The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy
The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy
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DOI：
10.1007/s13311-014-0272-3
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发表时间：
2014-07-01
影响因子：
5.7
通讯作者：
Raedt, Robrecht
中科院分区：
文献类型：
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作者：
De Taeye, Leen;Vonck, Kristl;Raedt, Robrecht
目前，迷走神经刺激（VNS）的作用机制尚不完全清楚，也不清楚哪些因素决定患者对治疗的反应。最近的临床前实验表明，蓝斑去甲肾上腺素能系统的激活对于 VNS 的抗癫痫作用至关重要。本研究旨在通过蓝斑去甲肾上腺素活性的无创标记物（事件相关电位的 P3 成分）评估 VNS 对人脑去甲肾上腺素信号传导的影响。我们研究了 VNS 是否对 VNS 应答者和 VNS 无应答者的 P3 成分进行差异调节。为此，我们招募了 20 名接受 VNS 治疗至少 18 个月的难治性癫痫患者。根据平均每月癫痫发作频率的降低情况，将患者分为 2 组：10 名有反应者 (> 50%) 和 10 名无反应者（千分之一货币符号 50%）。比较了两种刺激条件：VNS 关闭和 VNS 开启。在每种情况下，P3 分量都是在奇怪的听觉范例中测量的。仅在 VNS 反应者中，VNS 诱导顶叶中线电极处的 P3 振幅显着增加。此外，逻辑回归分析表明，P3振幅的增加可以作为VNS反应者的无创指标。这些结果支持蓝斑去甲肾上腺素能系统的激活与 VNS 的抗癫痫作用相关的假设。应进一步研究 P3 振幅的调节作为 VNS 对难治性癫痫患者治疗效果的无创生物标志物。
Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient's response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (> 50 %) and 10 nonresponders (a parts per thousand currency sign50 %). Two stimulation conditions were compared: VNS OFF and VNS ON. In each condition, the P3 component was measured during an auditory oddball paradigm. VNS induced a significant increase of the P3 amplitude at the parietal midline electrode, in VNS responders only. In addition, logistic regression analysis showed that the increase of P3 amplitude can be used as a noninvasive indicator for VNS responders. These results support the hypothesis that activation of the locus coeruleus noradrenergic system is associated with the antiepileptic effect of VNS. Modulation of the P3 amplitude should be further investigated as a noninvasive biomarker for the therapeutic efficacy of VNS in patients with refractory epilepsy.