Posters and abstracts

Purpose: The mechanisms of action of Vagus Nerve Stimulation (VNS) for treating Refractory Epilepsy are still unclear, and a more personalized approach to titration is currently lacking. The Locus Coeruleus (LC) plays a vital role by releasing norepinephrine, contributing to the antiepileptic effects of VNS. LC activity also influences pupil dilation, potentially serving as a biomarker for VNS-dose response. Therefore, investigating dose-dependent pupillary responses may offer new neurophysiological insights to differentiate responders (R) from non-responders (NR) and provide an objective personalized titration approach.

Methods: Thirteen VNS-implanted patients (9R, 4NR) were included. VNS intensities were varied from 0.25mA to 2.25mA or up to maximum tolerance. VNS artifact was monitored using two electrodes placed in the laryngeal prominence region, while left eye pupil dilation was tracked. Subjective perceptions were retrieved after each block of stimulation. Analyses focused on the maximum early peak dilation within 2.5s after VNS onset and the mean pupil dilation response between the early peak and 2.5s after (Mean PDR), the latter being specific to VNS. Statistical analysis involved individual fitting curves and quadratic mixed-effect models to examine interactions and trends.

Results: Increasing VNS intensities induced increasing mean PDR, following a U-inverted curve pattern in most patients (7R, 2NR) (R > 0.25). The quadratic mixed-effect model indicated a significant interaction between VNS and R/NR status, with higher mean PDR in R compared to NR (p = 0.003), independent of perception.

Conclusion: Our findings indicate that responders show higher pupil dilation responses in response to VNS compared to non-responders. In addition, a dose-response relationship between increasing VNS intensities and pupil dilation was observed, which mainly followed a U-inverted pattern