Semaphorin 6A Improves Functional Recovery in Conjunction with Motor Training after Cerebral Ischemia

Background: We have previously identified Semaphorin 6a (Sema6A) as an upregulated gene product in a gene expression screen in cortical ischemia [1]. Semaphorin 6a was regulated during the recovery phase following ischemia in the cortex. Semaphorin 6a is a member of the superfamily of semaphorins involved in axon guidance and other functions. We hypothesized that the upregulation indicates a crucial role of this molecule in post-stroke rewiring of the brain. Here we have tested this hypothesis by overexpressing semaphorin 6a in the cortex by microinjection of a modified AAV2-virus. A circumscribed cortical infarct was induced, and the recovery of rats monitored for up to 4 weeks using a well-established test battery (accelerated rotarod training paradigm, cylinder test, adhesive tape removal). We observed a significant improvement in post-ischemic recovery of animals injected with the semaphorin 6a virus versus animals treated with a control virus. We conclude that semaphorin 6a overexpressed in the cortex enhances recovery after cerebral ischemia

How to improve walking, balance and social participation following stroke: a comparison of the long term effects of two walking aids--canes and an orthosis TheraTogs--on the recovery of gait following acute stroke. A study protocol for a multi-centre, single blind, randomised control trial

<p>Abstract</p> <p>Background</p> <p>Annually, some 9000 people in Switzerland suffer a first time stroke. Of these 60% are left with moderate to severe walking disability. Evidence shows that rehabilitation techniques which emphasise activity of the hemiplegic side increase ipsilesional cortical plasticity and improve functional outcomes. Canes are commonly used in gait rehabilitation although they significantly reduce hemiplegic muscle activity. We have shown that an orthosis "TheraTogs" (a corset with elasticated strapping) significantly increases hemiplegic muscle activity during gait. The aim of the present study is to investigate the long term effects on the recovery of gait, balance and social participation of gait rehabilitation with TheraTogs compared to gait rehabilitation with a cane following first time acute stroke.</p> <p>Methods/Design</p> <p>Multi-centre, single blind, randomised trial with 120 patients after first stroke. When subjects have reached Functional Ambulation Category 3 they will be randomly allocated into TheraTogs or cane group. TheraTogs will be applied to support hip extensor and abductor musculature according to a standardised procedure. Cane walking held at the level of the radial styloid of the sound wrist. Subjects will walk throughout the day with only the assigned walking aid. Standard therapy treatments and usual care will remain unchanged and documented. The intervention will continue for five weeks or until patients have reached Functional Ambulation category 5. Outcome measures will be assessed the day before begin of intervention, the day after completion, 3 months, 6 months and 2 years. Primary outcome: Timed "up and go" test, secondary outcomes: peak surface EMG of gluteus maximus and gluteus medius, activation patterns of hemiplegic leg musculature, temporo-spatial gait parameters, hemiplegic hip kinematics in the frontal and sagittal planes, dynamic balance, daily activity measured by accelerometry, Stroke Impact Scale. Significance levels will be 5% with 95% CI's. IntentionToTreat analyses will be performed. Descriptive statistics will be presented.</p> <p>Discussion</p> <p>This study could have significant implications for the clinical practice of gait rehabilitation after stroke, particularly the effect and appropriate use of walking aids.</p> <p>The results could be important for the development of clinical guidelines and for the socio-economic costs of post-stroke care</p> <p>Trial registration number</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01366729">NCT01366729</a>.</p

SANTIA: a Matlab-based open-source toolbox for artifact detection and removal from extracellular neuronal signals

Neuronal signals generally represent activation of the neuronal networks and give insights into brain functionalities. They are considered as fingerprints of actions and their processing across different structures of the brain. These recordings generate a large volume of data that are susceptible to noise and artifacts. Therefore, the review of these data to ensure high quality by automatically detecting and removing the artifacts is imperative. Toward this aim, this work proposes a custom-developed automatic artifact removal toolbox named, SANTIA (SigMate Advanced: a Novel Tool for Identification of Artifacts in Neuronal Signals). Developed in Matlab, SANTIA is an open-source toolbox that applies neural network-based machine learning techniques to label and train models to detect artifacts from the invasive neuronal signals known as local field potentials

Prediction of setup times for an advanced upper limb functional electrical stimulation system

Introduction: Rehabilitation devices take time to don, and longer or unpredictable setup time impacts on usage. This paper reports on the development of a model to predict setup time for upper limb functional electrical stimulation. Methods: Participants’ level of impairment (Fugl Meyer-Upper Extremity Scale), function (Action Research Arm Test) and mental status (Mini Mental Scale) were measured. Setup times for each stage of the setup process and total setup times were recorded. A predictive model of setup time was devised using upper limb impairment and task complexity. Results: Six participants with stroke were recruited, mean age 60 (�17) years and mean time since stroke 9.8 (�9.6) years. Mean Fugl Meyer-Upper Extremity score was 31.1 (�6), Action Research Arm Test 10.4 (�7.9) and Mini Mental Scale 26.1 (�2.7). Linear regression analysis showed that upper limb impairment and task complexity most effectively predicted setup time (51% as compared with 39%) (F(2,21) ¼ 12.782, adjusted R2 ¼ 0.506; p<.05). Conclusions: A model to predict setup time based on upper limb impairment and task complexity accounted for 51% of the variation in setup time. Further studies are required to test the model in real-world settings and to identify other contributing factors

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; &lt;4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Task-specific reach-to-grasp training after stroke: Development and description of a home-based intervention

© The Author(s) 2015. This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is to transparently describe the process of developing a complex intervention for people after stroke as part of a feasibility randomised controlled trial. Objective: To describe and justify the development of a home-based, task-specific upper limb training intervention to improve reach-to-grasp after stroke and pilot it for feasibility and acceptability prior to a randomized controlled trial. Intervention description: The intervention is based on intensive practice of whole reach-to-grasp tasks and part-practice of essential reach-to-grasp components. A 'pilot' manual of activities covering the domains of self-care, leisure and productivity was developed for the feasibility study. The intervention comprises 14 hours of therapist-delivered sessions over six weeks, with additional self-practice recommended for 42 hours (i.e. one hour every day). As part of a feasibility randomized controlled trial, 24 people with a wide range of upper limb impairment after stroke experienced the intervention to test adherence and acceptability. The median number of repetitions in one-hour therapist-delivered sessions was 157 (interquartile range IQR 96-211). The amount of self-practice was poorly documented. Where recorded, the median amount of practice was 30 minutes (interquartile range 22-45) per day. Findings demonstrated that the majority of participants found the intensity, content and level of difficulty of the intervention acceptable, and the programme to be beneficial. Comments on the content and presentation of the self-practice material were incorporated in a revised 'final' intervention manual. Discussion: A comprehensive training intervention to improve reach-to-grasp for people living at home after stroke has been described in accordance with the Template for Intervention Description and Replication (TIDieR) reporting guidelines. The intervention has been piloted, and found to be acceptable and feasible in the home setting. Trial registration: ISRCTN5671658

Single Collateral Reconstructions Reveal Distinct Phases of Corticospinal Remodeling after Spinal Cord Injury

Injuries to the spinal cord often result in severe functional deficits that, in case of incomplete injuries, can be partially compensated by axonal remodeling. The corticospinal tract (CST), for example, responds to a thoracic transection with the formation of an intraspinal detour circuit. The key step for the formation of the detour circuit is the sprouting of new CST collaterals in the cervical spinal cord that contact local interneurons. How individual collaterals are formed and refined over time is incompletely understood

The DARS (Dopamine Augmented Rehabilitation in Stroke) trial: protocol for a randomised controlled trial of Co-careldopa treatment in addition to routine NHS occupational and physical therapy after stroke

Background: Stroke has a huge impact, leaving more than a third of affected people with lasting disability and rehabilitation remains a cornerstone treatment in the National Health Service (NHS). Recovery of mobility and arm function post-stroke occurs through re-learning to use the affected body parts and/or learning to compensate with the lesser affected side. Promising evidence suggests that the addition of Co-careldopa to physical therapy and occupational therapy may improve the recovery of arm and leg movement and lead to improved function. Methods/design: Dopamine Augmented Rehabilitation in Stroke (DARS) is a multi-centre double-blind, randomised, placebo, controlled clinical trial of Co-careldopa in addition to routine NHS occupational therapy and physical therapy as part of early stroke rehabilitation. Participants will be randomised on a 1:1 basis to either Co-careldopa or placebo. The primary objective of the trial is to determine whether the addition of six weeks of Co-careldopa treatment to rehabilitation therapy can improve the proportion of patients who can walk independently eight weeks post-randomisation. Discussion: The DARS trial will provide evidence as to whether Co-careldopa, in addition to routine NHS occupational and physical therapy, leads to a greater recovery of motor function, a reduction in carer dependency and advance rehabilitation treatments for people with stroke. Trial registration: ISRCTN99643613 assigned on 4 December 2009