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

局灶性癫痫发作期间的呼吸和觉醒障碍：脑干的作用

• 批准号: 10799997
• 负责人: Susanne G. Mueller
• 金额: $ 43.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10799997
• 关键词: Age; Arousal; Atrophic; Brain; Brain Stem; Cessation of life; Cluster Analysis; Compensation; Complex; Dorsal; Electroencephalography; Epilepsy; Functional Magnetic Resonance Imaging; Gender; Goals; Hypoxemia; Image; Impairment; Intractable Epilepsy; Magnetic Resonance Imaging; Measures; Midbrain structure; Monitor; Partial Epilepsies; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Phase; Recovery; Refractory; Respiration; Respiratory physiology; Risk; Role; Seizures; Severities; Structure; System; Telemetry; Testing; comparison control; experience; functional magnetic resonance imaging/electroencephalography; graph theory; insight; interest; midbrain central gray substance; morphometry; nervous system disorder; premature; respiratory; structural imaging; sudden unexpected death in epilepsy

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.

项目概要/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) 尽管进行了充分的药物治疗，但仍继续出现癫痫发作，这使他们面临突发意外的风险 癫痫死亡（SUDEP）。 SUDEP 通常发生在发作后恢复阶段，其特点是 觉醒受损随后出现心肺衰竭，表明关键的脑干功能关闭。 然而，呼吸系统紊乱严重到足以导致发作期低氧血症 (PIH) 和呼吸功能受损的迹象。 觉醒，例如广泛的发作后脑电图减慢（PIES）或发作后全身脑电图抑制（PGES） 也发生在非致命性癫痫发作期间。 PIH、PIES 和 PGES 的机制以及它们与 SUDEP 的关系 没有被很好地理解。因此，该项目的总体目标是使用 MRI 来表征结构和 耐药性癫痫和控制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。这不仅将允许 更好地理解这些常见的发作期紊乱的机制，同时也提供了 深入了解它们与 SUDEP 的关系。具体来说，假设 PIH 是结构性和 中脑呼吸调节复合体的功能紊乱，但不影响呼吸模式 发电机位于下髓质。 PIES 与脑干唤醒网络异常有关 推测 PGES 与觉醒和呼吸调节器的严重异常有关 网络。将对 200 名药物难治性非病变患者进行结构成像和无任务 fMRI 采集 癫痫 (PWE) 在 3 个癫痫中心接受长期视频脑电图遥测和 SpO2 监测。这 主要的关注指标是 PIH 和 PIES/PGES 的发生（是/否）。新的脑干分割 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用于识别无任务功能磁共振成像中的不同大脑状态。 40 年龄和性别匹配的健康对照 (CON) 将接受与 PWE 相同的成像。