Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial.

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke. OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury. METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS treatment by sex, age (≥62 years), time from stroke (>2 years), severity (baseline FMA-UE score >34), paretic side of body, country of enrollment (USA vs UK) and presence of cortical involvement of the index infarction. We assessed whether there was any interaction with treatment. FINDINGS: The primary outcome increased by 5.0 points (SD 4.4) in the VNS group and by 2.4 points (SD 3.8) in the Control group (P = .001, between group difference 2.6, 95% CI 1.03-4.2). The between group difference was similar across all subgroups and there were no significant treatment interactions. There was no important difference in rates of adverse events across subgroups. CONCLUSION: The response was similar across subgroups examined. The findings suggest that the effects of paired VNS observed in the VNS-REHAB trial are likely to be consistent in wide range of stroke survivors with moderate to severe upper extremity impairment.

Dynamic hand orthoses for the recovery of hand and arm function in adults after stroke: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Repetitive, functional-based rehabilitation is recommended after stroke. However, impaired active digital extension is common after stroke, which limits functional-based rehabilitation and recovery. Non-robotic dynamic hand orthoses (DHOs) may address this. OBJECTIVES: We did a systematic review and meta-analysis to determine whether non-robotic DHOs improve upper limb recovery after stroke in comparison to i)placebo or no intervention and ii)usual care. METHODS: We followed PRISMA guidelines. We included randomized controlled trials (RCTs) assessing upper limb recovery associated with the use of non-robotic DHOs in adults after stroke. Outcomes of interest were functional upper limb movement and activities of daily living.We performed searches on 27 September 2019 in 10 bibliographic databases including Cochrane Stroke Groups Specialized Trials Register and Cochrane Central Register of Controlled Trials. We also searched gray literature and citations from included studies.Two reviewers independently screened abstracts and full text, extracted data and assessed risk of bias using a Cochrane risk of bias tool. RESULTS: We reviewed 7225 titles and included four studies involving 56 randomized participants, all with a high risk of bias. A positive effect in favor of non-robotic DHOs was observed for two outcomes; upper limb function (mean difference (MD) 6.23, 95% confidence interval (CI) 0.28-12.19 (p = 0.04)) and dexterity (MD 2.99, 95% CI 0.39-5.60 (p = 0.02). CONCLUSIONS: The results are encouraging but included studies were small with high risk of bias meaning there is currently insufficient evidence that non-robotic DHOs improve upper limb recovery after stroke. REVIEW REGISTRATION: PROSPERO, CRD42020179180. Registered on 20 May 2020.

SaeboGlove therapy for upper limb disability and severe hand impairment after stroke (SUSHI): Study protocol for a randomised controlled trial.

BACKGROUND: Impaired active digital extension is common after stroke, hindering functional rehabilitation, and predicting poor recovery. The SaeboGlove assists digital extension and may improve outcome after stroke. We recently performed a single group, open, pilot trial of the SaeboGlove early after stroke which demonstrated satisfactory safety, feasibility and acceptability. An adequately powered randomised clinical trial is now needed to assess the clinical effectiveness of the SaeboGlove. METHODS: SUSHI is a pragmatic, multicentre, parallel-group, randomised controlled trial with blinded outcome assessment, and embedded process and economic evaluations. Adults, 7-60 days post-stroke, with upper limb disability and severe hand impairment, including reduced active digital extension, will be recruited from NHS inpatient stroke services in Scotland. Participants will be randomised on a 1:1 basis to receive 6 weeks of self-directed, repetitive, functional-based practice involving a SaeboGlove plus usual care, or usual care only. The primary outcome is upper limb function measured by the Action Research Arm Test (ARAT) at 6 weeks. Secondary outcomes will be measured at 6 and 14 weeks. A process evaluation will be performed via interviews with 'intervention' participants, and their carers and clinical therapists. A within-trial cost-effectiveness analysis will be performed. 110 participants are required to detect a difference between groups of 9 in the ARAT with 90% power at a 5% significance level allowing for 11% attrition. DISCUSSION: SUSHI will determine if SaeboGlove self-directed, repetitive, functional-based practice improves upper limb function after stroke, whether it is acceptable to stroke survivors and whether it is cost-effective.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient.

BACKGROUND: Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitation can enhance neural plasticity in the primary sensory and motor cortices, improve forelimb function after stroke in animal models and improve motor function in patients with arm weakness after stroke. OBJECTIVE: To gain "first-in-man" experience of VNS paired with tactile training in a patient with severe sensory impairment after stroke. METHODS: During the long-term follow-up phase of a clinical trial of VNS paired with motor rehabilitation, a 71-year-old man who had made good motor recovery had ongoing severe sensory loss in his left hand and arm. He received VNS paired with tactile therapy in an attempt to improve his sensory function. During twenty 2-hour sessions, each passive and active tactile event was paired with a 0.5 second burst of 0.8 mA VNS. Sensory function was measured before, halfway through, and after this therapy. RESULTS: The patient did not report any side effects during or following VNS+Tactile therapy. Quantitative measures revealed lasting and clinically meaningful improvements in tactile threshold, proprioception, and stereognosis. After VNS+Tactile therapy, the patient was able to detect tactile stimulation to his affected hand that was eight times less intense, identify the joint position of his fingers in the affected hand three times more often, and identify everyday objects using his affected hand seven times more often, compared to baseline. CONCLUSIONS: Sensory function significantly improved in this man following VNS paired with tactile stimulation. This approach merits further study in controlled clinical trials.

Physical activity in the prevention and treatment of stroke.

The role of physical activity in the prevention of stroke is of great interest due to the high mortality and significant impact of stroke-related morbidity on the individual and on healthcare resources. The use of physical activity as a therapeutic strategy to maximise functional recovery in the rehabilitation of stroke survivors has a growing evidence base. This narrative review examines the existing literature surrounding the use of exercise and physical therapy in the primary and secondary prevention of stroke. It explores the effect of gender, exercise intensities and the duration of observed benefit. It details the most recent evidence for physical activity in improving functional outcome in stroke patients. The review summaries the current guidelines and recommendations for exercise therapy and highlights areas in which further research and investigation would be useful to determine optimal exercise prescription for effective prevention and rehabilitation in stroke.