Disorders of consciousness are common after surgery for severe spontaneous intracerebral hemorrhage and are associated with high mortality, disability, and long-term dependence. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique that may enhance arousal-network activity, modulate secondary brain injury, and promote recovery of consciousness.
This multicenter, prospective, double-blind, randomized, sham-controlled trial will enroll 160 adults aged 18 to 75 years who underwent hematoma evacuation within 48 hours after spontaneous intracerebral hemorrhage and have a Glasgow Coma Scale score of 5 to 9 on postoperative day 5 while not sedated. Participants will be assigned 1:1 to active taVNS or sham stimulation for 8 hours once daily for 6 weeks. The primary outcome is the proportion of participants who remain in a disorder of consciousness (unresponsive wakefulness syndrome/vegetative state or minimally conscious state) at postoperative day 90, determined using the Coma Recovery Scale-Revised by blinded assessors.
Nested mechanistic substudies will investigate how taVNS may affect recovery through multimodal assessment of structural and functional brain networks, cerebral perfusion, electrophysiology, autonomic function, and circulating or cerebrospinal-fluid biomarkers. Depending on clinical stability, site capability, sample availability, and additional consent, assessments may include computed tomography, computed tomography angiography and perfusion, structural and functional magnetic resonance imaging, diffusion imaging, arterial spin labeling, electroencephalography, blood samples, and cerebrospinal fluid obtained during clinically indicated procedures.