Prevention and Risk Identification of SUDEP Mortality - the PRISM Project

描述(申请人提供)：每年高达1%的难治性癫痫患者突然死亡，这是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特别工作组，建议对SUDEP进行假设驱动的、前瞻性的多中心研究，并使用包括心血管、呼吸、自主神经和生化因素在内的多模式癫痫参数。这一方法至关重要，因为SUDEP很可能是与癫痫有关的事件。在SUDEP中，我们假设夸大的桥上癫痫发作影响会导致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5-羟色胺能失调可能与此有关。然而，研究存在关键障碍，包括1)每年0.5-1%的SUDEP发病率，这使得大型多中心研究成为必要；2)收集和分析非常大的多模式癫痫数据集(视频、脑电(EEG)、心电(EKG)、血压、O2和CO2测量、睡眠数据)；对这些从秒到秒变化的多参数的传统视觉和统计分析非常困难。为了克服这些障碍，需要一个复杂的生物信息学系统来从不同中心的各种缉获监测系统中获取、标准化和分析这些数据。拟议的SUDEP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，创建一个新颖的、集成的多模式数据采集和管理系统，称为MEDCIS(多模式癫痫数据捕获和集成系统)。通过MEDCIS，我们的目标是收集大规模、多中心、预期的癫痫患者队列，接受癫痫发作监测。MEDCIS将前瞻性地创建SUDEP的监视登记。2)我们将致力于建立SUDEP和近SUDEP病例与队列幸存者的综合比较研究能力，以确定临床癫痫和多模式生理性癫痫发作数据的差异，包括EEG、EKG、自主神经、心血管、呼吸、睡眠、内分泌和诱发电位特征，以表征和量化癫痫诱发的脑干功能障碍。3)还将在MEDCIS内建立SUDEP脑库和遗传学数据库，以补充现有的大量材料，以研究遗传影响和5-羟色胺能脑功能障碍。PRISM项目将形成后续无围墙的SUDEP中心的核心，并将使SUDEP研究中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.