Spinal Cord Stimulation for Poststroke Hemiparesis: A Scoping Review.

IMPORTANCE: Spinal cord stimulation (SCS) is a neuromodulation technique that can improve paresis in individuals with spinal cord injury. SCS is emerging as a technique that can address upper and lower limb hemiparesis. Little is understood about its effectiveness with the poststroke population. OBJECTIVE: To summarize the evidence for SCS after stroke and any changes in upper extremity and lower extremity motor function. DATA SOURCES: PubMed, Web of Science, Embase, and CINAHL. The reviewers used hand searches and reference searches of retrieved articles. There were no limitations regarding publication year. STUDY SELECTION AND DATA COLLECTION: This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The inclusion and exclusion criteria included a broad range of study characteristics. Studies were excluded if the intervention did not meet the definition of SCS intervention, used only animals or healthy participants, did not address upper or lower limb motor function, or examined neurological conditions other than stroke. FINDINGS: Fourteen articles met the criteria for this review. Seven studies found a significant improvement in motor function in groups receiving SCS. CONCLUSIONS AND RELEVANCE: Results indicate that SCS may provide an alternative means to improve motor function in the poststroke population. Plain-Language Summary: The results of this study show that spinal cord stimulation may provide an alternative way to improve motor function after stroke. Previous neuromodulation methods have targeted the impaired supraspinal circuitry after stroke. Although downregulated, spinal cord circuitry is largely intact and offers new possibilities for motor recovery.

Combining high dose therapy, bilateral motor priming, and vagus nerve stimulation to treat the hemiparetic upper limb in chronic stroke survivors: a perspective on enhancing recovery.

Stroke is a leading cause of disability worldwide and upper limb hemiparesis is the most common post-stroke disability. Recent studies suggest that clinically significant motor recovery is possible in chronic stroke survivors with severe impairment of the upper limb. Three promising strategies that have been investigated are (1) high dose rehabilitation therapy (2) bilateral motor priming and (3) vagus nerve stimulation. We propose that the future of effective and efficient upper limb rehabilitation will likely require a combination of these approaches.

Use of cyproheptadine hydrochloride (HCl) to reduce neuromuscular hypertonicity in stroke survivors: A Randomized Trial: Reducing Hypertonicity in Stroke.

OBJECTIVES: The goal of this study was to examine how the administration and dosing of the anti-serotonergic medication cyproheptadine hydrochloride (HCl) affects involuntary muscle hypertonicity of the spastic and paretic hands of stroke survivors. MATERIALS AND METHODS: A randomized, double-blinded, placebo-controlled longitudinal intervention study was performed as a component of a larger clinical trial. 94 stroke survivors with chronic, severe hand impairment, rated as levels 2 or 3 on the Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H), were block randomized to groups receiving doses of cyproheptadine HCl or matched doses of placebo. Doses were increased from 4 mg BID to 8 mg TID over 3 weeks. Outcomes were assessed at baseline and after each of the three weeks of intervention. Primary outcome measure was grip termination time; other measures included muscle strength, spasticity, coactivation of the long finger flexors, and recording of potential adverse effects such as sleepiness and depression. RESULTS: 89 participants (receiving cyproheptadine HCl: 44, receiving placebo: 45) completed the study. The Cyproheptadine group displayed significant reduction in grip termination time, in comparison with the Placebo group (p<0.05). Significant change in the Cyproheptadine group (45% time reduction) was observed after only one week at the 4mg BID dosage. The effect was pronounced for those participants in the Cyproheptadine group with more severe hand impairment (CMSA-H level 2) at baseline. Conversely, no significant effect of Group * Session interaction was observed for spasticity (p=0.6) or coactivation (p=0.53). There were no significant changes in strength (p=0.234) or depression (p=0.441) during the trial. CONCLUSIONS: Use of cyproheptadine HCl was associated with a significant reduction in relaxation time of finger flexor muscles, without adversely affecting voluntary strength, although spasticity and coactivation were unchanged. Decreasing the duration of involuntary flexor activity can facilitate object release and repeated prehensile task performance. REGISTRATION: Clinical Trial number: NCT02418949.

Bilateral upper extremity motor priming (BUMP) plus task-specific training for severe, chronic upper limb hemiparesis: study protocol for a randomized clinical trial.

BACKGROUND: Various priming techniques to enhance neuroplasticity have been examined in stroke rehabilitation research. Most priming techniques are costly and approved only for research. Here, we describe a priming technique that is cost-effective and has potential to significantly change clinical practice. Bilateral motor priming uses the Exsurgo priming device (Exsurgo Rehabilitation, Auckland, NZ) so that the less affected limb drives the more affected limb in bilateral symmetrical wrist flexion and extension. The aim of this study is to determine the effects of a 5-week protocol of bilateral motor priming in combination with task-specific training on motor impairment of the affected limb, bimanual motor function, and interhemispheric inhibition in moderate to severely impaired people with stroke. METHODS: Seventy-six participants will be randomized to receive either 15, 2-h sessions, 3 times per week for 5 weeks (30 h of intervention) of bilateral motor priming and task-specific training (experimental group) or the same dose of control priming plus the task-specific training protocol. The experimental group performs bilateral symmetrical arm movements via the Exsurgo priming device which allows both wrists to move in rhythmic, symmetrical wrist flexion and extension for 15 min. The goal is one cycle (wrist flexion and wrist extension) per second. The control priming group receives transcutaneous electrical stimulation below sensory threshold for 15 min prior to the same 45 min of task-specific training. Outcome measures are collected at pre-intervention, post-intervention, and follow-up (8 weeks post-intervention). The primary outcome measure is the Fugl-Meyer Test of Upper Extremity Function. The secondary outcome is the Chedoke Arm and Hand Activity Index-Nine, an assessment of bimanual functional tasks. DISCUSSION: To date, there are only 6 studies documenting the efficacy of priming using bilateral movements, 4 of which are pilot or feasibility studies. This is the first large-scale clinical trial of bilateral priming plus task-specific training. We have previously completed a feasibility intervention study of bilateral motor priming plus task-specific training and have considerable experience using this protocol. TRIAL REGISTRATION: ClinicalTrials.gov NCT03517657 . Retrospectively registered on May 7, 2018.

Use of an EMG-Controlled Game as a Therapeutic Tool to Retrain Hand Muscle Activation Patterns Following Stroke: A Pilot Study.

BACKGROUND/PURPOSE: To determine the feasibility of training with electromyographically (EMG) controlled games to improve control of muscle activation patterns in stroke survivors. METHODS: Twenty chronic stroke survivors (>6 months) with moderate hand impairment were randomized to train either unilaterally (paretic only) or bilaterally over 9 one-hour training sessions. EMG signals from the unilateral or bilateral limbs controlled a cursor location on a computer screen for gameplay. The EMG muscle activation vector was projected onto the plane defined by the first 2 principal components of the activation workspace for the nonparetic hand. These principal components formed the x- and y-axes of the computer screen. RESULTS: The recruitment goal (n = 20) was met over 9 months, with no screen failure, no attrition, and 97.8% adherence rate. After training, both groups significantly decreased the time to move the cursor to a novel sequence of targets (P = 0.006) by reducing normalized path length of the cursor movement (P = 0.005), and improved the Wolf Motor Function Test (WMFT) quality score (P = 0.01). No significant group difference was observed. No significant change was seen in the WMFT time or Box and Block Test. DISCUSSION/CONCLUSIONS: Stroke survivors could successfully use the EMG-controlled games to train control of muscle activation patterns. While the nonparetic limb EMG was used in this study to create target EMG patterns, the system supports various means for creating target patterns per user desires. Future studies will employ training with the EMG-controlled games in conjunction with functional task practice for a longer intervention duration to improve overall hand function.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A379).

Characteristics of the severely impaired hand in survivors of stroke with chronic impairments.

BACKGROUND: Diminished sensorimotor control of the hand is one of the most common outcomes following stroke. This hand impairment substantially impacts overall function and quality of life; standard therapy often results in limited improvement. Mechanisms of dysfunction of the severely impaired post-stroke hand are still incompletely understood, thereby impeding the development of new targeted treatments. OBJECTIVE: To identify and determine potential relationships among the mechanisms responsible for hand impairment following stroke. METHODS: This cohort study observed stroke survivors (n = 95) with severe, chronic hand impairment (Chedoke-McMaster Hand score = 2-3). Custom instrumentation created precise perturbations and measured kinematic responses. Muscle activation was recorded through electromyography. Strength, spasticity, muscle relaxation time, and muscle coactivation were quantified. RESULTS: Maximum grip strength in the paretic hand was only 12% of that achieved by the nonparetic hand, and only 6 of 95 participants were able to produce any net extension force. Despite force deficits, spastic reflex response of the finger flexor evoked by imposed stretch averaged 90.1 ± 26.8% of maximum voluntary activation, relaxation time averaged 3.8 ± 0.8 seconds, and coactivation during voluntary extension exceeded 30% of maximum contraction, thereby resulting in substantial net flexion. Surprisingly, these hypertonicity measures were not significantly correlated with each other. CONCLUSIONS: Survivors of severe, chronic hemiparetic stroke experience profound weakness of both flexion and extension that arises from increased involuntary antagonist activation and decreased voluntary activation. The lack of correlation amongst hypertonicity measures suggests that these phenomena may arise from multiple, potentially independent mechanisms that could require different treatments.

Examining recruitment feasibility and related outcomes in adults post-stroke.

BACKGROUND: There are limited effective and evidence-based interventions for upper extremity hemiparesis post-stroke. To prepare for an RCT and minimize misuse of resources, there is value in conducting a feasibility study. OBJECTIVE: To examine the feasibility of recruitment and other related outcomes for an intense upper limb intervention. METHODOLOGY: Feasibility outcomes included retention, adherence, accrual rate, sample characteristics, and identification of productive recruitment methods. Other outcomes included satisfaction with the study, fidelity, and equipoise of both staff and participants. RESULTS: Participants were enrolled at a rate of 1.33 per month. The recruitment timeline had to be extended by 4 months, to meet the target of 16 randomized participants. Staggered recruitment was the most successful strategy. We found that following up with individuals who missed initial appointments prior to study enrollment led to decreased adherence. CONCLUSION: It is feasible to recruit and retain post-stroke participants for an intense intervention study. TRIAL REGISTRATION: NCT02277028.

Survivors of Chronic Stroke Experience Continued Impairment of Dexterity But Not Strength in the Nonparetic Upper Limb.

OBJECTIVE: To investigate the performance of the less affected upper limb in people with stroke compared with normative values. To examine less affected upper limb function in those whose prestroke dominant limb became paretic and those whose prestroke nondominant limb became paretic. DESIGN: Cohort study of survivors of chronic stroke (7.2±6.7y post incident). SETTING: The study was performed at a freestanding academic rehabilitation hospital. PARTICIPANTS: Survivors of chronic stroke (N=40) with severe hand impairment (Chedoke-McMaster Stroke Assessment rating of 2-3 on Stage of Hand) participated in the study. In 20 participants the prestroke dominant hand (DH) was tested (nondominant hand [NH] affected by stroke), and in 20 participants the prestroke NH was tested (DH affected by stroke). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Jebsen-Taylor Hand Function Test. Data from survivors of stroke were compared with normative age- and sex-matched data from neurologically intact individuals. RESULTS: When combined, DH and NH groups performed significantly worse on fine motor tasks with their nonparetic hand relative to normative data (P<.007 for all measures). Even the participants who continued to use their prestroke DH as their primary hand after the stroke demonstrated reduced fine motor skills compared with normative data. In contrast, grip strength was not significantly affected in either group of survivors of stroke (P>.140). CONCLUSIONS: Survivors of stroke with severe impairment of the paretic limb continue to present significant upper extremity impairment in their nominally nonparetic limb even years after stroke. This phenomenon was observed regardless of whether the DH or NH hand was primarily affected. Because this group of survivors of stroke is especially dependent on the nonparetic limb for performing functional tasks, our results suggest that the nonparetic upper limb should be targeted for rehabilitation.

Home-based Upper Extremity Stroke Therapy Using a Multiuser Virtual Reality Environment: A Randomized Trial.

OBJECTIVE: To compare participation and subjective experience of participants in both home-based multiuser virtual reality (VR) therapy and home-based single-user (SU) VR therapy. DESIGN: Crossover, randomized trial. SETTING: Initial training and evaluations occurred in a rehabilitation hospital; the interventions took place in participants' homes. PARTICIPANTS: Survivors of stroke with chronic upper extremity impairment (N=20). INTERVENTIONS: Four weeks of in-home treatment using a custom, multiuser virtual reality system (VERGE): 2 weeks of both multiuser (MU) and SU versions of VERGE. The order of presentation of SU and MU versions was randomized such that participants were divided into 2 groups, First MU and First SU. MAIN OUTCOME MEASURES: We measured arm displacement during each session (m) as the primary outcome measure. Secondary outcome measures include time participants spent using each MU and SU VERGE and Intrinsic Motivation Inventory scores. Fugl-Meyer Assessment of Motor Recovery After Stroke Upper Extremity (FMA-UE) score and compliance with prescribed training were also evaluated. Measures were recorded before, midway, and after the treatment. Activity and movement were measured during each training session. RESULTS: Arm displacement during a session was significantly affected the mode of therapy (MU: 414.6m, SU: 327.0m, P=.019). Compliance was very high (99% compliance for MU mode and 89% for SU mode). Within a given session, participants spent significantly more time training in the MU mode than in the SU mode (P=.04). FMA-UE score improved significantly across all participants (Δ3.2, P=.001). CONCLUSIONS: Multiuser VR exercises may provide an effective means of extending clinical therapy into the home.

Bilateral motor priming for post stroke upper extremity hemiparesis: A randomized pilot study.

BACKGROUND: Bilateral priming, device assisted bilateral symmetrical wrist flexion/extension, is a noninvasive neuromodulation technique that can be used in the clinic. OBJECTIVE: We examined the additive effect of bilateral motor priming and task specific training in individuals with severe upper limb hemiparesis. METHODS: This is a parallel assignment, single-masked, randomized exploratory pilot study with three timepoints (pre-/post-intervention and follow up). Participants received either bilateral motor priming or health care education followed by task specific training. Sixteen participants who were at least 6 months post-stroke and had a Fugl Meyer Upper Extremity (FMUE) score between 23 and 38 were randomized. Our primary and secondary measures were Chedoke Arm & Hand Activity Index 9 (CAHAI-9) and the FMUE respectively. We determined changes in interhemispheric inhibition using transcranial magnetic stimulation. We hypothesized that improvement in the priming group would persist at follow up. RESULTS: There was no between-group difference in the CAHAI. The improvement in the FMUE was significantly greater in the experimental group at follow up (t = 2.241, p = 0.045). CONCLUSIONS: Both groups improved in the CAHAI. There was a significant between-group difference in the secondary outcome measure (FMUE) where the bilateral priming group had an average increase of 10 points from pre-intervention to follow up.

Development of an EMG-Controlled Serious Game for Rehabilitation.

A majority of the seven million stroke survivors in the U.S. have hand impairments, adversely affecting performance of a variety of activities of daily living, because of the fundamental role of the hand in performing functional tasks. Disability in stroke survivors is largely attributable to damaged neuronal pathways, which result in inappropriate activation of muscles, a condition prevalent in distal upper extremity muscles following stroke. While conventional rehabilitation methods focus on the amplification of existing muscle activation, the effectiveness of therapy targeting the reorganization of pathological activation patterns is often unexplored. To encourage modulation of activation level and exploration of the activation workspace, we developed a novel platform for playing a serious game through electromyographic control. This system was evaluated by a group of neurologically intact subjects over multiple sessions held on different days. Subjects were assigned to one of two groups, training either with their non-dominant hand only (unilateral) or with both hands (bilateral). Both groups of subjects displayed improved performance in controlling the cursor with their non-dominant hand, with retention from one session to the next. The system holds promise for rehabilitation of control of muscle activation patterns.

Movement-Based Priming: Clinical Applications and Neural Mechanisms.

Priming can be described as behavior change generated by preceding stimuli. Although various types of priming have been long studied in the field of psychology, priming that targets motor cortex is a relatively new topic of research in the fields of motor control and rehabilitation. In reference to a rehabilitation intervention, priming is categorized as a restorative approach. There are a myriad of possible priming approaches including noninvasive brain stimulation, motor imagery, and sensory-based priming, to name a few. The authors report on movement-based priming which, compared to other priming types, is less frequently examined and under reported. Movement-based priming includes, but is not limited to, bilateral motor priming, unilateral priming, and aerobic exercise. Clinical and neural mechanistic aspects of movement-based priming techniques are explored.

Junior Investigators Thinking About Quitting Research: A Survey.

OBJECTIVE: Junior tenure-track faculty report high levels of stress and low satisfaction; the increasingly competitive funding environment compounds this discontent. We examined factors associated with junior investigators who were thinking about quitting research. METHOD: Data were collected as part of a program evaluation of an interdisciplinary research mentoring program in an academic medical center. RESULTS: Of the 62 mentees, 44 responded to the survey (71%). When asked "In the past year, have you considered quitting research?" 39 mentees answered the question; 17 (44%) answered in the affirmative. Those who had considered quitting had lower scores on the Clinical Research Appraisal Inventory-12 (CRAI-12) and job satisfaction and higher scores on burnout. In a regression model, we found that only CRAI-12 scores were significantly, inversely associated with thinking about quitting. CONCLUSION: Factors associated with thinking about quitting included lower confidence in research skills, reduced job satisfaction, and higher levels of burnout.

Benefits of Using a Voice and EMG-Driven Actuated Glove to Support Occupational Therapy for Stroke Survivors.

Many mechatronic devices exist to facilitate hand rehabilitation, however few directly address deficits in muscle activation patterns while also enabling functional task practice. We developed an innovative voice and electromyography-driven actuated (VAEDA) glove, which is sufficiently flexible/portable for incorporation into hand-focused therapy post-stroke. The therapeutic benefits of this device were examined in a longitudinal intervention study. Twenty-two participants with chronic, moderate hand impairment [Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H = 4)] enrolled > 8 months post-stroke for 18 1-h training sessions ( 3 × week) employing a novel hand-focused occupational therapy paradigm, either with (VAEDA) or without (No-VAEDA) actuated assistance. Outcome measures included CMSA-H, Wolf Motor Function Test (WMFT), Action Research Arm Test, Fugl-Meyer Upper Extremity Motor Assessment (FMUE), grip and pinch strength and hand kinematics. All outcomes were recorded at baseline and endpoint (immediately after and four weeks post-training). Significant improvement was observed following training for some measures for the VAEDA group (n = 11) but for none of the measures for the No-VAEDA group (n = 11). Specifically, statistically significant gains were observed for CMSA-H (p = 0.038) and WMFT (p = 0.012) as well as maximum digit aperture subset (p = 0.003, n = 7), but not for the FMUE or grip or pinch strengths. In conclusion, therapy effectiveness appeared to be increased by employment of the VAEDA glove, which directly targets deficits in muscle activation patterns.

Motor priming in neurorehabilitation.

Priming is a type of implicit learning wherein a stimulus prompts a change in behavior. Priming has been long studied in the field of psychology. More recently, rehabilitation researchers have studied motor priming as a possible way to facilitate motor learning. For example, priming of the motor cortex is associated with changes in neuroplasticity that are associated with improvements in motor performance. Of the numerous motor priming paradigms under investigation, only a few are practical for the current clinical environment, and the optimal priming modalities for specific clinical presentations are not known. Accordingly, developing an understanding of the various types of motor priming paradigms and their underlying neural mechanisms is an important step for therapists in neurorehabilitation. Most importantly, an understanding of the methods and their underlying mechanisms is essential for optimizing rehabilitation outcomes. The future of neurorehabilitation is likely to include these priming methods, which are delivered prior to or in conjunction with primary neurorehabilitation therapies. In this Special Interest article, we discuss those priming paradigms that are supported by the greatest amount of evidence, including (i) stimulation-based priming, (ii) motor imagery and action observation, (iii) sensory priming, (iv) movement-based priming, and (v) pharmacological priming.Video Abstract available. (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A86) for more insights from the authors.

Transient impact of prolonged versus repetitive stretch on hand motor control in chronic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the influence of prolonged and repetitive passive range of motion (PROM) stretching of the fingers on hand function in stroke survivors. PARTICIPANTS: Fifteen chronic stroke survivors with moderate to severe hand impairment took part in the study. METHOD: Participants underwent 3 experimental sessions consisting of 30 minutes of rest, prolonged, or repetitive stretching of the finger flexor muscles by a powered glove orthosis (X-Glove). Outcome measures, comprised of 3 selected tasks from the Graded Wolf Motor Function Test (GWMFT), grip strength, lateral pinch strength, and grip relaxation time, were recorded at the start and end of each session. Change in outcome score for each session was used for analysis. RESULTS: Data suggested a trend for improvement following stretching, especially for the repetitive PROM case. For one GWMFT task (lift washcloth), the effect of stretching condition on performance time approached a statistical significance (P = .015), with repetitive PROM stretching producing the greatest mean reduction. Similarly, repetitive stretching led to a 12% ± 16% increase in grip strength, although this change was not statistically different across groups (P = .356); and grip termination time was reduced, albeit non-significantly, by 66% ± 133%. CONCLUSION: Repetitive PROM stretching exhibited trends to be more effective than prolonged stretching for improving hand motor control. Although the results were highly variable and the effects are undoubtedly transient, an extended period of repetitive PROM stretching may prove advantageous prior to hand therapy sessions to maximize treatment.

Active-passive bilateral therapy as a priming mechanism for individuals in the subacute phase of post-stroke recovery: a feasibility study.

OBJECTIVE: To assess the feasibility of treating inpatient stroke survivors with active-passive bilateral therapy as a motor priming technique before occupational therapy. DESIGN: Single case series with two matched pairs in the subacute post-stroke rehabilitation phase. The test patients received active-passive bilateral therapy plus upper limb motor training. Control patients received only the motor training. RESULTS: Both Fugl-Meyer Upper Extremity scores and Action Research Arm Test scores improved in this small group of test and control patients. The magnitude of improvement was greater in test patients who received active-passive bilateral therapy plus unilateral training. CONCLUSIONS: We conclude that it is feasible and safe to administer active-passive bilateral therapy in a hospital setting.

A pneumatic glove and immersive virtual reality environment for hand rehabilitative training after stroke.

While a number of devices have recently been developed to facilitate hand rehabilitation after stroke, most place some restrictions on movement of the digits or arm. Thus, a novel glove was developed which can provide independent extension assistance to each digit while still allowing full arm movement. This pneumatic glove, the PneuGlove, can be used for training grasp-and-release movements either with real objects or with virtual objects in a virtual reality environment. Two groups of stroke survivors, with seven subjects in each group, completed a six-week rehabilitation training protocol, consisting of three 1-h sessions held each week. One group wore the PneuGlove during training, performed both within a novel virtual reality environment and outside of it with physical objects, while the other group completed the same training without the device. Across subjects, significant improvements were observed in the Fugl-Meyer Assessment for the upper extremity (p < 0.001), the hand/wrist portion of the Fugl-Meyer Assessment (p < 0.001), the Box and Blocks test (p < 0.005), and palmar pinch strength (p < 0.005). While changes in the two groups were not statistically different, the group using the PneuGlove did show greater mean improvement on each of these measures, such as gains of 3.7 versus 2.4 points on the hand/wrist portion of the Fugl-Meyer Assessment and 14 N versus 5 N in palmar pinch.

Use of a pneumatic glove for hand rehabilitation following stroke.

Hand impairment is common following stroke and is often resistant to traditional therapy methods. Successful interventions have stressed the importance of repeated practice to facilitate rehabilitation. Thus, we have developed a servo-controlled glove to assist extension of individual digits to promote practice of grasp-and-release movements with the hand. This glove, the PneuGlove, permits free movement of the arm throughout its workspace. A novel immersive virtual reality environment was created for training movement in conjunction with the device. Seven stroke survivors with chronic hand impairment participated in 18 training sessions with the PneuGlove over 6 weeks. Overall, subjects displayed a significant 6-point improvement in the upper extremity score on the Fugl-Meyer assessment and this increase was maintained at the evaluation held one month after conclusion of all training (p < 0.01). The majority of this gain came from an increase in the hand/wrist score (3.8-point increase, p < 0.01). Thus, the system shows promise for rehabilitative training of hand movements after stroke.