Peri-ictal respiratory and arousal disturbances in focal epilepsy: Role of the brainstem

项目总结/摘要 癫痫是美国第四大常见的神经系统疾病。20-30%的癫痫患者（PWE） 继续经历癫痫发作，尽管充分的药物治疗，使他们在风险突然意外 癫痫死亡（SUDEP）SUDEP通常发生在发作后恢复期，其特征在于： 觉醒受损，随后出现心肺功能衰竭，表明脑干关键功能关闭。 然而，呼吸紊乱严重到足以引起发作期低氧血症（PIH）和受损的体征， 觉醒，如广泛发作后EEG减慢（PIES）或发作后全身性EEG抑制（PGES） 也发生在非致命性癫痫发作期间。PIH、PIES和PGES的发病机制及其与SUDEP的关系 并没有得到很好的理解。因此，本项目的总体目标是使用MRI来表征结构和 控制耐药性癫痫患者呼吸和觉醒的脑干系统的功能改变， 研究它们如何影响这些非致命性干扰的发生。这不仅可以让一个 更好地了解这些常见的发作期紊乱的机制， 他们是如何与SUDEP联系起来的。具体而言，假设PIH是结构性和 中脑呼吸调节复合体的功能障碍，但保留了呼吸模式 下髓质的发电机PIES与脑干唤醒网络的异常有关， 假设PGES与觉醒和呼吸调节剂的严重异常有关 网络将在200例药物难治性、非病变性脑梗死患者中进行结构成像和无任务功能磁共振成像。 癫痫（PWE）在3个癫痫中心接受长期视频EEG遥测和SpO 2监测。的 关注的主要指标是PIH和PIES/PGES的发生率（是/否）。一种新的脑干分割方法 方法将用于识别感兴趣的脑干结构。动态功能连接分析 结合聚类分析和图论将被用来识别不同的大脑状态，在无任务功能磁共振成像。40 年龄和性别匹配的健康对照（CON）将经历与PWE相同的成像。

Project Summary/Abstract Epilepsy is the fourth most common neurological disease in the US. 20-30% of the patients with epilepsy (PWE) continue to experience seizures despite adequate drug treatment which puts them at risk for sudden unexpected death in epilepsy (SUDEP). SUDEP typically occurs in the postictal recovery phase and is characterized by impaired arousal followed by cardiorespiratory breakdown suggesting a shutdown of critical brainstem functions. However, respiratory disturbances severe enough to cause peri-ictal hypoxemia (PIH) and signs of impaired arousal such as widespread post-ictal EEG slowing (PIES), or postictal generalized EEG suppression (PGES) occur also during non-fatal seizures. The mechanisms of PIH, PIES and PGES and how they relate to SUDEP are not well understood. The overall goal of this project is therefore to use MRI to characterize structural and functional alterations of the brainstem systems controlling respiration and arousal in drug-resistant epilepsy and to investigate how they influence the occurrence of these non-fatal disturbances. This will not only allow for a better understanding of the mechanism underlying these common peri-ictal disturbances but also provide insights how they relate to SUDEP. Specifically, it is hypothesized that PIH is a consequence of structural and functional disturbances of the midbrain respiratory modulator complex but spares the respiratory pattern generator in the lower medulla. PIES are associated with abnormalities in the brainstem arousal network and PGES is hypothesized to be associated with severe abnormalities in the arousal as well as respiratory modulator network. Structural imaging and task-free fMRI will be acquired in 200 patients with drug-refractory, non-lesional epilepsy (PWE) undergoing long-term video-EEG telemetry and SpO2 monitoring in 3 epilepsy centers. The primary measure of interest is the occurrence (yes/no) of PIH and PIES/PGES. A new brainstem segmentation approach will be used to identify brainstem structures of interest. Dynamic functional connectivity analysis combining cluster analysis and graph theory will be used to identify different brain states in task free fMRI. 40 age and gender matched healthy controls (CON) will undergo the same imaging as PWE.