VNS-induced dose-dependent pupillary response in refractory epilepsy

IF 3.6 3区医学 Q1 CLINICAL NEUROLOGY Clinical Neurophysiology Pub Date : 2025-03-01 Epub Date: 2025-01-27 DOI:10.1016/j.clinph.2025.01.006

Andrés Torres Sánchez , Marie Dawant , Venethia Danthine , Inci Cakiroglu , Roberto Santalucia , Enrique Ignacio Germany Morrison , Antoine Nonclercq , Riëm El Tahry

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Abstract

Purpose

The Locus Coeruleus (LC) plays a vital role by releasing norepinephrine, which contributes to the antiepileptic effects of Vagus Nerve Stimulation (VNS). LC activity also influences pupil dilation. Investigating VNS dose-dependent Pupillary Dilation Response (PDR) may provide novel neurophysiological insights into therapeutic response and allow for an objective and personalized optimization of stimulation parameters.

Methods

Fourteen VNS-implanted patients (9 responders, 5 non-responders) treated for at least 6 months were retrospectively recruited. VNS intensities were adjusted from 0.25 mA to 2.25 mA, or to the highest tolerable level. Concurrently, we tracked pupil size in the left eye and gathered patients’ subjective perception scores. Individual curve fitting was used to explore the relationship between VNS intensity and PDR.

Results

PDR increased with stimulation intensity, particularly in responders. In 6 patients, an inverted U-shaped relationship between intensity and PDR was observed 2–3 s after stimulation onset. A significant interaction was found between VNS intensity and responder status, independent of subjective perception.

Conclusions

VNS induces a dose-dependent PDR, which differs between responders and non-responders. In nearly half the patients, the dose–response relationship was characterized by an inverted U-shape with a maximal VNS effect.

Significance

We propose VNS-induced PDR as a novel biomarker of VNS response.

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难治性癫痫中vns诱导的剂量依赖性瞳孔反应。

目的：蓝斑（LC）通过释放去甲肾上腺素在迷走神经刺激（VNS）的抗癫痫作用中发挥重要作用。LC活动也影响瞳孔扩张。研究VNS剂量依赖性瞳孔扩张反应（PDR）可能为治疗反应提供新的神经生理学见解，并允许客观和个性化的刺激参数优化。方法：回顾性招募14例治疗至少6个月的vns植入患者（9例有反应，5例无反应）。VNS强度从0.25 mA调整到2.25 mA，或调整到最高可容忍水平。同时，我们追踪了左眼瞳孔的大小，并收集了患者的主观知觉评分。采用个体曲线拟合探讨VNS强度与PDR之间的关系。结果：PDR随着刺激强度的增加而增加，特别是在反应者中。6例患者在刺激开始后2 ~ 3 s，强度与PDR呈倒u型关系。VNS强度与应答者状态之间存在显著的相互作用，独立于主观知觉。结论：VNS诱导的PDR是剂量依赖性的，反应者和无反应者之间存在差异。在近一半的患者中，剂量-反应关系呈倒u型，VNS效应最大。意义：我们提出VNS诱导的PDR作为VNS反应的一种新的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Neurophysiology 医学-临床神经学

CiteScore

8.70

自引率

6.40%

发文量

932

审稿时长

59 days

期刊介绍： As of January 1999, The journal Electroencephalography and Clinical Neurophysiology, and its two sections Electromyography and Motor Control and Evoked Potentials have amalgamated to become this journal - Clinical Neurophysiology. Clinical Neurophysiology is the official journal of the International Federation of Clinical Neurophysiology, the Brazilian Society of Clinical Neurophysiology, the Czech Society of Clinical Neurophysiology, the Italian Clinical Neurophysiology Society and the International Society of Intraoperative Neurophysiology.The journal is dedicated to fostering research and disseminating information on all aspects of both normal and abnormal functioning of the nervous system. The key aim of the publication is to disseminate scholarly reports on the pathophysiology underlying diseases of the central and peripheral nervous system of human patients. Clinical trials that use neurophysiological measures to document change are encouraged, as are manuscripts reporting data on integrated neuroimaging of central nervous function including, but not limited to, functional MRI, MEG, EEG, PET and other neuroimaging modalities.