Mapping Cortical Anatomical and Electrophysiological Abnormalities in Human MTLE

描述(由申请人提供)：NINDS和几个癫痫组织已经建立了基准，强调需要开发新的治疗策略，并优化目前治疗和治愈癫痫的方法。内侧颞叶癫痫(MTLE)合并海马区硬化(HS)是最常见的耐药癫痫类型。这种类型的癫痫患者经常接受手术治疗，但手术结果研究表明，太多的患者术后仍有癫痫发作。手术切除的基础是确定致痫区域(EZ)，即产生自发性癫痫发作所必需和足够的脑区，手术失败被认为是由于EZ切除不完全所致。定义EZ的根本挑战是不能直接测量EZ，而是从诊断试验中推断出来，其中最重要的是定位发作性发作和早期传播的部位以及是否存在致痫灶。我们最近在MTLE患者中使用高级结构成像的工作发现，与不同类型的发作期相关的特定空间模式和水平的海马萎缩。这些数据表明，合并HS的MTLE可能有几种类型，每种类型都与特定的解剖异常、发作期和发作期的电生理障碍和临床特征有关。如果这一假设是正确的，那么这些致痫指标的组合可以确定EZ，并为无癫痫发作的手术结果提供重要的预后信息。拟议的研究将使用结构成像和功能测量方法，试图准确地描绘MTLE患者的EZ。具体地说，首先，我们将定量评估具有不同类型电极记录的发作起始点和临床特征的患者的海马和新皮质灰质萎缩的空间模式和水平。其次，我们将描述病理性高频振荡(PHFO)的特征，并定位其在海马和新皮质网络中的发生部位，包括发作区、早期传播区和远程区。我们和其他人的研究表明，PHFOS是导致自发发作发生的基本神经元障碍，由于这些异常事件发生在发作间期和发作期，记录PHFOS将使我们能够比捕获癫痫发作更快地识别致痫区域。第三，我们将通过将这些致痫指标的移除与无癫痫发作的手术结果相关联来确定这些致痫指标的组合是否准确地定义了EZ。我们预计这些特定目标的完成将发展出更安全、更准确和更便宜的方法来确定EZ，并增加术后癫痫发作自由的可能性。此外，我们期望拟议的研究结果将为MTLE中EZ的基本神经元基础提供有价值的见解。

DESCRIPTION (provided by applicant): The NINDS and several epilepsy organizations have established benchmarks that emphasize the need to develop new therapeutic strategies and optimize current approaches to treat and cure epilepsy. Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) is the most common type of pharmacoresistant epilepsy. Patients with this type of epilepsy are often treated surgically, but surgical outcome studies indicate too many patients continue to have postoperative seizures. Surgical resection is based on determining the epileptogenic zone (EZ), i.e. the brain areas necessary and sufficient for generating spontaneous seizures, and surgical failure is believed to result from an incomplete resection of the EZ. The fundamental challenge in defining the EZ is that it can not be measured directly, but is inferred from diagnostic tests, most important of which is localization of sites of ictal onset and early propagation and the presence of an epileptogenic lesion. Our recent work using advanced structural imaging in patients with MTLE found specific spatial patterns and levels of hippocampal atrophy that were associated with different types of ictal onset. These data indicate there could be several types of MTLE with HS and each associated with specific anatomical abnormalities, ictal and interictal electrophysiological disturbances and clinical features. If this hypothesis is correct, then a combination of these measures of epileptogenicity could define the EZ and provide important information on prognosis for a seizure-free surgical outcome. The proposed studies will use structural imaging and functional measures in an attempt to accurately delineate the EZ in patients with MTLE. Specifically, first, we will quantitatively evaluate the spatial patterns and levels of hippocampal and neocortical gray matter atrophy in patients with different types of depth electrode-recorded ictal onsets and clinical features. Second, we will characterize pathological high frequency oscillations (pHFOs) and localize their sites of generation in hippocampal and neocortical networks that include areas of ictal onset and early propagation and remote areas. Studies by us and others suggest pHFOs represent fundamental neuronal disturbances responsible for spontaneous seizure genesis, and because these abnormal events occur during interictal as well as during ictal periods, recording pHFOs will allow us to identify areas of epileptogenicity more rapidly than capturing seizures. And third, we will determine whether a combination of these measures of epileptogenicity accurately defines the EZ by correlating their removal with seizure-free surgical outcomes. We anticipate completion of these specific aims will develop safer, more accurate and less expensive approaches to defining the EZ and increase the likelihood for postoperative seizure freedom. In addition, we expect that the results of the proposed studies will provide valuable insights into the fundamental neuronal basis of the EZ in MTLE.