Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients

项目摘要 多达三分之一的小儿癫痫患者是医学上难以治愈的，需要切除神经外科手术 以获得癫痫发作的自由。如果在生命早期进行，癫痫手术可以提供重要的认知和 发展收益改善癫痫儿童的生活质量。手术成功的关键是 一个强大的术前生物标志物的可用性，以确定癫痫区（EZ），皮质的区域， 这对于癫痫发作的产生是不可或缺的。完全切除EZ可能导致癫痫发作 自由，并可能改善社会，心理和认知发展。由于无法测量EZ 直接地，基于来自多个测试的一致数据来估计其位置。然而，这些结果 检查结果往往不够一致或不确定，导致需要进行颅内长期检查。 记录，其由于其侵入性而呈现许多缺点。因此，术前评估 患有难治性癫痫的患者通常具有挑战性或不成功。为了提高手术的疗效， 对EZ的可靠的非侵入性生物标志物的压倒一切的需要。高频振荡（HFO） 在过去的十年中建立了生物标志物划定的EZ。然而，其有效使用， 特区的生物标志物仍处于早期阶段。主要挑战之一仍然是难以检测， 非侵入性地定位它们。该R21应用旨在非侵入性地检测和可靠地定位HFO， 使用高密度头皮脑电图（EEG）的难治性癫痫儿童患者， 脑磁图（MEG），识别其发作发生器，并与该发生器的切除相关 病人的术后结果。我们假设高密度头皮脑电图和脑磁图可以无创地 识别并准确定位HFO发作发生器，移除HFO可获得更好的术后结局 与去除HFO传播区域相比。为了验证我们的假设，我们的目标是：（i）检测 用EEG和MEG定位发作间期HFO，（ii）定位发作间期HFO的起始发生器 HFO并将其与SOZ相关联，以及（iii）将HFO发作发生器的切除率与 患者的结果。我们将在患有难治性癫痫的儿童（0-18岁）中实现我们的目标。我们还将 记录10名年龄匹配的典型发育儿童的EEG和MEG数据，并将使用这些对照数据 来区分病理性和生理性HFO。对于幼儿，我们将使用BabyMEG，一种儿科 MEG系统具有独特的功能，专为3岁以下儿童设计。我们的研究将有一个 直接影响癫痫儿童的生活质量，因为它将提供一种新的非侵入性生物标志物 精确描绘EZ，最终将：（i）提高癫痫手术的成功率;（ii）减少 术后神经功能缺损;（iii）限制长期侵入性记录;（iv）能够评估 治疗干预，而无需等待癫痫发作发生;和（v）允许明确的鉴别诊断， 癫痫是由急性症状性癫痫发作引起的，因此可以立即开始治疗。

Project Summary Up to one third of pediatric patients with epilepsy are medically intractable and require resective neurosurgery to gain seizure freedom. If performed early in life, epilepsy surgery can offer significant cognitive and developmental gains improving the quality of life in children with epilepsy. Crucial to the success of surgery is the availability of a robust presurgical biomarker to identify the epileptogenic zone (EZ), the area of the cortex that is indispensable for the generation of epileptic seizures. Complete resection of the EZ may lead to seizure freedom and may improve social, psychological and cognitive development. Since the EZ cannot be measured directly, its location is estimated based on concordant data from a multitude of tests. Yet, the results of these tests are often insufficiently concordant or inconclusive, leading to the need for intracranial long-term recordings, which present many disadvantages due to their invasiveness. Thus, the presurgical evaluation of patient with refractory epilepsy is often challenging or unsuccessful. To improve the efficacy of surgery, there is an overriding need for a reliable noninvasive biomarker of the EZ. High Frequency Oscillations (HFOs) have established over the last decade as biomarkers for the delineation of the EZ. However, their effective use as biomarkers of the EZ is still at an early stage. One of the primary challenges remains the difficulty to detect and localize them noninvasively. This R21 application aims to noninvasively detect and reliably localize HFOs from pediatric patients with refractory epilepsy using high-density scalp electroencephalography (EEG) and magnetoencephalography (MEG), identify their onset generator, and correlate the resection of this generator with patients’ postsurgical outcome. We hypothesize that high-density scalp EEG and MEG can noninvasively identify and accurately localize the HFO onset generator whose removal leads to a better postsurgical outcome compared to the removal of the HFO propagation area. To test our hypothesis, we specifically aim to: (i) detect and localize noninvasively interictal HFOs with EEG and MEG, (ii) localize the onset generator of interictal HFOs and correlate it with the SOZ, and (iii) correlate the resection ratio of the HFO onset generator with patient’s outcome. We will pursue our aims in children (0-18 years old) with refractory epilepsy. We will also record EEG and MEG data from 10 age-matched typically-developing children, and will use these control data to distinguish pathological from physiological HFOs. For young children, we will use the BabyMEG, a pediatric MEG system with unique features designed specifically for children up to 3 years old. Our research will have a direct impact on the quality of life of children with epilepsy because it will provide a new noninvasive biomarker for the precise delineation of EZ that will eventually: (i) improve the success rate of epilepsy surgery; (ii) reduce postsurgical neurological deficits; (iii) limit long-term invasive recordings; (iv) enable to assess the efficacy of therapeutic interventions without waiting for a seizure to occur; and (v) permit definitive differential diagnosis of epilepsy from acute symptomatic seizures so treatment can begin immediately.