Summary Background Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. Methods In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18–85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. Findings The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43·7 s [IQR 26·1–68·0] to 29·7 s [21·4–45·2], 32·0% reduction for VRWii vs 38·0 s [IQR 28·0–64·1] to 27·1 s [21·2–45·5], 28·7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345] ; p=0·70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0·60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no significant difference between groups in the primary outcome (adjusted mean estimate of difference in WMFT: 4·1 s, 95% CI −14·4 to 22·6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and se...
Background and Purpose-Brain-derived neurotrophic factor (BDNF) is involved in neuronal survival, synaptic plasticity, learning and memory, and neuroplasticity. Further, exogenous treatment with BDNF or exposing animals to enrichment and exercise regimens, which also increase BDNF, enhances behavioral recovery after brain injury. Thus, the beneficial effects of rehabilitation in promoting recovery after stroke may also depend on BDNF. We tested this hypothesis by evaluating the contribution of BDNF to motor skill relearning after endothelin-1-induced middle cerebral artery occlusion in rats. Methods-Antisense BDNF oligonucleotide, which blocks the expression of BDNF (or saline vehicle) was infused into the contralateral lateral ventricle for 28 days after ischemia. Animals received either a graduated rehabilitation program, including running exercise and skilled reaching training, which simulates clinical practice, or no rehabilitation. Functional recovery was assessed with a battery of tests that measured skilled reaching, forelimb use asymmetry, and foraging ability. Results-Rehabilitation significantly improved skilled reaching ability in the staircase task. Antisense BDNF oligonucleotide effectively blocked BDNF mRNA, and negated the beneficial effects of rehabilitation on recovery of skilled reaching. Importantly, antisense BDNF oligonucleotide did not affect reaching with the unaffected limb, body weight, infarct size, or foraging ability, indicating the treatment was specific to relearning of motor skill after ischemia. Conclusions-This study is the first to identify a critical role for BDNF in rehabilitation-induced recovery after stroke, and our results suggest that new treatments to enhance BDNF would constitute a promising therapy for promoting recovery of function after stroke.
This commentary reviews selected biomedical and clinical research examining the relationship between physical exercise and cognitive function especially in youth with disability. Youth with physical disability may not benefit from the effects of exercise on cardiovascular fitness and brain health since they are less active than their non-disabled peers. In animal models, physical activity enhances memory and learning, promotes neurogenesis and protects the nervous system from injury and neurodegenerative disease. Neurotrophins, endogenous proteins that support brain plasticity likely mediate the beneficial effects of exercise on the brain. In clinical studies, exercise increases brain volume in areas implicated in executive processing, improves cognition in children with cerebral palsy and enhances phonemic skill in school children with reading difficulty. Studies examining the intensity of exercise required to optimize neurotrophins suggest that moderation is important. Sustained increases in neurotrophin levels occur with prolonged low intensity exercise, while higher intensity exercise, in a rat model of brain injury, elevates the stress hormone, corticosterone. Clearly, moderate physical activity is important for youth whose brains are highly plastic and perhaps even more critical for young people with physical disability.
Aerobic exercise may be a catalyst to promote neuroplasticity and recovery following stroke; however, the optimal methods to measure neuroplasticity and the effects of training parameters have not been fully elucidated. We conducted a systematic review and synthesis of clinical trials and studies in animal models to determine (1) the extent to which aerobic exercise influences poststroke markers of neuroplasticity, (2) the optimal parameters of exercise required to induce beneficial effects, and (3) consistent outcomes in animal models that could help inform the design of future trials. Synthesized findings show that forced exercise at moderate to high intensity increases brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I), nerve growth factor (NGF), and synaptogenesis in multiple brain regions. Dendritic branching was most responsive to moderate rather than intense training. Disparity between clinical stroke and stroke models (timing of initiation of exercise, age, gender) and clinically viable methods to measure neuroplasticity are some of the areas that should be addressed in future research.
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