Posts Tagged UE

[Abstract+References] Does Stroke Rehabilitation Really Matter? Part A: Proportional Stroke Recovery in the Rat


Background. In human upper-limb stroke, initial level of functional impairment or corticospinal tract injury can accurately predict the degree of poststroke recovery, independent of rehabilitation practices. This proportional recovery rule implies that current rehabilitation practices may play little or no role in brain repair, with recovery largely a result of spontaneous biological recovery processes.

Objective. The present study sought to determine if similar biomarkers predict recovery of poststroke function in rats, indicating that an endogenous biological recovery process might be preserved across mammalian species.

Methods. Using a cohort of 593 male Sprague-Dawley rats, we predicted poststroke change in pellet retrieval in the Montoya staircase-reaching task based on initial impairment alone. Stratification of the sample into “fitters” and “nonfitters” of the proportional recovery rule using hierarchical cluster analysis allowed identification of distinguishing characteristics of these subgroups.

Results. Approximately 30% of subjects were identified as fitters of the rule. These rats showed recovery in proportion to their initial level of impairment of 66% (95% CI = 62%-70%). This interval overlaps with those of multiple human clinical trials. A number of variables, including less severe infarct volumes and initial poststroke impairments distinguished fitters of the rule from nonfitters.

Conclusions. These findings suggest that proportional recovery is a cross-species phenomenon that can be used to uncover biological mechanisms contributing to stroke recovery.

1. Prabhakaran, S, Zarahn, E, Riley, C. Inter-individual variability in the capacity for motor recovery after ischemic stroke. Neurorehabil Neural Repair. 2008;22:6471Google ScholarLink
2. Winters, C, van Wegen, EEH, Daffertshofer, A, Kwakkel, G. Generalizability of the proportional recovery model for the upper extremity after an ischemic stroke. Neurorehabil Neural Repair. 2015;29:614622Google ScholarLinkISI
3. Byblow, WD, Stinear, CM, Barber, PA, Petoe, MA, Ackerley, SJ. Proportional recovery after stroke depends on corticomotor integrity. Ann Neurol. 2015;78:848859Google ScholarCrossrefMedline
4. Feng, W, Wang, J, Chhatbar, PY. Corticospinal tract lesion load: an imaging biomarker for stroke motor outcomes. Ann Neurol. 2015;78:860870Google ScholarCrossrefMedline
5. Stinear, CM, Byblow, WD, Ackerley, SJ, Smith, MC, Borges, VM, Barber, PA. Proportional motor recovery after stroke: implications for trial design. Stroke. 2017;48:795798Google ScholarCrossrefMedline
6. Smith, MC, Byblow, WD, Barber, PA, Stinear, CM. Proportional recovery from lower limb motor impairment after stroke. Stroke. 2017;48:14001403Google ScholarCrossrefMedline
7. Winters, C, van Wegen, EEH, Daffertshofer, A, Kwakkel, G. Generalizability of the maximum proportional recovery rule to visuospatial neglect early poststroke. Neurorehabil Neural Repair. 2017;31:334342Google ScholarLink
8. Lazar, RM, Minzer, B, Antoniello, D, Festa, JR, Krakauer, JW, Marshall, RS. Improvement in aphasia scores after stroke is well predicted by initial severity. Stroke. 2010;41:14851488Google ScholarCrossrefMedline
9. Krakauer, JW, Marshall, RS. The proportional recovery rule for stroke revisited. Ann Neurol. 2015;78:845847Google ScholarCrossrefMedline
10. Gladstone, DJ, Danells, CJ, Black, SE. The Fugl-Meyer assessment of motor recovery after stroke: a critical review of its measurement properties. Neurorehabil Neural Repair. 2002;16:232240Google ScholarLink
11. Carmichael, ST. Rodent models of focal stroke: size, mechanism, and purpose. NeuroRx. 2005;2:396409Google ScholarCrossrefMedline

via Does Stroke Rehabilitation Really Matter? Part A: Proportional Stroke Recovery in the RatNeurorehabilitation and Neural Repair – Matthew Strider Jeffers, Sudhir Karthikeyan, Dale Corbett, 2018


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[ARTICLE] Robotic Arm with Brain – Computer Interfacing – Full Text PDF


Brain Computer Interfaces (BCI), is a modern technology which is currently revolutionizing the field of signal processing. BCI helped in the evolution of a new world where man and computer had never been so close. Advancements in cognitive neuro-sciences facilitated us with better brain imaging techniques and thus interfaces between machines and the human brain became a reality. Electroencephalography (EEG), which is the measurement and recording of electric signals using sensors arrayed across the scalp can be used for applications like prosthetic devices, applications in warfare, gaming, virtual reality and robotics upon signal conditioning and processing.

This paper is entirely based on Brain-Computer Interface with an objective of actuating a robotic arm with the help of device commands derived from EEG signals. This system unlike any other existing technology is purely non-invasive in nature, cost effective and is one of its kinds that can serve various requirements such as prosthesis. This paper suggests a low cost system implementation that can even serve as a reliable substitute for the existing technologies of prosthesis like BIONICS. […]

via Robotic Arm with Brain – Computer Interfacing – ScienceDirect

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[ARTICLE] Innovative STRoke Interactive Virtual thErapy (STRIVE) online platform for community-dwelling stroke survivors: a randomised controlled trial protocol – Full Text


Introduction The STRoke Interactive Virtual thErapy (STRIVE) intervention provides community-dwelling stroke survivors access to individualised, remotely supervised progressive exercise training via an online platform. This trial aims to determine the clinical efficacy of the STRIVE intervention and its effect on brain activity in community-dwelling stroke survivors.

Methods and analysis In a multisite, assessor-blinded randomised controlled trial, 60 stroke survivors >3 months poststroke with mild-to-moderate upper extremity impairment will be recruited and equally randomised by location (Melbourne, Victoria or Launceston, Tasmania) to receive 8 weeks of virtual therapy (VT) at a local exercise training facility or usual care. Participants allocated to VT will perform 3–5 upper limb exercises individualised to their impairment severity and preference, while participants allocated to usual care will be asked to maintain their usual daily activities. The primary outcome measures will be upper limb motor function and impairment, which will be assessed using the Action Research Arm Test and Upper Extremity Fugl-Meyer, respectively. Secondary outcome measures include upper extremity function and spasticity, as measured by the box and block test and Modified AshworthScale, respectively, and task-related changes in bilateral sensorimotor cortex haemodynamics during hand reaching and wrist extension movements as measured by functional near-infrared spectroscopy. Quality of life will be measured using the Euro-Quality of Life-5 Dimension-5 Level Scale, and the Motor Activity Log-28 will be used to measure use of the hemiparetic arm. All measures will be assessed at baseline and immediately postintervention.

Ethics and dissemination The study was approved by the Deakin University Human Research Ethics Committee in May 2017 (No. 2017–087). The results will be disseminated in peer-reviewed journals and presented at major international stroke meetings.

Trial registration number ACTRN12617000745347; Pre-results.


Stroke is one of the leading causes of adult disability in Western countries,1 and for many stroke survivors, upper extremity (UE) paresis makes performing activities of daily living (ADLs) difficult. Up to 60% of community-dwelling stroke survivors live with severe motor impairments of the shoulders, elbows and/or wrists that significantly impacts their functional capacity and quality of life.2 Improved UE function is considered a rehabilitation priority after stroke,3 yet optimal recovery of arm function is poor.2 4 A large majority of stroke survivors experience a lack of support and access to rehabilitative services once they are discharged into the community,5 6 which can compromise their recovery. While most recovery occurs in the first weeks to months after stroke, improvements in function can still be experienced beyond this period.7

The use of virtual reality as a therapy, which is characterised by the participant being immersed in, and interacting with, a computer-generated environment,8 is emerging as an efficacious treatment for UE impairment after stroke.9 10 Online virtual therapy (VT) systems can provide the fundamental elements needed for motor skill development; they can be individually tailored, involve many task-specific repetitions that are increasingly challenging in response to participant improvement and feedback can be embedded in the system. The enriched environment offered by VT is thought to be effective in training problem solving and functional task performance11 and can potentially increase participant engagement compared with non-VT rehabilitation platforms.12

Online VT systems have the potential to address the lack of community-based rehabilitation support experienced by stroke survivors by being affordable, accessible, user-friendly and importantly, have the ability to remotely monitor rehabilitation progress. VT systems, such as the Jintronix Rehabilitation System (Montreal, Canada) to be used in this study, can be administered affordably through commercially available products that include motion capture capabilities (eg, Microsoft Xbox Kinect V.2) and personal computers.13 Online VT systems can be easily implemented at a local community centre, which would enable patients with stroke to receive specialised treatment and monitoring remotely. Online VT platforms have been shown to be user-friendly and motivating,14 including interfaces that are engaging and easy to interact with, and software that can be run on any personal computer/device. In a Cochrane review, Laver et al 9 reported low-quality evidence suggesting VT is a more effective approach to improve arm function after stroke compared with conventional therapy.9 A recent multiple systematic review, including 10 randomised controlled trials and four systematic reviews, found VT therapy to be similar to standard rehabilitation for treatment of UE impairment and disabilities.15

To understand the effects of VT on cerebral activity in stroke rehabilitation, neuroimaging techniques such as functional MRI (fMRI) have been used previously to determine cortical reorganisation postrehabilitation.16 While fMRI is considered the gold-standard measure in neuroimaging, these techniques may be limited as they only allow for small movements to occur within the scanner that are very different from activities of daily living (ADLs). In this sense, functional near-infrared spectroscopy (fNIRS) may be a more suitable neuroimaging technique as it is able to measure changes in cerebral haemodynamic responses (ie, changes in oxyhaemoglobin and deoxyhaemoglobin (HbO2 and HHb)) in response to larger body and head movements that mimic ADLs. Previous studies have also established that cerebral haemodynamic measures from fNIRS are highly comparable with blood oxygen-level dependent signals from fMRI,17 18 which makes it a suitable surrogate to measure changes in brain activity following VT rehabilitation in people with stroke.

Given the advantages of increased accessibility to specialised treatment and monitoring that is afforded by VT, we aim to determine if an online VT system can provide efficacious UE rehabilitation for community-dwelling stroke survivors. We have chosen to focus our intervention on UE function as impaired arm function is highly common after stroke,2 which profoundly impacts the capacity to perform ADLs19 and only a small number of stroke survivors experience complete functional recovery of the UE.20 

Continue —>  Innovative STRoke Interactive Virtual thErapy (STRIVE) online platform for community-dwelling stroke survivors: a randomised controlled trial protocol | BMJ Open

Figure 2 Examples of VT therapy games that target UE mobility of the shoulders, elbows and wrists. UE, upper extremity; VT, Virtual therapy.

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[Abstract] Encouragement-induced real-world upper limb use after stroke by a tracking and feedback device: a study protocol for a multi-center, assessor-blinded, randomized controlled trial

Introduction: Retraining the paretic upper limb after stroke should be intense and specific to be effective. Hence, the best training is daily life use, which is often limited by motivation and effort. Tracking and feedback technology have the potential to encourage self-administered, context-specific training of upper limb use in the patients’ home environment. The aim of this study is to investigate post-intervention and long-term effects of a wrist-worn activity tracking device providing multimodal feedback on daily arm use in hemiparetic subjects beyond 3 months post-stroke.

Methods and Analysis: A prospective, multi-center, assessor-blinded, Phase 2 randomized controlled trial with a superiority framework. Sixty-two stroke patients will be randomized in two groups, with a 1:1 allocation ratio, stratified based on arm paresis severity (Fugl-Meyer Assessment – Upper Extremity subscale <32 and ≥32). The experimental group receives a wrist-worn activity tracking device providing multimodal feedback on daily arm use for 6 weeks. Controls wear an identical device providing no feedback. Sample size: 31 participants per group, based on a difference of 0.75±1.00 points on the Motor Activity Log – 14 Item Version, Amount of Use subscale (MAL-14 AOU), 80% power, two-sided alpha of 0.05, and a 10% attrition rate.

Outcomes: Primary outcome is the change in patient-reported amount of daily life upper limb use (MAL-14 AOU) from baseline to post-intervention. Secondary outcomes are change in upper limb motor function, upper limb capacity, global disability, patient-reported quality of daily life upper limb use, and quality of life from baseline to post-intervention and 6-week follow-up, as well as compliance and safety.

Discussion: The results of this study will show the possible efficacy of a wrist-worn tracking and feedback device on patient-reported amount of daily life upper limb use.

Ethics and Dissemination: The study is approved by the Cantonal Ethics Committees Zurich, and Northwest and Central Switzerland (BASEC-number 2017-00948) and registered in (NCT03294187) before recruitment started. This study will be carried out in compliance with the Declaration of Helsinki, ICH-GCP, ISO 14155:2011, and Swiss legal and regulatory requirements. Dissemination will include submission to a peer-reviewed journal, patient and healthcare professional magazines, and congress presentations.

via Frontiers | Encouragement-induced real-world upper limb use after stroke by a tracking and feedback device: a study protocol for a multi-center, assessor-blinded, randomized controlled trial | Neurology

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[Conference paper] Robotic Upper Limb Rehabilitation Using Armeo®Spring for Chronic Stroke Patients at University Malaya Medical Centre (UMMC) – Abstract+References


This is a retrospective study of patients with chronic partial arm paresis post stroke who attended neurorehabilitation at University Malaya Medical Centre, Malaysia. In this study we aimed to analyze the clinical and practical outcome of robotic-assisted upper limb rehabilitation. Specifically, we analyzed the impact of therapy on motor and function of chronic stroke arm paresis through structured therapy protocol. We extended our analysis towards user acceptance in robotic-assisted rehabilitation. We applied our Armeo®Spring Therapy Protocol on stroke patients with unilateral partial upper limb paresis of more than six months duration. The outcome measures were muscle strength, spasticity and hand dexterity. Thirty three patients who fulfilled the criteria of treatment protocol attended outpatient therapy session. Fourteen patients completed the treatment protocol in which ten participants were stroke patients. This study reported statistically significant improvement in multiple joint range of motions following therapy. Although there was non progressing arm spasticity, and improved paretic hand dexterity, both latter outcomes were not statistically significant at the end of therapy.


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via Robotic Upper Limb Rehabilitation Using Armeo®Spring for Chronic Stroke Patients at University Malaya Medical Centre (UMMC) | SpringerLink

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[Abstract] Virtual reality for stroke rehabilitation – Review


Virtual reality and interactive video gaming have emerged as recent treatment approaches in stroke rehabilitation with commercial gaming consoles in particular, being rapidly adopted in clinical settings. This is an update of a Cochrane Review published first in 2011 and then again in 2015.

Primary objective: to determine the efficacy of virtual reality compared with an alternative intervention or no intervention on upper limb function and activity.Secondary objectives: to determine the efficacy of virtual reality compared with an alternative intervention or no intervention on: gait and balance, global motor function, cognitive function, activity limitation, participation restriction, quality of life, and adverse events.

We searched the Cochrane Stroke Group Trials Register (April 2017), CENTRAL, MEDLINE, Embase, and seven additional databases. We also searched trials registries and reference lists.

Randomised and quasi-randomised trials of virtual reality (“an advanced form of human-computer interface that allows the user to ‘interact’ with and become ‘immersed’ in a computer-generated environment in a naturalistic fashion”) in adults after stroke. The primary outcome of interest was upper limb function and activity. Secondary outcomes included gait and balance and global motor function.

Two review authors independently selected trials based on pre-defined inclusion criteria, extracted data, and assessed risk of bias. A third review author moderated disagreements when required. The review authors contacted investigators to obtain missing information.

We included 72 trials that involved 2470 participants. This review includes 35 new studies in addition to the studies included in the previous version of this review. Study sample sizes were generally small and interventions varied in terms of both the goals of treatment and the virtual reality devices used. The risk of bias present in many studies was unclear due to poor reporting. Thus, while there are a large number of randomised controlled trials, the evidence remains mostly low quality when rated using the GRADE system. Control groups usually received no intervention or therapy based on a standard-care approach.

results were not statistically significant for upper limb function (standardised mean difference (SMD) 0.07, 95% confidence intervals (CI) -0.05 to 0.20, 22 studies, 1038 participants, low-quality evidence) when comparing virtual reality to conventional therapy. However, when virtual reality was used in addition to usual care (providing a higher dose of therapy for those in the intervention group) there was a statistically significant difference between groups (SMD 0.49, 0.21 to 0.77, 10 studies, 210 participants, low-quality evidence).

when compared to conventional therapy approaches there were no statistically significant effects for gait speed or balance. Results were statistically significant for the activities of daily living (ADL) outcome (SMD 0.25, 95% CI 0.06 to 0.43, 10 studies, 466 participants, moderate-quality evidence); however, we were unable to pool results for cognitive function, participation restriction, or quality of life. Twenty-three studies reported that they monitored for adverse events; across these studies there were few adverse events and those reported were relatively mild.

We found evidence that the use of virtual reality and interactive video gaming was not more beneficial than conventional therapy approaches in improving upper limb function. Virtual reality may be beneficial in improving upper limb function and activities of daily living function when used as an adjunct to usual care (to increase overall therapy time). There was insufficient evidence to reach conclusions about the effect of virtual reality and interactive video gaming on gait speed, balance, participation, or quality of life. This review found that time since onset of stroke, severity of impairment, and the type of device (commercial or customised) were not strong influencers of outcome. There was a trend suggesting that higher dose (more than 15 hours of total intervention) was preferable as were customised virtual reality programs; however, these findings were not statistically significant.

Update of
Virtual reality for stroke rehabilitation. [Cochrane Database Syst Rev. 2015]

via Virtual reality for stroke rehabilitation. – PubMed – NCBI

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[Abstract] A Dual-cable Hand Exoskeleton System for Virtual Reality


In this paper, a hand exoskeleton system for virtual reality is proposed. As a virtual reality interface for the hand, a wearable system should be able to measure the finger joint angles and apply force feedback to the fingers at the same time with a simple and light structure. In the proposed system, two different cable mechanisms are applied to achieve such requirements; three finger joint angles in the direction of the flexion/extension (F/E) motion are measured by a tendon-inspired cable mechanism and another cable is used for force feedback to the finger for one degree of freedom (DOF) actuation per finger. As two different types of cables are used, the system is termed a dual-cable hand exoskeleton system. Using the measured finger joint angles and motor current, the cable-driven actuation system applies the desired force to the fingers. That is, when the desired force is zero, the motor position is controlled to follow the finger posture while maintaining the appropriate cable slack; when the desired force needs to be applied, the motor current is controlled to generate the desired force. To achieve a smooth transition between the two control strategies, the control inputs were linearly integrated; and the desired motor position was generated to prevent a sudden motor rotation. A prototype of the proposed system was manufactured with a weight of 320g, a volume of 13 × 23 × 8cm3, maximum force up to 5 N. The proposed control algorithms were verified by experiments with virtual reality applications.


via A Dual-cable Hand Exoskeleton System for Virtual Reality

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[ARTICLE] Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial – Full Text



Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved (“active control zone”) after identification of a “spasticity zone”. Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function.


This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task.


This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries.


Stroke is a leading cause of long-term disability. Up to 85% of patients with sub-acute stroke present chronic upper limb (UL) sensorimotor deficits [1]. While post-stroke UL recovery has been a major focus of attention, efforts to identify effective rehabilitation interventions have been unsatisfactory. This study focuses on the delivery of personalized impairment-based UL training combined with low-cost state-of-the-art technology (non-invasive brain stimulation and commercially available virtual reality, VR) to enhance motor learning, which is becoming more readily available worldwide.

A major impairment following stroke is spasticity, leading to difficulty in daily activities and reduced quality of life [2]. Studies have identified that spasticity relates to disordered motor control due to deficits in the ability of the central nervous system to regulate motoneuronal thresholds through segmental and descending systems [34]. In the healthy nervous system, the motoneuronal threshold is expressed as the “spatial threshold” (ST) or the specific muscle length/joint angle at which the stretch reflex and other proprioceptive reflexes begin to act [567]. The range of ST regulation in the intact system is defined by the task-specific ability to activate muscles anywhere within the biomechanical joint range of motion (ROM). However, to relax the muscle completely, ST has to be shifted outside of the biomechanical range [8].

After stroke, the ability to regulate STs is impaired [3] such that the upper angular limit of ST regulation occurs within the biomechanical range of the joint resulting in spasticity (spasticity zone). Thus, resistance to stretch of the relaxed muscle has a spatial aspect in that it occurs within the defined spasticity zone. In other joint ranges, spasticity is not present and normal reciprocal muscle activation can occur (active control zone; [4] Fig. 1). This theory-based intervention investigates whether recovery of voluntary movement is linked to recovery of ST control.

Fig. 1Spatial thresholds (STs) in healthy and stroke participants. a The tonic stretch reflex threshold (TSRT) can be regulated throughout a range (filled bar) that exceeds the biomechanical range of the joint (open bar). Relaxation and active force can be produced at any angle within the biomechanical range. b The intersection of the diagonal line with the zero-velocity line defines the TSRT. In healthy subjects, TSRT lies outside of the biomechanical range of the joint (arrow) during the relaxed state. c In patients with stroke, TSRT may lie within the biomechanical range in the relaxed state, defining the joint angle at which spasticity begins to appear (spasticity zone). In the other joint ranges, spasticity is not present (active zone)

We also consider that inter-hemispheric balance is disrupted after stroke, interfering with recovery. UL motor function depends on the modulation of inter-hemispheric inhibition between cortical areas via transcallosal projections [910] and descending projections to fingers, hand and arm [11]. Unilateral hemispheric damage reduces activity in the affected hemisphere while activity in the unaffected hemisphere increases [12], becoming more dominant. UL recovery may relate to rebalancing of inter-hemispheric inhibition [13] using, for example, anodal transcranial direct current stimulation (a-tDCS) over the affected hemisphere [1415]. a-tDCS is considered a safe technique with transient adverse effects, such as slight scalp itching or tingling and/or mild headaches, that are not expected to impede the patient’s ability to participate in the training protocol [16].

The underlying idea of this proposal is that recovery of voluntary movement is tightly linked to the recovery of threshold control. We propose an intervention that combines current knowledge about motor learning and disorders in ST control. The intervention involves personalized UL reach training designed according to the spatial structure of motor deficits of an individual, with excitatory a-tDCS over the sensorimotor areas of the affected hemisphere. […]


Continue —> Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial | Trials | Full Text

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[Abstract+References] Interactive System for Hands and Wrist Rehabilitation – Proceedings of the International Conference on Information Technology & Systems (ICITS 2018)


An Interactive system is presented for the rehabilitation of hands and wrists using the leap motion device and the Unity3D software. Two applications were created with several movements were by programming such as flexion, wrist extension, pronation, supination and adduction. Through the interfaces the users have immersion and perform the exercises correctly because at the end of the game a visual and audible feedback is presented. Five people used the system and then the SEQ usability test was applied with results of 59.6. This indicates that the system has a good acceptance and can be used for rehabilitation.


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[ARTICLE] Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke – Full Text


Background and Purpose—Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke.

Methods—Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl–Meyer Assessment-Upper Extremity).

Results—Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl–Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, −0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl–Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6).

Conclusions—This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed.


Arm weakness is common after stroke, and its treatment is recognized as an area of considerable need.1 Approximately 85% of patients with stroke present with arm weakness,2 and 60% of stroke survivors with nonfunctional arms at 1 week do not recover function by 6 months.3Current treatment for arm weakness typically comprises intensive, task-specific, and repetitive rehabilitative interventions or occasionally methods such as constraint-induced movement therapy and electric neurostimulation.4 A recent meta-analysis and large-scale trials show the effects of current treatments for arm weakness to be modest.5,6 Novel and more effective treatments are needed. Improvement in arm function should improve quality of life for stroke survivors, reduce comorbidities associated with loss of independence, and reduce cost to the healthcare system.7

Intensive training has been shown to facilitate a range of neuroplastic brain events.8 It is possible that augmentation of neuroplasticity to promote reorganization of neural networks is required to more fully recover motor function.9 However, no practical and effective method exists to achieve this and even if such changes occur, it is unclear whether they are clinically meaningful or long term. This study is a preliminary investigation of an intervention designed to promote specific neuroplasticity; vagus nerve stimulation (VNS) paired with movement to drive task-specific plasticity in the motor cortex.1012 VNS activates neurons in the basal forebrain and locus coeruleus and results in release of acetylcholine and norepinephrine, respectively, which are known to facilitate reorganization of cortical networks.13 We recently demonstrated in a rat model of ischemic stroke that pairing forelimb rehabilitation with VNS significantly increases recovery of forelimb speed and strength when compared with rehabilitation alone.14,15 Our subsequent studies demonstrated that VNS paired with rehabilitative training also improves recovery in a rat model of intracerebral hemorrhage,16 and that precise timing of VNS with specific motor movements yields optimal recovery.17

We hypothesize that VNS paired with upper-limb rehabilitation therapy will result in greater recovery of arm function than rehabilitation alone in adults with chronic ischemic stroke. We performed the first-in-human evaluation of VNS paired with upper-limb rehabilitation after ischemic stroke. The main objective of the study was to evaluate the safety and feasibility of paired VNS therapy after stroke and to provide clinical data for sample size calculations for larger studies. […]


Continue —> Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke | Stroke

Figure 1. Schematic of vagus nerve stimulation device use in a typical therapy session.

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