Andrés Torres Sánchez , Marie Dawant , Venethia Danthine , Inci Cakiroglu , Roberto Santalucia , Enrique Ignacio Germany Morrison , Antoine Nonclercq , Riëm El Tahry
{"title":"VNS-induced dose-dependent pupillary response in refractory epilepsy","authors":"Andrés Torres Sánchez , Marie Dawant , Venethia Danthine , Inci Cakiroglu , Roberto Santalucia , Enrique Ignacio Germany Morrison , Antoine Nonclercq , Riëm El Tahry","doi":"10.1016/j.clinph.2025.01.006","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div><div><h3>Significance</h3><div>We propose VNS-induced PDR as a novel biomarker of VNS response.</div></div>","PeriodicalId":10671,"journal":{"name":"Clinical Neurophysiology","volume":"171 ","pages":"Pages 67-75"},"PeriodicalIF":3.7000,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Neurophysiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1388245725000161","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.