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颅内脑电图生物标志物可预测癫痫患者在治疗前对反应性神经刺激的有效反应。

Intracranial electroencephalographic biomarker predicts effective responsive neurostimulation for epilepsy prior to treatment.

机构信息

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

出版信息

Epilepsia. 2022 Mar;63(3):652-662. doi: 10.1111/epi.17163. Epub 2022 Jan 7.

Abstract

OBJECTIVE

Despite the overall success of responsive neurostimulation (RNS) therapy for drug-resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS-ideally before device implantation-are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy.

METHODS

We assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy.

RESULTS

Ictal measures of synchronizability in the high-γ band (95-105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high-γ synchronizability is inversely associated with the degree of therapeutic response.

SIGNIFICANCE

This study provides a proof-of-concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.

摘要

目的

尽管反应性神经刺激(RNS)疗法在治疗耐药性局灶性癫痫方面总体上取得了成功,但个体的临床结果差异很大,且难以预测。目前急需能够指示 RNS 临床疗效的生物标志物-理想情况下在植入设备之前-但面临的挑战包括 RNS 患者人群的固有异质性以及各癫痫中心临床管理的变异性。本研究的目的是使用多中心数据集来评估颅内脑电图(iEEG)记录中的候选生物标志物,该标志物可预测随后 RNS 治疗的临床结果。

方法

我们汇集了来自三个主要癫痫中心的 30 名患者的回顾性队列的 iEEG 记录的联邦数据集,这些记录是在 RNS 植入之前收集的。每个中心都使用发作性 iEEG 记录独立计算了网络同步性,这是一种指示癫痫大脑网络对 RNS 治疗敏感性的候选生物标志物。

结果

在当前的 RNS 治疗指南下,至少 3 年的治疗后,高γ带(95-105 Hz)的发作性同步性测量值在 RNS 反应良好和反应不佳的患者之间有显著区别(曲线下面积=0.83)。此外,发作性高γ同步性与治疗反应的程度呈负相关。

意义

这项研究为在联邦数据中进行协作生物标志物评估提供了概念验证路线图,其中实际考虑因素阻碍了中心之间的完整数据共享。我们的研究结果表明,网络同步性可以帮助预测 RNS 治疗的治疗反应。进一步验证后,这种生物标志物可以帮助选择患者,并有助于避免对不太可能受益的患者进行昂贵的、有创的干预。

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