Breathing Rescue for SUDEP Prevention (BreatheS)

预防 SUDEP 的呼吸救援 (BreatheS)

• 批准号: 10719638
• 负责人: Nuria Lacuey Lecumberri
• 金额: $ 63.03万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10719638
• 关键词: Acceleration; Address; Affect; Age; Air Movements; Amygdaloid structure; Anatomy; Anterior; Apnea; Beds; Brain; Breathing; Carbon Dioxide; Cardiovascular system; Cell Nucleus; Central Sleep Apnea; Cessation of life; Chronic; Clinical Trials; Complication; Coupled; Data; Electric Stimulation; Electrocardiogram; Electrodes; Electroencephalography; Epilepsy; Europe; Evaluation; Failure; Frequencies; Goals; Graph; Heart Arrest; Heart failure; Hippocampus; Hospitals; Implant; Individual; Insula of Reil; Intervention; Intractable Epilepsy; Knowledge; Life Expectancy; Medial; Medical; Monitor; Motor; Motor Seizures; National Institute of Neurological Disorders and Stroke; Nose; Operative Surgical Procedures; Oral; Oxygen; Patients; Persons; Physiologic pulse; Plethysmography; Population; Prevention strategy; Preventive; Prone Position; Prosencephalon; Refractory; Research; Respiration; Respiratory Failure; Risk; Risk Factors; Seizures; Sensory; Signal Transduction; Site; Stimulus; Stroke; Structure; System; Testing; Thalamic structure; Tidal Volume; Time; Training; Vulnerable Populations; Width; Work; cingulate cortex; cohort; connectome; design; efficacy clinical trial; high risk; innovation; insight; millisecond; nervous system disorder; neuroregulation; patient population; premature; prevent; preventable epilepsy; public health relevance; respiratory; response; restoration; sex; study population; sudden unexpected death in epilepsy; translational impact; ventilation

PROJECT SUMMARY Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of epilepsy and a leading cause of premature death in persons with chronic uncontrolled epilepsy. Despite the major impact on life expectancy in these individuals, no targeted SUDEP preventive strategies currently exist. Most SUDEPs occur after a generalized convulsive seizure, and victims are typically found in bed in the prone position. Until recently, SUDEP was thought to be due to cardiovascular failure, but research on patients who died while being monitored in hospital epilepsy units reveal that most SUDEP is due to post-convulsive central apnea. Crucially, a three-minute post convulsive window of opportunity was identified, beyond which the terminal cascade of respiratory and cardiac failure appears irrevocable. By advancing our understanding of forebrain breathing networks, we can develop neuromodulatory strategies for respiratory facilitation and apnea rescue that may prevent SUDEP during this critical time window. The objective of this project is to understand forebrain modulation of breathing by using anatomically precise intracranial stereotactic electroencephalography (SEEG) data that can determine optimal stimulation paradigms for breathing enhancement. The study population are patients with medically refractory epilepsy undergoing 1) intracranial SEEG evaluation with implanted depth electrodes for epilepsy surgery, and 2) simultaneous polygraphic cardiorespiratory monitoring of thoracoabdominal excursions, nasal and oral airflow, oxygen saturation, carbon dioxide, plethysmography and EKG. To achieve this goal, in Aim 1, we will identify forebrain regions in which electrical activity is coupled with respiratory activity by using spontaneous and task-related breathing data and monitoring simultaneous brain signal dynamics. We will further analyze functional connectivity to graph networks as a function of breathing tasks, in order to establish network hubs as candidate regions for stimulation targets and in order to reveal a comprehensive cortical connectome. In Aim 2, we will apply electrical stimulus to these regions to assess neuromodulatory effects on respiration. Effective stimulation paradigms/sites will be tested in the immediate post-convulsive state in the latter part of this study, to prove feasibility of neuromodulation in this state, and these seizures will be compared with non-stimulated seizures obtained from the NINDS Center for SUDEP Research, using 1:5 matching (matched for age, sex, SUDEP risk factors-duration of epilepsy and GCS frequency). Our project will identify effective stimulation sites and paradigms for breathing rescue as well as will establish feasibility of stimulation approaches in the post- convulsive state. Our results will set the stage for a clinical trial of efficacy of neuromodulation for apnea rescue as potential anti-SUDEP therapy, in individuals who at high SUDEP risk. This work will also provide insights into potential treatment of central apnea associated with other neurological diseases, heart failure, and stroke. .

项目摘要 癫痫（SUDEP）突然出乎意料的死亡是癫痫的毁灭性并发症和主要原因 患有慢性不受控制的癫痫的人过早死亡。尽管对预期寿命产生了重大影响 在这些人中，目前尚无针对性的SUDEP预防策略。大多数泡沫发生在 普遍的抽搐癫痫发作，受害者通常在俯卧位的床上发现。直到最近，Sudep 被认为是由于心血管衰竭，但对在监测中死亡的患者的研究 医院癫痫病显示，大多数SUDEP都是由于后备音中央呼吸暂停引起的。至关重要的是三分钟 确定了抽搐后的机会窗口，除此之外 心脏衰竭似乎是不可撤销的。通过促进我们对前脑呼吸网络的理解，我们可以 制定神经调节策略，用于呼吸道促进和呼吸暂停救援，这可能会阻止SUDEP 这个关键的时间窗口。该项目的目的是通过使用前脑调节呼吸的前脑调节 解剖学上精确的颅内立体定向脑电图（SEEG）数据，可以确定最佳 呼吸增强的刺激范例。研究人群是医学上难治性的患者 接受癫痫内的癫痫病接受癫痫手术的深度电极和 2）同时对胸腔腹部偏移，鼻和口服的多向心脏呼吸监测 气流，氧饱和度，二氧化碳，散布物理学和EKG。为了实现这一目标，在AIM 1中，我们将 确定通过自发和使用自发和 与任务相关的呼吸数据和同时监测大脑信号动力学。我们将进一步分析功能 与呼吸任务的函数连接到图形网络，以建立网络中心作为候选 刺激靶标的区域，以揭示全面的皮质连接组。在AIM 2中，我们将 将电刺激应用于这些区域，以评估神经调节对呼吸的影响。有效刺激 范式/地点将在本研究后期的立即引人注目的状态下进行测试，以证明 在该状态下神经调节的可行性，这些癫痫发作将与未刺激的癫痫发作进行比较 使用1：5匹配（适合年龄，性别，SUDEP风险匹配）从Ninds Sudep研究中心获得 癫痫和GCS频率的因素延伸）。我们的项目将确定有效的刺激站点，并 呼吸救援的范例，并将在后的后建立刺激方法的可行性 抽搐状态。我们的结果将为神经调节功效的呼吸暂停救援疗效奠定基础。 作为潜在的抗疾病疗法，在高SUDEP风险的个体中。这项工作还将提供有关 与其他神经疾病，心力衰竭和中风相关的中央呼吸暂停的潜在治疗。 。