Clinical-Res-Project2

项目2--摘要 癫痫在UCD中被认为是一种罕见的表现(1)。然而，我们发现 经常发生亚临床脑电图性惊厥；脑电波检测到惊厥 在急性高氨血症(HA)发作期间) 患者，特别是新生儿，参加了UCDC纵向研究(LS)。这一新发现 提出了癫痫是否在脑血管疾病的病理生理学中起重要作用的问题。 UCD患者的神经认知障碍和/或可代表与以下因素相关的生物标志物 这些疾病中的大脑损伤。在这个项目中，我们建议系统地研究范围 和ES在我们的LS UCD人群中的作用，特征是发病，频率，持续时间， 局部性(局灶性或广泛性)脑电背景特征、生化和临床 关联，以及ES或EEG背景与后续 癫痫的发展。 我们假设： 1)血氨和/或谷氨酰胺的显著升高之间存在相关性 水平和ES的发展，以及 2)ES在HA脑病后不良的神经认知结局中起一定作用，尤其是在 新生儿尿失禁。 如果ES事实上与不良的神经认知结果有关，无论是作为原因还是作为 相关生物标记物，该项目将提供临床试验就绪数据以供后续测试 抗癫痫药物作为神经保护剂在UCD的HA治疗中的作用 有机会和迫切需要开发新的治疗策略，以针对 大脑。UCDC多站点联合体是获取这一信息的理想场所。

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.