Consequences of Prolonged Febrile Seizures in Childhood

儿童时期长期热性惊厥的后果

基本信息

批准号：
9320060
负责人：
Shlomo Shinnar
金额：
$ 10万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9320060
关键词：
Acute Address Animal Model Anxiety Appearance Behavioral Benign Biological Markers Brain Injuries Child Childhood Chronic Clinical Clinical Trials Comorbidity Control Groups DNA Data Development Electroencephalography Electrophysiology (science)Epilepsy Evaluation Evolution Febrile Convulsions Fever Funding Future Genetic Genomics Goals Growth Health Herpesviridae Hippocampus (Brain)Hour Human Image Impaired cognition Impairment Infection Injury Intervention Studies Intervention Trial Laboratories Longitudinal Studies Magnetic Resonance Imaging Memory Memory impairment Mental Depression National Institute of Child Health and Human Development Neuropsychological Tests Pattern Phase Pilot Projects Positioning Attribute Prevention Process Prospective Studies Psychological Tests Recruitment Activity Risk Factors Sampling Scanning Seizures Signal Transduction Specimen Status Epilepticus Surrogate Endpoint Surrogate Markers Syndrome Temporal Lobe Epilepsy Testing Time Viral attenuation biomarker development cognitive function cohort design disability executive function follow-up high risk hippocampal atrophy hippocampal sclerosis meetings prevent prospective psychologic repository therapeutic target

项目摘要

DESCRIPTION (provided by applicant): The FEBSTAT study examines the consequences of febrile status epilepticus (FSE) and is clarifying the relationship between FSE, hippocampal atrophy, hippocampal sclerosis (HS), and the development of subsequent temporal lobe epilepsy (TLE) and cognitive impairment. We prospectively recruited 199 children as part of the FEBSTAT cohort and 23 more as part of the pilot study at Duke. The FEBSTAT cohort had MRIs and EEGs within 72 hours as well as viral studies and baseline neuropsychological testing. Repeat studies have been performed at one year in the FEBSTAT cohort. A group of 96 children with first simple febrile convulsions (FC) recruited as part of Dr. Hesdorffer's NICHD funded study that had imaging studies at baseline and one year serve as controls. To date we have demonstrated abnormal hippocampal T2 signal in the FSE cases as well as subtle developmental hippocampal abnormalities that may predispose to FSE. At one year, those with abnormal T2 at baseline demonstrate loss of hippocampal volume and persistent T2 signal meeting radiologic criteria for HS. FSE cases with normal signal at baseline had less hippocampal growth than the simple FC control group. Acute EEG abnormalities were common, were associated with hippocampal T2 signal abnormality and often persisted on follow-up EEGs. The goals of this proposal are 1. Study the epileptogenic process leading to the development of clinical TLE utilizing serial MR imaging, EEG, and evaluation of cognitive function including memory and executive function, as well as evaluation of behavioral and psychiatric comorbidity. These evaluations occur at 5, 10 and 15 years and if epilepsy develops. In this phase we propose completing the FEBSTAT 5 year evaluations and doing the 10 year ones as well performing 10 and 15 year evaluations in the Duke cohort. DNA and genomic specimens are being collected. Hypotheses to be tested include that acute hippocampal imaging abnormalities and focal slowing/attenuation on the EEG will be associated with both subsequent HS and development of TLE and that children with hippocampal volume loss will demonstrate impairment of memory. 2. Ascertain and characterize the emergence of TLE and other forms of epilepsy in the FEBSTAT cohort and thereby determine the validity of putative clinical and laboratory biomarkers of HS and TLE following FSE. We predict that in addition to initial MRI and EEG abnormalities and their pattern of evolution, other parameters such as FSE duration and locality, genetic factors and HHV6,7 infection will predict hippocampal volume loss, HS and TLE after FSE. Given the estimated latency of 8-11 years from the time of FSE until development of clinical TLE, we expect the next 5 years to be critical to addressing the questions posed by the FEBSTAT study. The FEBSTAT study will likely identify surrogate markers for the development of hippocampal atrophy, HS and TLE following FSE and may also identify therapeutic targets such as prevention of hippocampal volume loss for future intervention trials.

描述（由申请人提供）：FEBSTAT 研究检查了发热性癫痫持续状态 (FSE) 的后果，并阐明了 FSE、海马萎缩、海马硬化 (HS) 以及随后颞叶癫痫 (TLE) 和认知功能障碍之间的关系损害。我们前瞻性地招募了 199 名儿童作为 FEBSTAT 队列的一部分，另外招募了 23 名儿童作为杜克大学试点研究的一部分。 FEBSTAT 队列在 72 小时内进行了 MRI 和脑电图检查，以及病毒研究和基线神经心理学测试。 FEBSTAT 队列一年后进行了重复研究。 Hesdorffer 博士资助的 NICHD 研究招募了 96 名首次出现单纯性热性惊厥 (FC) 的儿童作为对照，该研究在基线和一年内进行了影像学研究。迄今为止，我们已经证明 FSE 病例中存在异常的海马 T2 信号，以及可能诱发 FSE 的微妙的发育性海马异常。一年后，基线 T2 异常的患者表现出海马体积损失，且持续 T2 信号符合 HS 的放射学标准。基线时信号正常的 FSE 病例比简单 FC 对照组的海马生长较少。急性脑电图异常很常见，与海马 T2 信号异常相关，并且在后续脑电图检查中经常持续存在。该提案的目标是 1. 利用系列 MR 成像、EEG 和认知功能（包括记忆和执行功能）评估以及行为和精神合并症评估，研究导致临床 TLE 发展的癫痫过程。这些评估会在 5、10 和 15 岁时以及癫痫发生时进行。在此阶段，我们建议完成 FEBSTAT 5 年评估并进行 10 年评估，并在杜克大学队列中进行 10 年和 15 年评估。 DNA 和基因组样本正在收集中。待检验的假设包括急性海马成像异常和脑电图焦点减慢/衰减与随后的 HS 和 TLE 的发展有关，并且海马体积减少的儿童将表现出记忆障碍。 2. 确定并表征 FEBSTAT 队列中 TLE 和其他形式癫痫的出现，从而确定 FSE 后 HS 和 TLE 的假定临床和实验室生物标志物的有效性。我们预测，除了最初的 MRI 和 EEG 异常及其演变模式外，其他参数（例如 FSE 持续时间和地点、遗传因素和 HHV6,7 感染）将预测 FSE 后的海马体积损失、HS 和 TLE。鉴于从 FSE 到临床 TLE 发展的估计潜伏期为 8-11 年，我们预计未来 5 年对于解决 FEBSTAT 研究提出的问题至关重要。 FEBSTAT 研究可能会确定 FSE 后海马萎缩、HS 和 TLE 发展的替代标志物，还可能确定治疗目标，例如预防未来干预试验的海马体积损失。