Defining the Epileptogenic Network and Identifying which Components Generate Seizures

定义癫痫发作网络并确定哪些成分会导致癫痫发作

• 批准号: 10201767
• 负责人: Richard Staba
• 金额: $ 54.58万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201767
• 关键词: Address; Affect; Area; Bilateral; Brain; Brain region; Caring; Chronic; Coupling; Data; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Drug resistance; Electrodes; Electroencephalography; Epilepsy; Etiology; Event; Excision; Failure; Fiber; Freedom; Generations; High Frequency Oscillation; Hippocampus (Brain); Histopathology; Individual; Intractable Epilepsy; Knowledge; Learning; Lesion; Magnetic Resonance Imaging; Measures; Morphology; Neocortex; Neuropsychology; Observational Study; Operative Surgical Procedures; Outcome; Partial Epilepsies; Pathology; Pathway interactions; Patients; Pattern; Pharmacotherapy; Play; Positron-Emission Tomography; Prognosis; Property; Research; Risk; Role; Scalp structure; Seizures; Site; Spatial Distribution; Structural defect; Structure; Surgically-Created Resection Cavity; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Tissues; White Fiber; Work; brain abnormalities; cell type; clinical care; comorbidity; effective therapy; gray matter; hippocampal sclerosis; improved; interest; magnetic resonance imaging/electroencephalography; mortality; mortality risk; neocortical; nervous system disorder; novel; novel strategies; novel therapeutics; potential biomarker; public health relevance; white matter; white matter change

Project Summary Epilepsy is a serious neurological disorder characterized by spontaneous seizures and increased risk of mortality, especially for one-third of the individuals with chronic seizures that cannot be controlled in spite of optimal drug therapy. Currently, the most effective treatment for drug-resistant seizures is resective surgery and in cases such as temporal lobe epilepsy (TLE) with hippocampal sclerosis, the most common form of drug- resistant epilepsy, surgery can reduce or eliminate seizures in most patients. However, it does not help all patients, particularly those with seizures suspected to begin in the temporal lobe but without a MRI lesion or MRI contains a lesion in hippocampus and neocortex or scalp EEG indicates bilaterally. In situations like these the extent of the epileptogenic zone (EZ), which is the brain area that is necessary and sufficient for generating seizures and minimum resection necessary for seizure relief, is uncertain. There is tremendous interest in studies of the epileptogenic network (EN), i.e. the larger brain region that supports the generation and spread of seizures and manifestation of epilepsy, and we hypothesize in difficult cases of TLE, knowledge of the EN could help us to localize the EZ. Even with recent progress from studies of the EN, we still do not know the full extent of brain abnormalities that define the EN, what part is necessary for generating seizures, or how much of the EN needs to be removed to eliminate seizures. This project addresses these issues and we have developed a comprehensive approach to study them, including novel structural and diffusion MRI and EEG functional connectivity tests, as well as studies of high frequency oscillations (HFOs), which are a potential biomarker of the EZ. We will apply this approach to presurgical patients with suspected TLE who require invasive EEG tests as part of their standard diagnostic care. To help us define the EN in Aim 1, we will evaluate structural MRI for gray matter abnormalities and morphological covariance between brain areas; in Aim 2, we will assess diffusion MRI for white matter microstructural and fiber tract anomalies; in Aim 3, we will use a new approach called gamma event coupling in combination with unit and HFO recordings to investigate the functional connectivity encompassing the EN and identify which parts of it are generating seizures and spread; and lastly in Aim 4, we will determine which components of the EN and how much of it needs to be removed to eliminate seizures. In this project, defining the EN should provide important information on the structural and functional mechanisms generating seizures, and ultimately this will help us to localize the EZ, improve diagnosis, advance surgical and non-surgical therapies, develop new therapies, and increase the likelihood for seizure freedom.

项目概要 癫痫是一种严重的神经系统疾病，其特征是自发性癫痫发作和增加的风险 死亡率，特别是对于三分之一患有慢性癫痫发作的人来说，尽管癫痫发作仍无法控制 最佳药物治疗。目前，治疗耐药性癫痫最有效的治疗方法是切除手术 在颞叶癫痫 (TLE) 伴海马硬化等病例中，最常见的药物形式是 对于难治性癫痫，手术可以减少或消除大多数患者的癫痫发作。然而，它并不能帮助所有 患者，特别是疑似癫痫发作始于颞叶但无 MRI 病变的患者，或 MRI 包含海马和新皮质的病变或头皮脑电图显示双侧。在这样的情况下 致癫痫区 (EZ) 的范围，该区域是产生癫痫的必要且充分的大脑区域 癫痫发作和缓解癫痫发作所需的最小切除术尚不确定。人们对此非常感兴趣 致癫痫网络（EN）的研究，即支持癫痫发作和传播的较大大脑区域 癫痫发作和癫痫的表现，我们假设在困难的 TLE 病例中，对 EN 的了解 可以帮助我们本地化 EZ。即使 EN 研究取得了最新进展，我们仍然不知道完整的情况 定义 EN 的大脑异常程度、产生癫痫发作所必需的部分，或者有多少 需要去除 EN 以消除癫痫发作。这个项目解决了这些问题，我们开发了一个 研究它们的综合方法，包括新颖的结构和扩散 MRI 以及脑电图功能 连接测试以及高频振荡 (HFO) 研究，高频振荡是潜在的生物标志物 易区。我们将把这种方法应用于疑似 TLE 且需要侵入性脑电图检查的术前患者 作为他们标准诊断护理的一部分。为了帮助我们定义目标 1 中的 EN，我们将评估结构 MRI 灰质异常和大脑区域之间的形态协方差；在目标 2 中，我们将评估 用于白质微结构和纤维束异常的扩散 MRI；在目标 3 中，我们将使用一种新方法 称为伽玛事件耦合，与单元和 HFO 记录相结合，以研究功能 围绕 EN 的连通性并确定其哪些部分正在产生癫痫发作和传播；最后 在目标 4 中，我们将确定需要移除 EN 的哪些组件以及需要移除多少组件才能消除 癫痫发作。在这个项目中，定义 EN 应提供有关结构和 产生癫痫发作的功能机制，最终这将帮助我们定位 EZ，改善 诊断，推进手术和非手术治疗，开发新疗法，并增加治疗的可能性 扣押自由。