Invasive Vagus Nerve Stimulation Paired With Rehabilitation After Stroke

Stroke is a major cause of long-term disability, and upper-limb motor impairment is one of the most common and disabling consequences after stroke. Vagus nerve stimulation (VNS) paired with rehabilitation is a neuromodulation approach designed to enhance activity-dependent neural plasticity during motor training.

This single-center study investigated the clinical feasibility and preliminary effects of invasive vagus nerve stimulation paired with structured upper-limb rehabilitation in participants with chronic stroke-related upper-limb motor dysfunction. Participants underwent left cervical vagus nerve stimulation implantation and completed a 6-week supervised in-clinic rehabilitation program followed by a 90-day home-based rehabilitation phase.

Clinical outcomes included the Fugl-Meyer Assessment Upper Extremity score, additional motor and sensory functional assessments, Modified Ashworth Scale scores for spasticity evaluation, and health-related quality of life assessment. Safety and stimulation-related tolerability were also evaluated throughout follow-up.

Exploratory imaging analyses using positron emission tomography/computed tomography and arterial spin labeling were conducted in selected participants to describe changes in metabolic activity and cerebral perfusion within motor-related cortical and subcortical regions.

The study provides preliminary clinical observations regarding the application of invasive vagus nerve stimulation paired with rehabilitation for stroke-related motor recovery and may support future controlled clinical studies.

Inclusion criteria

• Adults aged 18 years or older.
• Documented history of stroke with persistent upper-limb motor dysfunction.
• Completion of invasive vagus nerve stimulation implantation.
• Completion of paired upper-limb rehabilitation after stimulation.
• Availability of clinical assessments during follow-up.

Exclusion criteria

• Other central nervous system disorders affecting motor function assessment.
• Severe disturbance of consciousness or inability to complete standardized functional assessments.
• Severe cognitive, communication, musculoskeletal, or peripheral nerve disorders interfering with upper-limb function evaluation.
• Missing key clinical or follow-up data.