Transcutaneous Auricular Vagus Nerve Stimulation Reduces Inflammatory Biomarkers after Large Vessel Occlusion Stroke:...

Inflammation exacerbates brain injury following acute ischemic stroke (AIS). Transcutaneous auricular vagus nerve stimulation (taVNS) reduces systemic inflammation, but its efficacy in AIS remains unexplored. We examined the safety and anti-inflammatory effect of taVNS in AIS patients. Prospective Randomized Open-label blinded endpoint design, sham-controlled trial. Anterior circulation large vessel occlusion (LVO) AIS patients were assigned to twice-daily taVNS or sham stimulation for five days or until discharge. Inclusion criteria: age≥18 years, NIHSS≥6, anterior circulation LVO, and enrollment within 36-hours of last known normal (LKN). Primary endpoints were changes in inflammatory biomarkers (interleukins (IL)-1β, 6, 10, 17α, and tumor necrosis factor alpha (TNFα) on Days 0, 1, 3, 5, and 7). TaVNS safety endpoints included bradycardia, hypotension, infection, and death. Thirty-five patients (17 taVNS, 18 sham) were enrolled and taVNS/sham treatment started a mean of 0.99 days (SD 0.26 days) from LKN. Mean stimulations received were 8.24 (SD 2.77) and 7.33 (SD 3.20), for treatment vs. sham respectively. The rate of protocol adherence was 77%. TaVNS treatment significantly changed IL-6 levels compared to sham treatment (overall p=0.0001). Although overall trajectories of other cytokines did not significantly differ between groups, a post-hoc analysis found significant differences on day 3 cytokine levels between groups for: IL-1β (p=0.024), IL-6 (p=0.045), and IL-17α (p=0.044). No significant difference between treatment groups in safety endpoints were found. taVNS safely reduced post-AIS inflammation in anterior circulation LVO patients. These findings warrant further investigation in larger clinical trials.ClinicalTrials.gov ID: NCT05390580, https://clinicaltrials.gov/study/NCT05390580 -Study started/registered: September 26, 2022.