MS) without mobility assistive devices. One-hundred and seven relapsing-remitting patients diagnosed with MS, 62 women aged 42.8 (S.D.=12.0), participated in this investigation. Participants were divided into groups based on fall history; 47 had no history during the past 6 months and 60 had a history of at least one fall within the same period. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris® Medical GmbH, Germany). The patients self-reported questionnaire, the Falls Efficacy Scale International (FES-I), was used to assess the level of concern relating to falls. People with MS classified as fallers exhibited increased center of pressure (CoP) path length, sway velocity and greater overall sway area. CoP path length performed with eyes open was found to explain 42% of the variance related to at least one fall during the past six months; R(2)=0.424, χ(2)(1)=40.727, P<0.01. The correlation between the FES-I and CoP path length was 0.620 (P<0.001). Measurement of the CoP trajectories with instrumented posturography should be considered in managing fall risk in the MS population.

Quantifying Gait Impairment Using an Instrumented Treadmill in People with Multiple Sclerosis

Background and Objective. Treadmill gait analysis has been proposed as an attractive alternative for overground walking measuring systems. The purpose of this study was twofold: first to determine spatiotemporal parameters of treadmill gait in patients with multiple sclerosis (MS) and second to examine whether these parameters are associated with specific functional impairments in this cohort. Method. Eighty-seven relapsing-remitting patients diagnosed with MS, 50 women and 37 men, aged 40.9 ± 11.9 with an expanded disability status scale (EDSS) score of 2.7 ± 1.6, participated in this study. Twenty-five apparently healthy subjects, 14 women and 11 men, aged 38.5 ± 9.4, served as controls. Spatiotemporal gait parameters were obtained using the Zebris FDM-T Treadmill (Zebris Medical GmbH, Germany). People with MS demonstrated significantly shorter steps, extended stride time, wider base of support, longer step time, reduced single support phase, and a prolonged double support phase compared to the healthy controls. The EDSS score was significantly correlated with all spatiotemporal gait parameters. Conclusion. The instrumented treadmill may be an effective tool in assessing ambulation capabilities of people with MS.

The relationship between fear of falling to spatiotemporal gait parameters measured by an instrumented treadmill in people with multiple sclerosis

People with multiple sclerosis (MS) identify mobility limitations as one of the greatest challenges of this disease. Continued loss of mobility and falls are among their greatest concerns for the future. Our objective was to determine if fear of falling is associated with spatial and temporal gait parameters in persons with MS, when measured by an instrumented treadmill. This observational case control study was performed at the MS Center, Center of Advanced Technologies in Rehabilitation, Sheba Medical Center, Tel Hashomer, Israel. Sixty-eight relapsing-remitting patients diagnosed with MS, 38 women, aged 40.9 (S.D. = 11.9), participated in this investigation. Twenty-five healthy subjects, 14 women, aged 39.5 (S.D. = 9.4) served as controls gait controls. Gait spatiotemporal parameters were obtained using the Zebris FDM-T Treadmill (Zebris(®) Medical GmbH, Germany). The Falls Efficacy Scale International was used to assess the level of concern relating to falls. Forty-one people with MS were classified as highly fearful of falling. Twenty-seven patients were slightly concerned. Highly fearful of falling patients walked slower had a shorter step length, a wider base of support and prolonged double support phase compared to slightly concerned patients. Fearful patients also demonstrated elevated variability of the center of pressure (CoP) trajectory compared to slightly concerned MS patients. Fear of falling and spatiotemporal gait alterations in people with MS are linked. Additionally, variability of the CoP during walking appears to be connected with the level of concern.

Efficacy of exercise intervention programs on cognition in people suffering from multiple sclerosis, stroke and Parkinson's disease: A systematic review and meta-analysis of current evidence.

BACKGROUND Cognitive impairment is a well-established sequela of people suffering from neurological pathologies. OBJECTIVE To examine the effects of exercise intervention programs on cognitive performance in participants suffering from stroke, multiple sclerosis and Parkinsons disease. METHODS Four online databases (CINAHL, Cochrane Library, MEDLINE, PEDro) were comprehensively searched from their inception through December 2014. The search query was phrased as follows: In people suffering from MS, stroke or Parkinsons disease, do exercise intervention programs improve cognitive performance? RESULTS Twelve controlled clinical trials met our inclusion criteria. Studies were classified according to three clinical subgroups: Parkinsons disease (n = 3), stroke (n = 1) and multiple sclerosis (n = 8). Eight studies employed an aerobic intervention program; one used an active exercise program based on virtual reality systems, three reports examined the effect of yoga and one compared the intervention program with sport climbing. Significant improvements in cognition were found in nine out of the twelve studies. Nevertheless, the total effect size was non-significant (0.18 (95% CI, - 4.1, 3.8)) for changes in executive functions. CONCLUSION Due to lack of commonality between measures of cognition, training sequences and intervention period, it remains unclear as to whether exercise training can be effective in improving the cognitive functions of neurological patients.

Effects of a new sensory re-education training tool on hand sensibility and manual dexterity in people with multiple sclerosis

OBJECTIVE To describe and evaluate the effects of a new home-based sensory re-education training tool on hand sensibility and manual dexterity in people with MS experiencing upper limb sensory deficits. METHODS Twenty-five people with relapsing-remitting MS (18 women), mean age 50.6 years (SD = 11.4), volunteered to participate. Participants were initially assigned to a 7-week control phase followed by a 3-week home-based sensory re-education phase. Measurements used were the nine-hole peg test, the two point discrimination test, the monofilaments test and the functional dexterity test. Measurements were collected at baseline, following the control phase and at the end of the trial. RESULTS Participants demonstrated an improvement in the nine-hole peg (26.8 (SD = 3.5) vs. 22.6 (SD = 3.2); mean difference (95% CI) 4.9 (0.9, 7.1), P = 0.03) and functional dexterity tests (38.6 (SD = 4.4) vs. 33.8 (SD = 4.9); mean difference (95% CI) 4.8 (1.8, 7.0); P = 0.02) at the end of the sensory re-education phase compared to the end of the control phase. No differences were observed as to the monofilaments and two-point discrimination tests. CONCLUSIONS Sensory re-education training does not affect the level of sensory impairment in the hand but may lead to improvement in select measures of manual dexterity.

Association between perceived fatigue and gait parameters measured by an instrumented treadmill in people with multiple sclerosis: a cross-sectional study.

BackgroundMultiple sclerosis (MS) is a multi-focal progressive disorder of the central nervous system often resulting in diverse clinical manifestations. Symptomatic fatigue is quite common in people with MS (PwMS), with prevalence as high as 85%. Nevertheless, it remains poorly understood and its association with walking capabilities unclear. Therefore, the objective of this investigation was to examine the relationship between symptomatic fatigue and spatio-temporal parameters of gait in PwMS based on an instrumented treadmill.MethodsOne hundred and twenty-four relapsing-remitting patients diagnosed with MS, 84 women and 40 men aged 42.6 (S.D = 11.9), participated in this investigation. A convenience sample of 25 apparently healthy subjects, 15 women and 10 men aged 40.3 (S.D = 11.1), served as controls. Gait spatiotemporal parameters were obtained using the Zebris FDM-T Treadmill (Zebris1 Medical GmbH, Germany). The Modified Fatigue Impact Scale (MFIS), a self-reported questionnaire, was used to determine the level of symptomatic fatigue in the MS study group. PwMS were divided into two groups: fatigued and non-fatigued.ResultsForty-four PwMS were classified as suffering from fatigue (mean MFIS = 52.0, S.D = 13.7); 80 were classified as non-fatigued (mean MFIS = 14.5, S.D = 14.5). Individuals in the fatigued group walked slower than those in the non-fatigued group; 1.7 (S.D = 2.4) vs. 2.4 (S.D = 1.0); P < 0.001, respectively. Moreover, fatigued patients took smaller steps, had a shorter stride length, prolonged stance, double support phase and a shorter single support phase compared to the non-fatigued group. In the total group, fatigue was significantly correlated with 10 (out of 14) spatiotemporal parameters of gait, however, correlation scores <0.40 were considered as weak correlations. According to step one of the linear logistic regression analysis, the temporal gait component was found to explain 5.1% of the variance related to symptomatic fatigue, R2 = 0.051, χ2 (1) = 6.511, P = 0.011. Step two of the model added the gait spatial component, thus increasing the explaining variance to 9.3%; R2 = 0.093, χ2 (2) = 12.12, P = 0.002. The asymmetry gait parameter did not contribute to the equation.ConclusionsPerceived fatigue is related to walking speed in PwMS, nevertheless its contribution to level of fatigue is limited.

Gait and jogging parameters in people with minimally impaired multiple sclerosis

Increasing awareness of the significance of ambulatory limitations in people with multiple sclerosis (MS) requires a regular assessment of walking ability in order to monitor disease dynamics. However, it is questionable whether the standard tools are sufficiently sensitive to detect mobility deficits in patients who are minimally impaired. Therefore, the main objective of this study was to examine an extended assessment tool characterizing spatio-temporal parameters of gait and jogging in people with minimally impaired MS. Twenty relapsing remitting patients diagnosed with MS, 8 women and 12 men, aged 36.3 ± 9.2 y, EDSS mean score 1.8 ± 1.2, were recruited from the Multiple Sclerosis Center, Sheba Medical Center, Tel Hashomer, Israel to participate in the study. Twenty apparently healthy subjects (10 women and 10 men), aged 34.3 ± 7.4 years served as controls. Balance-, gait- and jogging-related spatio-temporal parameters were obtained using the Zebris FDM-T Treadmill (Zebris(®) Medical GmbH, Germany). Each subject completed a sequence of 3 jogging tests under different conditions. Gait and balance tests were performed prior and after jogging trials. When comparing gait evaluation, jogging revealed additional abnormalities in the MS group vs. the healthy controls. In addition to step time asymmetry and larger step width, jogging was associated with a slower self-selected velocity, shorter step length, longer stance phase and a prolonged double support phase. People minimally affected by MS have the ability to jog. However, clinicians should be aware of the possible deficits accompanying this popular activity.