An informatics framework for SUDEP Risk Marker Identification and Risk Assessment

项目摘要 癫痫猝死（SUDEP）是癫痫相关死亡的主要方式。最近 据估计，美国每年约有7,000人死于SUDEP 是中风后成人寿命年数损失的第二大常见原因。到 加速SUDEP研究，国家神经疾病和中风研究所（NINDS）在NIH- 资助的SUDEP研究中心（CSR），一个由14个机构组成的网络， 基础科学和临床方法来研究潜在的生物学机制， 可预防的死亡率，并为干预措施开发预测性生物标志物。确定和通报 改变SUDEP危险因素是降低SUDEP发生率的重要策略。 然而，由于一些原因，目前尚无法对SUDEP风险进行系统的个体化评估。 挑战通常，所需的信息嵌入在位于不同的、未链接的数据集中的数据中， 系统;缺乏用于精确提取SUDEP风险因素的特定受控词汇 语义一致的信息;以及相应的计算算法和工具， 从临床文本和电生理信号中提取重要的风险标记尚待充分开发。 我们建议通过开发SUDEP风险标记提取系统SURME来克服这些挑战 用于从多模态CSR数据存储库中自动提取已知和假定的SUDEP风险标记 （称为MEDCIS），其中包含7个医疗中心的癫痫监测单位招募的1，600多名患者 中心.在目标1中，我们将根据我们自己的癫痫和癫痫发作开发一个专用的受控词汇库 本体和现有的SUDEP风险指南和报告的风险因素。我们将开发一条开采管道， 利用我们早期的癫痫表型提取工具，从临床文本中检测风险标志物。在目标2中 我们将开发一种可扩展的方法，用于检测两种重要的假定生理生物标志物， 电生理信号：发作后广义EEG抑制; 连续R-R间期。在目标3中，我们将在MEDCIS上进行SURME的试点实施，以实现自动化 使用“SUDEP-7清单”和“SUDEP和扣押安全清单”进行风险评估，以及 使用CSR队列评估假定的SUDEP风险因素。我们希望SURME及其未来版本 成为一个宝贵的SUDEP风险评估工具，作为标准癫痫治疗的一部分。的长期目标 本研究旨在创建基于证据的SUDEP风险评估工具，以改善癫痫护理， 个性化的风险评分和管理可修改风险的建议，最终降低 SUDEP死亡率和改善癫痫患者护理。

PROJECT SUMMARY Sudden Unexpected Death in Epilepsy (SUDEP) is the leading mode of epilepsy related death. Recent estimates indicate that SUDEP is responsible for approximately 7,000 deaths each year in the United States and Europe, and is the second most common cause of the number of adult life years lost after stroke. To accelerate SUDEP research, the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH- funded Center for SUDEP Research (CSR), a network of 14 institutions collaborating in a broad spectrum of basic science and clinical approaches to study possible biological mechanisms underlying this potentially preventable mortality and develop predictive biomarkers for interventions. Identification and communication of alterable SUDEP risk factors to affected patients is an important strategy to lower SUDEP incidence. However, systematic individualized assessment of SUDEP risk is currently unavailable due to a number of challenges. Often the required information is embedded in data residing in disparate, unlinked datasets and systems; there is a lack of a specific controlled vocabulary for precise extraction of SUDEP risk factor information with semantic uniformity; and the corresponding computational algorithms and tools needed for important risk marker extraction from clinical text and electrophysiological signals are yet to be fully developed. We propose to overcome these challenges by developing SURME, a SUDEP Risk Marker Extraction system for automated extraction of known and putative SUDEP risk markers from the multimodal CSR data repository (called MEDCIS) which contains over 1,600 patients enrolled from Epilepsy Monitoring Units in 7 medical centers. In Aim 1 we will develop a dedicated controlled vocabulary building on our own Epilepsy and Seizure Ontology and existing SUDEP risk guidelines and reported risk factors. We will develop an extraction pipeline, leveraging our earlier epilepsy phenotype extraction tools, for detecting risk markers from clinical text. In Aim 2 we will develop a scalable approach for detecting two significant putative physiological biomarkers from electrophysiological signals: postictal generalized EEG suppression; and root mean square differences of successive R-R intervals. In Aim 3 we will perform pilot implementation of SURME on MEDCIS for automated risk assessment using “SUDEP-7 Inventory” and “SUDEP and Seizure Safety Checklist”, as well as assessment of putative SUDEP risk factors using CSR cohort. We expect SURME and its future versions to become an invaluable SUDEP risk assessment tool as a part of standard epilepsy care. The long-term goal of this study is to create evidence-based SUDEP risk assessment tools to improve epilepsy care, with individualized risk scores and recommendations for managing modifiable risks, ultimately leading to reduced SUDEP mortality and improved epilepsy patient care.