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 癫痫猝死（SUDEP）是癫痫的一种毁灭性并发症，也是导致癫痫发作的主要原因之一。 在患有慢性不受控制的癫痫的人中过早死亡。尽管对预期寿命有重大影响 在这些个体中，目前不存在针对性的SUDEP预防策略。大多数SUDEP发生在 全身性惊厥发作，受害者通常是在床上发现的俯卧位。直到最近， 被认为是由于心血管衰竭，但对在监测期间死亡的患者的研究表明， 医院癫痫科揭示大多数SUDEP是由于惊厥后中枢性呼吸暂停。最重要的是， 确定了惊厥后的机会窗口，超过该窗口，呼吸和 心力衰竭似乎无法挽回通过推进我们对前脑呼吸网络的理解， 制定呼吸促进和呼吸暂停抢救的神经调节策略， 这个关键的时间窗口。这个项目的目的是了解前脑调制呼吸使用 解剖学上精确的颅内立体定向脑电图（SEEG）数据，可以确定最佳的 呼吸增强的刺激范例。研究人群为医学难治性 接受1）植入深部电极进行癫痫手术的颅内SEEG评价的癫痫，以及 2)胸腹部偏移的同步多导心电图监测，鼻和口 气流、氧饱和度、二氧化碳、体积描记法和EKG。为了实现这一目标，在目标1中， 识别前脑区域，其中电活动与呼吸活动耦合， 与任务相关的呼吸数据和同时监测大脑信号动态。我们将进一步分析功能 连接到图网络作为呼吸任务的函数，以建立网络枢纽作为候选 区域的刺激目标，以揭示一个全面的皮层连接体。在目标2中，我们将 对这些区域施加电刺激以评估对呼吸的神经调节作用。有效刺激 在本研究的后半部分，将在惊厥后即刻状态下对范例/部位进行测试，以证明 在这种状态下神经调节的可行性，这些癫痫发作将与非刺激性癫痫发作进行比较 从NINDS SUDEP研究中心获得，使用1：5匹配（年龄，性别，SUDEP风险匹配） 因素-癫痫持续时间和GCS频率）。我们的项目将确定有效的刺激部位， 呼吸救援的范例，以及将建立刺激方法的可行性后， 痉挛状态我们的研究结果将为呼吸暂停抢救的神经调节功效的临床试验奠定基础 作为潜在的抗SUDEP治疗，在高SUDEP风险的个人。这项工作还将提供见解， 与其他神经系统疾病、心力衰竭和中风相关的中枢性呼吸暂停的潜在治疗。 .