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，强调需要制定新的治疗策略并优化当前治疗和治疗癫痫的方法。海马硬化症（HS）是最常见的药物疗法癫痫类型。这种类型的癫痫患者经常通过外科手术治疗，但是手术结果研究表明，太多患者继续进行术后癫痫发作。手术切除基于确定癫痫发作区（EZ），即大脑区域所需的大脑区域，足以产生自发性癫痫发作，并且据信手术衰竭是由于EZ的不完全切除而导致的。定义EZ的基本挑战是不能直接测量它，而是根据诊断测试来推断出来的，其中最重要的是诊断性发作和早期传播部位的定位以及癫痫病变的存在。我们最近使用先进的结构成像在患有MTLE的患者的工作发现了与不同类型的ICTAL发作有关的特定空间模式和海马萎缩水平。这些数据表明，可能有几种具有HS的MTLE，每种MTLE可能与特定的解剖异常，ICTAL和ICTICTAICT电生理障碍和临床特征有关。如果该假设是正确的，那么这些癫痫发作的措施的结合可以定义EZ，并提供有关预后的重要信息，以示癫痫发作。拟议的研究将使用结构成像和功能措施，以尝试准确地描绘MTLE患者的EZ。具体而言，首先，我们将在具有不同类型的深度电极录制的发射异常和临床特征的患者中定量评估海马和新皮层灰质萎缩的空间模式和水平。其次，我们将表征病理高频振荡（PHFO），并将其在海马和新皮层网络中定位，包括ICTAL发病和早期传播以及偏远地区的领域。我们和其他人的研究表明，PHFO代表了负责自发癫痫发作起源的基本神经元障碍，并且由于这些异常事件发生在间歇性和发作时期内发生，因此记录PHFO将使我们能够比捕获癫痫发作更快地识别癫痫病的区域。第三，我们将确定这些癫痫发生度量的组合是否通过将其去除与无癫痫发作的外科手术结局相关联，可以准确地定义了EZ。我们预计这些特定目标的完成将开发出更安全，更准确，更便宜的方法来定义EZ并增加术后癫痫发作自由的可能性。此外，我们预计拟议的研究的结果将为MTLE中EZ的基本神经元基础提供宝贵的见解。 公共卫生相关性：控制癫痫病不足的人及其家庭和社区维持大量的身体，社会和经济成本。这项研究旨在确定特定的解剖学和电生理障碍，这些障碍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机制，改善外科手术治疗并开发新的疗法以消除癫痫发作和癫痫的负担。