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

项目摘要/摘要 癫痫是美国第四大最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，尽管进行了适当的药物治疗，使他们面临突然意外的风险 癫痫死亡(SUDEP)。SUDEP通常发生在后遗症恢复期，其特征是 觉醒功能受损，随后出现心肺功能衰竭，表明关键的脑干功能关闭。 然而，严重的呼吸紊乱足以引起发作期低氧血症(PIH)和受损的体征 觉醒，如发作后广泛性脑电减慢(PIES)或发作后广泛性脑电抑制(PGES) 也可发生在非致命性癫痫发作期间。PIH、PIES和PGE的机制及其与SUDEP的关系 都没有被很好地理解。因此，该项目的总体目标是使用磁共振成像来表征结构和 难治性癫痫患者控制呼吸和觉醒的脑干系统功能改变 调查它们如何影响这些非致命骚乱的发生。这不仅将允许 更好地了解这些常见发作期扰动的机制，也提供了 洞察它们与SUDEP的关系。具体地说，它假设妊高征是结构性和结构性的结果 中脑呼吸调节器复合体的功能障碍，但不影响呼吸模式 在下半部延髓中有发电机。馅饼与脑干唤醒网络的异常有关， 推测PSES与觉醒和呼吸调节器的严重异常有关。 网络。200名药物难治性、非皮损性患者将接受结构成像和无任务功能磁共振成像 在3个癫痫中心进行长期视频脑电遥测和血氧饱和度监测。这个 主要的利益衡量标准是妊高征和馅饼/馅饼的发生情况(是/否)。一种新的脑干分割方法 该方法将用于识别感兴趣的脑干结构。动态功能连通性分析 结合聚类分析和图论，将被用来识别无任务功能磁共振成像中的不同大脑状态。40岁 年龄和性别匹配的健康对照(CON)将接受与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.