Virtual reality-based neuroproprioceptive physiotherapy in multiple sclerosis: a protocol for a double-arm randomised assessor-blinded controlled trial on upper extremity function, postural function and quality of life, with molecular and functional MRI a

Upper limb (UL) impairment is common in people with multiple sclerosis (pwMS), and functional recovery of the UL is a key rehabilitation goal. Technology-based approaches, like virtual reality (VR), are increasingly promising. While most VR environments are task-oriented, our clinical approach integrates neuroproprioceptive 'facilitation and inhibition' (NFI) principles. To advance this, we developed immersive VR software based on NFI principles targeting UL function and sit-to-stand ability. This study aims to evaluate the effectiveness of this VR therapy compared with conventional NFI-based physical therapy in pwMS. Our study uniquely applies advanced imaging techniques, along with biological molecular assessments, to explore adaptive processes induced by VR rehabilitation. This double-arm, randomised, assessor-blinded, controlled trial runs over 2 months (1 hour, 2 times per week). PwMS with mild to severe disability will receive either VR therapy or real-world physical therapy. Primary outcomes include the nine-hole peg test, box and block test, handgrip strength, tremor and five times sit-to-stand test. Secondary measures include the Multiple Sclerosis Impact Scale, the 5-level EQ-5D questionnaire and kinematic analysis. Adaptive processes will be monitored using imaging techniques (functional MRI and tractography), molecular genetic methods (long non-coding RNAs) and immune system markers (leukocytes, dendritic cells). The International Classification of Functioning, Disability and Health brief set for MS will map the bio-psycho-social context of participants. This project and its amendments were approved by the Ethics Committee of the Institute for Clinical and Experimental Medicine and Thomayer Hospital (1983/21+4772/21 (G-21-02) and the Ethics Committee of Kralovske Vinohrady University Hospital (EK-VP/38/0/2021) in Prague, Czechia (with single enrolment). The findings of this project will be disseminated through scientific publications, conferences, professional networks, public engagement, educational materials and stakeholder briefings to ensure a broad impact across clinical, academic and public domains. clinicaltrials.gov (NCT04807738).

Miznerova B ，Reissigova J ，Vasa L ，Frank J ，Hudec M ，Rodina L ，Herynkova A ，Havlik J ，Tintera J ，Rydlo J ，Ibrahim I ，O'Leary VB ，Cerna M ，Jurickova I ，Pokorna M ，Philipp T ，Hlinovska J ，Stetkarova I ，Rasova K ... -  《BMJ Open》

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》

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》

Virtual reality for multiple sclerosis rehabilitation.

Multiple sclerosis (MS) is the most common neurological disease in young adults. Virtual reality (VR) offers a promising rehabilitation tool by providing controllable, personalised environments for safe, adaptable and engaging training. Virtual reality can be tailored to patients' motor and cognitive skills, enhancing motivation through exciting scenarios and feedback. Primary objective To assess the effects of virtual reality interventions compared with an alternative or no intervention on lower limb and gait function, and balance and postural control in people with MS. Secondary objective To assess the effects of virtual reality interventions compared with an alternative or no intervention on upper limb function, cognitive function, fatigue, global motor function, activity limitation, participation restriction and quality of life, and adverse events in people with MS. We identified relevant articles through electronic searches of CENTRAL, MEDLINE, Embase, PEDro, CINAHL and Scopus. We also searched trials registries (ClinicalTrials.gov and the WHO ICTRP search portal) and checked reference lists. We carried out all searches up until August 2022. We included only (quasi-)randomised controlled trials (RCTs) that assessed virtual reality interventions, defined as "an artificial, computer-generated simulation or creation of a real-life environment or situation allowing the user to navigate through and interact with", in people with MS. The primary outcomes were lower limb and gait function, and balance and postural control. Secondary outcome measures were upper limb function, cognitive function, fatigue, global motor function, activity limitation, participation and quality of life, and adverse events. Eligible participants were people with MS who were 18 years or older. Two review authors independently screened the studies based on pre-specified criteria, extracted study data and assessed the risk of bias of the included studies. We used the risk of bias 2 tool (RoB 2). A third review author was consulted to resolve conflicts. We included 33 RCTs with 1294 people with MS. The sample sizes of the included studies were relatively small and there was considerable heterogeneity between studies regarding the virtual reality devices and the outcome measures used. The control group either received no intervention, conventional therapy or an alternative intervention (an intervention that does not fit the description of conventional therapy for the rehabilitation of people with MS). We most frequently judged the risk of bias as 'some concerns' across domains, leading to an overall high risk of bias in the majority of included studies for all outcome measures. Primary outcomes When compared with no intervention, virtual reality interventions may result in no difference in lower limb and gait function (Timed Up and Go, mean difference (MD) -0.43 sec, 95% confidence interval (CI) -0.85 to 0.00; 6 studies, 264 participants; low-certainty evidence) or balance and postural control (Berg Balance Scale, MD 0.29 points, 95% CI -0.1 to 0.68; 4 studies, 137 participants; very low-certainty evidence). When virtual reality interventions are compared to conventional therapy, results for lower limb and gait function probably do not differ between interventions (Timed Up and Go, MD -0.2 sec, -1.65 to 1.25; 4 studies, 107 participants; moderate-certainty evidence). However, virtual reality interventions probably improve balance and postural control (Berg Balance Scale, MD 2.39 points, 95% CI 1.22 to 3.57; 7 studies, 201 participants; moderate-certainty evidence), almost reaching the clinically important difference (3 points). Secondary outcomes Compared to no intervention, the use of virtual reality may also improve upper limb function (9-Hole Peg Test, MD -4.19 sec, 95% CI -5.86 to -2.52; 2 studies, 84 participants; low-certainty evidence), almost reaching the clinically important difference (4.38 points) and participation and quality of life, but the evidence is very uncertain (MS International QoL, MD 9.24 points, 95% CI 5.76 to 12.73; 2 studies, 82 participants; very low-certainty evidence). Compared to conventional therapy, virtual reality interventions may improve participation and quality of life (Falls Efficacy Scale-1, MD -3.07 points, 95% CI -5.99 to -0.15; 3 studies, 101 participants; low-certainty evidence), but not upper limb function (9-Hole Peg Test, MD 0.10 sec, 95% CI -1.70 to 1.89; 3 studies, 93 participants; low-certainty evidence). For other key secondary outcome measures, i.e. global motor function and adverse events, there were no data available as these were not measured in the studies. We found evidence that the use of virtual reality may be more effective than no intervention in improving upper limb function and participation and quality of life. Training with virtual reality may be superior to conventional therapy for improving balance and postural control, and participation and quality of life. For the other outcomes, there was no clear difference between virtual reality and conventional therapy. There was insufficient evidence to reach conclusions about the effect of virtual reality on global motor function, activity limitations and adverse events. Additional high-quality, large-scale studies are needed to expand and confirm these findings.

De Keersmaecker E ，Guida S ，Denissen S ，Dewolf L ，Nagels G ，Jansen B ，Beckwée D ，Swinnen E ... -  《Cochrane Database of Systematic Reviews》

The effect of a telerehabilitation virtual reality intervention on functional upper limb activities in people with multiple sclerosis: a study protocol for the TEAMS pilot randomized controlled trial.

Kalron A ，Achiron A ，Pau M ，Cocco E ... -  《-》