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：
8259777
负责人：
Shlomo Shinnar
金额：
$ 196.72万
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/8259777
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 Lobe 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

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.

颞叶癫痫（TLE）带有介体颞硬化（MTS）通常与发热病史有关癫痫发作（FC）。但是，FCS和MTS之间提出的因果关系仍然存在争议。在设计针对的干预措施之前，必须识别有高风险的儿童开发MTS或TLE 预防。 Febstat研究检查了癫痫持续状态（FSE）的后果，并将澄清FSE，海马萎缩，MTS和随后的癫痫和认知之间的关系损害。我们已经前瞻性地招募了144名FSE儿童（预计在第5年底会有165名）和在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，我们已经展示了急性海马成像 38％的27％和急性脑电图异常的变化。我们还证明了人类疱疹病毒6 7（HHV6,7）占所有FSE的35％。此外，> 80％的受试者返回了一年的研究包括MRI和EEG在内，证明了我们保留队列的能力。在此应用程序中，我们提出了长期的建议 FEBSTAT队列的随访，并进行了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1。在成像，脑电图，神经心理学功能和临床TLE 2的发展。评估预测因素的重要性，例如HHV 6,7感染，FSE 持续时间和焦点是海马萎缩，MT和TLE的风险。要测试的假设包括：I-II：急性海马成像或脑电图异常的存在将与以后的发展有关海马萎缩，MTS和TLE。我们将探讨伤害的程度是否超出海马。 III：患有Happocampal萎缩的FSE儿童，无论他们是否有开发的临床TLE将对与海马功能相关的任务有特定的障碍，例如记忆。 IV：FSE发作和焦点FSE发作时的急性HHV 6,7感染与增加有关 FSE之后，出现海马萎缩，MTS和TLE的风险。我们期望的演变 MRI和慢性脑电图异常的海马变化将在基本上发展因此，临床TLE可以用作替代生物标志物以及潜在的治疗终点未来的临床试验。该研究对CURE癫痫会议的基准1A2响应 “其他人类协作成像研究，例如长期发热的后果”和 “识别和表征癫痫发生和癫痫的潜在替代标记”的基准。这也对参议院报告109-287也有回应，该报告敦促Ninds研究可能的角色 SE和MTS中的HHV-6。我们迄今为止的结果表明，Febstat研究可能会确定 FSE之后的海马萎缩，MTS和TLE的替代标记。在高温疾病的背景下发生的癫痫发作是最常见的癫痫发作类型在童年时期，所有儿童中有2-5％发生。这些高温癫痫发作通常是简短的和良性，但是延长时，它们与脑损伤和颞叶癫痫。这项前瞻性研究是招募200个发作的儿童长时间，超过30分钟的发热性癫痫发作（癫痫持续状态）和使用来自串行检查的临床，成像，电生理和心理数据检查这些长时间癫痫发作的后果并提供信息设计干预研究以防止脑损伤和随后的发展残疾，难以治疗癫痫的形式。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Animal models.

动物模型。

DOI：
10.1007/978-1-4419-6306-2_18
发表时间：
2010
期刊：
Advances in experimental medicine and biology
影响因子：
0
作者：
Walker,EllenA
通讯作者：
Walker,EllenA

Status epilepticus in children.

儿童癫痫持续状态。

DOI：
10.1016/b978-0-444-52899-5.00028-9
发表时间：
2012
期刊：
Handbook of clinical neurology
影响因子：
0
作者：
Holland,Katherine;Shinnar,Shlomo
通讯作者：
Shinnar,Shlomo

Classification of the epilepsies: New concepts for discussion and debate-Special report of the ILAE Classification Task Force of the Commission for Classification and Terminology.

DOI：
10.1002/epi4.5
发表时间：
2016-09
期刊：
Epilepsia open
影响因子：
3
作者：
Scheffer IE;French J;Hirsch E;Jain S;Mathern GW;Moshé SL;Perucca E;Tomson T;Wiebe S;Zhang YH;Zuberi SM
通讯作者：
Zuberi SM

Introduction of a Pediatric Neurology Hospitalist Service With Continuous Electroencephalography Monitoring at a Children's Hospital.

在儿童医院推出具有连续脑电图监测功能的儿科神经内科住院医师服务。