Imaging tryptophan metabolism in children with epilepsy

癫痫儿童色氨酸代谢成像

• 批准号: 6728777
• 负责人: DIANE C CHUGANI
• 金额: $ 31.52万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6728777
• 关键词: adolescence (12-20); aminoacid metabolism; bioimaging /biomedical imaging; brain electrical activity; brain imaging /visualization /scanning; brain metabolism; cerebral cortex; clinical research; electrodes; electroencephalography; epilepsy; glucose metabolism; human therapy evaluation; immunocytochemistry; kynurenine; middle childhood (6-11); neurosurgery; partial seizure; patient oriented research; positron emission tomography; preschool child (1-5); serotonin; tryptophan

DESCRIPTION (provided by applicant): Approximately 0.5% to 1.0% of the population suffers from epilepsy. Fifteen to 20% of these individuals have seizures which cannot be controlled with anticonvulsants. Epilepsy is particularly devastating in children, in whom recurrent prolonged seizures may result in impaired cognitive development. The major goal of this proposal is to provide improved preoperative localization of epileptogenic brain tissue in children with medically uncontrolled neocortical epilepsy who are being treated with surgical resection of the epileptic focus. The central hypothesis of this proposal is that abnormalities in brain tryptophan metabolism via the serotonin and/or kynurenine pathways contribute to the pathophysiology and localization of neocortical epilepsy. Brain tryptophan metabolism will be measured in vivo in drug-resistant epilepsy patients using the tracer alpha [C-11 ]methyl-L-tryptophan (AMT) with positron emission tomography (PET). Our preliminary data show increased AMT accumulation in epileptogenic cortex in approximately one-half of patients assessed for epilepsy surgery. The focus of increased AMT uptake is typically much smaller than the large areas of hypometabolism seen on glucose metabolism PET scanning. In the present grant application, we propose to confirm and extend these findings by comparing AMT PET results to quantitative electrophysiological measures obtained during presurgical evaluation. In order to better understand the pathophysiology underlying altered AMT uptake by epileptic brain tissue, we will perform biochemical measurements in the tissue which is surgically resected for control of intractable epilepsy. Three specific aims will be addressed: 1. To determine the extent to which AMT PET and glucose metabolism PET regions of abnormality localize neocortical epileptogenic regions defined by subdural electrode recordings in both lesional and nonlesional neocortical epilepsy. 2. To determine whether resection of cortex with increased AMT uptake is related to outcome of epilepsy surgery. 3. To determine the underlying biochemical mechanism for the observed focal increases in cortical AMT uptake in patients with epilepsy. Our research will contribute to a better understanding of the pathophysiology and improve localization of focal epilepsy.

描述(申请人提供)：约0.5%至1.0%的人口患有癫痫。这些人中有15%到20%的人有癫痫发作，这是抗惊厥药物无法控制的。癫痫在儿童中尤其具有破坏性，反复长时间的癫痫发作可能会导致认知发展受损。这项建议的主要目标是在接受癫痫灶外科切除治疗的未经医学控制的新皮质癫痫儿童中，提供更好的术前致痫脑组织定位。这一建议的中心假设是，大脑色氨酸代谢的异常通过5-羟色胺和/或犬尿氨酸途径参与了新皮质癫痫的病理生理学和定位。采用正电子发射断层扫描(PET)示踪剂α[C-11]甲基L色氨酸(AMT)，对耐药癫痫患者的脑色氨酸代谢进行活体检测。我们的初步数据显示，在接受癫痫手术评估的患者中，大约有一半的患者致痫皮质中AMT积聚增加。AMT摄取增加的病灶通常比葡萄糖代谢PET扫描所见的大片低代谢区域小得多。在目前的赠款申请中，我们建议通过将AMT PET结果与术前评估期间获得的定量电生理测量进行比较来确认和扩展这些发现。为了更好地了解癫痫脑组织摄取AMT改变的病理生理学基础，我们将对手术切除的组织进行生化测量，以控制难治性癫痫。本研究将探讨三个具体目标：1.在皮损性和非皮质性新皮质癫痫中，确定AMT、PET和葡萄糖代谢PET异常区域在多大程度上定位于硬膜下电极记录所确定的新皮质致痫区域。2.确定切除皮质并增加AMT摄取是否与癫痫手术结果有关。3.确定癫痫患者皮质AMT摄取局灶性增加的潜在生化机制。我们的研究将有助于更好地了解癫痫的病理生理机制，提高局灶性癫痫的定位。