Combined robot motor assistance with neural circuit-based virtual reality (NeuCir-VR) lower extremity rehabilitation training in patients after stroke: a study protocol for a single-centre randomised controlled trial.

Improving lower extremity motor function is the focus and difficulty of post-stroke rehabilitation treatment. More recently, robot-assisted and virtual reality (VR) training are commonly used in post-stroke rehabilitation and are considered feasible treatment methods. Here, we developed a rehabilitation system combining robot motor assistance with neural circuit-based VR (NeuCir-VR) rehabilitation programme involving procedural lower extremity rehabilitation with reward mechanisms, from muscle strength training, posture control and balance training to simple and complex ground walking training. The study aims to explore the effectiveness and neurological mechanisms of combining robot motor assistance and NeuCir-VR lower extremity rehabilitation training in patients after stroke. This is a single-centre, observer-blinded, randomised controlled trial. 40 patients with lower extremity hemiparesis after stroke will be recruited and randomly divided into a control group (combined robot assistance and VR training) and an intervention group (combined robot assistance and NeuCir-VR training) by the ratio of 1:1. Each group will receive five 30 min sessions per week for 4 weeks. The primary outcome will be Fugl-Meyer assessment of the lower extremity. Secondary outcomes will include Berg Balance Scale, Modified Ashworth Scale and functional connectivity measured by resting-state functional MRI. Outcomes will be measured at baseline (T0), post-intervention (T1) and follow-ups (T2-T4). The trial was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Traditional Medicine (Grant No. 2019-014). The results will be submitted to a peer-reviewed journal or at a conference. ChiCTR2100052133.

Zhou ZQ ，Hua XY ，Wu JJ ，Xu JJ ，Ren M ，Shan CL ，Xu JG ... -  《BMJ Open》

Evaluating the effect and mechanism of upper limb motor function recovery induced by immersive virtual-reality-based rehabilitation for subacute stroke subjects: study protocol for a randomized controlled trial.

Huang Q ，Wu W ，Chen X ，Wu B ，Wu L ，Huang X ，Jiang S ，Huang L ... -  《Trials》

Feasibility and efficacy of virtual reality rehabilitation compared with conventional physiotherapy for upper extremity impairment due to ischaemic stroke: protocol for a randomised controlled trial.

Approximately half of all stroke survivors have persistent upper extremity functional impairment, leading to reduced self-care, independence and quality of life. High-intensity, task-oriented virtual reality rehabilitation improves motor recovery. However, its clinical efficacy over standard rehabilitation remains uncertain. This study aims to evaluate the feasibility and efficacy of a virtual reality-based comprehensive rehabilitation gaming system (VR-cRGS) in stroke survivors with upper extremity impairment and to characterise the structural and functional plasticity of the affected regions in the brain due to the proposed rehabilitation. This study is a multicentric, open-label, randomised controlled trial with an intention-to-treat analysis. A total of 162 patients will be enrolled in two academic institutes in India that specialise in stroke care. Patients with a first-ever ischaemic stroke (18-70 years and 1-6 months of stroke onset) with upper extremity impairment with 1 and 1+ grades of spasticity as per the modified Ashworth Scale and 3, 4 or 5 stages on Brunnstrom recovery staging will be enrolled. They will be randomised (1:1) into two treatment groups to receive 12 weeks of training either on VR-cRGS or on conventional physiotherapy. The primary feasibility outcome is compliance with the treatment. The primary efficacy outcome is the functional recovery of the upper extremity assessed by the Fugl-Meyer Assessment-Upper Extremity and Wolf Motor Function Test. The secondary outcomes are the Barthel Index and the 36-item Short-Form Health Survey. Multimodal brain imaging will be done in all enrolled patients at baseline and post-treatment to evaluate the structural and functional connectivity changes. The outcome measures will be analysed using paired t-tests or non-parametric tests. The study has been approved by the Institutional Ethics Review Board of the Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India (SCT/IEC/1415/AUGUST-2019) and the National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India (NIMHANS/IEC (BS and NS DIV.)/32nd Meeting/21). All participants will sign an informed consent form prior to participation. The study results will be disseminated through scholarly publication. CTRI/2021/11/038339.

Paul R ，Elango S ，Chakravarthy S ，Sinha A ，P R S ，Raju B ，C K ，Sarma PS ，Hafsath S ，Francis AJA ，Darshini D ，Sylaja PN ... -  《BMJ Open》

Effectiveness of Using Virtual Reality-Supported Exercise Therapy for Upper Extremity Motor Rehabilitation in Patients With Stroke: Systematic Review and Meta-analysis of Randomized Controlled Trials.

In recent years, efforts have been made to implement virtual reality (VR) to support the delivery of poststroke upper extremity motor rehabilitation exercises. Therefore, it is important to review and analyze the existing research evidence of its effectiveness. Through a systematic review and meta-analysis of randomized controlled trials, this study examined the effectiveness of using VR-supported exercise therapy for upper extremity motor rehabilitation in patients with stroke. This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The CINAHL Plus, MEDLINE, Web of Science, Embase, and Cochrane Library databases were searched on December 31, 2021. Changes in outcomes related to impairments in upper extremity functions and structures, activity limitations, and participation restrictions in life situations from baseline to after intervention, after intervention to follow-up assessment, and baseline to follow-up assessment were examined. Standardized mean differences (SMDs) were calculated using a random-effects model. Subgroup analyses were performed to determine whether the differences in treatment outcomes depended on age, stroke recovery stage, VR program type, therapy delivery format, similarities in intervention duration between study groups, intervention duration in VR groups, and trial length. A total of 42 publications representing 43 trials (aggregated sample size=1893) were analyzed. Compared with the control groups that used either conventional therapy or no therapy, the intervention groups that used VR to support exercise therapy showed significant improvements in upper extremity motor function (Fugl-Meyer Assessment-Upper Extremity; SMD 0.45, 95% CI 0.21-0.68; P<.001), range of motion (goniometer; SMD 1.01, 95% CI 0.50-1.52; P<.001), muscle strength (Manual Muscle Testing; SMD 0.79, 95% CI 0.28-1.30; P=.002), and independence in day-to-day activities (Functional Independence Measure; SMD 0.23, 95% CI 0.06-0.40; P=.01, and modified Rankin Scale; SMD 0.57, 95% CI 0.01-1.12; P=.046). Significant subgroup differences were observed in hand dexterity (Box and Block Test), spasticity (Ashworth Scale or modified Ashworth Scale), arm and hand motor ability (Wolf Motor Function Test and Manual Function Test), hand motor ability (Jebsen Hand Function Test), and quality of life (Stroke Impact Scale). There was no evidence that the benefits of VR-supported exercise therapy were maintained after the intervention ended. VR-supported upper extremity exercise therapy can be effective in improving motor rehabilitation results. Our review showed that of the 12 rehabilitation outcomes examined during the course of VR-based therapy, significant improvements were detected in 2 (upper extremity motor function and range of motion), and both significant and nonsignificant improvements were observed in another 2 (muscle strength and independence in day-to-day activities), depending on the measurement tools or methods used. PROSPERO CRD42021256826; https://tinyurl.com/2uarftbh.

Chen J ，Or CK ，Chen T 《JOURNAL OF MEDICAL INTERNET RESEARCH》

Effectiveness of robot-assisted virtual reality mirror therapy for upper limb motor dysfunction after stroke: study protocol for a single-center randomized controlled clinical trial.

Upper limb motor dysfunction is a common sequela of stroke, and its clinical efficacy needs to be improved. This protocol describes a trial to verify the clinical efficacy of robot-assisted virtual reality mirror therapy (RAVRMT) in improving upper limb motor dysfunction in stroke patients, and to explore the central mechanism by using functional magnetic resonance imaging (fMRI). This trial will be a single-center, assessor-blinded, randomized controlled clinical study. Thirty-two eligible patients will be randomly divided into 2 groups according to the ratio of 1:1, namely virtual reality mirror therapy (VRMT) group and robot-assisted virtual reality mirror therapy (RAVRMT) group. The interventions will be performed once a day for 4 weeks. Primary outcome is Fugl-Meyer motor function assessment-Upper Extremity (FMA-UE), secondary outcomes are the Montreal Cognitive Assessment (MoCA), activities of daily living (ADL), quality of life (QOL), the pain visual analogue scale (VAS-pain) and fMRI. Adverse events will be recorded, and severe adverse events will be used as criteria to discontinue the intervention. Combined application of robot-assisted therapy and virtual reality mirror therapy could theoretically activate mirror neuron system and reward circuits to a greater extent, but further high-quality research is needed. The results of this trial will determine whether RAVRMT could better improve upper limb motor dysfunction after stroke and explore its central mechanism using fMRI. This trial was prospectively registered at ClinicalTrials.gov (ChiCTR2200061721; 01 July 2022).

Wei D ，Hua XY ，Zheng MX ，Wu JJ ，Xu JG ... -  《BMC Neurology》