Mapping Cortical Anatomical and Electrophysiological Abnormalities in Human MTLE

绘制人类 MTLE 的皮质解剖学和电生理学异常

• 批准号: 8217082
• 负责人: Richard Staba
• 金额: $ 33.69万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217082
• 关键词: Area; Atrophic; Benchmarking; Brain; Characteristics; Clinical; Communities; Contralateral; Data; Deformity; Diagnostic; Diagnostic tests; Diffuse; Electrodes; Electroencephalography; Epilepsy; Evaluation; Event; Excision; Failure; Family; Freedom; Frequencies; Functional Imaging; Functional disorder; Generations; Goals; High Frequency Oscillation; Hippocampus (Brain); Human; Image; Individual; Ipsilateral; Lead; Lesion; Location; Magnetic Resonance Imaging; Maps; Measures; Methods; National Institute of Neurological Disorders and Stroke; Neocortex; Neurons; Operative Surgical Procedures; Outcome; Outcome Study; Patients; Pattern; Postoperative Period; Research; Resected; Sclerosis; Seizures; Site; Spatial Distribution; Temporal Lobe Epilepsy; Thick; Work; base; cellular pathology; design; early onset; economic cost; effective therapy; gray matter; hippocampal atrophy; imaging modality; improved; innovation; insight; neocortical; neuron loss; novel therapeutics; outcome forecast; public health relevance; social; success; voltage

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. PUBLIC HEALTH RELEVANCE: Individuals with poorly controlled epilepsy, as well as their families and communities, sustain considerable physical, social and economic costs. This study is designed to identify specific anatomical and electrophysiological disturbances that define the brain areas capable of generating spontaneous seizures in order to more clearly understand mechanisms of seizure genesis, improve surgical treatment and develop new therapies to eliminate seizures and the burden of epilepsy.

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当前治疗和治愈癫痫的方法。伴有海马硬化（HS）的内侧颞叶癫痫（MTLE）是最常见的耐药性癫痫类型。此类癫痫患者通常接受手术治疗，但手术结果研究表明太多患者术后仍出现癫痫发作。手术切除的基础是确定致痫区（EZ），即产生自发性癫痫发作所必需且充分的大脑区域，并且手术失败被认为是由于 EZ 切除不完全造成的。定义 EZ 的基本挑战是它不能直接测量，而是通过诊断测试推断，其中最重要的是发作发作和早期传播的部位以及致癫痫病变的存在。我们最近对 MTLE 患者使用先进结构成像进行的研究发现，海马萎缩的特定空间模式和水平与不同类型的发作发作相关。这些数据表明，伴有 HS 的 MTLE 可能有多种类型，每种类型都与特定的解剖异常、发作期和发作间期电生理学紊乱以及临床特征相关。如果这个假设是正确的，那么这些致痫性测量的组合可以定义 EZ，并为无癫痫手术结果的预后提供重要信息。拟议的研究将使用结构成像和功能测量来准确描绘 MTLE 患者的 EZ。具体来说，首先，我们将定量评估不同类型深度电极记录的发作发作和临床特征的患者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，并将其在海马和新皮质网络中的产生部位定位，包括发作发作区域、早期传播区域和偏远区域。我们和其他人的研究表明，pHFO 代表了导致自发性癫痫发作的基本神经元紊乱，并且由于这些异常事件发生在发作间期和发作期间，因此记录 pHFO 将使我们能够比捕获癫痫发作更快地识别致癫痫区域。第三，我们将通过将这些致癫痫性测量方法的去除与无癫痫手术结果相关联，确定这些致癫痫性测量方法的组合是否能够准确定义 EZ。我们预计这些具体目标的完成将开发出更安全、更准确和更便宜的方法来定义 EZ，并增加术后无癫痫发作的可能性。此外，我们期望所提出的研究结果将为 MTLE 中 EZ 的基本神经元基础提供有价值的见解。 公共卫生相关性：癫痫控制不佳的个人及其家庭和社区承受着相当大的身体、社会和经济成本。本研究旨在确定特定的解剖学和电生理学紊乱，这些紊乱定义了能够产生自发性癫痫发作的大脑区域，以便更清楚地了解癫痫发作的发生机制，改进手术治疗并开发新的疗法来消除癫痫发作和癫痫负担。