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: 8606662
• 负责人: Richard Staba
• 金额: $ 33.35万
• 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/8606662
• 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.

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。内侧颞叶癫痫（MTLE）合并海马硬化（HS）是最常见的药物抵抗性癫痫类型。这种类型的癫痫患者通常采用手术治疗，但手术结果研究表明，太多患者术后仍有癫痫发作。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和充分的大脑区域，手术失败被认为是由于EZ切除不完全造成的。定义EZ的根本挑战在于，它不能直接测量，而是从诊断测试中推断出来的，其中最重要的是对癫痫发作和早期传播部位的定位以及癫痫性病变的存在。我们最近使用先进的结构成像技术在MTLE患者中发现了与不同类型的癫痫发作相关的特定的空间模式和海马萎缩水平。这些数据表明，伴有HS的MTLE可能有几种类型，每种类型都与特定的解剖异常、发作期和发作间期电生理障碍和临床特征相关。如果这个假设是正确的，那么结合这些致痫性的测量可以定义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来试图准确描述MTLE患者的EZ。具体而言，首先，我们将定量评估具有不同类型深度电极记录的癫痫发作和临床特征的患者的海马和新皮层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层网络中的产生位点，包括初始发作和早期传播区域以及偏远区域。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紊乱，而且由于这些异常事件发生在发作间期和发作期间，记录phfo将使我们能够比捕捉癫痫发作更快地确定致痫区域。第三，我们将通过将这些致痫性措施的去除与无癫痫发作的手术结果相关联，确定这些措施的组合是否准确地定义了EZ。我们预计完成这些具体目标将开发更安全、更准确、更便宜的方法来定义EZ，并增加术后癫痫自由发作的可能性。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。