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） 尽管有足够的药物治疗，仍会继续癫痫发作，这使他们有突然意外的风险 癫痫死亡（SUDEP）。 SUDEP通常发生在邮政恢复阶段，其特征是 唤醒障碍，然后进行心肺崩溃，表明关键的脑干功能关闭。 但是，呼吸障碍严重到足以引起ict症状缺氧（PIH）和受损的迹象 唤醒，例如广泛的剧院后脑电图放慢（馅饼），或公告后的EEG抑制（PGES） 在非致命癫痫发作期间也发生。 PIH，PIE和PGES的机制及其与Sudep的关系 不太了解。因此，该项目的总体目标是使用MRI来表征结构和 脑干系统控制呼吸和抗药性癫痫和唤醒的功能改变 研究它们如何影响这些非致命障碍的发生。这不仅允许 更好地理解这些常见的周围障碍的机制，但也提供 见解它们与Sudep的关系。具体而言，假设PIH是结构性和 中脑呼吸调节剂复合物的功能性障碍，但释放了呼吸模式 下部髓质中的发电机。派与脑干唤醒网络中的异常有关， 假设PGE与唤醒和呼吸调节剂中的严重异常有关 网络。在200例药物难治性的患者中，将获得结构成像和无任务fMRI 癫痫（PWE）在3个癫痫中心进行长期视频遥测和SPO2监测。这 感兴趣的主要度量是PIH和PIE/PGE的发生（是/否）。新的脑干细分 方法将用于识别感兴趣的脑干结构。动态功能连接分析 组合群集分析和图理论将用于识别无任务fMRI中的不同大脑状态。 40 年龄和性别匹配的健康对照（CON）将与PWE进行相同的成像。