Prevention and Risk Identification of SUDEP Mortality - the PRISM Project

描述（由申请人提供）：每年高达1%的难治性癫痫患者猝死于一种无法解释的现象，称为癫痫猝死（SUDEP）。2008年，美国癫痫学会和癫痫基金会联合召集了一个工作组，建议对癫痫发作参数包括心血管、呼吸、自主神经和生化因素的多模式癫痫发作进行假设驱动、前瞻性、多中心的研究。这种方法至关重要，因为SUDEP很可能是癫痫发作相关事件。在SUDEP中，我们假设过度的桥上癫痫影响会产生严重的自主神经功能障碍，表现为深度低血压、致命性心律失常或呼吸暂停。遗传易感性和脑干血清素能失调可能起作用。然而，研究存在的关键障碍包括：1)每年0.5-1%的SUDEP发病率使得需要进行大型多中心研究；2)收集和分析非常大的多模态癫痫发作数据集（视频、脑电图（EEG）、心电图（EKG）、血压、O2和CO2测量、睡眠数据）；对这些每秒变化的多个参数进行传统的视觉和统计分析是非常困难的。为了克服这些障碍，需要一个复杂的生物信息学系统来获取、标准化和分析来自不同中心的各种癫痫监测系统的数据。拟议的猝死症死亡率预防和风险识别（PRISM）项目将1)利用我们中心现有的专业知识和基础设施，创建一个名为MEDCIS（多模态癫痫数据捕获和集成系统）的新型综合多模态数据采集和管理系统。通过MEDCIS，我们的目标是收集一个大规模的、多中心的、接受癫痫监测的癫痫患者的前瞻性队列。MEDCIS有望建立一个SUDEP的监测登记册。2)旨在建立癫痫发作性脑干功能障碍的综合比较研究能力，以确定临床癫痫和多模态癫痫生理数据的差异，包括脑电图、心电图、自主神经、心血管、呼吸、睡眠、内分泌和诱发电位特征，以表征和量化癫痫发作性脑干功能障碍。3) MEDCIS还将建立SUDEP脑库和遗传数据库，以增加现有的大量材料收集，以研究遗传影响和血清素能性脑功能障碍。PRISM项目将成为后续SUDEP无墙中心的核心，并将使SUDEP研究的多学科合作取得成功。这种方法最有可能产生有效的SUDEP预防战略。

DESCRIPTION (provided by applicant): Up to 1% of patients with refractory epilepsy die suddenly every year in an unexplained phenomenon called Sudden Unexpected Death in Epilepsy (SUDEP). In 2008 a joint American Epilepsy Society and Epilepsy Foundation convened Task Force recommended hypothesis-driven, prospective, multicenter research into SUDEP with multi-modal seizure parameters including cardiovascular, respiratory, autonomic and biochemical factors. This approach is vital as SUDEP is most likely a seizure related event. In SUDEP, we hypothesize exaggerated supra-pontine seizure influences produce severe autonomic dysfunction manifested as profound hypotension, fatal arrhythmia or apnea. Genetic predisposition and brainstem serotonergic dysregulation may contribute. However, critical barriers to research exist including 1) an annual SUDEP incidence of 0.5-1% making large multi-center studies necessary and 2) the collection and analysis of very large datasets of multi-modal seizure data (video, electroencephalography (EEG), electrocardiography (EKG), blood pressure, O2 & CO2 measurements, sleep data); traditional visual and statistical analyses of these multiple parameters that vary from second to second are very difficult. To overcome these barriers, a sophisticated bio-informatics system is required to acquire, standardize and analyze such data from a wide range of seizure monitoring systems in different centers. The proposed Prevention and Risk Identification of SUDEP Mortality (PRISM) Project will 1) leverage existing expertise and infrastructure at our Center to create a novel, integrated multi-modal data acquisition and management system called MEDCIS (Multi-modality Epilepsy Data Capture and Integration System). Through MEDCIS, we will aim to collect a large scale, multicenter, prospective cohort of epilepsy patients undergoing seizure monitoring. MEDCIS will prospectively create a surveillance register of SUDEP. We will 2) aim to establish capability for comprehensive comparative studies of SUDEP and near-SUDEP cases vs. cohort survivors to ascertain differences in clinical epilepsy and multi-modal physiological seizure data including EEG, EKG, autonomic, cardiovascular, respiration, sleep, endocrine and evoked potential features in order to characterize and quantify seizure induced brainstem dysfunction. 3) A SUDEP brain bank and genetics database will also be established within MEDCIS adding to an existing, substantial collection of material to investigate genetic influences and serotonergic brain dysfunction. The PRISM Project will form the core of a subsequent SUDEP Center Without Walls and will enable multi-disciplinary collaborations in SUDEP research to succeed. Such an approach is the most likely to produce effective SUDEP prevention strategies. PUBLIC HEALTH RELEVANCE: Sudden Unexpected Death in Epilepsy (SUDEP) is a public health problem that affects ~5000 individuals with epilepsy in the USA every year. How this happens is poorly understood and therefore no targeted prevention strategies exist. The goal of this research is to bring together a wide range of established expertise into a multi-disciplinary, multi-center collaboration and conduct exploratory research using sophisticated computational infrastructure and techniques that will significantly advance SUDEP research. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.