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: 8188003
• 负责人: JENNIFER J. VANNEST
• 金额: $ 50.06万
• 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/8188003
• 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. PUBLIC HEALTH RELEVANCE: This project examines how seizures, and abnormal brain activity, affect language skill in children with Benign Childhood Epilepsy with Centro-Temporal Spikes (BECTS). BECTS is a common type of childhood epilepsy, and while BECTS patients stop having seizures by their late teenage years, many studies have shown that these children have language problems that may lead to academic and social difficulties. Using standardized language testing, monitoring of brain activity, and MRI brain imaging, this project aims to determine what particular combination of BECTS symptoms put children most at risk for language problems and what dose of the anti-epileptic medication levetiracetam may be helpful. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of the individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.

描述（由申请人提供）：良性儿童癫痫伴中央颞叶棘波（BECTS）是一种非常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，特别是语言功能，通常受损。然而，目前尚不清楚癫痫发作，中央颞区尖峰（CTS）或其他因素是否会导致可能影响学校表现和社会交往的负面认知后果。BECTS患者有分散的癫痫发作，但非常频繁的CTS，并可能患有未诊断的认知和语言缺陷。这表明CTS的因果作用尚未详细调查。该项目将研究癫痫发作和CTS对BECTS患者在诊断时和一年后神经认知功能的影响。我们将收集关于抗癫痫药物左乙拉西坦对CTS影响的关键信息，这将为未来旨在消除CTS和改善长期结局的III期临床试验提供信息。 本研究将探讨CTS，癫痫发作和神经心理学结果之间的相互作用，使用功能磁共振成像的语言，以破译神经回路的变化，在BECTS儿童中发现的语言缺陷的基础。在诊断时使用标准化的神经心理学测试和fMRI，本研究将首先描述BECTS儿童语言问题的性质和发生率，分离CTS和癫痫发作的影响。预计BECTS儿童在语言技能测试中的表现将低于规范标准，伴随着功能磁共振成像测试中支持语言处理的神经回路的畸变。这些数据也将使我们能够通过考虑癫痫发作次数、发病年龄、CTS频率和偏侧化等因素，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进行未来双盲III期随机临床试验（RCT）儿童所需的关键信息，旨在通过消除CTS来改善语言结果。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耐受性良好，应用于III期试验。我们还将通过1年随访神经心理学测试和fMRI检查与对照组相比，LEV治疗和未治疗的BECTS中语言功能和语言神经回路的变化程度（这将记录未治疗的BECTS儿童神经心理功能的自然史，并提供有关左乙拉西坦影响的额外信息）。未来的双盲RCT将比较左乙拉西坦与卡马西平（目前的标准治疗，不能消除CTS）在BECTS中的作用。这项未来的研究将通过证明所有BECTS儿童需要AED治疗来消除CTS，从而改善长期的语言和认知结果，从而改变临床实践。 公共卫生相关性：本项目研究癫痫发作和异常的大脑活动如何影响患有良性儿童癫痫伴中央颞叶棘波（BECTS）的儿童的语言技能。BECTS是一种常见的儿童癫痫类型，虽然BECTS患者在青少年后期停止癫痫发作，但许多研究表明，这些儿童存在语言问题，可能导致学习和社交困难。使用标准化的语言测试，大脑活动监测和MRI脑成像，该项目旨在确定BECTS症状的特定组合使儿童最有可能出现语言问题，以及抗癫痫药物左乙拉西坦的剂量可能有所帮助。 免责声明：请注意，以下评论由审查员在研究部分会议之前准备，并以基本上未经编辑的形式提供。 虽然审查人员有机会根据小组讨论情况更新或修订其书面评价，但不能保证在会议讨论之后更新了个人评论。 因此，这些评论可能并不完全反映小组讨论结束时单个评审员的最终意见或小组的最终多数意见。因此，讨论的简历和摘要是评审员在会议上实际认为关键的最后一句话。