Imaging tryptophan metabolism in children with epilepsy

癫痫儿童色氨酸代谢成像

• 批准号: 7001243
• 负责人: DIANE C CHUGANI
• 金额: $ 29.96万
• 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/7001243
• 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（由申请人提供）：约0.5%至1.0%的人口患有癫痫。15%到20%的人癫痫发作不能用抗惊厥药控制。癫痫对儿童的危害尤其严重，反复发作的长时间癫痫可能导致认知发育受损。本建议的主要目的是为正在接受手术切除癫痫病灶治疗的医学上不受控制的新皮质癫痫患儿提供更好的癫痫性脑组织术前定位。该建议的中心假设是，通过血清素和/或犬尿氨酸途径的脑色氨酸代谢异常有助于新皮质癫痫的病理生理和定位。使用示踪剂α [C-11]甲基- l-色氨酸（AMT）和正电子发射断层扫描（PET）在体内测量耐药癫痫患者的脑色氨酸代谢。我们的初步数据显示，在大约一半接受癫痫手术评估的患者中，AMT在致癫痫皮质的积累增加。AMT摄取增加的焦点通常比葡萄糖代谢PET扫描上看到的大面积低代谢区域小得多。在目前的拨款申请中，我们建议通过将AMT PET结果与术前评估中获得的定量电生理测量结果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改变AMT摄取的病理生理学，我们将在手术切除的组织中进行生化测量，以控制难治性癫痫。将讨论三个具体目标：1。通过硬膜下电极记录确定病变性和非病变性新皮质癫痫患者的AMT PET和糖代谢PET异常区域在多大程度上定位于新皮质癫痫发生区。2. 目的：确定AMT摄取增加的皮质切除术是否与癫痫手术的预后有关。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局灶性癫痫的病理生理和定位。