Clinical-Res-Project2

临床研究项目2

• 批准号: 10241409
• 负责人: Andrea Lynne Gropman
• 金额: $ 15.49万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241409
• 关键词: Acute; Ammonia; Anatomy; Animals; Antiepileptic Agents; Biochemical; Biochemistry; Biological Markers; Blood; Brain; Brain Edema; Brain Injuries; Brain imaging; Chronology; Citrulline; Clinical; Clinical Research; Clinical Trials; Cognitive; Cognitive deficits; Critically ill children; Data; Development; Disease; Disease Marker; Distal; Doctor of Medicine; Electroencephalogram; Electroencephalography; Encephalopathies; Energy Metabolism; Enrollment; Epilepsy; Etiology; Event; Frequencies; Functional disorder; Glutamine; Hospitalization; Hyperammonemia; Image; Individual; Injury; Intervention; Intervention Trial; Knowledge; Laboratories; Longitudinal Studies; Magnetic Resonance Imaging; Metabolic; Modeling; Monitor; Natural History; Neonatal; Nervous System Trauma; Neurocognitive; Neurocognitive Deficit; Neuroprotective Agents; Outcome; Patients; Phase; Plasma; Play; Population; Predictive Value; Prevalence; Production; Rare Diseases; Resolution; Risk; Role; Seizures; Severities; Severity of illness; Testing; Time; Urea cycle disorders; base; clinical trial readiness; experience; multi-component intervention; neonate; neural circuit; neurocognitive test; neurodevelopment; neuroimaging; neuroprotection; novel therapeutic intervention; predictive modeling; prognostic significance; safety and feasibility; standard measure; standard of care; study population

PROJECT 2 - ABSTRACT Epilepsy has been considered an infrequent manifestation in UCD (1). However, we found the frequent occurrence of sub-clinical electrographic seizures ((ES); seizures detected on EEG without accompanying clinical manifestations) during acute hyperammonemic (HA) episodes in patients, especially neonates, enrolled in the UCDC longitudinal study (LS). This new finding raises the question of whether seizures play an important role in the pathophysiology of neurocognitive deficits in UCD patients and/or can represent a biomarker that correlates with brain damage in these disorders. In this project, we propose to systematically study the scope and role of ES in our LS UCD population, characterizing the onset, frequency, duration, localization (focal or generalized) EEG background features, and biochemical and clinical correlates, as well as any association of ES or EEG background with the subsequent development of epilepsy. We hypothesize that: 1) There is a correlation between significant increases in plasma ammonia and/or glutamine levels and the development of ES, and 2) ES play a role in the adverse neurocognitive outcome after HA encephalopathy, especially in the neonate with UCD. If ES are in fact associated with adverse neurocognitive outcome, whether as a cause or as an associated biomarker, this project will provide clinical trial readiness data to subsequently test the role of anti-epileptic drugs as neuroprotection agents during HA in UCD, and presents both an opportunity and critical need to develop new therapeutic strategies that are targeted to the brain. The UCDC multisite consortium represents an ideal venue to capture this information.

项目2 -摘要 癫痫被认为是UCD的罕见表现（1）。然而，我们发现， 频繁发生亚临床电图癫痫发作（（ES）; EEG检测到癫痫发作 无伴随临床表现）， 入选UCDC纵向研究（LS）的患者，尤其是新生儿。这一新发现 提出了一个问题，癫痫发作是否在癫痫的病理生理学中起重要作用， UCD患者的神经认知缺陷和/或可以代表与以下相关的生物标志物： 脑损伤的症状在本项目中，我们建议系统地研究 以及ES在我们LS UCD人群中的作用，描述了ES的发病、频率、持续时间， 定位（局灶性或全身性）EEG背景特征，以及生化和临床 相关，以及ES或EEG背景与随后的 癫痫的发展。 我们假设： 1)血浆氨和/或谷氨酰胺的显著增加与 水平和ES的发展，以及 2)ES在HA脑病后的不良神经认知结果中发挥作用，特别是在 患有强迫症的新生儿 如果ES实际上与不良神经认知结果相关，无论是作为原因还是作为 相关生物标志物，该项目将提供临床试验准备数据，以进行后续测试 抗癫痫药物在UCD HA期间作为神经保护剂的作用，并介绍了 一个机会和迫切需要开发新的治疗策略，针对 个脑袋UCDC多站点联盟是获取此信息的理想场所。