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:7617684
- 负责人:
- 金额:$ 205.73万
- 依托单位:
- 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:
- 关键词:AbbreviationsAccountingAchievementAcuteAmygdaloid structureAnisotropyAreaAtrophicBehaviorBenchmarkingBenignBiological MarkersBrainBrain InjuriesChicagoChildChildhoodChronicClinicalClinical TrialsComplexContralateralDNADataDevelopmentDiffusionDiffusion Magnetic Resonance ImagingDiffusion weighted imagingEcho-Planar ImagingElectroencephalographyEnrollmentEpilepsyEpileptogenesisEvaluationEvolutionFebrile ConvulsionsFeverFundingFutureGoalsGrowthHerpesviridaeHippocampus (Brain)HospitalsHourHumanHuman Herpesvirus 6ImageImpaired cognitionImpairmentIncidenceInfectionInjuryIntelligenceIntervention StudiesIpsilateralLongitudinal StudiesMagnetic Resonance ImagingMatched GroupMeasuresMedical centerMemoryNational Institute of Neurological Disorders and StrokeNeuropsychological TestsParietalPhasePhysiologic pulsePredictive FactorPreventionProceduresProcessProspective StudiesPsychological TestsRecording of previous eventsRecruitment ActivityRelaxationReportingResearchRiskRisk FactorsRoleScanningScheduleSclerosisSeizuresSideSignal TransductionStatus EpilepticusStructureSurrogate EndpointSurrogate MarkersTemporal LobeTemporal Lobe EpilepsyTestingTherapeuticTimeUniversitiesViralVirginiaVisualattenuationbasecognitive functioncohortdesigndisabilityexecutive functionfollow-upfrontal lobegray matterhigh riskhippocampal atrophyinterestmedical schoolsneuropsychologicalpreventprospectivepsychologicrepositorysymposiumtherapy designwhite 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):伴有颞叶内侧硬化症(MTS)的颞叶癫痫(TLE)通常与热性惊厥(FC)病史相关。然而,FC 和 MTS 之间拟议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,有必要识别发生 MTS 或 TLE 的高风险儿童。 FEBSTAT 研究检查了发热性癫痫持续状态 (FSE) 的后果,并将阐明 FSE、海马萎缩、MTS 以及随后的癫痫和认知障碍之间的关系。我们前瞻性地招募了 144 名 FSE 儿童(预计到第 5 年底将招募 165 名),并在 72 小时内进行 MRI 和 EEG 以及病毒研究和基线神经心理学测试。一年后进行了重复研究。迄今为止,我们已证实 27% 的患者出现急性海马成像变化,38% 的患者出现急性脑电图异常。我们还证明人类疱疹病毒 6 型和 7 型 (HHV6,7) 占所有 FSE 的 35%。此外,超过 80% 的受试者已返回进行为期一年的研究,包括 MRI 和 EEG,这证明了我们保留队列的能力。在此申请中,我们建议对 FEBSTAT 队列进行长期随访,并进行为期 5 年的重新评估,包括影像学、脑电图和神经心理学测试。如果发生癫痫,也将进行相同的评估。该提案的目标是 1. 从影像学、脑电图、神经心理功能和临床 TLE 发展方面研究致癫痫过程的演变 2. 评估 HHV 6,7 感染、FSE 持续时间和焦点等预测因素的重要性海马萎缩、MTS 和 TLE 的风险。待检验的假设包括: I-II:急性海马成像或脑电图异常的存在将与海马萎缩、MTS 和 TLE 的后期发展相关。我们将探讨损伤的程度是否超出海马体。 III:出现海马萎缩的 FSE 儿童,无论是否出现临床 TLE,都会在与海马功能相关的任务(例如记忆)上出现特定的损伤。 IV:FSE 和局灶性 FSE 发作时的急性 HHV 6,7 感染与 FSE 后发生海马萎缩、MTS 和 TLE 的风险增加相关。我们预计 MRI 上海马变化和慢性脑电图异常的演变将大大先于临床 TLE 的发展,因此可以作为替代生物标志物以及未来临床试验中的潜在治疗终点。该研究响应了 2000 年治愈癫痫会议的基准 1A2“额外的人类协作成像研究,例如长期热性惊厥的后果”,以及“识别和表征癫痫发生和癫痫的潜在替代标志物”的基准。它还响应参议院第 109-287 号报告,该报告敦促 NINDS 参与研究 HHV-6 在 SE 和 MTS 中可能发挥的作用。我们迄今为止的结果表明,FEBSTAT 研究可能会确定 FSE 后海马萎缩、MTS 和 TLE 发展的替代标志物。发热性疾病引起的癫痫发作是儿童期最常见的癫痫发作类型,占所有儿童的 2-5%。这些热性惊厥通常是短暂且良性的,但如果持续时间较长,则可能与脑损伤和颞叶癫痫有关。这项前瞻性研究招募了 200 名患有长时间、超过 30 分钟的热性惊厥(热性癫痫持续状态)的儿童,并使用一系列检查中的临床、影像、电生理和心理数据来检查这些长时间惊厥的后果,并提供设计干预研究以预防脑损伤以及随后发展为致残且难以治疗的癫痫形式所需的信息。
项目成果
期刊论文数量(0)
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Shlomo Shinnar其他文献
Shlomo Shinnar的其他文献
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{{ truncateString('Shlomo Shinnar', 18)}}的其他基金
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
9320060 - 财政年份:2015
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
9229028 - 财政年份:2015
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
7807056 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
8058666 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
7186645 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
7471236 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
8495567 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
6846321 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
6579966 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
Consequences of Prolonged Febrile Seizures in Childhood
儿童时期长期热性惊厥的后果
- 批准号:
7912515 - 财政年份:2003
- 资助金额:
$ 205.73万 - 项目类别:
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Consequences of Prolonged Febrile Seizures in Childhood
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