Effectiveness of immersive VR-based rehabilitation on upper extremity recovery in subacute stroke: a randomized controlled trial

Background and Purpose Few effective treatments improve upper extremity (UE) function after stroke. Immersive Virtual Reality (imVR) is a novel and promising strategy for stroke UE recovery. However, research on immersive VR-based UE rehabilitation has been minimal. Here we present a randomized controlled trial to assess the effectiveness of imVR-based UE rehabilitation in patients with subacute stroke and explore the underlying brain network related to imVR-based rehabilitation. Methods A single-blinded, randomized controlled trial was performed with 40 subjects randomly assigned to either the imVR or the control group (1:1 allocation), each receiving rehabilitation 5 times per week for 3 weeks. Subjects in the imVR group received both immersive VR and conventional rehabilitation, while those in the control group received conventional rehabilitation only. The Fugl-Meyer assessment’s upper extremity subscale (FMA-UE) and the Barthel Index (BI) were our primary and secondary outcomes, respectively. Subjects received assessments and MRI scans at each of the following three time points: immediately after randomization (baseline, Week 0), immediately following conclusion of the randomized rehabilitation program (post-intervention, Week 3), and follow-up 12 weeks after completing the rehabilitation program (follow-up, Week 15). Brain functional connectivity (FC) and a parameter derived from it, degree, were used to assess the performance of immersive VR-based rehabilitation and to relate the change of brain activity to motor recovery. Results Both intention-to-treat (ITT) and per-protocol (PP) analyses demonstrated the effectiveness of imVR-based UE rehabilitation on subacute stroke. The FMA-UE score was significantly greater in the imVR group compared with the control group at the post-intervention (mean difference: 9.11, 95% CI (1.57-16.64); p = 0.019 (ITT); 12.46, 95% CI (4.56 -20.36); p = 0.003 (PP)), and at the follow-up (mean difference:11.47, p = 0.020 (ITT); 18.85, 95% CI (6.01-31.69); p = 0.006 (PP)). The results were consistent for BI scores at the post-intervention (mean difference: 8.28, 95% CI (0.082-16.48); p = 0.048 (ITT); 9.77, 95% CI (0.58-18.95); p = 0.038 (PP)), and at the follow-up (mean difference: 4.81, 95% CI (0.85-8.77); p = 0.019 (ITT); 6.69, 95% CI (0.54-12.84); p = 0.034 for (PP)). Moreover, brain functional connectivity analysis found that the motor function improvements are significantly associated with a change in brain functional connectivity in ipsilesional premotor cortex and ipsilesional dorsolateral prefrontal cortex immediately following the intervention and in ipsilesional visual region and ipsilesional middle frontal gyrus after the 12-week follow-up. In addition, a significant increase in the motor recovery rate of the imVR group was observed between the baseline and post-intervention time points ( p = 0.002). Conclusions The imVR-based rehabilitation is an effective rehabilitation tool that can improve the recovery of UE functional capabilities of subacute stroke patients when added to standard care. These improvements are associated with distinctive brain reorganizations at two post-stroke timepoints. The study results will benefit future patients with stroke and may provide a new and better method of stroke rehabilitation. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03086889 ### Funding Statement This study was funded by the Wenzhou Bureau of Science and Technology (No. Y20190042) and the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (No. 2017198456). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Institutional Review Board of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University(No.2017LCKY-09) and all participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.