Introduction: Vagus Nerve Stimulation (VNS) paired with rehabilitation induces movement specific plasticity in rat motor cortex and improves forepaw function in a rat ischemic model compared to rehabilitation alone. A 20 subject first-in-human study in the UK indicated acceptable safety and feasibility of this approach in patients with arm weakness after stroke and showed a significant difference in favour of VNS paired with rehabilitation in the per-protocol analysis (Upper Extremity Fugl Meyer difference of 9.6 points for VNS vs. 3.0 Control; p = 0.038). We conducted a new, double-blind sham controlled study to further assess this technique.
Methods: Subjects with chronic moderate to severe upper extremity hemiparesis secondary to ischemic stroke (Upper Extremity Fugl Meyer (UEFM) 20-50) were enrolled at four sites (3 US, 1 UK). After baseline assessments subjects were implanted with a vagus nerve stimulation device if all eligibility criteria were met. Following implantation, randomization was made to either paired VNS (1/2 second, 30 Hz., 0.8 mA, 100 uS stimulation with task-specific movement) or sham control (stimulation only on first 5 movements). All received the same intensive and task-specific rehabilitation and had 18 treatment sessions (2-hourly, 3 times a week for 6-weeks, approximately 50 repetitions per task and 300 to 400 repetition movements per session). Outcomes were assessed on the first and 30th day following completion of the 6-week therapy course.
Results: Sixteen patients (8 female) were implanted (8 VNS, 8 Control). Mean age (SD) was 63.2(6.9), with an average (SD) of 21.7 months (12.9) post stroke. One study related serious adverse event was reported (a wound infection that resolved with IV antibiotics). Blinded results (change in UEFM, WMFT, and UEFM responders for both groups) will be available and presented.
Conclusions: A pivotal study of VNS paired with rehabilitation movements will be justified if preliminary results are confirmed.