Disclosures: Gerard E. Francisco, MD: Allergan (Products/Services: Yes) (Consultant/Advisory Board, Research Grant or Support)Ekso (Products/Services: No) (Consultant/Advisory Board, Research Grant or Support)Indego (Products/Services: Yes) (Research Grant or Support)Ipsen (Products/Services: No) (Research Grant or Support)Merz (Products/Services: No) (Consultant/Advisory Board, Research Grant or Support)Microtransponder (Products/Services: No) (Research Grant or Support)Revance (Products/Services: No) (Research Grant or Support)ReWalk (Products/Services: No) (Research Grant or Support)Saol (Products/Services: No) (Consultant/Advisory Board)Shionogi (Products/Services: No) (Consultant/Advisory Board)Sword Health (Products/Services: No) (Consultant/Advisory Board)

Objective: Pilot studies suggested that vagus nerve stimulation (VNS) paired with upper limb rehabilitation (VNS+Rehab) was safe, feasible, and potentially beneficial in persons with chronic upper limb impairment after ischemic stroke. This pivotal study seeks to confirm if VNS+Rehab is a safe and effective therapy to improve arm function after a stroke.

Design: Randomized, triple-blind, sham-controlled trial. All participants were implanted with VNS device, and randomized to receive VNS+Rehab (active; n=53) or Sham+Rehab (control; n=55).Setting : Nineteen sites (USA and UK)Participants : One-hundred six of original 108 subjects completed the study. Major inclusion criteria: 1) age22 years and 80 years; 2) unilateral supratentorial ischemic stroke 9–120 months prior to enrollment; 3) moderate-to-severe arm impairment (Fugl-Meyer Assessment Upper Extremity [FMA-UE] score between 20-50).

Interventions: VNS implantation followed by upper limb rehabilitation paired with either VNS or sham stimulation. Rehabilitation consisted of 6 weeks of in-clinic therapy followed by home exercise program.

Main Outcome Measures: Primary: change in impairment from baseline measured FMA-UE on day-1 post-completion of in-clinic therapy. Secondary: 1) clinically meaningful response on FMA-UE score (≥6-point improvement) at day-90; 2) Wolf Motor Function Test-Functional (WMFT-M) score change at day-90; 3) FMA-UE change at day-90.

Results: Primary outcome: mean (±SD) FMA-UE score increased by 5 (±4.4) points in VNS+Rehab versus 2.4 (±3.8) points in Sham+Rehab (p=0.001). Secondary outcomes: clinically meaningful response on the FMA-UE score achieved by 47% in the VNS+Rehab, compared to 24% in Sham+Rehab (p=0.01). WMFT-M scores increased by 0.46 (±0.40) points in VNS+Rehab compared to 0.16 (±0.30) points in Sham+Rehab groups (p < 0.0001); FMA-UE score increased by 5.8 (±6.0) points from baseline in VNS+Rehab versus 2.8 (±5.2) points in Sham+Rehab (p=0.008). One serious surgery-related adverse event (vocal cord paresis, which subsequently improved) occurred.Conclusions: VNS+Rehab significantly decreased motor impairment and improved function in persons with moderate-to-severe arm impairment post-ischemic stroke compared to Sham+Rehab.

Level of Evidence: Level I

« Back to AAPM&R Annual Assembly 2021

PM&R Meeting Abstracts - https://pmrjabstracts.org/abstract/vagus-nerve-stimulation-paired-with-rehabilitation-decreases-impairment-and-improves-upper-limb-function-after-ischemic-stroke-results-of-a-randomized-controlled-multi-center-phase-iii-trial/