Impaired Discrimination of Electrocutaneous Stimulation in the Paretic Hand of Stroke Survivors.

Artificial sensory feedback via electrocutaneous stimulation can be used to assist or rehabilitate stroke survivors with sensory deficits. Conveying the magnitude of tactile stimuli is an important aspect of artificial sensory feedback. Here, we explore how stroke-related sensory deficits impact the ability of electrocutaneous stimulation to convey the magnitude of tactile stimuli. Using classical psychophysical methods, we quantified the threshold of detection and the just-noticeable difference of electrocutaneous stimulation current in five stroke survivors with unilateral sensory deficits. We show significantly greater (40%) stimulation currents are needed for initial perception on the paretic hand compared to the non-paretic hand. We also show significantly greater percent changes in stimulation current (140%) are needed for reliable incremental perception on the paretic hand compared to the non-paretic hand. Lastly, we show little correlation between electrocutaneous discrimination performance and clinical sensory assessments of light-touch and spatial mechanoperception. These findings can help guide the implementation of artificial sensory feedback as an assistive or rehabilitative intervention for individuals experiencing sensory loss after a stroke.Clinical Relevance- Our results can help guide the implementation of electrical stimulation as an assistive or rehabilitative intervention for individuals with sensory loss after stroke.

Myoelectric Arm Orthosis Assists Functional Activities: A 3-Month Home Use Outcome Report.

Objective: The objective was to compare task performance in individuals with upper limb impairments with and without a myoelectric arm orthosis. Design: Three-month observational study. Participants met at 4 time points after receiving their myoelectric orthosis (2-Weeks, Month-1, Month-2, Month-3) to complete 4 standardized common daily tasks. Setting: Nationwide sessions completed remotely over videoconference calls at home. There were no specific clinic affiliations. Participants: Adults with upper limb impairment due to stroke who were in the process of being fit with a myoelectric arm orthosis as a first-time user. Interventions: The orthosis was a custom-fabricated myoelectric arm orthosis called the MyoPro®. Main Outcome Measures: Functional tasks were completed at each session with and without the MyoPro. Participants were evaluated on their success and the time required to complete each functional task. Longitudinal mixed and longitudinal mixed logistic regression models were analyzed. Results: Eighteen individuals with chronic arm weakness due to stroke were included in the analysis. Statistically significant and clinically meaningful improvements were observed on the functional tasks in the participants' homes. By 3 months, participants successfully used the MyoPro to accomplish the tasks, reduced the amount of time spent to complete the tasks, and had a higher probability of success as compared with at 2 weeks. With the MyoPro, participants showed significant improvement in overall task completion and completed the tasks in a significantly decreased time as compared with without the MyoPro. Conclusions: The MyoPro provides a stabilizing support to the weak arm of individuals after stroke and enables individuals to use their impaired arm to complete functional tasks independently in the home environment.

Cognitive Deficits After Stroke.

Cognition is a central feature of human existence and brain function. Cognitive deficits are common after stroke and may strongly impact functional outcome. Recent years have seen substantial advances in our understanding of cognitive functions in the healthy state, and this new body of knowledge promises to open new avenues for understanding and treating poststroke impairments, including cognitive deficits. The 5 reviews in this Focused Update from an international cast of experts provide excellent updates on cognitive syndromes that commonly contribute to poststroke disability: neglect, aphasia, apraxia, loss of executive function, and memory disorders. Cognitive impairment remains a major source of morbidity after stroke; these reviews approach this problem by considering clinical presentations, pathophysiology, measurement tools, and treatment approaches. In doing so, they highlight a number of key questions and critical gaps. A number of issues emerge as common across cognitive domains poststroke and are summarized herein. There is a need for improved methods to measure cognitive impairments, as well as for improved insights into pathophysiology of symptom onset and mechanisms of recovery after stroke, including validated biomarkers. These 5 state of the art summaries are sure to prove useful toward these goals.

Therapies Targeting Stroke Recovery.

Stroke recovery therapeutics include many classes of intervention and numerous treatment targets. Stroke is a very heterogeneous disease. As such, stroke recovery therapeutics benefit from a personalized medicine approach that considers intersubject differences, such as in infarct location or stroke severity, when assigning treatment. Prediction of treatment responders can be improved by incorporating biological measures, such as neural injury and neural function, as the bedside behavioral phenotype has an incomplete relationship with the biological events underlying stroke recovery. Another ramification of high variability between patients is the need to examine effects of restorative therapies in relation to dose, time poststroke, and stroke severity in clinical trials. For example, enrollment across a wide time interval poststroke or in a population with a very broad range of deficits means high variance across patients in the biological state of the brain. The doses of rehabilitation therapy being studied are often low; it takes substantial practice to acquire a skill in the healthy brain; this is more, not less, pronounced after a stroke. Recognition and treatment of poststroke depression represents a major unmet need. These points are considered in the context of a review of recent advances in stroke recovery therapeutics.

Intimate Relationships and Stroke: Piloting a Dyadic Intervention to Improve Depression.

Stroke affects not only the survivor but also their romantic partner. Post-stroke depression is common in both partners and can have significant negative consequences, yet few effective interventions are available. The purpose of this study was to pilot test a novel 8-week remotely administered dyadic intervention (ReStoreD) designed to help couples better cope with stroke-related changes and reduce depressive symptoms. Thirty-four cohabitating survivor-partner dyads at least 3 months post-stroke and reporting some changes in mood were enrolled. Depressive symptoms were assessed pre- and post-intervention and at 3-month follow-up. Repeated measures analysis of variance was used to assess the effects of ReStoreD over time on depressive symptoms in stroke survivors and their partners. Twenty-six dyads completed the study. Although statistical significance was not reached, there was a large effect size for improvements in depressive symptoms for stroke survivors. There was no significant improvement for partners, and the effect size was minimal. Those with more significant depressive symptoms at baseline were more likely to benefit from the intervention. This pilot study established proof-of-concept by demonstrating that depressive symptoms can be lessened in stroke survivors and partners with more severe depressive symptoms. Future research will establish the efficacy of the intervention in a fully powered study.

Advances in Stroke: Therapies Targeting Stroke Recovery.

Stroke recovery therapies promote favorable neural plasticity, both during spontaneous recovery and the chronic phase. Activity-based therapies based on intense practice, some aided by integration of computers and telehealth, have shown promise. These studies emphasize key therapeutic variables such as dose, intensity, and timing. Preclinical drug studies have shown promise, but human translation has been challenged by identifying the target patient subgroup, requirements for concomitant training, and aligning biomarkers with preclinical evidence.

Lifestyle Modification Group for Lymphedema and Obesity Results in Significant Health Outcomes.

This study investigated whether a lifestyle modification program that encouraged a ketogenic diet (KD) for participants with lymphedema and obesity would reduce weight and limb volume and improve quality of life. A total of 12 participants with lymphedema and obesity (mean body mass index = 38.38; SD = 7.02) were enrolled in a lifestyle modification group. The timespan from baseline data collection to 30-day follow-up was 18 weeks. Retention rate was 83.3%. Data were analyzed with repeated-measures ANOVA and Pearson correlation. Participants demonstrated statistically significant improvement in most outcome measures. Mean weight loss was 5.18 kg-F(4, 36) = 11.17; P < .001-or 4.8% of mean baseline weight. The average limb volume reduction was 698.9 ml-F(4, 36) = 9.4; P < .001-and was positively correlated with weight loss (r = 0.8; P = .005). There appeared to be a tendency for participants who used a KD (n = 6) to demonstrate superior results in most outcome measures compared with those who did not use the diet (n = 4), although the sample size of the 2 groups was too small to report definitive results. This lifestyle modification program provided insight into the possible value of a KD for obesity and lymphedema management.

Predicting Motor Outcomes in Stroke Patients Using Diffusion Spectrum MRI Microstructural Measures.

Improved understanding of neuroimaging signal changes and their relation to patient outcomes after ischemic stroke is needed to improve ability to predict motor improvement and make therapy recommendations. The posterior limb of the internal capsule (PLIC) is a hub of afferent and efferent motor signaling and this work proposes new, image-based methods for prognosis based on interhemispheric differences in the PLIC. In this work, nine acute supratentorial ischemic stroke patients with motor impairment received a baseline, 203-direction diffusion brain MRI and a clinical assessment 3-12 days post-stroke and were compared to nine age-matched healthy controls. Asymmetries based on the mean and Kullback-Leibler divergence in the ipsilesional and contralesional PLIC were calculated for diffusion tensor imaging (DTI) and diffusion spectrum imaging (DSI) measures from the baseline MRI. Predictions of upper extremity Fugl-Meyer (FM) scores at 5-weeks follow-up from baseline measures of PLIC asymmetry in diffusion tensor imaging (DTI) and diffusion spectrum imaging (DSI) models were evaluated. For the stroke participants, the baseline asymmetry measures in the PLIC for the orientation dispersion index of the neurite orientation dispersion and density imaging (NODDI) model were highly correlated with upper extremity FM outcomes (r 2 = 0.83). Use of DSI and the NODDI orientation dispersion index parameter shows promise of being more predictive of stroke recovery and to help better understand white matter changes in stroke, beyond DTI measures. The new finding that baseline interhemispheric differences in the PLIC calculated from the orientation dispersion index of the NODDI model are highly correlated with upper extremity functional outcomes may lead to improved image-based motor-outcome prediction after middle cerebral artery ischemic stroke.

Simultaneous NODDI and GFA parameter map generation from subsampled q-space imaging using deep learning.

PURPOSE: To develop a robust multidimensional deep-learning based method to simultaneously generate accurate neurite orientation dispersion and density imaging (NODDI) and generalized fractional anisotropy (GFA) parameter maps from undersampled q-space datasets for use in stroke imaging. METHODS: Traditional diffusion spectrum imaging (DSI) capable of producing accurate NODDI and GFA parameter maps requires hundreds of q-space samples which renders the scan time clinically untenable. A convolutional neural network (CNN) was trained to generated NODDI and GFA parameter maps simultaneously from 10× undersampled q-space data. A total of 48 DSI scans from 15 stroke patients and 14 normal subjects were acquired for training, validating, and testing this method. The proposed network was compared to previously proposed voxel-wise machine learning based approaches for q-space imaging. Network-generated images were used to predict stroke functional outcome measures. RESULTS: The proposed network achieves significant performance advantages compared to previously proposed machine learning approaches, showing significant improvements across image quality metrics. Generating these parameter maps using CNNs also comes with the computational benefits of only needing to generate and train a single network instead of multiple networks for each parameter type. Post-stroke outcome prediction metrics do not appreciably change when using images generated from this proposed technique. Over three test participants, the predicted stroke functional outcome scores were within 1-6% of the clinical evaluations. CONCLUSIONS: Estimates of NODDI and GFA parameters estimated simultaneously with a deep learning network from highly undersampled q-space data were improved compared to other state-of-the-art methods providing a 10-fold reduction scan time compared to conventional methods.

Speed and Rhythm Affect Temporal Structure of Variability in Reaching Poststroke: A Pilot Study.

Temporal structure reveals the potential adaptive strategies employed during upper extremity movements. The authors compared the temporal structure of upper extremity joints under 3 different reaching conditions: preferred speed, fast speed, and reaching with rhythmic auditory cues in 10 individuals poststroke. They also investigated the temporal structure of these 3 reaching conditions in 8 healthy controls to aid in the interpretation of the observed patterns in the poststroke cohort. Approximate entropy (ApEn) was used to measure the temporal structure of the upper extremity joints. ApEn was similar between conditions in controls. After stroke, ApEn was significantly higher for shoulder, elbow, and wrist both at fast speed and with rhythmic cues compared with preferred speed. ApEn at index finger was significantly higher only with rhythmic cues compared with preferred speed. The authors propose that practice reaching at faster speed and with rhythmic cues as a component of rehabilitation interventions may enhance adaptability after stroke.

Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: The aim of this guideline is to provide a synopsis of best clinical practices in the rehabilitative care of adults recovering from stroke. METHODS: Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council's Scientific Statement Oversight Committee and the AHA's Manuscript Oversight Committee. The panel reviewed relevant articles on adults using computerized searches of the medical literature through 2014. The evidence is organized within the context of the AHA framework and is classified according to the joint AHA/American College of Cardiology and supplementary AHA methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive AHA internal and external peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. RESULTS: Stroke rehabilitation requires a sustained and coordinated effort from a large team, including the patient and his or her goals, family and friends, other caregivers (eg, personal care attendants), physicians, nurses, physical and occupational therapists, speech-language pathologists, recreation therapists, psychologists, nutritionists, social workers, and others. Communication and coordination among these team members are paramount in maximizing the effectiveness and efficiency of rehabilitation and underlie this entire guideline. Without communication and coordination, isolated efforts to rehabilitate the stroke survivor are unlikely to achieve their full potential. CONCLUSIONS: As systems of care evolve in response to healthcare reform efforts, postacute care and rehabilitation are often considered a costly area of care to be trimmed but without recognition of their clinical impact and ability to reduce the risk of downstream medical morbidity resulting from immobility, depression, loss of autonomy, and reduced functional independence. The provision of comprehensive rehabilitation programs with adequate resources, dose, and duration is an essential aspect of stroke care and should be a priority in these redesign efforts. (Stroke.2016;47:e98-e169. DOI: 10.1161/STR.0000000000000098.).

Predictors and brain connectivity changes associated with arm motor function improvement from intensive practice in chronic stroke.

Background and Purpose: The brain changes that underlie therapy-induced improvement in motor function after stroke remain obscure. This study sought to demonstrate the feasibility and utility of measuring motor system physiology in a clinical trial of intensive upper extremity rehabilitation in chronic stroke-related hemiparesis. Methods: This was a substudy of two multi-center clinical trials of intensive robotic arm therapy in chronic, significantly hemiparetic, stroke patients. Transcranial magnetic stimulation was used to measure motor cortical output to the biceps and extensor digitorum communus muscles. Magnetic resonance imaging (MRI) was used to determine the cortical anatomy, as well as to measure fractional anisotropy, and blood oxygenation (BOLD) during an eyes-closed rest state. Region-of-interest time-series correlation analysis was performed on the BOLD signal to determine interregional connectivity. Functional status was measured with the upper extremity Fugl-Meyer and Wolf Motor Function Test. Results: Motor evoked potential (MEP) presence was associated with better functional outcomes, but the effect was not significant when considering baseline impairment. Affected side internal capsule fractional anisotropy was associated with better function at baseline. Affected side primary motor cortex (M1) activity became more correlated with other frontal motor regions after treatment. Resting state connectivity between affected hemisphere M1 and dorsal premotor area (PMAd) predicted recovery.  Conclusions: Presence of motor evoked potentials in the affected motor cortex and its functional connectivity with PMAd may be useful in predicting recovery. Functional connectivity in the motor network shows a trends towards increasing after intensive robotic or non-robotic arm therapy. Clinical Trial Registration URL:  http://www.clinicaltrials.gov. Unique identifiers:  CT00372411 & NCT00333983.

A pilot randomized controlled trial of D-cycloserine and distributed practice as adjuvants to constraint-induced movement therapy after stroke.

Background. Phase III trials of rehabilitation of paresis after stroke have proven the effectiveness of intensive and extended task practice, but they have also shown that many patients do not qualify, because of severity of impairment, and that many of those who are treated are left with clinically significant deficits. Objective. To test the value of 2 potential adjuvants to normal learning processes engaged in constraint-induced movement therapy (CIMT): greater distribution of treatment over time and the coadministration of d-cycloserine, a competitive agonist at the glycine site of the N-methyl-D-aspartate glutamate receptor. Methods. A prospective randomized single-blind parallel-group trial of more versus less condensed therapy (2 vs 10 weeks) and d-cycloserine (50 mg) each treatment day versus placebo (in a 2 × 2 design), as potential adjuvants to 60 hours of CIMT. Results. Twenty-four participants entered the study, and 22 completed it and were assessed at the completion of treatment and 3 months later. Neither greater distribution of treatment nor treatment with d-cycloserine significantly augmented retention of gains achieved with CIMT. Conclusions. Greater distribution of practice and treatment with d-cycloserine do not appear to augment retention of gains achieved with CIMT. However, concentration of CIMT over 2 weeks ("massed practice") appears to confer no advantage either.

Assessment of white matter microstructure in stroke patients using NODDI.

Diffusion weighted imaging (DWI) is widely used to study changes in white matter following stroke. In various studies employing diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) modalities, it has been shown that fractional anisotropy (FA), mean diffusivity (MD), and generalized FA (GFA) can be used as measures of white matter tract integrity in stroke patients. However, these measures may be non-specific, as they do not directly delineate changes in tissue microstructure. Multi-compartment models overcome this limitation by modeling DWI data using a set of indices that are directly related to white matter microstructure. One of these models which is gaining popularity, is neurite orientation dispersion and density imaging (NODDI). This model uses conventional single or multi-shell HARDI data to describe fiber orientation dispersion as well as densities of different tissue types in the imaging voxel. In this paper, we apply for the first time the NODDI model to 4-shell HARDI stroke data. By computing NODDI indices over the entire brain in two stroke patients, and comparing tissue regions in ipsilesional and contralesional hemispheres, we demonstrate that NODDI modeling provides specific information on tissue microstructural changes. We also introduce an information theoretic analysis framework to investigate the non-local effects of stroke in the white matter. Our initial results suggest that the NODDI indices might be more specific markers of white matter reorganization following stroke than other measures previously used in studies of stroke recovery.

Rasch analysis staging methodology to classify upper extremity movement impairment after stroke.

OBJECTIVES: To define Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) cutoff scores that demarcate 1 level of upper extremity (UE) impairment from another, and describe motor behaviors for each category in terms of expected FMA-UE item performance. DESIGN: Analysis of existing FMA-UE data. SETTING: University research laboratory. PARTICIPANTS: Persons (N=512) 0 to 145 days poststroke, 42 to 90 years of age. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: An item response Rasch analysis staging method was used to calculate cutoff scores, which were defined as the Rasch-Andrich threshold values of 2 criterion FMA-UE items derived from an analysis of this sample. The analysis enabled conversion of cutoff scores, in logit units, to FMA-UE points assessed on 30 FMA-UE voluntary movement items (60 possible points). RESULTS: The boundary between severe and moderate impairment was defined as -1.59 ± .27 logits or 19 ± 2 points; and between moderate and mild impairment was defined as 2.44 ± .27 logits or 47 ± 2 points. A description of expected performance in each impairment level shows that patients with severe impairment exhibited some distal movements, and patients with mild impairment had difficulties with some proximal movements. CONCLUSIONS: The cutoff scores, which link to a description of specific movements a patient can, can partially, and cannot perform, may enable formation of heterogeneous patient groups, advance efforts to identify specific movement therapy targets, and define treatment response in terms of specific movement that changed or did not change with therapy.

Temporal structure of variability decreases in upper extremity movements post stroke.

BACKGROUND: The objective of this study was to determine movement variability in the more-affected upper-extremity in chronic stroke survivors. We investigated two hypotheses: (1) individuals with stroke will have increased amount of variability and altered structure of variability in upper-extremity joint movement patterns as compared to age-matched controls; and (2) the degree of motor impairment and joint kinematics will be correlated with the temporal structure of variability. METHODS: Sixteen participants with chronic stroke and nine age-matched controls performed three trials of functional reach-to-grasp. The amount of variability was quantified by computing the standard deviation of shoulder, elbow, wrist and index finger flexion/extension joint angles. The temporal structure of variability was determined by calculating approximate entropy in shoulder, elbow, wrist and index finger flexion/extension joint angles. FINDINGS: Individuals with stroke demonstrated greater standard deviations and significantly reduced approximate entropy values as compared to controls. Furthermore, motor impairments and kinematics demonstrated moderate to strong correlations with temporal structure of variability. INTERPRETATION: Changes in the temporal structure of variability in upper-extremity joint angles suggest that movement patterns used by stroke survivors are less adaptable. This knowledge may yield additional insights into the impaired motor system and suggest better interventions that can enhance upper-extremity movement adaptability.

Effect of intense functional task training upon temporal structure of variability of upper extremity post stroke.

STUDY DESIGN: Quasi-experimental design. INTRODUCTION: Although the effectiveness of constraint-induced movement therapy (CIMT) in upper extremity (UE) rehabilitation post stroke is well known, the efficacy of CIMT to enhance the temporal structure of variability in upper extremity movement is not known. PURPOSE: The purpose of this study was to investigate whether CIMT could enhance the temporal structure of variability in upper extremity movement in individuals with chronic stroke. METHODS: Six participants with chronic stroke underwent CIMT for 4 h/day for 2 weeks. Participants performed three trials of functional reach-to-grasp before and after CIMT. Temporal structure of variability was determined by calculating approximate entropy (ApEn) in shoulder, elbow and wrist flexion/extension joint angles. RESULTS: ApEn increased post CIMT, however, statistical significance was not achieved (p > 0.0167). CONCLUSION: Future studies with larger sample size are warranted to investigate the effect of CIMT upon temporal structure of variability in UE movement. LEVEL OF EVIDENCE: 4.

An economic analysis of robot-assisted therapy for long-term upper-limb impairment after stroke.

BACKGROUND AND PURPOSE: Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. METHODS: We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. RESULTS: A total of 127 participants were randomized to usual care plus robot therapy (n=49), usual care plus intensive comparison therapy (n=50), or usual care alone (n=28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (P<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different. CONCLUSIONS: The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00372411.

Robot-assisted therapy for long-term upper-limb impairment after stroke.

BACKGROUND: Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. METHODS: In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. RESULTS: At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], -0.23 to 4.58) and worse than that for patients receiving intensive comparison therapy (difference, -0.14 points; 95% CI, -2.94 to 2.65), but the differences were not significant. The results on the Stroke Impact Scale were significantly better for patients receiving robot-assisted therapy than for those receiving usual care (difference, 7.64 points; 95% CI, 2.03 to 13.24). No other treatment comparisons were significant at 12 weeks. Secondary analyses showed that at 36 weeks, robot-assisted therapy significantly improved the Fugl-Meyer score (difference, 2.88 points; 95% CI, 0.57 to 5.18) and the time on the Wolf Motor Function Test (difference, -8.10 seconds; 95% CI, -13.61 to -2.60) as compared with usual care but not with intensive therapy. No serious adverse events were reported. CONCLUSIONS: In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy. In secondary analyses, robot-assisted therapy improved outcomes over 36 weeks as compared with usual care but not with intensive therapy. (ClinicalTrials.gov number, NCT00372411.)