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.

Efficacy of constraint-induced movement therapy on involved upper-extremity use in children with hemiplegic cerebral palsy is not age-dependent.

OBJECTIVES: Constraint-induced (CI) movement therapy has been shown recently to be promising for improving upper-limb function in children with cerebral palsy (CP). Because little is known about patient characteristics predicting treatment efficacy, not all children may benefit from this intervention. Here we examine the relationship between efficacy of a child-friendly form of CI therapy and age on involved upper-extremity function. DESIGN: Twenty children with hemiplegic CP age 4 to 13 years received CI therapy and completed evaluations. Based on established functional and neuromaturational changes in hand skill development, the children were divided into a "younger group" (age 4-8 years, n = 12) and "older group" (age 9-13 years, n = 8). Children wore a sling on their noninvolved upper extremity for 6 hours per day for 10 of 12 consecutive days, during which time they were engaged in play and functional activities. Each child was evaluated by trained evaluators who were blinded to the fact that the children received treatment. The evaluations took place once before the intervention and at 1 week, 1 month, and 6 months after the intervention. Efficacy was examined at the movement efficiency (Jebsen-Taylor Test of Hand Function, subtest 8 of the Bruininks-Oseretsky Test of Motor Proficiency), environmental (caregiver frequency and quality of involved upper-limb use), and impairment (strength, tactile sensitivity, and muscle tone) levels. RESULTS: Children in both age groups had significant improvements in involved hand-movement efficiency and environmental functional limitations, which were retained through the 6-month posttest. However, there were no differences in efficacy between younger and older children. Both hand severity and the children's behavior during testing (number of redirections), with the latter serving as a reasonable correlate for attention during the intervention, were related to changes in performance in the younger group but not in the older group. CONCLUSIONS: The results suggest that the intensive practice associated with CI therapy can improve movement efficiency and environmental functional limitations among a carefully selected subgroup of children with hemiplegic CP of varying ages and that this efficacy is not age-dependent.