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：
8495567
负责人：
Shlomo Shinnar
金额：
$ 163.15万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
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 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8495567
关键词：
Acute Address Animal Model Anxiety Appearance Behavioral Benign Biological Markers Brain Injuries Child Childhood Chronic Clinical Clinical Trials Comorbidity Control Groups Critiques DNA Data Development Electroencephalography Epilepsy Evaluation Evolution Febrile Convulsions Fever Funding Future Genetic Genomics Goals Growth Herpesviridae Hippocampus (Brain)Hour Human Image Impaired cognition Impairment Individual 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 Outcome Pattern Phase Pilot Projects Positioning Attribute Prevention Process Prospective Studies Psychological Tests Recruitment Activity Risk Factors Sampling Scanning Sclerosis Seizures Signal Transduction Specimen Status Epilepticus Surrogate Endpoint Surrogate Markers Syndrome Temporal Lobe Epilepsy Testing Time Update Viral attenuation cognitive function cohort design disability executive function follow-up high risk hippocampal atrophy meetings prevent prospective psychologic public health relevance repository therapeutic target

Acute Address Animal Model Anxiety Appearance Behavioral Benign Biological Markers Brain Injuries Child Childhood Chronic Clinical Clinical Trials Comorbidity Control Groups Critiques DNA Data Development Electroencephalography Epilepsy Evaluation Evolution Febrile Convulsions Fever Funding Future Genetic Genomics Goals Growth Herpesviridae Hippocampus (Brain)Hour Human Image Impaired cognition Impairment Individual 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 Outcome Pattern Phase Pilot Projects Positioning Attribute Prevention Process Prospective Studies Psychological Tests Recruitment Activity Risk Factors Sampling Scanning Sclerosis Seizures Signal Transduction Specimen Status Epilepticus Surrogate Endpoint Surrogate Markers Syndrome Temporal Lobe Epilepsy Testing Time Update Viral attenuation cognitive function cohort design disability executive function follow-up high risk hippocampal atrophy meetings prevent prospective psychologic public health relevance repository therapeutic target

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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研究检查了发热状态癫痫持续状态（FSE）的后果，并阐明了FSE，海马萎缩，海马硬化症（HS）和随后的颞叶癫痫（TLE）和认知障碍之间的关系。我们前瞻性地招募了199名儿童，作为Febstat队列的一部分，另外23名作为杜克大学试点研究的一部分。 Febstat队列在72小时内具有MRI和EEG，以及病毒研究和基线神经心理学测试。在Febstat队列中，重复研究已在一年中进行。作为Hesdorffer博士NICHD资助的研究的一部分，一组96名具有首次简单高热惊厥（FC）的儿童（FC）在基线上进行了成像研究，并作为对照组进行了成像研究。迄今为止，我们已经在FSE病例中证明了海马T2信号异常，以及可能易于FSE的微妙发展海马异常。一年的一年，基线时T2异常的人表明海马体积的损失和持续的T2信号符合HS的放射标准。基线时具有正常信号的FSE病例的海马生长少于简单的FC对照组。急性脑电图异常很常见，与海马T2信号异常有关，并且经常持续在随访中。该提案的目标是1。研究癫痫发生过程，从而利用串行MR成像，脑电图和评估认知功能的评估，包括记忆和执行功能，以及对行为和精神病合并症的评估。这些评估发生在5、10和15年，如果癫痫发育。在此阶段，我们提议完成Febstat 5年评估并进行10年的评估，并在公爵队列中进行10年和15年的评估。正在收集DNA和基因组标本。要测试的假设包括急性海马成像异常和脑电图的局灶性放缓/衰减将与随后的HS和TLE的发展有关，并且海马体积损失的儿童将证明记忆力受损。 2。确定并表征了FEBSTAT队列中TLE和其他形式的癫痫的出现，从而确定了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，除了初始MRI和EEG异常及其进化模式外，其他参数（例如FSE持续时间和位置），遗传因素和HHV6,7感染将预测HAPPOCAMPAL量损失，HS和FSE之后的TLE。鉴于从FSE开始到临床TLE的发展，估计的潜伏期为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之后海马萎缩，HS和TLE的发展的替代标记物，并且还可以鉴定出治疗靶标，例如预防未来干预试验海马体积损失。