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：
8105600
负责人：
Shlomo Shinnar
金额：
$ 14.64万
依托单位：
MONTEFIORE MEDICAL CENTER (BRONX, NY)
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-02-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8105600
关键词：
Abbreviations Accounting Achievement Acute Amygdaloid structure Anisotropy Area Atrophic Behavior Benchmarking Benign Biological Markers Brain Brain Injuries Chicago Child Childhood Chronic Clinical Clinical Trials Complex Contralateral DNA Data Development Diffusion Diffusion Magnetic Resonance Imaging Diffusion weighted imaging Echo-Planar Imaging Electroencephalography Enrollment Epilepsy Epileptogenesis Evaluation Evolution Febrile Convulsions Fever Funding Future Goals Growth Herpesviridae Hippocampus (Brain)Hospitals Hour Human Human Herpesvirus 6 Image Impaired cognition Impairment Incidence Infection Injury Intelligence Intervention Studies Ipsilateral Longitudinal Studies Magnetic Resonance Imaging Matched Group Measures Medical center Memory National Institute of Neurological Disorders and Stroke Neuropsychological Tests Parietal Phase Physiologic pulse Predictive Factor Prevention Procedures Process Prospective Studies Psychological Tests Recording of previous events Recruitment Activity Relaxation Reporting Research Risk Risk Factors Role Scanning Schedule Sclerosis Seizures Side Signal Transduction Status Epilepticus Structure Surrogate Endpoint Surrogate Markers Temporal Lobe Temporal Lobe Epilepsy Testing Therapeutic Time Universities Viral Virginia Visual attenuation base cognitive function cohort design disability executive function follow-up frontal lobe gray matter high risk hippocampal atrophy interest medical schools neuropsychological prevent prospective psychologic repository symposium therapy design white matter

项目摘要

DESCRIPTION (provided by applicant): Temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) is often associated with a history of febrile seizures (FC). However, the proposed causal relationship between FCs and MTS remains controversial. Identification of children at high risk to develop MTS or TLE is necessary before designing interventions aimed at prevention. The FEBSTAT study examines the consequences of febrile status epilepticus (FSE) and will clarify the relationship between FSE, hippocampal atrophy, MTS, and subsequent epilepsy and cognitive impairment. We have prospectively recruited 144 children with FSE (165 are expected by end of year 5) and performed MRIs and EEGs within 72 hours as well as viral studies and baseline neuropsychological testing. Repeat studies have been performed at one year. To date we have demonstrated acute hippocampal imaging changes in 27% and acute EEG abnormalities in 38%. We have also demonstrated that human herpes virus 6 and 7 (HHV6,7) account for 35% of all FSE. Moreover >80% of subjects have returned for one year studies including MRI and EEG demonstrating our ability to retain the cohort. In this application we propose long term follow-up of the FEBSTAT cohort with 5-year reevaluations consisting of imaging, EEG and neuropsychological testing. Identical assessments will also be done if epilepsy develops. The goals of this proposal are to 1. Study the evolution of the epileptogenic process in terms of imaging, EEG, neuropsychological function and development of clinical TLE 2. Assess the importance of predictive factors such as HHV 6,7 infection, FSE duration and focality on the risk of hippocampal atrophy, MTS and TLE. Hypotheses to be tested include: I-II: The presence of acute hippocampal imaging or EEG abnormalities will be associated with later development of hippocampal atrophy, MTS and TLE. We will explore whether the extent of injury extends beyond the hippocampus. III: Children with FSE who develop hippocampal atrophy, regardless of whether they have developed clinical TLE, will have specific impairments on tasks associated with hippocampal function such as memory. IV: Acute HHV 6,7 infection at the episode of FSE and focal FSE are associated with an increased risk of developing hippocampal atrophy, MTS and TLE following FSE . We expect that the evolution of hippocampal changes on MRI and of chronic EEG abnormalities will substantially precede the development of clinical TLE and therefore can serve as surrogate biomarkers as well as potential therapeutic endpoints in future clinical trials. The research is responsive to Benchmark 1A2 from The Cure Epilepsy 2000 conference "Additional human collaborative imaging studies such as consequences of prolonged febrile seizures" and to the benchmark on "identifying and characterizing potential surrogate markers of epileptogenesis and epilepsy". It is also responsive to Senate Report 109-287 that urges NINDS to engage in research into the possible role of HHV-6 in SE and MTS. Our results to date suggest that the FEBSTAT study will likely identify surrogate markers for the development of hippocampal atrophy, MTS and TLE following FSE. Seizures that occur in the context of a febrile illness are the most common type of seizure in childhood, occurring in 2-5% of all children. These febrile seizures are generally brief and benign, but when prolonged, they have been associated with brain injury and temporal lobe epilepsy. This prospective study is recruiting 200 children with an episode of prolonged, longer than 30 min, febrile seizures (febrile status epilepticus) and using clinical, imaging, electrophysiological, and psychological data from serial examinations to examine the consequences of these prolonged seizures and provide the information necessary to design intervention studies to prevent brain damage and the subsequent development of a disabling, difficult to treat form of epilepsy.

描述（由申请人提供）：具有介体时间硬化症（MTS）的颞叶癫痫（TLE）通常与发热癫痫病史（FC）有关。但是，FCS和MTS之间提出的因果关系仍然存在争议。在设计旨在预防的干预措施之前，必须识别有高风险的儿童开发MTS或TLE。 FebStat研究检查了发热状态癫痫症（FSE）的后果，并将阐明FSE，海马萎缩，MTS和随后的癫痫和认知障碍之间的关系。我们已经前瞻性地招募了144名FSE儿童（预计在5年级结束时将有165名儿童）在72小时内进行了MRI和EEG，以及病毒研究和基线神经心理学测试。重复研究已在一年中进行。迄今为止，我们已经证明了27％的急性海马成像变化，急性脑电图异常为38％。我们还证明了人类疱疹病毒6和7（HHV6,7）占所有FSE的35％。此外，> 80％的受试者已返回一年的研究，包括MRI和EEG，证明了我们保留该队列的能力。在此应用中，我们提出了Febstat队列的长期随访，并通过5年重新评估包括成像，脑电图和神经心理学测试。如果癫痫发展也将进行相同的评估。该提案的目标是至1。研究癫痫发生过程的演变，从成像，脑电图，神经心理学功能和临床TLE 2。评估预测因素的重要性，例如HHV 6,7感染，FSE感染，FSE持续时间和焦点，并关注海马萎缩，MT和TLE的风险。要测试的假设包括：I-II：急性海马成像或EEG异常的存在将与后来的海马萎缩，MTS和TLE有关。我们将探索伤害的程度是否超出海马。 III：有FSE患有海马萎缩的儿童，无论他们是否开发了临床TLE，都会对与海马功能（如记忆）相关的任务有特定的损害。 IV：FSE发作和局灶性FSE发作中的急性HHV 6,7感染与FSE后发生海马萎缩，MTS和TLE的风险增加有关。我们预计，MRI和慢性脑电图异常的海马变化的演变基本上将在临床TLE的发展之前，因此可以作为替代生物标志物以及未来临床试验的潜在治疗终点。这项研究对CURE癫痫2000会议的基准1A2响应了“其他人类协作成像研究，例如长时间发热性癫痫发作的后果”，以及基准在“识别和表征癫痫生成和癫痫病的潜在替代标志”的基准下”。这也是对参议院报告109-287的反应，该报告敦促Ninds研究HHV-6在SE和MTS中的可能作用。迄今为止，我们的结果表明，FEBSTAT研究可能会确定FSE后海马萎缩，MTS和TLE的发展的替代标记。在高热疾病的背景下发生的癫痫发作是儿童期最常见的癫痫发作类型，所有儿童中有2-5％发生。这些发热的癫痫发作通常是简短和良性的，但是延长时，它们与脑损伤和颞叶癫痫有关。这项前瞻性研究是招募200名儿童，其中有长时间，超过30分钟的发作，发热性癫痫发作（高热状态 - 癫痫持续状态），并使用临床，影像学，电生理学和序列检查中的心理数据，以检查这些长期癫痫发作的后果，并为预防大脑损害的设计所必需的信息，以防止大脑损害和不断发展的型号，并进行了不断发展的形式。