Neurorehabilitation and Neural Repair

ObjectivesSpatial neglect, a debilitating cognitive syndrome and predictor of poor functional outcome, affects attention and awareness after stroke. Early rehabilitation is essential but neglect itself may impede participation in therapy. In a proof-of-concept study nested within an RCT, we investigated whether the oft-reported immediate effects of prism adaptation training (PAT) might enable engagement if introduced at the start of an occupational therapy session. MethodsEarly after stroke we video-recorded in-patients carrying out a standardised activity in their first RCT occupational therapy session, before and after PAT (or a control therapy activity). Level of engagement was later scored by a video-rater, experienced in therapy, blind to arm allocation (intervention/control) and whether randomly presented videos were recorded pre-or post-therapy. The rater recorded engagement scores on a 100mm visual analogue scale. Treating therapists also reported, on a 3-point Likert scale, whether or not engagement changed. Results49 of the RCTs 53 patients were recruited (37 PAT, 12 control), 43 of whom consented to be video-recorded. Regression analysis did not suggest improvement in engagement following one session of PAT, using the blinded expert video scoring method: mean difference (95% CI) = -0.5 (-7.4 to 6.4) mm; p=0.89). Similarly, post-hoc re-rating of engagement scores (the video-rater viewed paired pre- and post-therapy recordings but remained blind to arm allocation) excluded any material difference in engagement following PAT: mean difference (95% CI) = 1.2 (-2.5 to 4.9) mm; p=.52). Impressions of level of engagement provided by the treating occupational therapists also suggested no change: OR (95% CI) = 1.3 (0.13 to 13); p=0.81). ConclusionsDespite the need to enable neglect patients to engage in the therapy they are offered, we are confident that a single session of PAT at the start of a therapy session does not enhance immediate engagement in occupational therapy early after stroke. Our study does not address the alternative definition of engagement as a longitudinal, rapport-building process which could meaningfully be explored.

In stroke rehabilitation, muscle synergies have been investigated to provide information on the level of upper limb motor impairment, but not yet for explaining motor recovery after therapy. In this study, we analysed muscle synergies parameters extracted from 62 people with stroke who underwent a specific upper limb treatment (20 sessions, 1h/day, 5d/week, 4 weeks) consisting of virtual reality, robotic or conventional treatment. Overall, participants improved upper limb motor function (Fugl-Meyer Assessment Upper Extremity-FMA-UE: {Delta}= 7.14 {+/-} 7.46, p< 0.001) but the number of muscle synergies of the impaired side (N-aff) did not change after treatment (N-aff: T0= 8.8 {+/-} 1.5; T1=8.7 {+/-} 1.4; p=0.374). Then, we stratified the sample into Responder (No.=34) and Non-Responder (No.=28) participants, based on the Minimal Clinical Important Difference value of FMA-UE ({Delta} >5 points). We investigated merging and fractionation indexes in both subgroups and only the Responder subgroup significantly decreased the percentage of merged muscle synergies (p=0.004). No significant changes in the fractionation index resulted in either subgroup. Finally, we identified vocabularies of affected upper limb motor synergies, before (No. 13 synergies) and after treatment (No. 14 synergies), and in unaffected upper limb (No. 16 synergies). We identified upper limb motor functions associated with each muscle synergy in each vocabulary based on the muscles represented in the muscle synergy. There were no differences in motor functions characterizing Responder patients. However, after therapy, both Responder and Non-Responder subgroups were characterized by the same distribution of motor functions across muscle synergies observed in the unaffected limb. Trial registrationThe trial is registered in ClinicalTrial.gov, identifier number NCT03530358 (https://clinicaltrials.gov/study/NCT03530358). Key messagesO_LIRehabilitation therapy for the upper limb induces reduction of muscle synergies merging in people with stroke expressing clinically important improvement of motor function. This muscular pattern is in accordance with motor control mechanisms underpinning functional recovery. C_LIO_LIMotor function of the affected upper limb at baseline did not characterize the muscular profile of patients responding to rehabilitation treatment (Responder). C_LIO_LIAfter therapy, all patients regardless the amount of motor function improvement (i.e., Responder, Non-Responder) express a muscular profile of the affected upper limb like the unaffected upper limb. C_LI

BackgroundPeople with stroke often have asymmetric motor impairment. Investigating asymmetries in, and dynamic properties of, centre of pressure movement during quiet standing can inform how well balance is controlled. Research questionWhat are the test-retest reliabilities of novel measures of quiet standing balance control in people with chronic stroke? MethodsTwenty people with chronic stroke (>6 months post-stroke), who were able to stand for at least 30 seconds without support, were recruited. Participants completed two 30-second quiet standing trials in a standardized position. Novel measures of quiet standing balance control included: symmetry of variability in centre of pressure displacement and velocity, between-limb synchronization, and sample entropy. Root mean square of centre of pressure displacement and velocity in the antero-posterior and medio-lateral directions were also calculated. Intraclass correlation coefficients (ICCs) were used to determine test-retest reliability, and Bland-Altman plots were created to examine proportional biases. ResultsICC3,2 were between 0.79 and 0.95 for all variables, indicating good to excellent reliability (>0.75). However, ICC3,1 for symmetry indices and between-limb synchronization were <0.75. Bland-Altman plots revealed possible proportional biases for root mean square of medio-lateral centre of pressure displacement and velocity and between-limb synchronization, with larger between-trial differences for participants with worse values. SignificanceThese findings suggest that centre of pressure measures extracted from a single 30-second quiet standing trial may have sufficient reliability for some research studies in chronic stroke. However, for clinical applications, the average of at least two trials may be required.

BackgroundAfter stroke, patients can experience a rapid and generalised improvement in the control of movements, including movements that have not been trained (spontaneous recovery). This generalised improvement in motor control (or behavioural repair) is more effective in supporting functional recovery than task-specific training or behavioural compensation but has to date only been observed in the first few months after stroke. MethodsWe studied 81 chronic stroke patients at two time points, 3-weeks apart. 52 patients underwent a 3-week high-dose high-intensity upper limb neurorehabilitation programme (QSUL), and 29 chronic stroke patients receiving no treatment acted as control subjects (SC). At each time point, we assessed arm motor control kinematically using a 2D-planar reaching, a task which cannot be improved through compensation nor functional task training in 3D during neurorehabilitation. In addition, we measured strength, active range of joint motion and the upper extremity Fugl-Meyer score (FMA-UL). ResultsThe FMA-UL increased by 6 points (IQR 3-8) in the QSUL-group and 0 points (IQR -1-1) in the SC-group. There were significant improvements in smoothness, movement time and accuracy of 2D-planar reaching in the QSUL-group compared to SC-group (all group x timepoint interactions P<0.03), which were independent of changes in strength or active range of joint motion. ConclusionsChronic stroke patients retain the capacity for generalised improvement in motor control in response to high-dose high-intensity neurorehabilitation. Normal or closer to normal motor control should remain a therapeutic target for improving arm paresis at all stages after stroke.

BackgroundAn ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the mechanisms underneath the reshaping of cortical functionality are widely unknown. ObjectiveWe investigated the spatio-temporal features of motor-evoked cortical activity associated with generalized recovery after stroke, and its dependence on the type of rehabilitative treatment. MethodsWe designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. Specifically, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin-2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (i.e. individually administered optogenetic stimulation or motor training). ResultsWe found that only the combined therapy promotes generalized recovery of forelimb function and the rescue of spatio-temporal features of motor-evoked activity. Generalized recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. ConclusionsOur findings demonstrate that though behavioral recovery is not necessarily associated with the restoration of pre-stroke motor-evoked activity, the reestablishment of pre-stroke activation transients was a distinguishing feature of the most efficient therapeutic approach, the combined therapy.

ObjectiveThe primary objective of this study was to retrospectively assess current care practices to determine the routinely collected measures that are most predictive of paretic upper extremity (PUE) functional outcome post-stroke in patients undergoing acute inpatient rehabilitation (AR). MethodsWe conducted a longitudinal chart review of patients post-stroke who received care in the Emory University Hospital system for acute hospitalization, AR, and outpatient therapy in fiscal years 2016-2018. We identified eligible patients using previously established inclusion and exclusion criteria. We extracted demographics, stroke characteristics, and longitudinal documentation of post-stroke motor function from institutional electronic medical records. Serial assessments of PUE strength were estimated using available shoulder abduction and finger extension manual muscle test documentation (E-SAFE). Estimated Action Research Arm Test (E-ARAT) was used to quantify 3-month PUE functional outcome. Metric associations were explored through correlation and cluster analyses, Kruskal-Wallis tests, classification and regression tree (CART) analysis. ResultsThirty-four patients met study eligibility criteria. E-SAFE assessments performed closest to acute hospitalization day-3 (Acute E-SAFE) and upon AR admission (AR E-SAFE) were correlated with E-ARAT. Cluster analysis produced three distinct outcome groups and aligned closely to previous outcome categories. Outcome groups significantly differed in Acute E-SAFE and AR E-SAFE. Exploratory CART analysis selected AR E-SAFE to classify patient outcome with 70.6% accuracy. ConclusionsCurrent study findings reveal that: PUE E-SAFE, measured both acutely and at AR admission, is associated with PUE motor recovery outcome; categorizations of outcome are consistent with previous studies; and predictive models can identify recovery outcome category in patients undergoing AR. Impact StatementOur findings highlight the clinical utility of SAFE as an easy-to-acquire, readily implementable screening metric. Early, intentional use of SAFE in AR settings may improve clinical decision-making, enabling therapists to deliver precision-based interventions that serve to speed or enhance recovery outcome for patients post-stroke.

BackgroundThe reproducible beneficial effect of constraint-induced movement therapy (CIMT) in hemiparetic stroke patients makes it a good model to study brain plasticity during rehabilitation procedures. ObjectiveAssess the functional brain reorganization induced by each of the two components of CIMT: (i) non-affected upper-limb constraint and (ii) intensive training of the paretic arm. MethodsBrain activity of a right hemiparetic chronic stroke patient and of 10 healthy controls was recorded with a functional magnetic resonance imaging (fMRI) during a finger opposition task. For the patient, a total of 8 assessments were performed, before and after each component of CIMT. At each time point, brain activity during movement was compared with rest. Patients results were first compared to the control group and then correlated to motor performance across sessions. ResultsConstraint-therapy-related improvement was correlated with a decrease of cerebral activity in sensory-motor regions of both the affected and the non-affected hemispheres. Intensive-therapy-related improvement was correlated with the recruitment of pre-motor cortices and cerebellum in both hemispheres. ConclusionsTwo different patterns of brain activity underlie the effects of intensive training and constraint which could account for the respective effect of each component of the therapy.

BackgroundAction Observation Therapy (AOT) leverages mirror neuron system (MNS) activation to enhance neuroplasticity and motor recovery after stroke. While AOT has demonstrated positive effects, the neural mechanisms underlying its efficacy, particularly regarding task type and motor network engagement, remain unclear. This observational cohort study investigates cortical activation during the observation of goal-oriented Activities of Daily Living (ADLs) in healthy individuals and chronic stroke patients. MethodsTwenty stroke survivors with right hemiparesis ([&ge;]6 months post-stroke) and 23 age-matched healthy controls observed standardized videos of finalized actions (FA), non-finalized actions (NFA), and control videos (CV). A time-frequency electroencephalography (EEG) signal analysis examined sensorimotor rhythm modulation during action observation (AO), Event-Related Spectral Perturbation (ERSP) analysis was used to quantify mu rhythm desynchronization (8-13 Hz) and beta suppression (14-25 Hz). ResultsHealthy individuals exhibited significant mu rhythm desynchronization, predominantly in the beta band, with stronger and prolonged responses to goal-directed actions (self-care and feeding). Stroke patients showed delayed and attenuated beta suppression, particularly in the affected hemisphere, but retained selective responsiveness to goal-oriented tasks. Rebound effects occurred in all categories in both groups but were most pronounced for NFA and CV, particularly in the beta band (e.g., t(44) = -4.28, p < 0.0001 and t(44) = -2.163, p = 0.04 in healthy individuals). ConclusionsThis study underscores the importance of task specificity in AOT, demonstrating that goal-directed actions optimize motor network engagement. Attenuated but preserved beta suppression in stroke survivors supports the integration of standardized ADLs into AOT protocols to enhance neuroplasticity and motor recovery. Findings highlight the potential for EEG-based biomarkers to monitor AOT efficacy and personalize stroke rehabilitation, with possible implications for digital health and telerehabilitation applications. Clinical Trial RegistrationClinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT04047134.

BackgroundAccumulating results suggest that reticulospinal tract (RST) excitability increases after stroke. While animal studies suggest this hyperexcitability may compensate for corticospinal tract (CST) damage, its role in motor function in people with stroke (PwS) remains debated. This study aimed to: (1) replicate findings of RST hyperexcitability in PwS using the StartReact paradigm, measuring acceleration of motor response to a startling auditory stimulus; (2) examine the relationship between RST hyperexcitability and motor impairments after stroke; and (3) explore whether RST hyperexcitability provides functional benefits in severely impaired PwS. MethodsForty-six PwS completed the StartReact paradigm and motor assessments (Fugl-Meyer, ARAT, grip strength, Modified Ashworth Scale). PwS were categorized into high StartReact effect and typical StartReact effect subgroups based on comparisons with a healthy control group (n=37). Severe impairment was defined as ARAT [&le;]10. ResultsPwS exhibited significantly greater StartReact effects than controls. The high StartReact effect subgroup showed worse motor function, weaker grip strength, and higher spasticity. Among severely impaired PwS, high StartReact effect was not associated with improved grip strength. ConclusionsThese findings confirm the existence of RST hyperexcitability after stroke and suggest it is associated with poorer motor outcomes, likely due to reduced cortical input to the brainstem. The absence of functional benefit in severely impaired individuals supports the interpretation that RST hyperexcitability is a maladaptive rather than a compensatory reaction to brain damage. These findings provide insight into the neurophysiological mechanisms underlying motor impairments after stroke and do no imply direct clinical or therapeutic applications.

BackgroundProprioceptive impairment is a potential contributing factor to the clinical presentation of Unilateral Neglect (UN), a common and debilitating condition that can occur after stroke. To date there has not been a comprehensive review of studies examining the various aspects of proprioception in UN after stroke.\n\nAimTo determine if the presence of UN is associated with more severe proprioceptive deficit in stroke affected populations.\n\nMethodsThe MEDLINE, Embase, Scopus, CINAHL and Web of Science databases were searched from inception to January 2019 using an a priori search strategy. Two independent reviewers screened abstracts and full texts. Two reviewers then independently extracted data from each full text. A third reviewer resolved disagreements at each step. Risk of bias was assessed using the AXIS Quality Assessment tool. For full protocol see PROSPERO, registration number CRD42018086070. One-hundred and sixty-seven abstracts were identified, of which fifty-four were eligible for full text screening. A total of 18 papers were included in the review.\n\nConclusionsMore severe proprioceptive deficit is associated with the presence of UN after stroke. However, the available evidence is limited by the large heterogeneity of assessment of both UN and proprioception, and level of study quality. UN and proprioception are seldom completely assessed in research, and it is likely this is true in everyday clinical practice.

Background and purposeReactive balance training (RBT) has shown promise for enhancing reactive balance control and reducing falls post-stroke. However, the optimal training parameters (e.g., intensity, duration) are unknown. This study aimed to investigate the relationship between different reactive balance training characteristics and improvements in reactive balance control and fall rates. MethodsPeople with chronic stroke completed up to 12 one-hour reactive balance training sessions, twice per week. Training included experiencing losses of balance due to internal or external perturbations while performing voluntary tasks. The tasks were of four types: stable, quasi-mobile, mobile, and unpredictable, each with choice of three difficulty levels (normal, increased, or reduced). We analyzed the relationships between training characteristics (total number of perturbations, difficulty levels, perceived level challenge, and success rate) and fall rates post-training and changes in the reactive balance control sub-score of the mini-Balance Evaluation Systems Test (mini-BESTest). ResultsA higher number of perturbations was significantly associated with better post-intervention reactive balance scores on the mini-BEST (p=0.010). There were no significant associations with any other training characteristics and post-intervention mini-BEST Scores. For falls in daily life there was no significant association between any training characteristic. DiscussionGreater exposure to RBT was associated with improvements in reactive balance control among individuals with chronic stroke. Participants who completed more sessions, and consequently experienced more perturbations, achieved better outcomes. These findings highlight the importance of sufficient training volume, suggesting that a higher number of perturbations may be optimizing the effects of RBT in stroke rehabilitation. Trial registrationISRCTN05434601

In 1951, the neurologist Thomas Twitchell published a seminal paper in Brain describing the time-course of recovery from hemiplegia after stroke in 25 participants from hospitalization to when they reached what he deemed steady state. His main emphasis was on the evolution of voluntary movements at the shoulder, elbow and hand, first within an obligatory flexor synergy, and then independently out-of-synergy. We thought that 75 years later, an update using modern motion capture technology should be attempted as it would allow for finer granularity in the characterization of the time courses of both functional recovery and of the flexor synergy, and then relate them to each other, to weakness and to well-established clinical scales. To this end, we used marker-less 3D kinematics to assess task performance and intrusion of synergies in thirty-three stroke participants longitudinally, from the early sub-acute stage (1 - 8 weeks post-stroke) to the chronic stage (24 - 64 weeks post-stroke). Participants performed an out-of-flexor synergy (shoulder flexion and elbow extension) reaching task. We assessed the time course of recovery of obligatory intrusion of pathological synergies based on measures derived from the angular velocity profiles of the shoulder and the elbow joints. Task-related kinematic measures were obtained and compared to sixteen healthy controls. Grip strength, Motor impairment (FMA), and function (ARAT) scores were also collected. Task kinematics were different from controls in the early, late sub-acute, and chronic stages, but showed gradual recovery over time. Weakness in the hand remained impaired at all time points. Flexor-synergy intrusion was maximal in the early sub-acute stage and then began to subside. Regression analysis with functional kinematic and clinical (FMA, ARAT) measures indicated that flexor-synergy intrusion was a significant predictor in the early and late sub-acute stages, but not in the chronic stage, while weakness remained a significant predictor at all stages of recovery. To better address the relationship between synergies, weakness, and function, we analyzed the more severe cases (ARAT<21) separately. In the sub-acute stage, most of them (11/13) suffered from intrusion of synergies, whereas in the chronic phase, only a minority (2/8) did. Weakness seemed to be the main contributor to poor outcome in the chronic phase. We conclude that weakness and synergy intrusion evolve separately from the subacute to the chronic phase, perhaps more so when neurorehabilitation is given at a dose higher than standard of care.

BackgroundThe capacity to reacquire motor skills lost after a stroke is crucial to promote upper-limb motor recovery but the impact of lesion location on motor skill acquisition and the underlying neurophysiological mechanisms remain uncertain. MethodsWe used transcranial magnetic stimulation to investigate associations between excitatory and inhibitory cortico-spinal excitability measures and the capacity to acquire a novel motor skill with the most affected hand in 103 individuals with cortical (n=34) or subcortical (n=69) lesions. ResultsBoth groups showed similar motor skill acquisition, but subcortical lesions exhibited more impairment in the most affected hand and lower excitability in the ipsilesional hemisphere. In cortical lesions, motor skill acquisition was associated with lower motor thresholds ({beta}=-0.25, 95% CI [-0.47,-0.03]; p=0.024) and higher intracortical inhibition ({beta}=-3.93, 95% CI [-6.89,-0.98]; p=0.011) in the ipsilesional hemisphere. In contrast, in subcortical lesions motor skill acquisition was associated with smaller motor evoked potentials ({beta}=-4.46, 95% CI [-8.54,-0.38]; p=0.033), less intracortical inhibition ({beta}=3.45, 95% CI [0.34,6.56]; p=0.030) and higher facilitation ({beta}=1.34,95% CI [0.15,2.54]; p= 0.028) ipsilesionally. Sensitivity analyses revealed that associations with intracortical inhibition and facilitation in the subcortical group were driven by lesions affecting the corticospinal tract. No associations were found in the contralesional hemisphere. ConclusionsReinforcing the existence of lesion-specific neurophysiological patterns, individuals with cortical and subcortical lesions show divergent associations between cortico-spinal excitability and motor skill acquisition. The use of cortico-spinal excitability as a biomarker to predict upper-limb recovery post-stroke or guide motor recovery interventions such as non-invasive brain stimulation should consider lesion location.

BackgroundCurrent guidelines recommend combining botulinum toxin type A (BoNT-A) with adjunctive therapies for upper limb spasticity management, but evidence for individualized splinting remains limited and inconsistent. ObjectiveThis pilot randomized controlled trial investigated whether adding individualized splint therapy to BoNT-A enhances therapeutic outcomes compared to BoNT-A alone in chronic stroke patients with upper limb spasticity. MethodsTwenty-six chronic stroke patients with upper limb spasticity were randomized to receive either BoNT-A plus custom-made thermoplastic splint therapy (n=13) or BoNT-A alone (n=13). Both groups received standardized self-training instructions. Primary outcomes were passive range of motion (ROM) for wrist dorsiflexion and middle finger extension. Secondary outcomes included Modified Ashworth Scale (MAS) scores and Disability Assessment Scale (DAS) scores. Assessments were conducted at six time points over 3 months using mixed-effects models for analysis. ResultsBoth groups demonstrated substantial improvements in wrist dorsiflexion ROM (partial 2 = 0.455) and middle finger extension ROM (partial 2 = 0.306), significant reductions in MAS scores and improvements in DAS scores. No significant group effects or group x time interactions were observed for ROM, MAS, or DAS measures, indicating equivalent treatment responses. ConclusionsAdding individualized splint therapy to BoNT-A did not provide significant additional benefits for managing upper limb spasticity in chronic stroke patients. Both treatment approaches achieved similar improvements in plasticity and functional outcomes. These findings suggest that for patients who can engage in regular self-training, the addition of a static splint may not offer significant clinical advantages over a 3-month period.

ObjectiveEffective interventions have demonstrated the ability to improve motor function by reengaging ipsilesional resources, which has been shown to be critical and feasible for hand function recovery even in individuals with severe chronic stroke. However, the question remains how these focal activity changes (i.e., changes in activity within motor regions) relate to altered cortico-cortico interactions within/across multiple regions. MethodsEight individuals with severe chronic stroke participated in a device-assisted intervention. Pre- and post-intervention, we collected EEG while performing hand opening with/without lifting the paretic arm. We quantified changes in focal cortical activity at movement execution and connectivity during movement preparation. ResultsPost-intervention, individuals displayed a reduction in coupling from ipsilesional M1 to contralesional M1 within gamma frequencies during movement preparation for hand opening. This was followed by a reduction in activity in contralesional primary sensorimotor cortex during movement execution. Meanwhile, during lifting and opening, a more inhibitory coupling within ipsilesional M1 from gamma to beta frequencies was accompanied by an increase in ipsilesional primary sensorimotor cortex activity. ConclusionsChanges in coupling within or between motor regions during movement preparation complement topographical activity changes at movement execution. SignificanceOur results suggest that changes in cortico-cortico interactions may lead to corresponding changes in focal cortical activity.

BackgroundPeople with stroke often have low cardiorespiratory fitness, hindering daily activities and rehabilitation participation. Cardiorespiratory exercise (CRE) early post-stroke can improve fitness, facilitating participation in rehabilitation, and may promote neuroplasticity. This longitudinal observational study aimed to determine the effect of CRE during routine inpatient stroke rehabilitation on motor and cognitive function, functional ambulation, and motor impairment. MethodsData were collected from charts of patients (n=504) admitted to two rehabilitation hospitals in Ontario, Canada, over 14 month periods. Patients were classified into three groups: Prescribed, Incidental, or no cardiorespiratory exercise ( None). Functional independence Measure (FIM), Functional Ambulation Category (FAC), and Chedoke-McMaster Stroke Assessment (CMSA) scores were compared between groups at discharge from rehabilitation, controlling for age, length of stay, and scores at baseline. ResultsPatients who had cardiorespiratory exercise included in their treatment plan (i.e., Prescribed group) had higher FIM total and motor sub-scores at discharge than the None group (Site A; FIM total mean between-group difference: 13.2, p<0.0001; FIM motor mean between-group difference: 13.1, p<0.0001), or than those that completed cardiorespiratory exercise without a prescription ( Incidental group; Site B; FIM Total mean between-group difference: 13.6, p=0.031; FIM motor mean between-group difference: 12.9, p=0.010). At both sites, FIM cognitive sub-scores and CMSA leg scores were higher at discharge for the Prescribed group than the None group (FIM cognitive mean between-group difference: 1.2, p=0.038; CMSA leg mean between-group difference: 0.5, p=0.0099). FAC scores were higher at discharge for the two exercise groups compared to the group that did not complete cardiorespiratory exercise at Site A only (p=0.0010). ConclusionsFindings support that cardiorespiratory exercise as part of routine in-patient rehabilitation early post-stroke is associated with improved functional independence and ambulation. However, the observational design limits causal inferences, highlighting the need for controlled studies to confirm cardiorespiratory exercise benefits in early stroke recovery.

BackgroundAbnormal muscle co-activation contributes to arm impairment after stroke. This single-blind, randomized, sham-controlled trial evaluated the feasibility and efficacy of home-based, personalized myoelectric interface for neurorehabilitation (MINT) conditioning to reduce abnormal co-activation and enhance arm function and determine the optimal number of abnormally co-activating muscles to target during training. MethodsModerately to severely impaired chronic stroke survivors were randomized to one of three MINT groups (who played customized games requiring independent activation of 2 or 3 abnormally co-activating muscles) or a sham control group (played using one muscle). All groups trained 90 minutes/day, 5 days/week at home and 1 day/week in lab, for 6 weeks, and changed trained muscle sets every 2-3 weeks. The primary outcome was the Wolf Motor Function Test (WMFT) at 6 weeks. ResultsFifty-nine participants completed the training. Participants performed 315 {+/-} 85 (mean {+/-} SD) repetitions daily. At week 6, participants in all MINT groups combined improved by 4 s on WMFT (p=0.0008), exceeding the minimal clinically important difference (1.5 s). Participants who trained 3 muscles simultaneously improved by 6.8 s (p=0.001), while the 2-muscle and sham groups did not change significantly. In per-protocol analysis, the 3-muscle group, but not 2-muscle groups, improved significantly more than sham (p=0.046), though not in intention-to-treat analysis. All MINT groups continued improving at 4 weeks post-training. Importantly, severely impaired participants in combined MINT groups improved more than those in sham (p=0.02). Importantly, combined MINT groups also improved their reaching range of motion significantly more than sham. Co-activation decreased by 76% in MINT groups during training. Notably, reduction in co-activation during reaching correlated significantly with improved arm function and range of motion. Other secondary outcomes did not show clinically important improvement. Stroke involving the posterior limb of the internal capsule negatively predicted response to MINT. ConclusionsHome-based MINT conditioning, especially the 3-muscle variant, is feasible, reduces co-activation, and improves arm movement and function. Clinical Trial RegistrationClinicalTrials.gov (NCT03401762)

Background and AimUnilateral spatial neglect (UN) impairs patients ability to detect and respond to stimuli on the contralesional side, severely limiting functional recovery after right-hemispheric stroke. Neck muscle vibration (NMV) has been shown as a bottom-up, proprioceptive intervention to modulate spatial neglect. Although preliminary studies found promising effects, the isolated efficacy of NMV for neglect rehabilitation has not yet been tested in a randomized, blinded controlled trial. This study aimed to evaluate whether NMV alone improves neglect symptoms and activities of daily living. MethodsTwenty patients with right-hemispheric stroke and UN were randomly assigned to receive either active or placebo NMV over two weeks (5 sessions/week). Both groups received 20-minute daily vibration sessions. Standard neglect therapy was withheld in the active group but administered in the placebo group. Assessments included standard neglect diagnostics (e.g., Letter Cancellation, Bells Test), the Free Exploration Test (FET), and two ADL-based measures (NET, CBS), conducted before, immediately after, and (for the NMV group) one month post-treatment. ResultsThe active NMV group showed significant improvements in three of four standard neglect tests, exploration behavior (FET), and ADL performance, with effects remaining stable at one-month follow-up. The placebo group showed comparable gains in ADL outcomes but improved in one standard neglect test only. Between-group analyses revealed no statistically significant differences, suggesting similar efficacy of both interventions. ConclusionNMV alone yields clinically meaningful and lasting improvements in neglect symptoms and daily functioning, comparable to standard active exploration therapy. Its passive nature makes it a promising tool, especially for early rehabilitation.

PurposeThe prognosis of post-stroke ataxia remains controversial. It is unclear whether the proportional recovery rule (PRR) established for hemiparesis applies to ataxia, given that cerebellar plasticity suggests trajectories may not depend solely on initial severity. This study was conducted to quantitatively decompose longitudinal ataxia recovery trajectories into proportional recovery coefficient (r) and time constant ({tau}) using a Bayesian nonlinear mixed-effects model, and elucidate their independent determinants and associations with functional walking independence. MethodsWe analyzed longitudinal SARA scores of 80 subacute patients with stroke to estimate individual initial severity (), r, and {tau}. Recovery patterns were clustered based on these parameters. We analyzed the attainment of independent walking using the Kaplan-Meier method and identified predictors via hierarchical multiple regression analysis. ResultsThree distinct clusters were identified. The moderate group (younger, preserved attention) achieved rapid improvement and early walking independence. In contrast, the severe group showed a significantly prolonged time constant ({tau}) but maintained a high proportional recovery coefficient (r), ultimately achieving walking independence in over 90% of cases. Regression analysis revealed a dissociation: biological age constrained the recovery ceiling (r), while attentional function independently regulated recovery speed ({tau}). ConclusionsRecovery from post-stroke ataxia bifurcates into rapid neurological restoration and a delayed process driven by compensatory learning. Especially in severe cases, long-term learning using attentional resources is crucial. These findings challenge prognosis prediction based solely on initial severity, supporting stratified rehabilitation strategies tailored to individual recovery ceilings and learning speeds.

BackgroundPediatric traumatic brain injury can lead to severe disability. Currently used standard clinical measures effectively capture secondary functional impairments, but do not measure neurologic impairment directly. ObjectiveEvaluate the feasibility of walking dynamic motor control (walk-DMC) assessments to more directly measure neurological impairment and recovery for individuals post-traumatic brain injury. MethodsThe trajectory of walk-DMC and standard clinical measures of balance, mobility, and function were assessed in a cohort of individuals post-traumatic brain injury. Measures were collected throughout participants inpatient rehabilitation stay and at short- and long-term follow-up assessments. ResultsFour pediatric participants with severe traumatic brain injury enrolled. All participants demonstrated substantial neurological impairment at enrollment. All clinical measures showed an initial deficit followed by recovery, with most returning to nondisabled ranges over the study period for all participants. In contrast, walk-DMC scores demonstrated an initial acute deficit and did not reach nondisabled ranges for two of the participants, indicating persistent neurologic impairment. ConclusionWalk-DMC shows promise in its ability to identify subtle ongoing neurologic impairment compared to traditionally used clinical assessments of balance, mobility, and function. Further work in a larger cohort of participants with traumatic brain injury will improve understanding of how walking dynamic motor control changes with injury severity and where such a measure can serve as a leading indicator of neurologic and functional recovery.