Invasive vagus nerve stimulation paired with upper limb motor rehabilitation after intracerebral hemorrhage: A single-arm pilot cohort study

ABSTRACT: Invasive vagus nerve stimulation paired with rehabilitation improves upper-limb recovery after ischemic stroke, but clinical evidence after intracerebral hemorrhage remains limited. We evaluated the feasibility, safety, and descriptive functional signal of invasive vagus nerve stimulation-paired rehabilitation in chronic intracerebral hemorrhage. Twelve participants with chronic upper-limb motor dysfunction after intracerebral hemorrhage underwent left cervical invasive vagus nerve stimulation implantation followed by 6 weeks of supervised in-clinic rehabilitation and 90 days of home-based rehabilitation. The primary outcome was change in Fugl-Meyer Assessment Upper Extremity from baseline to day 1 after inclinic rehabilitation. Secondary and exploratory outcomes included Fugl-Meyer Assessment Upper Extremity change on day 90, Fugl-Meyer Assessment Upper Extremity subscores, modified Ashworth scale scores, quality of life, safety, and exploratory positron emission tomography/computed tomography and arterial spin labeling findings. All participants completed follow-up. Fugl-Meyer Assessment Upper Extremity increased from 23.50 ± 15.63 points at baseline to 27.58 ± 17.15 on day 1, with a mean change of 4.08 ± 3.48 points (P = 0.002). On day 90, Fugl-Meyer Assessment Upper Extremity was 27.75 ± 17.23 points, with a mean change of 4.25 ± 3.60 points from baseline. Six participants reached the minimal clinically important difference threshold on days 1 and 90. No serious perioperative complications were observed in this small cohort. Exploratory imaging in two participants showed postoperative changes in metabolic and perfusion ratios within cortical-subcortical motor-network regions. Invasive vagus nerve stimulation-paired rehabilitation was feasible and had an acceptable safety profile in this pilot intracerebral hemorrhage cohort, with a descriptive signal of upper-limb functional improvement. This study was registered on ClinicalTrials.gov (Identifier: NCT07736573).