Imaging the effect of centrotemporal spikes and seizures on language in children

颞叶中央尖峰和癫痫发作对儿童语言影响的成像

• 批准号: 8518484
• 负责人: JENNIFER J. VANNEST
• 金额: $ 52.96万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518484
• 关键词: Academic achievement; Accounting; Adolescence; Affect; Age; Age of Onset; Antiepileptic Agents; Attention; Behavior; Benign; Brain; Brain imaging; Carbamazepine; Characteristics; Child; Childhood; Clinical Trials; Cognitive; Cognitive deficits; Control Groups; Critiques; Data; Diagnosis; Disease; Dose; Double-Blind Method; Electroencephalography; Epilepsy; Evaluation; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Hour; Image; Impact Seizures; Impairment; Incidence; Individual; Intelligence; Language; Language Disorders; Language Tests; Lead; Left; Levetiracetam; Magnetic Resonance Imaging; Maps; Measures; Memory; Monitor; Natural History; Nature; Neurocognitive; Neuropsychological Tests; Outcome; Outcome Measure; Participant; Patients; Performance; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Randomized Clinical Trials; Recording of previous events; Risk; Rolandic Epilepsy; Role; Schools; Seizures; Social Interaction; Study Section; Symptoms; Testing; Time; Update; Visuospatial; Writing; base; clinical practice; cognitive function; design; executive function; follow-up; imprint; improved; indexing; language processing; meetings; neural circuit; neuropsychological; open label; performance tests; primary outcome; processing speed; research clinical testing; secondary outcome; skills; social; standard of care

DESCRIPTION (provided by applicant): Benign Childhood Epilepsy with CentroTemporal Spikes (BECTS), an extremely common type of childhood epilepsy, is traditionally assumed to have a benign course, but recent studies have shown that cognitive function, especially language, is often impaired in BECTS patients. However, it is not clear whether the seizures, the centrotemporal spikes (CTS), or other factors cause the negative cognitive consequences that may impact school performance and social interaction. BECTS patients have scattered seizures but very frequent CTS, and may be suffering with undiagnosed cognitive and language deficits. This suggests a causal role for CTS that has not yet been investigated in detail. This project will examine the impact of seizures and CTS on neurocognitive function in BECTS patients, at diagnosis and after one year. We will gather critical information regarding the effect of the antiepileptic medication levetiracetam on CTS, which will inform a future Phase III clinical trial aimed at eliminating CTS and improving long term outcome. This study will explore the interactions between CTS, seizures and neuropsychological outcomes using Functional MRI of language in order to decipher changes in neural circuitry that underlie language deficits found in children with BECTS. Using standardized neuropsychological testing and fMRI at the time of diagnosis, this study will first characterize the nature and incidence of language problems in children with BECTS, separating the effects of CTS and seizures. It is expected that children with BECTS will perform below normative standards on tests of language skill, accompanied by aberrations in the neural circuitry supporting language processing as tested with fMRI. These data will also make it possible to characterize which children with BECTS are most at risk for language problems, by taking into account contributing factors such as number of seizures, age of onset, and frequency and lateralization of CTS. The proposed exploratory clinical trial will also provide key information needed to properly design and conduct a future double blind Phase III randomized clinical trial (RCT) children aimed at improving language outcome through elimination of CTS. Using an open-label dose-ranging selection design and 1-year follow up, we will determine which dose of levetiracetam control seizures, eliminate CTS is well tolerated and should be used in the Phase III trial. We will also examine the extent of changes in language function and neural circuitry of language with 1-year follow-up neuropsychological testing and fMRI in LEV-treated and untreated BECTS compared to controls (which will document the natural history of neuropsychological function in untreated BECTS children and give additional information about the effect of levetiracetam). The future double blind RCT will compare levetiracetam to carbamazepine (the current standard of care that does not eliminate CTS) in BECTS. This future study would change clinical practice by demonstrating the need for AED treatment in all BECTS children to eliminate CTS, in turn improving long term language and cognitive outcome.

描述（由申请人提供）：伴有中央颞区棘波的良性儿童癫痫 (BECTS) 是一种极其常见的儿童癫痫类型，传统上被认为具有良性病程，但最近的研究表明，BECTS 患者的认知功能，尤其是语言，经常受损。然而，尚不清楚癫痫发作、中央颞叶尖峰 (CTS) 或其他因素是否会导致可能影响学校表现和社交互动的负面认知后果。 BECTS 患者有分散性癫痫发作，但 CTS 非常频繁，并且可能患有未确诊的认知和语言缺陷。这表明 CTS 的因果作用尚未得到详细研究。该项目将研究癫痫发作和 CTS 对 BECTS 患者诊断时和一年后神经认知功能的影响。我们将收集有关抗癫痫药物左乙拉西坦对 CTS 影响的重要信息，这将为未来旨在消除 CTS 和改善长期结果的 III 期临床试验提供信息。 本研究将利用语言功能 MRI 来探索 CTS、癫痫发作和神经心理学结果之间的相互作用，以破译 BECTS 儿童语言缺陷背后的神经回路变化。这项研究将在诊断时使用标准化的神经心理学测试和功能磁共振成像，首先描述 BECTS 儿童语言问题的性质和发生率，区分 CTS 和癫痫发作的影响。预计患有 BECTS 的儿童在语言技能测试中的表现将低于规范标准，并且通过功能磁共振成像测试，支持语言处理的神经回路会出现异常。这些数据还可以通过考虑癫痫发作次数、发病年龄、CTS 频率和偏侧等影响因素，来确定哪些 BECTS 儿童最有可能出现语言问题。 拟议的探索性临床试验还将提供正确设计和开展未来双盲 III 期随机临床试验 (RCT) 所需的关键信息，该试验旨在通过消除 CTS 来改善儿童的语言结果。使用开放标签剂量范围选择设计和 1 年随访，我们将确定哪种剂量的左乙拉西坦控制癫痫发作、消除 CTS 具有良好的耐受性，并应在 III 期试验中使用。我们还将通过 1 年随访神经心理学测试和功能磁共振成像检查 LEV 治疗和未治疗的 BECTS 与对照组相比，语言功能和语言神经回路的变化程度（这将记录未经治疗的 BECTS 儿童的神经心理功能的自然史，并提供有关左乙拉西坦作用的更多信息）。未来的双盲随机对照试验将在 BECTS 中比较左乙拉西坦与卡马西平（目前不消除 CTS 的护理标准）。这项未来的研究将通过证明所有 BECTS 儿童需要使用 AED 治疗来消除 CTS，进而改善长期语言和认知结果，从而改变临床实践。