EEG and Epilepsy Unit, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
LivaNova PLC (or a Subsidiary), London, Great Britain, UK.
Brain Stimul. 2022 May-Jun;15(3):814-821. doi: 10.1016/j.brs.2022.05.016. Epub 2022 May 25.
While vagus nerve stimulation (VNS) has been in use for over two decades, little professional guidance exists to describe dosing and titration of therapy which is the consequence of a limited amount of evidence developed during the pre-market phase of therapy development. Post-market surveillance of dosing practice has revealed significant deviations from dosing and titration guidance offered by professional societies as well as the manufacturer.
This analysis aims to identify a target dose for VNS Therapy in Epilepsy.
Herein, VNS clinical outcomes are linked to the patient-specific dosing parameters for each study visit (n = 1178 patients). A generalized linear mixed model was built to ascertain the relationship between key stimulation parameters (i.e., Output Current, Pulse Width, Signal Frequency, and Duty Cycle) and clinical response, defined as a 50% or greater reduction in seizure frequency from baseline. Other demographic parameters of interest, such as duration of epilepsy and age at implant, were also explored.
A population level target output current and duty cycle for VNS therapy for epilepsy was identified as 1.61 mA and 17.1% duty cycle. Patients with shorter duration of epilepsy were identified to have a higher likelihood to respond to VNS therapy (p < 0.001). While patients who were on the therapy longer were more likely to respond to the therapy, the effect did not interact with the dosing settings - suggesting that patients who have been chronically underdosed may still benefit from achieving the target dose.
An opportunity exists to improve upon VNS outcomes by aligning clinical practice around this evidence-based target dose.
迷走神经刺激（VNS）已经应用了二十多年，但几乎没有专业指导来描述治疗的剂量和滴定，这是治疗开发的前期阶段证据有限的结果。治疗剂量实践的上市后监测表明，剂量和滴定指导与专业协会以及制造商提供的指导有很大偏差。
本分析旨在确定癫痫迷走神经刺激治疗的目标剂量。
在此，将 VNS 临床结果与每位研究就诊的患者特定剂量参数相关联（n=1178 名患者）。建立了一个广义线性混合模型，以确定关键刺激参数（即输出电流、脉冲宽度、信号频率和占空比）与临床反应之间的关系，临床反应定义为与基线相比癫痫发作频率降低 50%或更多。还探讨了其他感兴趣的人口统计学参数，如癫痫持续时间和植入年龄。
确定了癫痫迷走神经刺激治疗的人群水平目标输出电流和占空比为 1.61 mA 和 17.1%占空比。癫痫持续时间较短的患者被认为更有可能对 VNS 治疗有反应（p<0.001）。虽然接受治疗时间较长的患者更有可能对治疗有反应，但这种效果与剂量设置没有相互作用——这表明长期剂量不足的患者仍可能受益于达到目标剂量。
通过围绕这一基于证据的目标剂量调整临床实践，有可能改善 VNS 结果。
