Prevention and Risk Identification of SUDEP Mortality - the PRISM Project

SUDEP 死亡率的预防和风险识别 - PRISM 项目

• 批准号: 8535262
• 负责人: Samden Lhatoo
• 金额: $ 45.63万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2014-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8535262
• 关键词: Address; Advisory Committees; Affect; American; Animal Structures; Apnea; Architecture; Area; Arrhythmia; Autonomic Dysfunction; Autonomic nervous system; Biochemical; Biochemical Genetics; Bioinformatics; Blood Pressure; Brain; Brain Stem; Carbon Dioxide; Cardiovascular system; Cessation of life; Characteristics; Clinical; Collaborations; Collection; Comparative Study; Complex; Computational Technique; Critiques; Data; Data Collection; Data Set; Databases; Electrocardiogram; Electroencephalography; Endocrine; Epidemiologic Studies; Epidemiology; Epilepsy; Evaluation; Event; Evoked Potentials; Family history of; Family member; Foundations; Functional disorder; Funding; Genetic; Genetic Databases; Genetic Predisposition to Disease; Goals; Grant; Heart; Hypercapnic respiratory failure; Hypotension; Hypoxia; Incidence; Individual; Informatics; Joints; Lead; Literature; Modality; Modification; Monitor; Multicenter Studies; National Institute of Neurological Disorders and Stroke; Online Systems; Patients; Phase; Phenotype; Physiological; Play; Polysomnography; Pontine structure; Prevention; Prevention strategy; Preventive Intervention; Process; Public Health; Refractory; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Respiration; Risk; Risk Marker; Role; Seizures; Sleep; Societies; Structure; Study Section; Sudden Death; Sudden infant death syndrome; Survivors; System; Systems Integration; United States National Institutes of Health; Update; Visual; Writing; base; cohort; computer infrastructure; data acquisition; data management; data mining; digital; exome; experience; genome sequencing; meetings; mortality; multidisciplinary; novel; programs; prospective; respiratory; response; study characteristics

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.

描述（由申请人提供）：每年高达1%的难治性癫痫患者突然死亡，这种无法解释的现象称为癫痫猝死（SUDEP）。2008年，美国癫痫协会和癫痫基金会联合召开了一个工作组，建议对SUDEP进行假设驱动的前瞻性多中心研究，多模式癫痫发作参数包括心血管，呼吸，自主神经和生化因素。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发作影响会产生严重的自主神经功能障碍，表现为严重的低血压、致命的心律失常或呼吸暂停。遗传易感性和脑干肾上腺素能失调可能起作用。然而，研究存在关键障碍，包括1）每年0.5-1%的SUDEP发生率，需要进行大型多中心研究，以及2）收集和分析非常大的多模式癫痫发作数据集（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，需要有一个先进的生物信息系统，以获取、标准化和分析来自不同中心各种缉获监测系统的此类数据。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，创建一个新型的集成多模式数据采集和管理系统，称为MEDCIS（多模式癫痫数据采集和集成系统）。通过MEDCIS，我们的目标是收集一个大规模，多中心，前瞻性队列癫痫患者进行癫痫发作监测。MEDCIS将前瞻性地创建SUDEP的监督登记册。我们将2）旨在建立对SUDEP和近SUDEP病例与队列幸存者进行全面比较研究的能力，以确定临床癫痫和多模态生理癫痫发作数据（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）的差异，从而表征和量化癫痫发作诱导的脑干功能障碍。3)一个SUDEP脑库和遗传学数据库也将建立在MEDCIS内，增加了现有的，大量的材料收集，以调查遗传影响和多巴胺能脑功能障碍。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预防策略。

项目成果

Postictal generalized EEG suppression is not associated with periictal cardiac autonomic instability in people with convulsive seizures.

• DOI: 10.1111/epi.12021
• 发表时间: 2013-03
• 期刊: Epilepsia
• 影响因子: 5.6
• 作者: Lamberts RJ;Laranjo S;Kalitzin SN;Velis DN;Rocha I;Sander JW;Thijs RD
• 通讯作者: Thijs RD

Complex epilepsy phenotype extraction from narrative clinical discharge summaries.

• DOI: 10.1016/j.jbi.2014.06.006
• 发表时间: 2014-10
• 期刊: JOURNAL OF BIOMEDICAL INFORMATICS
• 影响因子: 4.5
• 作者: Cui, Licong;Sahoo, Satya S.;Lhatoo, Samden D.;Garg, Gaurav;Rai, Prashant;Bozorgi, Alireza;Zhang, Guo-Qiang
• 通讯作者: Zhang, Guo-Qiang

Increased prevalence of ECG markers for sudden cardiac arrest in refractory epilepsy.

• DOI: 10.1136/jnnp-2014-307772
• 发表时间: 2015-03
• 期刊: Journal of neurology, neurosurgery, and psychiatry
• 作者: Lamberts RJ;Blom MT;Novy J;Belluzzo M;Seldenrijk A;Penninx BW;Sander JW;Tan HL;Thijs RD
• 通讯作者: Thijs RD

From classification to epilepsy ontology and informatics.

从分类到癫痫本体论和信息学。

• DOI: 10.1111/j.1528-1167.2012.03556.x
• 发表时间: 2012
• 期刊: Epilepsia
• 影响因子: 5.6
• 作者: Zhang,Guo-Qiang;Sahoo,SatyaS;Lhatoo,SamdenD
• 通讯作者: Lhatoo,SamdenD

Age-specific periictal electroclinical features of generalized tonic-clonic seizures and potential risk of sudden unexpected death in epilepsy (SUDEP).

• DOI: 10.1016/j.yebeh.2013.08.010
• 发表时间: 2013-11
• 期刊: Epilepsy & behavior : E&B
• 作者: Freitas J;Kaur G;Fernandez GB;Tatsuoka C;Kaffashi F;Loparo KA;Rao S;Loplumlert J;Kaiboriboon K;Amina S;Tuxhorn I;Lhatoo SD
• 通讯作者: Lhatoo SD