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To develop a simple and effective risk score for predicting which stroke patients will have persistent impairment of upper extremity motor function at 90 days. Post hoc analysis of clinical trial patients hospitalized with acute ischemic stroke who were followed for 90 days to determine functional outcome. Patient were hospitalized at facilities across the United States. We created a harmonized cohort of individual patients (N=1653) from the NINDS tPA, ALIAS part 2, IMS-III, DEFUSE 3, and FAST-MAG trials. We split the cohort into balanced derivation and validation samples. Not applicable. The primary outcome was persistent arm impairment, defined as a National Institutes of Health Stroke Scale (NIHSS) arm domain score of 2 to 4 at 90 days in patients who had a 24-hour NIHSS arm score of 1 or more. We used least absolute shrinkage and selection operator regression to determine the elements of the persistent upper extremity impairment (PUPPI) index, which we validated as a predictive tool. We included 1653 patients (827 derivation, 826 validation), of whom 803 (48.6%) had persistent arm impairment. The PUPPI index gives 1 point each for age 55 years or older and NIHSS values of worse arm (4), worse leg (>2), facial palsy (3), and total NIHSS (≥10). The optimal cutpoint for the PUPPI index was 3 or greater, at which the area under the curve was greater than 0.75 for the derivation and validation cohorts and when using NIHSS values from either 24 hours or in a subacute or discharge time window. Results were similar across different levels of stroke severity. The PUPPI index uses readily available information to accurately predict persistent upper extremity motor impairment at 90 days poststroke. The PUPPI index can be administered in minutes and could be used as inclusion criterion in recovery-related clinical trials or, with additional development, as a prognostic tool for patients, caregivers, and clinicians. [ABSTRACT FROM AUTHOR]

Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium. [ABSTRACT FROM AUTHOR]

Rehabilitation for stroke survivors with severe motor impairment remains challenging. Early motor rehabilitation is critical for improving mobility function post stroke, but it is often delayed due to limited resources in clinical practice. The objectives of this study were to investigate the feasibility and effectiveness of early in-bed sensorimotor rehabilitation on acute stroke survivors with severe hemiplegia using a wearable ankle robot. Eighteen patients (9 in the study group and 9 in the control group) with severe hemiplegia and no active ankle movement were enrolled in acute/subacute phase post stroke. During a typical 3-week hospital stay, patients in the study group received ankle robot-guided in-bed training (50 minutes/session, 5 sessions/week), including motor relearning under real-time visual feedback of re-emerging motor output, strong passive stretching under intelligent control, and game-based active movement training with robotic assistance. Whereas the control group received passive ankle movement in the mid-range of motion and attempted active ankle movement without robotic assistance. After multi-session training, the study group achieved significantly greater improvements in Fugl-Meyer Lower Extremity motor score (p = 0.007), plantarflexor strength (p = 0.009), and active range of motion (p = 0.011) than controls. The study group showed earlier motor recovery for plantarflexion and dorsiflexion than the control group (p < 0.05). This study showed that in-bed sensorimotor rehabilitation guided by a wearable ankle robot through combining motor relearning in real-time feedback, strong passive stretching, and active movement training facilitated early motor recovery for stroke survivors with severe hemiplegia in the acute/subacute phase. [ABSTRACT FROM AUTHOR]

There are now a large number of technological and methodological approaches to the rehabilitation of motor function after stroke. It is important to employ these approaches in a manner that is tailored to specific patient impairments and desired functional outcomes, while avoiding the hype of overly broad or unsubstantiated claims for efficacy. Here we review the evidence for poststroke plasticity, including therapy-related plasticity and functional imaging data. Early demonstrations of remapping in somatomotor and somatosensory representations have been succeeded by findings of white matter plasticity and a focus on activity-dependent changes in neuronal properties and connections. The methods employed in neurorehabilitation have their roots in early understanding of neuronal circuitry and plasticity, and therapies involving large numbers of repetitions, such as robotic therapy and constraint-induced movement therapy (CIMT), change measurable nervous systems properties. Other methods that involve stimulation of brain and peripheral excitable structures have the potential to harness neuroplastic mechanisms, but remain experimental. Gaps in our understanding of the neural substrates targeted by neurorehabilitation technology and techniques remain, preventing their prescriptive application in individual patients as well as their general refinement. However, with ongoing research—facilitated in part by technologies that can capture quantitative information about motor performance—this gap is narrowing. These research approaches can improve efforts to attain the shared goal of better functional recovery after stroke. [ABSTRACT FROM AUTHOR]

Background and purpose: The preponderance of evidence from recent studies in human subjects supports a negative effect of the BDNF Val66Met polymorphism on motor outcomes and motor recovery. However prior studies have generally reported the effect of the Met allele in older stroke patients, while potential effects in younger stroke patients have remained essentially unexamined. The lack of research in younger patients is significant since aging effects on CNS repair and functional recovery after stroke are known to interact with the effects of genetic polymorphisms. Here we present a study of first-ever ischemic stroke patients aged 15–49 years that examines the effect of Met carrier status on functional disability. Methods: 829 patients with a first ischemic stroke (Average age = 41.4 years, SD = 6.9) were recruited from the Baltimore-Washington region. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington. Our sample contained 165 Met carriers and 664 non-Met carriers. Modified Rankin scores as recorded at discharge were obtained from the hospital records by study personnel blinded to genotype, and binarized into "Good" versus "Poor" outcomes (mRS 0–2 vs. 3+), with mRS scores 3+ reflecting a degree of disability that causes loss of independence. Results: Our analysis showed that the Met allele conveyed a proportionally greater risk for poor outcomes and disability-related loss of independence with mRS scores 3+ (adjusted OR 1.73, 95% CI 1.13–2.64, p = 0.01). Conclusions: The BDNF Val66Met polymorphism was negatively associated with functional outcomes at discharge in our sample of 829 young stroke patients. This finding stands in contrast to what would be predicted under the tenets of the resource modulation hypothesis (i.e. that younger patients would be spared from the negative effect of the Met allele on recovery since it is posited to arise as a manifestation of age-related decline in physiologic resources). [ABSTRACT FROM AUTHOR]

The development of clinical vectors to correct genetic mutations that cause inherited myopathies and related disorders of skeletal muscle is advancing at an impressive rate. Adeno-associated virus vectors are attractive for clinical use because (1) adeno-associated viruses do not cause human disease and (2) these vectors are able to persist for years. New vectors are now becoming available as gene therapy delivery tools, and recent preclinical experiments have demonstrated the feasibility, safety, and efficacy of gene therapy with adeno-associated virus for long-term correction of muscle pathology and weakness in myotubularin-deficient canine and murine disease models. In this review, recent advances in the application of gene therapies to treat inherited muscle disorders are presented, including Duchenne muscular dystrophy and x-linked myotubular myopathy. Potential areas for therapeutic synergies between rehabilitation medicine and genetics are also discussed. [ABSTRACT FROM AUTHOR]

Background. The extent to which pharmaceutical and behavioral therapies following central nervous system injury may either deter or encourage the development of compensatory movement patterns is a topic of considerable interest in neurorehabilitation. However, functional outcome measures alone are relatively insensitive to compensatory changes in movement patterns per se. Objective. This study used both functional outcome measures and kinematic analysis of forelimb movements to examine the effects of human adult bone marrow–derived somatic cells (hABM-SCs) on motor recovery in a rat model of stroke. Methods. Adult male Long–Evans black-hooded rats (n = 12) were trained in a forelimb reaching task and then underwent surgical middle cerebral artery occlusion, producing a stroke that impaired the trained paw. One week poststroke, animals were randomly assigned to either a hABM-SC injection or control injection group. Reaching behaviors were then compared at baseline and at 10 weeks poststroke. Results. Both groups improved their outcome scores during the 10-week recovery period. However, the hABM-SC group recovered significantly more function than controls in terms of the number of pellets retrieved. Furthermore, the control group appeared to improve their functional performance by using compensatory strategies that involved an increased number of trajectory adjustments, whereas the hABM-SC group’s kinematics more closely resembled prestroke movement patterns. Conclusions. This study demonstrates that kinematic measures established in stroke research on humans are also sensitive to performance differences prestroke versus poststroke in the rat model, reinforcing the utility of this method to evaluate treatments that may ultimately translate to patient populations. [ABSTRACT FROM PUBLISHER]

Furthermore, the animals in the VC group appeared to improve their functional performance by using compensatory strategies that involved an increased number of trajectory adjustments, whereas the SC-treated group's kinematics more closely resembled their prestroke performance. One week after stroke, the animals were randomly assigned to either a stem cell (SC) or vehicle control (VC) group. [Extracted from the article]