Interictal High Frequency Oscillations of Epileptogenecity in Pediatric Patients

小儿癫痫发作间期高频振荡

• 批准号: 10059130
• 负责人: Christos Papadelis
• 金额: $ 21.91万
• 依托单位: COOK CHILDREN'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-21 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059130
• 关键词: Interictal; Frequency; Oscillations; Epileptogenecity; Pediatric

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.

项目摘要 多达三分之一的儿童癫痫患者在医学上难以治愈，需要切除神经外科手术。 以获得癫痫的自由。如果在生命早期进行癫痫手术，可以提供显著的认知和 发展获得改善癫痫儿童的生活质量。手术成功的关键是 一种强大的术前生物标志物用于识别致痫区(EZ)，即大脑皮层区域 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EZ不能测量 直接来说，它的位置是基于大量测试的一致数据来估计的。然而，这些措施的结果 检查结果往往不够一致或不确定，导致需要进行长期的颅内检查。 录音，由于它们的侵入性而呈现出许多缺点。因此，术前评估 难治性癫痫患者往往具有挑战性或不成功。为了提高手术效果，有以下几种方法 对EZ可靠的非侵入性生物标志物的压倒一切的需求。高频振荡(HFO)具有 在过去的十年中被确定为划定EZ的生物标志物。然而，它们的有效使用 EZ生物标志物的研究还处于早期阶段。主要挑战之一仍然是难以发现和 非侵入性地将它们本地化。此R21应用程序旨在非侵入性地检测和可靠地定位来自 儿童难治性癫痫患者的高密度头皮脑电地形图和脑电地形图 脑磁图(MEG)，确定它们的起始源，并关联这个源的切除 患者手术后的转归。我们假设高密度头皮脑电和脑磁图可以无创地 识别和准确定位HFO发作发生器，移除其可带来更好的术后结果 与移除HFO传播区域相比。为了检验我们的假设，我们特别致力于：(I)检测 并利用EEG和MEG定位非侵袭性发作间期HFO，(Ii)定位发作间期的起始源 HFO，并将其与SOZ相关，以及(Iii)HFO发病生成器的切除率与 病人的转归。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脑电和脑磁图数据，并将使用这些对照数据 以区分病理性和生理性HFO。对于年幼的孩子，我们将使用BabyMEG，一种儿科 MEG系统具有独特的功能，专为3岁以下的儿童设计。我们的研究将会有一个 直接影响癫痫儿童的生活质量，因为它将提供一个新的非侵入性生物标志物 对于EZ的准确划定，最终将：(一)提高癫痫手术的成功率；(二)减少 手术后神经缺陷；(3)限制长期侵入性记录；(4)能够评估 不等待癫痫发作的治疗干预；和(V)允许明确的鉴别诊断 从急性症状性癫痫发作，因此治疗可以立即开始。

项目成果

Pediatric Magnetoencephalography in Clinical Practice and Research.

• DOI: 10.1016/j.nic.2020.02.002
• 发表时间: 2020-05
• 期刊: Neuroimaging clinics of North America
• 影响因子: 2.3
• 作者: Papadelis C;Chen YH
• 通讯作者: Chen YH

Mapping Functional Connectivity of Epileptogenic Networks through Virtual Implantation.

• DOI: 10.1109/embc46164.2021.9629686
• 发表时间: 2021-11
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
• 作者: Corona L;Tamilia E;Madsen JR;Stufflebeam SM;Pearl PL;Papadelis C
• 通讯作者: Papadelis C

Noninvasive Mapping of Ripple Onset Predicts Outcome in Epilepsy Surgery.

• DOI: 10.1002/ana.26066
• 发表时间: 2021-05
• 期刊: Annals of neurology
• 影响因子: 11.2
• 作者: Tamilia E;Matarrese MAG;Ntolkeras G;Grant PE;Madsen JR;Stufflebeam SM;Pearl PL;Papadelis C
• 通讯作者: Papadelis C

Reply to "Added value of high-resolution electrical source imaging of ictal activity in children with structural focal epilepsy".

回复“结构性局灶性癫痫儿童发作活动的高分辨率电源成像的附加值”。

• DOI: 10.1016/j.clinph.2022.06.001
• 发表时间: 2022
• 期刊: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
• 作者: Papadelis,Christos;Ricci,Lorenzo;Matarrese,MargheritaAG;Peters,JurriaanM;Tamilia,Eleonora;Madsen,Joseph;Pearl,PhillipL
• 通讯作者: Pearl,PhillipL

Virtual implantation using conventional scalp EEG delineates seizure onset and predicts surgical outcome in children with epilepsy.

• DOI: 10.1016/j.clinph.2022.04.009
• 发表时间: 2022-07
• 期刊: Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology