Evidence of rTMS for Motor or Cognitive Stroke Recovery: Hype or Hope?

BACKGROUND: Evidence of efficacy of repetitive transcranial magnetic stimulation (rTMS) for stroke recovery is hampered by an unexplained variability of reported effect sizes and an insufficient understanding of mechanisms of action. We aimed to (1) briefly summarize evidence of efficacy, (2) identify critical factors to explain the reported variation in effects, and (3) provide mechanism-based recommendations for future trials. METHODS: We performed a systematic review of the literature according to Cochrane and PRISMA Protocols. We included trials with ≥10 patients per treatment group. We classified outcome measures according to the International Classification of Functioning, Disability, and Health. Meta-analysis was done when at least 3 trials were reported on the same construct. In case of significant summary effect sizes with significant heterogeneity, we used sensitivity analyses to test for correlations and differences between found individual effect sizes and possible effect modifiers such as patient-, repetitive transcranial magnetic stimulation-, and trial characteristics. RESULTS: We included 57 articles (N=2595). Funnel plots showed no publication bias. We found significant effect sizes at the level of body function (upper limb synergies, muscle strength, language functioning, global cognitive functioning, visual/spatial inattention) with repetitive transcranial magnetic stimulation within or beyond 3 months after stroke. We also found significant effect sizes at the level of activities. We found no subgroup differences or significant correlations between individual summary effect sizes and any tested possible effect modifier. CONCLUSIONS: Repetitive transcranial magnetic stimulation holds the potential to benefit a range of motor and cognitive outcomes after stroke, but the evidence of efficacy is challenged by unexplained heterogeneity across many small sampled trials. We propose large trials with the collection of individual patient data on baseline severity and brain network integrity with sufficiently powered subgroup analyses, as well as protocolized time-locked training of the target behavior. Additional neurophysiological and biomechanical data may help in understanding mechanisms and identifying biomarkers of treatment efficacy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42022300330.

Can telerehabilitation services combined with caregiver-mediated exercises improve early supported discharge services poststroke? A study protocol for a multicentre, observer-blinded, randomized controlled trial.

BACKGROUND: Recovery of walking ability is an important goal for patients poststroke, and a basic level of mobility is critical for an early discharge home. Caregiver-mediated exercises could be a resource-efficient strategy to augment exercise therapy and improve mobility in the first months poststroke. A combination of telerehabilitation and face-to-face support, blended care, may empower patient-caregiver dyads and smoothen the transition from professional support to self-management. The Armed4Stroke study aims to investigate the effects of a caregiver-mediated exercise program using a blended care approach in addition to usual care, on recovery of mobility in the first 6 months poststroke. METHODS: A multicentre, observer-blinded randomized clinical trial in which 74 patient-caregiver dyads will be enrolled in the first 3 months poststroke. Dyads are randomly allocated to a caregiver-mediated exercises intervention or to a control group. The primary endpoint is the self-reported mobility domain of the Stroke Impact Scale. Secondary endpoints include care transition preparedness and psychological functioning of dyads, length of inpatient stay, gait-related measures and extended ADL of patients, and caregiver burden. Outcomes are assessed at enrolment, end of treatment and 6 months follow-up. RESULTS: During 8 weeks, caregivers are trained to become an exercise coach using a blended care approach. Dyads will receive a tailor-made, progressive training program containing task-specific exercises focusing on gait, balance, physical activity and outdoor activities. Dyads are asked to perform the training program a minimum of 5 times a week for 30 min per session, supported by a web-based telerehabilitation system with instruction videos and a messaging environment to communicate with their physiotherapist. CONCLUSIONS: We hypothesize that the Armed4Stroke program will increase self-reported mobility and independence in ADL, facilitating an early discharge poststroke. In addition, we hypothesize that active involvement of caregivers and providing support using blended care, will improve the care transition when professional support tapers off. Therefore, the Armed4Stroke program may complement early supported discharge services. TRIAL REGISTRATION: Netherlands Trial Register, NL7422 . Registered 11 December 2018.

Effect of an exercise intervention on global cognition after transient ischemic attack or minor stroke: the MoveIT randomized controlled trial.

BACKGROUND: Patients with a transient ischemic attack (TIA) or ischemic stroke are at increased risk of developing cognitive impairment in the subacute phase. At present, the effects of exercise on cognitive functioning following a TIA or stroke are not fully known. The purpose of this trial was to investigate the effect of exercise on global cognition. METHODS: The MoveIT trial is a single-centre, observer-blinded, randomized controlled trial involving a 1-year exercise intervention consisting of a 12-week group exercise program, combined with three counselling visits to the physiotherapists over a 9-month period. The control group received standard care. The primary outcome was global cognitive functioning, assessed at one year, using the Montreal Cognitive Assessment (MoCA). Secondary outcomes included cardiorespiratory fitness, the cardiovascular profile, and attainment of secondary prevention targets, anxiety, depression and fatigue at one and two years. RESULTS: The experimental group consisted of 60 patients, while the control group consisted of 59 patients. The mean age was 64.3 years and 41% were female. No between-group differences were found on global cognitive functioning (MD, 0.7 out of 30, 95% CI, - 0.2 to 1.6) or on secondary outcome measures at 12 months. The only significant between-group difference was found for fatigue, in favour of the experimental group at 12 months (MD, 0.6 out of 63, 95% CI, 0.1 to 1.1). CONCLUSIONS: No benefit of this exercise intervention was found regarding global cognition. Future studies need to focus on optimizing rehabilitation strategies for this vulnerable group of patients. TRIAL REGISTRATION: http://www.trialregister.nl . Unique identifier: NL3721 . Date first registration: 06-03-2013.

Predicting Upper Limb Motor Impairment Recovery after Stroke: A Mixture Model.

OBJECTIVE: Spontaneous recovery is an important determinant of upper extremity recovery after stroke and has been described by the 70% proportional recovery rule for the Fugl-Meyer motor upper extremity (FM-UE) scale. However, this rule is criticized for overestimating the predictability of FM-UE recovery. Our objectives were to develop a longitudinal mixture model of FM-UE recovery, identify FM-UE recovery subgroups, and internally validate the model predictions. METHODS: We developed an exponential recovery function with the following parameters: subgroup assignment probability, proportional recovery coefficient r k , time constant in weeks τ k , and distribution of the initial FM-UE scores. We fitted the model to FM-UE measurements of 412 first-ever ischemic stroke patients and cross-validated endpoint predictions and FM-UE recovery cluster assignment. RESULTS: The model distinguished 5 subgroups with different recovery parameters ( r1 = 0.09, τ1 = 5.3, r2 = 0.46, τ2 = 10.1, r3 = 0.86, τ3 = 9.8, r4 = 0.89, τ4 = 2.7, r5 = 0.93, τ5 = 1.2). Endpoint FM-UE was predicted with a median absolute error of 4.8 (interquartile range [IQR] = 1.3-12.8) at 1 week poststroke and 4.2 (IQR = 1.3-9.8) at 2 weeks. Overall accuracy of assignment to the poor (subgroup 1), moderate (subgroups 2 and 3), and good (subgroups 4 and 5) FM-UE recovery clusters was 0.79 (95% equal-tailed interval [ETI] = 0.78-0.80) at 1 week poststroke and 0.81 (95% ETI = 0.80-0.82) at 2 weeks. INTERPRETATION: FM-UE recovery reflects different subgroups, each with its own recovery profile. Cross-validation indicates that FM-UE endpoints and FM-UE recovery clusters can be well predicted. Results will contribute to the understanding of upper limb recovery patterns in the first 6 months after stroke. ANN NEUROL 2020;87:383-393 Ann Neurol 2020;87:383-393.

Computerised patient-specific prediction of the recovery profile of upper limb capacity within stroke services: the next step.

INTRODUCTION: Predicting upper limb capacity recovery is important to set treatment goals, select therapies and plan discharge. We introduce a prediction model of the patient-specific profile of upper limb capacity recovery up to 6 months poststroke by incorporating all serially assessed clinical information from patients. METHODS: Model input was recovery profile of 450 patients with a first-ever ischaemic hemispheric stroke measured using the Action Research Arm Test (ARAT). Subjects received at least three assessment sessions, starting within the first week until 6 months poststroke. We developed mixed-effects models that are able to deal with one or multiple measurements per subject, measured at non-fixed time points. The prediction accuracy of the different models was established by a fivefold cross-validation procedure. RESULTS: A model with only ARAT time course, finger extension and shoulder abduction performed as good as models with more covariates. For the final model, cross-validation prediction errors at 6 months poststroke decreased as the number of measurements per subject increased, from a median error of 8.4 points on the ARAT (Q1-Q3:1.7-28.1) when one measurement early poststroke was used, to 2.3 (Q1-Q3:1-7.2) for seven measurements. An online version of the recovery model was developed that can be linked to data acquisition environments. CONCLUSION: Our innovative dynamic model can predict real-time, patient-specific upper limb capacity recovery profiles up to 6 months poststroke. The model can use all available serially assessed data in a flexible way, creating a prediction at any desired moment poststroke, stand-alone or linked with an electronic health record system.

The effect of time spent in rehabilitation on activity limitation and impairment after stroke.

BACKGROUND: Stroke affects millions of people every year and is a leading cause of disability, resulting in significant financial cost and reduction in quality of life. Rehabilitation after stroke aims to reduce disability by facilitating recovery of impairment, activity, or participation. One aspect of stroke rehabilitation that may affect outcomes is the amount of time spent in rehabilitation, including minutes provided, frequency (i.e. days per week of rehabilitation), and duration (i.e. time period over which rehabilitation is provided). Effect of time spent in rehabilitation after stroke has been explored extensively in the literature, but findings are inconsistent. Previous systematic reviews with meta-analyses have included studies that differ not only in the amount provided, but also type of rehabilitation. OBJECTIVES: To assess the effect of 1. more time spent in the same type of rehabilitation on activity measures in people with stroke; 2. difference in total rehabilitation time (in minutes) on recovery of activity in people with stroke; and 3. rehabilitation schedule on activity in terms of: a. average time (minutes) per week undergoing rehabilitation, b. frequency (number of sessions per week) of rehabilitation, and c. total duration of rehabilitation. SEARCH METHODS: We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, eight other databases, and five trials registers to June 2021. We searched reference lists of identified studies, contacted key authors, and undertook reference searching using Web of Science Cited Reference Search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults with stroke that compared different amounts of time spent, greater than zero, in rehabilitation (any non-pharmacological, non-surgical intervention aimed to improve activity after stroke). Studies varied only in the amount of time in rehabilitation between experimental and control conditions. Primary outcome was activities of daily living (ADLs); secondary outcomes were activity measures of upper and lower limbs, motor impairment measures of upper and lower limbs, and serious adverse events (SAE)/death. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data, assessed methodological quality using the Cochrane RoB 2 tool, and assessed certainty of the evidence using GRADE. For continuous outcomes using different scales, we calculated pooled standardised mean difference (SMDs) and 95% confidence intervals (CIs). We expressed dichotomous outcomes as risk ratios (RR) with 95% CIs. MAIN RESULTS: The quantitative synthesis of this review comprised 21 parallel RCTs, involving analysed data from 1412 participants.  Time in rehabilitation varied between studies. Minutes provided per week were 90 to 1288. Days per week of rehabilitation were three to seven. Duration of rehabilitation was two weeks to six months. Thirteen studies provided upper limb rehabilitation, five general rehabilitation, two mobilisation training, and one lower limb training. Sixteen studies examined participants in the first six months following stroke; the remaining five included participants more than six months poststroke. Comparison of stroke severity or level of impairment was limited due to variations in measurement. The risk of bias assessment suggests there were issues with the methodological quality of the included studies. There were 76 outcome-level risk of bias assessments: 15 low risk, 37 some concerns, and 24 high risk. When comparing groups that spent more time versus less time in rehabilitation immediately after intervention, we found no difference in rehabilitation for ADL outcomes (SMD 0.13, 95% CI -0.02 to 0.28; P = 0.09; I2 = 7%; 14 studies, 864 participants; very low-certainty evidence), activity measures of the upper limb (SMD 0.09, 95% CI -0.11 to 0.29; P = 0.36; I2 = 0%; 12 studies, 426 participants; very low-certainty evidence), and activity measures of the lower limb (SMD 0.25, 95% CI -0.03 to 0.53; P = 0.08; I2 = 48%; 5 studies, 425 participants; very low-certainty evidence). We found an effect in favour of more time in rehabilitation for motor impairment measures of the upper limb (SMD 0.32, 95% CI 0.06 to 0.58; P = 0.01; I2 = 10%; 9 studies, 287 participants; low-certainty evidence) and of the lower limb (SMD 0.71, 95% CI 0.15 to 1.28; P = 0.01; 1 study, 51 participants; very low-certainty evidence). There were no intervention-related SAEs. More time in rehabilitation did not affect the risk of SAEs/death (RR 1.20, 95% CI 0.51 to 2.85; P = 0.68; I2 = 0%; 2 studies, 379 participants; low-certainty evidence), but few studies measured these outcomes. Predefined subgroup analyses comparing studies with a larger difference of total time spent in rehabilitation between intervention groups to studies with a smaller difference found greater improvements for studies with a larger difference. This was statistically significant for ADL outcomes (P = 0.02) and activity measures of the upper limb (P = 0.04), but not for activity measures of the lower limb (P = 0.41) or motor impairment measures of the upper limb (P = 0.06). AUTHORS' CONCLUSIONS: An increase in time spent in the same type of rehabilitation after stroke results in little to no difference in meaningful activities such as activities of daily living and activities of the upper and lower limb but a small benefit in measures of motor impairment (low- to very low-certainty evidence for all findings). If the increase in time spent in rehabilitation exceeds a threshold, this may lead to improved outcomes. There is currently insufficient evidence to recommend a minimum beneficial daily amount in clinical practice. The findings of this study are limited by a lack of studies with a significant contrast in amount of additional rehabilitation provided between control and intervention groups. Large, well-designed, high-quality RCTs that measure time spent in all rehabilitation activities (not just interventional) and provide a large contrast (minimum of 1000 minutes) in amount of rehabilitation between groups would provide further evidence for effect of time spent in rehabilitation.

Changes in muscle-tendon unit length-force characteristics following experimentally induced photothrombotic stroke cannot be explained by changes in muscle belly structure.

PURPOSE: The aim of this study was to assess the effects of experimentally induced photothrombotic stroke on structural and mechanical properties of rat m. flexor carpi ulnaris. METHODS: Two groups of Young-adult male Sprague-Dawley rats were measured: stroke (n = 9) and control (n = 7). Photothrombotic stroke was induced in the forelimb region of the primary sensorimotor cortex. Four weeks later, muscle-tendon unit and muscle belly length-force characteristics of the m. flexor carpi ulnaris, mechanical interaction with the neighbouring m. palmaris longus, the number of sarcomeres in series within muscle fibres, and the physiological cross-sectional area were measured. RESULTS: Stroke resulted in higher force and stiffness of the m. flexor carpi ulnaris at optimum muscle-tendon unit length, but only for the passive conditions. Stroke did not alter the length-force characteristics of m. flexor carpi ulnaris muscle belly, morphological characteristics, and the extent of mechanical interaction with m. palmaris longus muscle. CONCLUSION: The higher passive force and passive stiffness at the muscle-tendon unit level in the absence of changes in structural and mechanical characteristics of the muscle belly indicates that the experimentally induced stroke resulted in an increased stiffness of the tendon.

Getting into a "Flow" state: a systematic review of flow experience in neurological diseases.

BACKGROUND: Flow is a subjective psychological state that people report when they are fully involved in an activity to the point of forgetting time and their surrounding except the activity itself. Being in flow during physical/cognitive rehabilitation may have a considerable impact on functional outcome, especially when patients with neurological diseases engage in exercises using robotics, virtual/augmented reality, or serious games on tablets/computer. When developing new therapy games, measuring flow experience can indicate whether the game motivates one to train. The purpose of this study was to identify and systematically review current literature on flow experience assessed in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson's disease. Additionally, we critically appraised, compared and summarized the measurement properties of self-reported flow questionnaires used in neurorehabilitation setting. DESIGN: A systematic review using PRISMA and COSMIN guidelines. METHODS: MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, SCOPUS were searched. Inclusion criteria were (1) peer-reviewed studies that (2) focused on the investigation of flow experience in (3) patients with neurological diseases (i.e., stroke, traumatic brain injury, multiple sclerosis and/or Parkinson's disease). A qualitative data synthesis was performed to present the measurement properties of the used flow questionnaires. RESULTS: Ten studies out of 911 records met the inclusion criteria. Seven studies measured flow in the context of serious games in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson's disease. Three studies assessed flow in other activities than gaming (song-writing intervention and activities of daily living). Six different flow questionnaires were used, all of which were originally validated in healthy people. None of the studies presented psychometric data in their respective research population. CONCLUSION: The present review indicates that flow experience is increasingly measured in the physical/cognitive rehabilitation setting in patients with neurological diseases. However, psychometric properties of used flow questionnaires are lacking. For exergame developers working in the field of physical/cognitive rehabilitation in patients with neurological diseases, a valid flow questionnaire can help to further optimize the content of the games so that optimal engagement can occur during the gameplay. Whether flow experiences can ultimately have positive effects on physical/cognitive parameters needs further study.

Smoothness metric during reach-to-grasp after stroke: part 2. longitudinal association with motor impairment.

BACKGROUND: The cause of smoothness deficits as a proxy for quality of movement post stroke is currently unclear. Previous simulation analyses showed that spectral arc length (SPARC) is a valid metric for investigating smoothness during a multi-joint goal-directed reaching task. The goal of this observational study was to investigate how SPARC values change over time, and whether SPARC is longitudinally associated with the recovery from motor impairments reflected by the Fugl-Meyer motor assessment of the upper extremity (FM-UE) in the first 6 months after stroke. METHODS: Forty patients who suffered a first-ever unilateral ischemic stroke (22 males, aged 58.6 ± 12.5 years) with upper extremity paresis underwent kinematic and clinical measurements in weeks 1, 2, 3, 4, 5, 8, 12, and 26 post stroke. Clinical measures included amongst others FM-UE. SPARC was obtained by three-dimensional kinematic measurements using an electromagnetic motion tracking system during a reach-to-grasp movement. Kinematic assessments of 12 healthy, age-matched individuals served as reference. Longitudinal linear mixed model analyses were performed to determine SPARC change over time, compare smoothness in patients with reference values of healthy individuals, and establish the longitudinal association between SPARC and FM-UE scores. RESULTS: SPARC showed a significant positive longitudinal association with FM-UE (B: 31.73, 95%-CI: [27.27 36.20], P < 0.001), which encompassed significant within- and between-subject effects (B: 30.85, 95%-CI: [26.28 35.41], P < 0.001 and B: 50.59, 95%-CI: [29.97 71.21], P < 0.001, respectively). Until 5 weeks post stroke, progress of time contributed significantly to the increase in SPARC and FM-UE scores (P < 0.05), whereafter they levelled off. At group level, smoothness was lower in patients who suffered a stroke compared to healthy subjects at all time points (P < 0.05). CONCLUSIONS: The present findings show that, after stroke, recovery of smoothness in a multi-joint reaching task and recovery from motor impairments are longitudinally associated and follow a similar time course. This suggests that the reduction of smoothness deficits quantified by SPARC is a proper objective reflection of recovery from motor impairment, as reflected by FM-UE, probably driven by a common underlying process of spontaneous neurological recovery early post stroke.

Smoothness metrics for reaching performance after stroke. Part 1: which one to choose?

BACKGROUND: Smoothness is commonly used for measuring movement quality of the upper paretic limb during reaching tasks after stroke. Many different smoothness metrics have been used in stroke research, but a 'valid' metric has not been identified. A systematic review and subsequent rigorous analysis of smoothness metrics used in stroke research, in terms of their mathematical definitions and response to simulated perturbations, is needed to conclude whether they are valid for measuring smoothness. Our objective was to provide a recommendation for metrics that reflect smoothness after stroke based on: (1) a systematic review of smoothness metrics for reaching used in stroke research, (2) the mathematical description of the metrics, and (3) the response of metrics to simulated changes associated with smoothness deficits in the reaching profile. METHODS: The systematic review was performed by screening electronic databases using combined keyword groups Stroke, Reaching and Smoothness. Subsequently, each metric identified was assessed with mathematical criteria regarding smoothness: (a) being dimensionless, (b) being reproducible, (c) being based on rate of change of position, and (d) not being a linear transform of other smoothness metrics. The resulting metrics were tested for their response to simulated changes in reaching using models of velocity profiles with varying reaching distances and durations, harmonic disturbances, noise, and sub-movements. Two reaching tasks were simulated; reach-to-point and reach-to-grasp. The metrics that responded as expected in all simulation analyses were considered to be valid. RESULTS: The systematic review identified 32 different smoothness metrics, 17 of which were excluded based on mathematical criteria, and 13 more as they did not respond as expected in all simulation analyses. Eventually, we found that, for reach-to-point and reach-to-grasp movements, only Spectral Arc Length (SPARC) was found to be a valid metric. CONCLUSIONS: Based on this systematic review and simulation analyses, we recommend the use of SPARC as a valid smoothness metric in both reach-to-point and reach-to-grasp tasks of the upper limb after stroke. However, further research is needed to understand the time course of smoothness measured with SPARC for the upper limb early post stroke, preferably in longitudinal studies.

Moving exercise research in multiple sclerosis forward (the MoXFo initiative): Developing consensus statements for research.

Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and accelerate discovery, a new international partnership of MS-related experts in exercise has emerged with the goal of advancing the research agenda. As a first step, the expert panel met in May 2018 and identified the most urgent areas for moving the field forward, and discussed the framework for such a process. This led to identification of five themes, namely "Definitions and terminology," "Study methodology," "Reporting and outcomes," "Adherence to exercise," and "Mechanisms of action." Based on the identified themes, five expert groups have been formed, that will further (a) outline the challenges per theme and (b) provide recommendations for moving forward. We aim to involve and collaborate with people with MS/MS organizations (e.g. Multiple Sclerosis International Federation (MSIF) and European Multiple Sclerosis Platform (EMSP)) in all of these five themes. The generation of this thematic framework with multi-expert perspectives can bolster the quality and scope of exercise studies in MS that may ultimately improve the daily lives of people with MS.

Agreement and differences regarding family functioning between patients with acquired brain injury and their partners.

PRIMARY OBJECTIVE: To investigate the level of agreement and differences regarding the perception of family functioning between patients with acquired brain injury and their partners. Our hypothesis was that patients would report better family functioning than their partners. RESEARCH DESIGN: Cross-sectional studyMethods and Procedures: Baseline data were used from 77 patient-partner dyads (87.0% stroke) who were participating in the ongoing CARE4Patient and CARE4Carer trials. Family functioning was assessed using the General Functioning subscale of the McMaster Family Assessment Device (FAD-GF). Agreement was assessed with intraclass correlation coefficient, a Bland-Altman plot, percentages absolute agreement and weighted kappa values. Differences were tested with Wilcoxon signed-rank tests. MAIN OUTCOMES AND RESULTS: Patients and their partners differed in their perception of family functioning. Within-dyad agreement was poor regarding the overall FAD-GF scores with partners reporting significantly poorer family functioning compared to the patients (32.5% versus 18.2%). Agreement regarding the individual items ranged from slight to moderate. CONCLUSIONS: Health care professionals should assess family functioning after stroke in both patients and their partners, and any discrepancies should be discussed with both members of the patient-partner dyad.

Effectiveness of Botulinum Toxin Treatment for Upper Limb Spasticity Poststroke Over Different ICF Domains: A Systematic Review and Meta-Analysis.

OBJECTIVE: To provide a comprehensive overview of reported effects and scientific robustness of botulinum toxin (BoNT) treatment regarding the main clinical goals related to poststroke upper limb spasticity, using the International Classification of Functioning, Disability and Health. DATA SOURCES: Embase, PubMed, Wiley/Cochrane Library, and Ebsco/CINAHL were searched from inception up to May 16, 2018. STUDY SELECTION: We included randomized controlled trials comparing upper limb BoNT injections with a control intervention in patients with a history of stroke. A total of 1212 unique records were screened by 2 independent reviewers. Forty trials were identified, including 2718 patients with history of stroke. DATA EXTRACTION: Outcome data were pooled according to assessment timing (ie, 4-8wk and 12wk after injection), and categorized into 6 main clinical goals (ie, spasticity-related pain, involuntary movements, passive joint motion, care ability, arm and hand use, and standing and walking performance). Sensitivity analyses were performed for the influence of study and intervention characteristics, involvement of pharmaceutical industry, and publication bias. DATA SYNTHESIS: Robust evidence is shown for the effectiveness of BoNT in reducing resistance to passive movement, as measured with the (Modified) Ashworth Score, and improving self-care ability for the affected hand and arm after intervention (P<.005) and at follow-up (P<.005). In addition, robust evidence is shown for the absence of effect on arm-hand capacity at follow-up. BoNT was found to significantly reduce involuntary movements, spasticity-related pain, and caregiver burden, and improve passive range of motion, while no evidence was found for arm and hand use after intervention. CONCLUSIONS: In view of the robustness of current evidence, no further trials are needed to investigate BoNT for its favorable effects on resistance to passive movement of the spastic wrist and fingers, and on self-care. No trials are needed to further confirm the lack of effects of BoNT on arm-hand capacity, whereas additional trials are needed to establish the suggested favorable effects of BoNT on other body functions, which may result in clinically meaningful outcomes at activity and participation levels.

Prospectively Classifying Community Walkers After Stroke: Who Are They?

OBJECTIVE: To classify patients with stroke into subgroups based on their characteristics at the moment of discharge from inpatient rehabilitation in order to predict community ambulation outcome 6 months later. DESIGN: Prospective cohort study with a baseline measurement at discharge from inpatient care and final outcome determined after 6 months. SETTING: Community. PARTICIPANTS: A cohort of patients (N=243) with stroke, referred for outpatient physical therapy, after completing inpatient rehabilitation in The Netherlands. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A classification model was developed using Classification And Regression Tree (CART) analysis. Final outcome was determined using the community ambulation questionnaire. Potential baseline predictors included patient demographics, stroke characteristics, use of assistive devices, comfortable gait speed, balance, strength, motivation, falls efficacy, anxiety, and depression. RESULTS: The CART model accurately predicted independent community ambulation in 181 of 193 patients with stroke, based on a comfortable gait speed at discharge of 0.5 meters per second or faster. In contrast, 27 of 50 patients with gait speeds below 0.5 meters per second were correctly predicted to become noncommunity walkers. CONCLUSIONS: We show that comfortable gait speed is a key factor in the prognosis of community ambulation outcome. The CART model may support clinicians in organizing community services at the moment of discharge from inpatient care.

Short-Term Effects of Cerebellar tDCS on Standing Balance Performance in Patients with Chronic Stroke and Healthy Age-Matched Elderly.

Transcranial direct current stimulation (tDCS) may serve as an adjunct approach in stroke rehabilitation. The cerebellum could be a target during standing balance training due to its role in motor adaptation. We tested whether cerebellar tDCS can lead to short-term effects on standing balance performance in patients with chronic stroke. Fifteen patients with a chronic stroke were stimulated with anodal stimulation on the contra-lesional cerebellar hemisphere, ipsi-lesional cerebellar hemisphere, or sham stimulation, for 20 min with 1.5 mA in three sessions in randomized order. Ten healthy controls participated in two sessions with cerebellar stimulation ipsi-lateral to their dominant leg or sham stimulation. During stimulation, subjects performed a medio-lateral postural tracking task on a force platform. Standing balance performance was measured directly before and after each training session in several standing positions. Outcomes were center of pressure (CoP) amplitude and its standard deviation, and velocity and its standard deviation and range, subsequently combined into a CoP composite score (comp-score) as a qualitative outcome parameter. In the patient group, a decrease in comp-score in the tandem position was found after contra-lesional tDCS: ß = - 0.25, CI = - 0.48 to - 0.03, p = 0.03. No significant differences in demographics and clinical characteristics were found between patients who responded (N = 10) and patients who did not respond (N = 5) to the stimulation. Contra-lesional cerebellar tDCS shows promise for improving standing balance performance. Exploration of optimal timing, dose, and the relation between qualitative parameters and clinical improvements are needed to establish whether tDCS can augment standing balance performance after stroke.

Lifestyle Interventions to Prevent Cardiovascular Events After Stroke and Transient Ischemic Attack: Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Patients with a transient ischemic attack or ischemic stroke have an increased risk of subsequent cardiovascular events. The purpose of this systematic review and meta-analysis was to determine whether lifestyle interventions focusing on behaviorally modifiable risk factors with or without an exercise program are effective in terms of (1) preventing recurrent cardiovascular events, (2) reducing mortality, and (3) improving modifiable risk factors associated with cardiovascular disease in patients after a transient ischemic attack or ischemic stroke. METHODS: For this systematic review and meta-analysis, we systematically searched PubMed, Embase, PsycInfo, and the Cochrane Library from the start of the database to May 7, 2015. Subgroup analyses were conducted to explore the influence of therapy-related factors. RESULTS: Twenty-two randomized controlled trials were identified with a total of 2574 patients. Pooling showed a significant reduction in systolic blood pressure by the lifestyle interventions applied, compared with usual care (mean difference, -3.6 mm Hg; 95% confidence interval, -5.6 to -1.6, I2=33%). No significant effect was found on cardiovascular events, mortality, diastolic blood pressure, or cholesterol. In the subgroup analyses, the trials with cardiovascular fitness interventions, trials with an intervention that lasted longer than 4 months, and interventions that used >3 behavior change techniques were more effective in reducing systolic blood pressure. CONCLUSIONS: We found that lifestyle interventions are effective in lowering systolic blood pressure. About other end points, this systematic review found no effect of lifestyle interventions on cardiovascular event rate mortality, diastolic blood pressure, or total cholesterol.

Does aerobic training alleviate fatigue and improve societal participation in patients with multiple sclerosis? A randomized controlled trial.

BACKGROUND: Evidence supporting the effectiveness of aerobic training, specific for fatigue, in severely fatigued patients with multiple sclerosis (MS) is lacking. OBJECTIVE: To estimate the effectiveness of aerobic training on MS-related fatigue and societal participation in ambulant patients with severe MS-related fatigue. METHODS: Patients ( N = 90) with severe MS-related fatigue were allocated to 16-week aerobic training or control intervention. Primary outcomes were perceived fatigue (Checklist Individual Strength (CIS20r) fatigue subscale) and societal participation. An improvement of ⩾8 points on the CIS20r fatigue subscale was considered clinically relevant. Outcomes were assessed by a blinded observer at baseline, 2, 4, 6 and 12 months. RESULTS: Of the 89 patients that started treatment (median Expanded Disability Status Scale (interquartile range), 3.0 (2.0-3.6); mean CIS20r fatigue subscale (standard deviation (SD)), 42.6 (8.0)), 43 received aerobic training and 46 received the control intervention. A significant post-intervention between-group mean difference (MD) on the CIS20r fatigue subscale of 4.708 (95% confidence interval (CI) = 1.003-8.412; p = 0.014) points was found in favour of aerobic training that, however, was not sustained during follow-up. No effect was found on societal participation. CONCLUSION: Aerobic training in MS patients with severe fatigue does not lead to a clinically meaningful reduction in fatigue or societal participation when compared to a low-intensity control intervention.

Respiratory muscle training for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and exercise capacity. Respiratory muscle weakness can also lead to diminished performance on coughing, which may result in (aspiration) pneumonia or even acute ventilatory failure, complications that frequently cause death in MS. Training of the respiratory muscles might improve respiratory function and cough efficacy. OBJECTIVES: To assess the effects of respiratory muscle training versus any other type of training or no training for respiratory muscle function, pulmonary function and clinical outcomes in people with MS. SEARCH METHODS: We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group (3 February 2017), which contains trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, LILACS and the trial registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform. Two authors independently screened records yielded by the search, handsearched reference lists of review articles and primary studies, checked trial registers for protocols, and contacted experts in the field to identify further published or unpublished trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that investigated the efficacy of respiratory muscle training versus any control in people with MS. DATA COLLECTION AND ANALYSIS: One reviewer extracted study characteristics and study data from included RCTs, and two other reviewers independently cross-checked all extracted data. Two review authors independently assessed risk of bias with the Cochrane 'Risk of bias' assessment tool. When at least two RCTs provided data for the same type of outcome, we performed meta-analyses. We assessed the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included six RCTs, comprising 195 participants with MS. Two RCTs investigated inspiratory muscle training with a threshold device; three RCTs, expiratory muscle training with a threshold device; and one RCT, regular breathing exercises. Eighteen participants (˜ 10%) dropped out; trials reported no serious adverse events.We pooled and analyzed data of 5 trials (N=137) for both inspiratory and expiratory muscle training, using a fixed-effect model for all but one outcome. Compared to no active control, meta-analysis showed that inspiratory muscle training resulted in no significant difference in maximal inspiratory pressure (mean difference (MD) 6.50 cmH2O, 95% confidence interval (CI) -7.39 to 20.38, P = 0.36, I2 = 0%) or maximal expiratory pressure (MD -8.22 cmH2O, 95% CI -26.20 to 9.77, P = 0.37, I2 = 0%), but there was a significant benefit on the predicted maximal inspiratory pressure (MD 20.92 cmH2O, 95% CI 6.03 to 35.81, P = 0.006, I2 = 18%). Meta-analysis with a random-effects model failed to show a significant difference in predicted maximal expiratory pressure (MD 5.86 cmH2O, 95% CI -10.63 to 22.35, P = 0.49, I2 = 55%). These studies did not report outcomes for health-related quality of life.Three RCTS compared expiratory muscle training versus no active control or sham training. Under a fixed-effect model, meta-analysis failed to show a significant difference between groups with regard to maximal expiratory pressure (MD 8.33 cmH2O, 95% CI -0.93 to 17.59, P = 0.18, I2 = 42%) or maximal inspiratory pressure (MD 3.54 cmH2O, 95% CI -5.04 to 12.12, P = 0.42, I2 = 41%). One trial assessed quality of life, finding no differences between groups.For all predetermined secondary outcomes, such as forced expiratory volume, forced vital capacity and peak flow pooling was not possible. However, two trials on inspiratory muscle training assessed fatigue using the Fatigue Severity Scale (range of scores 0-56 ), finding no difference between groups (MD, -0.28 points, 95% CI-0.95 to 0.39, P = 0.42, I2 = 0%). Due to the low number of studies included, we could not perform cumulative meta-analysis or subgroup analyses. It was not possible to perform a meta-analysis for adverse events, no serious adverse were mentioned in any of the included trials.The quality of evidence was low for all outcomes because of limitations in design and implementation as well as imprecision of results. AUTHORS' CONCLUSIONS: This review provides low-quality evidence that resistive inspiratory muscle training with a resistive threshold device is moderately effective postintervention for improving predicted maximal inspiratory pressure in people with mild to moderate MS, whereas expiratory muscle training showed no significant effects. The sustainability of the favourable effect of inspiratory muscle training is unclear, as is the impact of the observed effects on quality of life.

Falls Are Associated With Lower Self-Reported Functional Status in Patients After Stroke.

OBJECTIVE: To evaluate the association between falls and functional status after stroke. DESIGN: Secondary analysis of data from the randomized controlled FIT-Stroke trial. Outcomes were measured at the time of discharge from inpatient rehabilitation (t0) and after 12 weeks (t1). Between t0 and t1, all patients attended an outpatient rehabilitation program that included the FIT-Stroke intervention. SETTING: Nine centers for rehabilitation medicine. PARTICIPANTS: Outpatients after stroke (N=250) with mild cognitive impairments (Mini-Mental State Examination [MMSE] score ≥24), discharged home after inpatient rehabilitation and able to walk 10m independently. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome was the change in Stroke Impact Scale (SIS)-16 score. The independent variable was ≥1 falls after stroke. The outcome was corrected for type of outpatient rehabilitation (group allocation), severity of hemiplegia (Motricity Index [MI]), and cognition (MMSE) at baseline using multiple regression analysis. RESULTS: Complete data were available for 199 patients, with a mean age of 58±10 years, MMSE score of 28.1±2, and MI score of 130±43. Fifty-five patients (28%) reported falls during the 12 weeks after discharge from inpatient rehabilitation. Falls were significantly associated with less improvement in functional status as assessed with the SIS-16 (P=.009). CONCLUSIONS: Almost 30% of this stroke population with minor cognitive deficits and moderate to high mobility scores reported falls during the 12 weeks of outpatient rehabilitation. Falls were negatively associated with self-reported functional status measured by the change in SIS-16 score. Therefore, it is important to identify patients with high risk of falls and implement strategies to reduce falls.

Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials.

BACKGROUND: Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. METHODS: We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055. RESULTS: We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. CONCLUSION: Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.