Simplified indices of exercise tolerance in patients with multiple sclerosis and healthy subjects: A case-control study.

Among patients with multiple sclerosis (MS), the impairment of exercise tolerance is closely related to disability. Maximal oxygen uptake (VO2max ) is the gold standard to assess exercise tolerance in healthy subjects (HS). Among patients with MS, the accuracy of VO2max measurement is often impaired because the patients are unable to reach the maximal exercise intensity due to interdependent factors linked to the disease (such as pathological fatigue, pain, lack of exercise habit, and lack of mobility). This study assesses the accuracy of simplified indices for assessing exercise tolerance, which are more suitable in patients with MS. They are simple in the way they are either measurable during submaximal exercise (oxygen uptake efficiency slopes (OUES), physical working capacity at 75% of maximal heart rate (PWC75% ), oxygen consumption at a respiratory exchange ratio of 1 (VO2 @RER1)) or not based on gas exchange analysis (peak work rate (PWR)-based predictive equation and PWC75% ). All indices were significantly lower in the MS group compared to the HS group (P < .001). OUES appeared highly correlated (r > .70, P < .001) with VO2peak , in both groups, without difference between groups. PWR-based prediction of VO2peak showed a standard error of the estimate of 315 mL min-1 in HS and 176 mL min-1 in MS. PWC75% did not correlate to VO2peak in neither group. These findings suggest an impairment of exercise tolerance functions in mildly disabled persons with MS, independently from other factors. Submaximal indices involving gas exchange analysis or peakWR-based estimation of VO2peak are usable to accurately assess exercise tolerance.

The Effect of Adaptive Sports on Individuals with Acquired Neurological Disabilities and Its Role in Rehabilitation: A Systematic Review.

The aims of this systematic review were to report on the feasibility of adaptive sports for individuals with acquired central neurological lesion; to analyze the effects of this approach according to the domains of the International Classification of Functioning, Health and Disability (ICF); and to emit guiding points for future research. Two authors searched PubMed, Scopus, Cochrane, Pedro, and SPORTdiscus for eligible trials. Data concerning demographics, outcome measures, results, and conclusions were extracted, and a qualitative synthesis was performed. Adaptive sports seem to be a feasible, efficient, and cost-effective complement to conventional rehabilitation. Significant effects were found on all domains of the ICF, except "environmental factors." Key factors, such as intervention volume, intensity, and type, play a determining role. This review is the first to expose the beneficial effects of adaptive sports practice among individuals with neurological lesions by relying on prospective evidence.

Does Nordic Walking restore the temporal organization of gait variability in Parkinson's disease?

BACKGROUND: Gait disorders of Parkinson's disease (PD) are characterized by the breakdown of the temporal organization of stride duration variability that was tightly associated to dynamic instability in PD. Activating the upper body during walking, Nordic Walking (NW) may be used as an external cueing to improve spatiotemporal parameters of gait, such as stride length or gait variability, in PD. The aim of this study was to evaluate the beneficial effects of NW on temporal organization of gait variability and spatiotemporal gait variables in PD. METHODS: Fourteen mild to moderate PD participants and ten age-matched healthy subjects performed 2 × 12 min overground walking sessions (with and without pole in a randomized order) at a comfortable speed. Gait speed, cadence, step length and temporal organization (i.e. long-range autocorrelations; LRA) of stride duration variability were studied on 512 consecutive gait cycles using a unidimensional accelerometer placed on the malleola of the most affected side in PD patients and of the dominant side in healthy controls. The presence of LRA was determined using the Rescaled Range Analysis (Hurst exponent) and the Power Spectral Density (α exponent). To assess NW and disease influences on gait, paired t-tests, Z-score and a two-way (pathological condition x walking condition) ANOVA repeated measure were used. RESULTS: Leading to significant improvement of LRA, NW enhances step length and reduces gait cadence without any change in gait speed in PD. Interestingly, LRA and step length collected from the NW session are similar to that of the healthy population. CONCLUSION: This cross-sectional controlled study demonstrates that NW may constitute a powerful way to struggle against the randomness of PD gait and the typical gait hypokinesia. Involving a voluntary intersegmental coordination, such improvement could also be due to the upper body rhythmic movements acting as rhythmical external cue to bypass their defective basal ganglia circuitries. ETHICS COMMITTEE'S REFERENCE NUMBER: B403201318916 TRIAL REGISTRATION: NCT02419768.

Rhythmic arm movements are less affected than discrete ones after a stroke.

Recent reports indicate that rhythmic and discrete upper-limb movements are two different motor primitives which recruit, at least partially, distinct neural circuitries. In particular, rhythmic movements recruit a smaller cortical network than discrete movements. The goal of this paper is to compare the levels of disability in performing rhythmic and discrete movements after a stroke. More precisely, we tested the hypothesis that rhythmic movements should be less affected than discrete ones, because they recruit neural circuitries that are less likely to be damaged by the stroke. Eleven stroke patients and eleven age-matched control subjects performed discrete and rhythmic movements using an end-effector robot (REAplan). The rhythmic movement condition was performed with and without visual targets to further decrease cortical recruitment. Movement kinematics was analyzed through specific metrics, capturing the degree of smoothness and harmonicity. We reported three main observations: (1) the movement smoothness of the paretic arm was more severely degraded for discrete movements than rhythmic movements; (2) most of the patients performed rhythmic movements with a lower harmonicity than controls; and (3) visually guided rhythmic movements were more altered than non-visually guided rhythmic movements. These results suggest a hierarchy in the levels of impairment: Discrete movements are more affected than rhythmic ones, which are more affected if they are visually guided. These results are a new illustration that discrete and rhythmic movements are two fundamental primitives in upper-limb movements. Moreover, this hierarchy of impairment opens new post-stroke rehabilitation perspectives.

Noninvasive analysis of overactive muscle structure and elasticity after botulinum toxin type A injection: a systematic review and meta-analysis.

INTRODUCTION: Injections of botulinum toxin type A (BoNT-A) are the first-line treatment for spastic muscle overactivity (MO). Some authors observed that BoNT-A injections lead to changes in muscle structure and muscle elasticity that are probably not completely reversible. This possible effect is critical, as it could lead to negative impacts on the effectiveness of BoNT-A interventions. Our study aimed to evaluate the current literature regarding changes in muscle elasticity and structure after BoNT-A injection, by diagnostic imaging, in neurological populations with MO. Our second objective was to pool all articles published on this topic in order to provide a quantitative synthesis of the data. EVIDENCE ACQUISITION: A systematic search was conducted between October 2021 and April 2023 using different databases in accordance with PRISMA guidelines. Two independent reviewers screened articles for inclusion, extracted data, and evaluated methodological quality of the studies. A meta-analysis was performed to compare muscle elasticity and structure before and after BoNT-A injections. EVIDENCE SYNTHESIS: A sample of 34 studies was selected for qualitative review and 19 studies for quantitative review. Meta-analysis of pre-post studies demonstrated significant improvement with a medium effect size (standardized mean difference=0.74; 95% CI 0.46-1.02; P<0.001) of muscle elasticity assessed by ultrasound elastography (USE) 4 weeks after BoNT-A injection. No statistically significant difference was found for muscle thickness, pennation angle, and muscle echo-intensity assessed by magnetic resonance imaging and/or ultrasonography at short-term. On the other hand, normalized muscle volume decreased with a small effect size (standardized mean difference = -0.17; 95% CI -0.25 - -0.09; P<0.001) 6 months after BoNT-A injection. CONCLUSIONS: Muscle elasticity measured by USE improves with a temporary effect at short-term following BoNT-A injections. Synthesis of studies that assesses muscle structure is hindered by methodological differences between studies. However, based on a small amount of data, normalized muscle volume seems to decrease at long-term after BoNT-A injections in children with CP suggesting that the timing of re-injection should be considered with caution in this population. Further work should focus on the long-term effect of repeated injections on muscle structure and elasticity in neurological populations.

Comparison of the effects of rhythmic vibrotactile stimulations and rhythmic auditory stimulations on Parkinson's disease patients' gait variability: a pilot study.

INTRODUCTION: Parkinson's disease patients' gait is characterized by shorter step length, reduced gait velocity and deterioration of temporal organization of stride duration variability (modified Long Range Autocorrelations). The objective of this study was to compare effects of rhythmic auditory stimulations (RAS) and Rhythmic Vibrotactile Stimulations (RVS) on Parkinson's disease patients' gait. METHODS: Ten Parkinson's disease patients performed three walking conditions lasting 5-7 min each: control condition (CC), RAS condition and RVS condition. Inertial measurement units were used to assess spatiotemporal gait parameters. Stride duration variability was assessed in terms of magnitude using coefficient of variation and in terms of temporal organization (i.e., Long Range Autocorrelations computation) using the evenly spaced averaged Detrended Fluctuation Analysis (α-DFA exponent). RESULTS: Gait velocity was significantly higher during RAS condition than during CC (Cohen's d = 0.52) and similar to RVS condition (Cohen's d = 0.17). Cadence was significantly higher during RAS (Cohen's d = 0.77) and RVS (Cohens' d = 0.56) conditions than during CC. Concerning variability, no difference was found either for mean coefficient of variation or mean α-DFA between conditions. However, a great variability of individual results between the RAS and the RVS conditions is to be noted concerning α-DFA. CONCLUSIONS: RAS and RVS improved similarly PD patients' spatiotemporal gait parameters, without modifying stride duration variability in terms of magnitude and temporal organization at group level. Future studies should evaluate the relevant parameters for administering the right cueing type for the right patient. TRIAL REGISTRATION: ClinicalTrial.gov registration number NCT05790759, date of registration: 16/03/2023, retrospectively registered.

Validation of the French version of the Multiple Sclerosis Intimacy And Sexuality Questionnaire-19: A preliminary study.

INTRODUCTION: Patients with multiple sclerosis (MS) suffer from various symptoms, including sexual dysfunction. The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a scale that explores the impact of MS on sexual activity and satisfaction. AIM: This observational cohort study aimed to provide a validated, cross-cultural, French version of the MSISQ-19 in patients with MS. METHODS: The original version of MSISQ-19 was translated into French according to standardized guidelines. Patients were asked to complete all questionnaires during the inclusion visit and the MSISQ-19 a second time two weeks later. Content validity was assessed by face validity. Internal consistency was evaluated using Cronbach's alpha. Construct validity was checked by the exploratory factor analysis. Concurrent validity was assessed by performing Spearman's correlation coefficient with the Female Sexual Function Index (FSFI), the Male Sexual Health Questionnaire (MSHQ), and the Multiple Sclerosis International Quality of Life questionnaire (MusiQoL). Spearman's correlation coefficient was also used to evaluate the relationship with the Expanded Disability Status Scale (EDSS), age, and disease duration. Test-retest reliability was assessed by intraclass correlation coefficient (ICC). Responsiveness was assessed by the standard error of measurement (SEM) and the minimum detectable change (MDC). MAIN OUTCOME MEASURES: MSISQ-19 is the main outcome measure. RESULTS: We enrolled 71 patients with MS (49 female, 22 male). The mean age was 42.6 ± 9.7 years with a median disease duration of 8 [3-16] years. Sixty-four (90%) patients had relapsing-remitting MS, 4 (6%) primary progressive MS, and 3 (4%) secondary progressive MS. French MSISQ-19 showed a Cronbach's alpha coefficient of 0.89. MSISQ-19 scores correlated significantly and moderately between each other and correlated significantly and moderately with scores on the FSFI, MSHQ, MusiQoL and EDSS. Reproducibility was excellent with intraclass correlation coefficients > 0.80. Exploratory factor analysis was performed using principal component analysis. A three-factor solution was adopted giving eigenvalues higher than 1, supporting the primary, secondary, and tertiary dimensions. SEM was 4.55 and MDC was 12.6 (13.3%). CONCLUSION: This study provides a preliminary validation of the French version of the MSISQ-19 which could be a reliable, and reproducible instrument to assess sexual dysfunction in patients with MS. These results need to be confirmed in a larger cohort which will be more representative of the general MS population.

Self-Rehabilitation for Post-Stroke Motor Function and Activity-A Systematic Review and Meta-Analysis.

Background. Due to an increasing stroke incidence, a lack of resources to implement effective rehabilitation and a significant proportion of patients with remaining impairments after treatment, there is a rise in demand for effective and prolonged rehabilitation. Development of self-rehabilitation programs provides an opportunity to meet these increasing demands.Objective. The primary aim of this meta-analysis was to determine the effect of self-rehabilitation on motor outcomes, in comparison to conventional rehabilitation, among patients with stroke. The secondary aim was to assess the influence of trial location (continent), technology, time since stroke (acute/subacute vs chronic), dose (total training duration > vs ≤ 15 hours), and intervention design (self-rehabilitation in addition/substitution to conventional therapy) on effect of self-rehabilitation.Methods. Studies were selected if participants were adults with stroke; the intervention consisted of a self-rehabilitation program defined as a tailored program where for most of the time, the patient performed rehabilitation exercises independently; the control group received conventional therapy; outcomes included motor function and activity; and the study was a randomized controlled trial with a PEDro score ≥5.Results. Thirty-five trials were selected (2225 participants) and included in quantitative synthesis regarding motor outcomes. Trials had a median PEDro Score of 7 [6-8]. Self-rehabilitation programs were shown to be as effective as conventional therapy. Trial location, use of technology, stroke stage, and intervention design did not appear to have a significant influence on outcomes.Conclusion. This meta-analysis showed low to moderate evidence that self-rehabilitation and conventional therapy efficacy was equally valuable for post-stroke motor function and activity.

Effects of prolonged-release fampridine on multiple sclerosis-related gait impairments. A crossover, double-blinded, placebo-controlled study.

BACKGROUND: People with multiple sclerosis have reduced walking speed and impaired gait pattern. Prolonged release-fampridine is a potassium channel blocker that improves nerve conduction in patients with multiple sclerosis, leading to walking benefits. Whether fampridine alters gait pattern is unknown. METHODS: In this crossover, randomized controlled trial, patients with multiple sclerosis were tested for responder status during a 4-week run-in period. Patients were considered responders if they improved their 25-ft walk test by 10% and improved their perceived walking capacity. Responders were randomized to prolonged release-fampridine (10 mg b.i.d.) or placebo for a 6-week period. After a 2-week wash-out period, they were allocated to the other treatment for 6 weeks. Participants were assessed before and after both conditions. Three-dimensional gait analysis assessed kinematic, kinetic, mechanic and energetic variables while walking on a treadmill at comfortable speed. Six-minute walk test and 25-ft walk test were used to assess walking speed on middle and short-distances, respectively. Patient-reported outcome measures were also used. Repeated measures ANCOVAs were applied to assess the treatment effects. FINDINGS: Out of 39 included patients, 24 responders (12 women; Expanded Disability Status Scale:4.25[4-5]; age:46 ± 10 years; maximal speed:0.93 ± 0.38 m·s-1) were identified. Among them, prolonged release-fampridine reduced the external mechanical work (-0.039 J·kg-1·m-1;p = 0.02), and improved knee flexion during swing phase (+5.3°; p = 0.02). No differences were found in other walking tests and patient-reported outcomes, at group-level. INTERPRETATION: Prolonged release-fampridine increases knee flexion during swing phase and lowers mechanical external work. Whether these changes are related to clinically meaningful improvements in walking capacity and other functional variables should be further investigated.

Effectiveness of a self-rehabilitation program to improve upper-extremity function after stroke in developing countries: A randomized controlled trial.

BACKGROUND: About two-thirds of stroke patients present long-term upper-limb impairment and limitations of activity, which constitutes a challenge in rehabilitation. This situation is particularly true in developing countries, where there is a need for inexpensive rehabilitation solutions. OBJECTIVE: This study assessed the effectiveness of a self-rehabilitation program including uni- or bi-manual functional exercises for improving upper-limb function after stroke with respect to the context in Benin, West Africa. METHODS: In this single-blind randomized controlled trial, chronic stroke individuals (>6 months post-stroke) performed a supervised home-based self-rehabilitation program for 8 weeks (intervention group); the control group did not receive any treatment. Participants were assessed before treatment (T0), at the end of treatment (T1) and 8 weeks after the end of treatment (T2). The primary outcome was the manual ability of the upper limb, assessed with ABILHAND-Stroke Benin. Secondary outcomes were grip force, motor impairment (Fugl-Meyer Assessment - Upper Extremity), gross manual ability (Box and Block test, Wolf Motor Function test) and quality of life (WHOQOL-26). RESULTS: We included 28 individuals in the intervention group and 31 in the control group. Adherence to the program was 83%. After 8 weeks of self-rehabilitation, individuals in the intervention group showed significantly improved manual ability and grip force as compared with the control group (P<0.001), with effect size 0.75 and 0.24, respectively. In the intervention group, the difference in average scores was 10% between T0 and T1 and between T0 and T2. Subscores of physical and psychological quality of life were also significantly improved in the intervention group. The other variables remained unchanged. CONCLUSIONS: A self-rehabilitation program was effective in improving manual ability, grip force and quality of life in individuals with stroke in Benin. More studies are needed to confirm these results in different contexts.

Gait rehabilitation after stroke: review of the evidence of predictors, clinical outcomes and timing for interventions.

The recovery of walking capacity is one of the main aims in stroke rehabilitation. Being able to predict if and when a patient is going to walk after stroke is of major interest in terms of management of the patients and their family's expectations and in terms of discharge destination and timing previsions. This article reviews the recent literature regarding the predictive factors for gait recovery and the best recommendations in terms of gait rehabilitation in stroke patients. Trunk control and lower limb motor control (e.g. hip extensor muscle force) seem to be the best predictors of gait recovery as shown by the TWIST algorithm, which is a simple tool that can be applied in clinical practice at 1 week post-stroke. In terms of walking performance, the 6-min walking test is the best predictor of community ambulation. Various techniques are available for gait rehabilitation, including treadmill training with or without body weight support, robotic-assisted therapy, virtual reality, circuit class training and self-rehabilitation programmes. These techniques should be applied at specific timing during post-stroke rehabilitation, according to patient's functional status.

Influence of Autocorrelated Rhythmic Auditory Stimulations on Parkinson's Disease Gait Variability: Comparison With Other Auditory Rhythm Variabilities and Perspectives.

Parkinson's Disease patients suffer from gait impairments such as reduced gait speed, shortened step length, and deterioration of the temporal organization of stride duration variability (i.e., breakdown in Long-Range Autocorrelations). The aim of this study was to compare the effects on Parkinson's Disease patients' gait of three Rhythmic Auditory Stimulations (RAS), each structured with a different rhythm variability (isochronous, random, and autocorrelated). Nine Parkinson's Disease patients performed four walking conditions of 10-15 min each: Control Condition (CC), Isochronous RAS (IRAS), Random RAS (RRAS), and Autocorrelated RAS (ARAS). Accelerometers were used to assess gait speed, cadence, step length, temporal organization (i.e., Long-Range Autocorrelations computation), and magnitude (i.e., coefficient of variation) of stride duration variability on 512 gait cycles. Long-Range Autocorrelations were assessed using the evenly spaced averaged Detrended Fluctuation Analysis (α-DFA exponent). Spatiotemporal gait parameters and coefficient of variation were not modified by the RAS. Long-Range Autocorrelations were present in all patients during CC and ARAS although all RAS conditions altered them. The α-DFA exponents were significantly lower during IRAS and RRAS than during CC, exhibiting anti-correlations during IRAS in seven patients. α-DFA during ARAS was the closest to the α-DFA during CC and within normative data of healthy subjects. In conclusion, Isochronous RAS modify patients' Long-Range Autocorrelations and the use of Autocorrelated RAS allows to maintain an acceptable level of Long-Range Autocorrelations for Parkinson's Disease patients' gait.

Telecommunication and rehabilitation for patients with multiple sclerosis: access and willingness to use. A cross-sectional study.

BACKGROUND: Telerehabilitation is a promising approach for patients with multiple sclerosis (MS), but uncertainties regarding patients' access and preferences remain. AIM: To investigate the access to telecommunication technologies and rehabilitation services of patients with MS, and their willingness to use these technologies for rehabilitation. DESIGN: Cross-sectional survey. SETTING: Outpatient neurological facility. POPULATION: Patients with MS. METHODS: Patients with MS attending consultations in the Neurology department were asked to fill in a paper questionnaire. This anonymous z was designed to gain information about needs and access to rehabilitation and telecommunication technologies, as well as interests and perspectives of telerehabilitation among these patients. Descriptive statistics, Chi-squared tests and logistic regressions were used to describe the sample and survey answers. RESULTS: Two hundred patients completed the questionnaire. Mean age was 44.41(±12.52) years. Seventy-one percent were women, and 49% were unemployed. Ninety-one percent of the patients regularly used internet and 73% used apps. Most patients were interested in using telecommunication technologies to receive a program of physical exercises (62%), for information and personalized advice about physical activity and MS (69%), and to communicate with caregivers (75%). Patients with EDSS>4 were less interested than patients with EDSS≤4 in communicating with the caregivers via apps (33% vs. 52%,Δ19%[CI-36%;-2%],P=0.04) but expressed greater interest in receiving information and personal advice about physical activity and MS via the internet (70% vs. 51%,Δ19%[CI+2%;+36%],P=0.03). One third of the patients was not interested in receiving telerehabilitation interventions (32%), notably patients with EDSS>4 and non-workers. CONCLUSIONS: Patients with MS are mainly interested in using telecommunication technologies for rehabilitation services, and most of these patients have access to the required technology. Being mildly disabled and having a professional activity are associated with a greater interest in telerehabilitation. In contrary, patients with moderate-to-severe disability and non-workers have reportedly less access and ease in using the required technologies. CLINICAL REHABILITATION IMPACT: Telerehabilitation is feasible and wished by patients with MS, specifically in patients with low EDSS scores and workers. Given the strong need for rehabilitation in more disabled patients, the barriers to its access, the lower access and ease of use of telecommunication technologies, a special effort is needed to facilitate their use in these patients.

Immersive Virtual Reality to Restore Natural Long-Range Autocorrelations in Parkinson's Disease Patients' Gait During Treadmill Walking.

Effects of treadmill walking on Parkinson's disease (PD) patients' spatiotemporal gait parameters and stride duration variability, in terms of magnitude [coefficient of variation (CV)] and temporal organization [long range autocorrelations (LRA)], are known. Conversely, effects on PD gait of adding an optic flow during treadmill walking using a virtual reality headset, to get closer to an ecological walk, is unknown. This pilot study aimed to compare PD gait during three conditions: Overground Walking (OW), Treadmill Walking (TW), and immersive Virtual Reality on Treadmill Walking (iVRTW). Ten PD patients completed the three conditions at a comfortable speed. iVRTW consisted in walking at the same speed as TW while wearing a virtual reality headset reproducing an optic flow. Gait parameters assessed were: speed, step length, cadence, magnitude (CV) and temporal organization (evenly spaced averaged Detrended Fluctuation Analysis, α exponent) of stride duration variability. Motion sickness was assessed after TW and iVRTW using the Simulator Sickness Questionnaire (SSQ). Step length was greater (p = 0.008) and cadence lower (p = 0.009) during iVRTW compared to TW while CV was similar (p = 0.177). α exponent was similar during OW (0.77 ± 0.07) and iVRTW (0.76 ± 0.09) (p = 0.553). During TW, α exponent (0.85 ± 0.07) was higher than during OW (p = 0.039) and iVRTW (p = 0.016). SSQ was similar between TW and iVRTW (p = 0.809). iVRTW is tolerable, could optimize TW effects on spatiotemporal parameters while not increasing CV in PD. Furthermore, iVRTW could help to capture the natural LRA of PD gait in laboratory settings and could potentially be a challenging second step in PD gait rehabilitation.

Is cognition considered in post-stroke upper limb robot-assisted therapy trials? A brief systematic review.

The aim of this systematic review was, first, to determine whether or not individuals with cognitive deficits after stroke were enrolled in trials that investigated upper limb robot-assisted therapy effectiveness, and, second, whether these trials measured cognitive outcomes. We retrieved 6 relevant systematic reviews covering, altogether, 66 articles and 2214 participants. Among these 66 clinical trials, only 10 (15%) enrolled stroke participants with impaired cognition, whereas 50 (76%) excluded those with impaired cognition. The remaining six trials (9%) were classified as unclear as they either excluded individuals unable to understand simple instructions or did not specify if those with cognitive disorders were included. Furthermore, only 5 trials (8%) used cognitive measures as outcomes. This review highlights a lack of consideration for individuals with cognitive impairments in upper limb robotic trials after stroke. However, cognition is important for complex motor relearning processes and should not be ignored.

Efficacy and Safety of AbobotulinumtoxinA for the Treatment of Hemiparesis in Adults with Lower Limb Spasticity Previously Treated With Other Botulinum Toxins: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To examine the safety and efficacy of abobotulinumtoxinA in patients previously treated with botulinum toxin type A (BoNT-A) products other than abobotulinumtoxinA. DESIGN: Secondary analysis from a phase 3, double-blind, single-cycle, randomized, placebo-controlled study. SETTING: Fifty-two centers (11 countries). PATIENTS: Adults with spastic hemiparesis were randomized (1:1:1) to receive abobotulinumtoxinA 1000 U, 1500 U, or placebo in their affected lower limb. MAIN OUTCOME MEASUREMENTS: Muscle tone (6-point Modified Ashworth Scale [MAS], 0-5) for the gastrocnemius-soleus complex (GSC); proportion of MAS responders (≥1-point improvement); angle of catch (XV3 ) and spasticity grade (Y) for the GSC and soleus. Assessments were at weeks 1, 4, and 12 post-injection. Only descriptive statistics are presented. RESULTS: Of 388 patients, 84 received previous BoNT-A treatment (abobotulinumtoxinA 1000 U: N = 30; abobotulinumtoxinA 1500 U: N = 28; placebo: N = 26). At week 4, mean (SD) changes in MAS score in the GSC were - 0.8 (1.1), -0.9 (1.0), and - 0.4 (0.7) for abobotulinumtoxinA 1000 U, 1500 U, and placebo, respectively. Greater MAS responder rates were observed for abobotulinumtoxinA versus placebo at all time points. Mean (SD) changes (week 4) for abobotulinumtoxinA 1000 U, 1500 U, and placebo for XV3 were: GSC, 8° (21), 6° (10) and 1° (7); soleus, 11° (21), 5° (9) and 0° (8), respectively; for Y: GSC, -0.4 (0.7), -0.6 (0.8) and - 0.0 (0.9); soleus, -0.5 (0.7), -0.5 (0.7) and - 0.1 (0.6), respectively. Safety data and adverse events were consistent with the overall known profile of abobotulinumtoxinA. CONCLUSIONS: Patients previously treated with other BoNT-As showed improved muscle tone and spasticity at week 4 following abobotulinumtoxinA injection versus placebo. These findings suggest that abobotulinumtoxinA, at the recommended doses, has a good safety and efficacy profile in adults with lower limb spasticity who were previously treated with other BoNT-A products.

Rhythmic robotic training enhances motor skills of both rhythmic and discrete upper-limb movements after stroke: a longitudinal pilot study.

Discrete and rhythmic movements are two fundamental motor primitives being, at least partially, controlled by separate neural circuitries. After a stroke, both primitives may be impaired in the upper limb. Currently, intensive functional movement therapy is recommended after stroke, but it is mainly composed of discrete movements. No recommendation is made for the specific training of rhythmic movements. However, if they form two different primitives, both should receive a specific training to recover the complete motor repertoire, as many daily live movements integrate both of them. This paper reports the effects of a pure unilateral rhythmic movement therapy on motor performance, after stroke. Thirteen patients with chronic stroke participated in this longitudinal pilot study. They were assessed twice before the therapy to validate their chronic state, and twice after the last session to establish the short-term and long-term effects of the therapy. The therapy itself was composed of 12 sessions spread over 1 month. The exercises consisted in performing straight or circular rhythmic movements, while receiving assistance as need through a robotic device. Short-term and long-term improvements were observed in rhythmic movements regarding smoothness, velocity, and harmonicity. More surprisingly, some transfer occurred to the untrained discrete movements. This finding disputes previous studies that reported no transfer from rhythmic to discrete movements with healthy participants.

Timed Up-and-Go and 2-Minute Walk Test in patients with multiple sclerosis with mild disability: reliability, responsiveness and link with perceived fatigue.

BACKGROUND: Mobility limitations are frequent in patients with multiple sclerosis (MS), and could already be present in patients with so-called mild neurological disability (Expanded Disability Status Scale≤4). Assessing mobility in these patients is therefore of paramount importance. Timed Up-and-Go Test (TUG) and 2-Minute Walk Test (2MWT) are two clinically feasible tests which reliability and responsiveness are unknown among these patients. Whether fatigue, which is the number one symptom among these patients, is linked to these limitations remains unknown. AIM: The aim of this study was to explore the intrarater reliability and minimal detectable change (MDC95), as an index of responsiveness, of TUG and 2MWT. To explore their link with perceived fatigue among patients with MS. DESIGN: Cross-sectional observational study, including two measures. SETTING: Two university hospital outpatient centers. POPULATION: Patients (N.=63, 49 seen twice) with MS with mild disability (Expanded Disability Status Scale≤4). METHODS: 2MWT and TUG were performed twice in one occasion, and repeated 2 weeks later. Modified fatigue impact scale (MFIS) was used to assess fatigue. Intraclass coefficient correlations were calculated for immediate and 2-week reliability. MDC95 were computed. Correlations between mobility indices and fatigue were explored using Spearman's ρ. RESULTS: Mobility was impaired in comparison to normative values (2MWT: -4.9% from normative distance; TUG: +32% from normative time). The immediate reliability was excellent for both the 2MWT (ICC=0.98) and TUG (ICC=0.98). Reliability at 2 weeks was excellent for 2MWT (ICC=0.95) and very good for TUG (ICC=0.90). MDC95 were respectively 20m (2MWT) and 1.3s (TUG). Both measures were significantly weakly correlated to total MFIS (ρ=-0.37 and 0.39, respectively; P<0.01). CONCLUSIONS: The 2MWT and TUG are highly reliable and responsive in the assessment of respectively the walking capacity and general mobility of patients with MS with mild disability. Mobility impairments are linked to perceived fatigue among these patients. CLINICAL REHABILITATION IMPACT: TUG and 2MWT are easy to administer and could be reliably used in so called mildly disabled patients with MS to assess mobility limitation.

Effectiveness of upper-limb robotic-assisted therapy in the early rehabilitation phase after stroke: A single-blind, randomised, controlled trial.

BACKGROUND: Upper-limb robotic-assisted therapy (RAT) is promising for stroke rehabilitation, particularly in the early phase. When RAT is provided as partial substitution of conventional therapy, it is expected to be at least as effective or might be more effective than conventional therapy. Assessments have usually been restricted to the first 2 domains of the International classification of functioning, disability and health (ICF). OBJECTIVE: This was a pragmatic, multicentric, single-blind, randomized controlled trial to evaluate the effectiveness of upper-limb RAT used as partial substitution to conventional therapy in the early phase of stroke rehabilitation, following the 3 ICF domains. METHODS: We randomized 45 patients with acute stroke into 2 groups (conventional therapy, n=22, and RAT, n=23). Both interventions were dose-matched regarding treatment duration and lasted 9 weeks. The conventional therapy group followed a standard rehabilitation. In the RAT group, 4 sessions of conventional therapy (25%) were substituted by RAT each week. RAT consisted of moving the paretic upper limb along a reference trajectory while the robot provided assistance as needed. A blinded assessor evaluated participants before, just after the intervention and 6 months post-stroke, according to the ICF domains UL motor impairments, activity limitations, and social participation restriction. RESULTS: In total, 28 individuals were assessed after the intervention. The following were more improved in the RAT than conventional therapy group at 6 months post-stroke: gross manual dexterity (Box and Block test +7.7 blocks; P=0.02), upper-limb ability during functional tasks (Wolf Motor Function test +12%; P=0.02) and patient social participation (Stroke Impact Scale +18%; P=0.01). Participants' abilities to perform manual activities and activities of daily living improved similarly in both groups. CONCLUSION: For the same duration of daily rehabilitation, RAT combined with conventional therapy during the early rehabilitation phase after stroke is more effective than conventional therapy alone to improve gross manual dexterity, upper-limb ability during functional tasks and patient social participation.

Effects of Fampridine in People with Multiple Sclerosis: A Systematic Review and Meta-analysis.

BACKGROUND: Prolonged-release (PR) fampridine is a potassium channel blocker used as a symptomatic treatment for walking disability in patients with multiple sclerosis (MS). Its clinical effects in such patients have not been systematically reviewed, and may be more wide-ranging than expected. OBJECTIVES: To summarize the evidence on the effects of PR fampridine in patients with MS. METHODS: A systematic search of Pubmed, Scopus (including EMBASE), and PsycINFO (completed in 01/2019) was carried out to identify randomized controlled trials (RCT) that compared PR fampridine to placebo. When appropriate, data were pooled using a random-effects model, and standardized mean differences (SMD) were computed. Study quality was assessed using the Downs and Black checklist. PRISMA guidelines were followed. All retrieved functional outcomes were categorized according to the International Classification of Functioning, Disability and Health (ICF). RESULTS: A total of 706 articles were screened for inclusion. Twenty RCTs involving 2616 patients met the eligibility criteria. Most studies were of good-to-excellent quality. PR fampridine administration resulted in significant benefits in relation to walking short distances (SMD: 1.23 (95% IC 0.65-1.81)) and perceived walking capacity (0.64 (0.27-1.02)). Its effects on muscle strength and middle-distance walking were not significant (0.53 (- 0.04 to 1.10) and 0.31 (- 0.18 to 0.80), respectively). No effect on higher-level cognitive functions (- 0.07 (- 0.58 to 0.45)) or hand and arm use (0.16 (- 0.33 to 0.64)) was observed. Individual studies reported effects on other outcomes across the ICF domains. CONCLUSIONS: There is strong evidence that PR fampridine exerts strong effects on the ability to walk short distances and on perceived walking capacity. Other effects of PR fampridine according to the ICF are possible but still unclear.