A Nomogram to Predict Seizure Outcomes after Resective Epilepsy Surgery

项目摘要 严重急性呼吸综合征冠状病毒2型(SARS-2)的全系列神经学表现 CoV-2)感染尚不清楚。以前的研究仅限于病例系列，并描述了 仅观察到服用新冠肺炎或住进重症监护病房的患者的神经系统并发症 单位。虽然这些研究提供了重要的信息，但它们并没有澄清神经学的范围 表现为个体在感染期间表现出不同严重程度的症状，神经系统的长期 他们没有提供任何关于疾病的病理生理学的理解。 在我们当前的项目(1R01NS097719-04-A1)中，我们已经构建了一个大型数据和生物样本基础设施 建立癫痫发作自由和认知结果个体化预测的统计模型 在脑部切除手术后耐药癫痫发作。在这项竞争性修订申请中，我们建议 将我们的基础设施(预测建模和基因组专业知识)与机构资源(克利夫兰诊所)配对 新冠肺炎注册和生物库)，以促进神经病学的流行病学和机制理解 新冠肺炎的并发症，特别是癫痫、中风和精神错乱，并生成诺模图和在线 相关神经系统新冠肺炎并发症的风险计算器。 这项修订建议的目标是表征新的新的发病率和表现表型。 我们的医疗保健部门诊断为COVID阳性的所有患者(截至5月7日为3,177人)均出现癫痫发作、中风和精神错乱 系统，建立和验证预测模型，以确定有神经并发症风险的个人，以及 系统地确定疾病模块(疾病病理生物学/生理学的分子决定因素) 新冠肺炎可以揭示SARS-CoV-2相关神经疾病的新潜在机制 表现形式。 老年、吸烟、糖尿病、高血压、心血管疾病、肾脏疾病、慢性肺病以及 在服用新冠肺炎的患者中，癌症与进展为严重疾病相关。我们假设 这些因素同样与神经系统并发症的更高风险相关。然而，这些“风险” 因素“不是特定的，以不同的组合出现，作为特定的单独指标具有有限的价值 神经系统并发症。我们团队的专业知识将用于生成诺模图和在线风险计算器 对于在CCHS新冠肺炎登记队列中观察到的相关神经并发症，请探讨 利用创新的人类蛋白质-蛋白质分析研究这些神经并发症的潜在机制， 并开发出可指导临床护理决策的工具。

Project Summary The full spectrum of neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection has not been clarified. Previous studies have been limited to case series and have described only neurological complications observed in patients hospitalized with COVID-19 or admitted to intensive care units. While these studies provide important information, they do not clarify the range of neurological manifestations in individuals showing different severities of symptoms during infection, the long-term neurological effects of the disease, and they do not provide any understanding of the pathophysiology of the disease. In our current project (1R01NS097719-04-A1), we have constructed a large data and biospecimen infrastructure to develop statistical models for individualized prediction of epileptic seizure-freedom and cognitive outcomes after resective brain surgery for drug resistant seizures. In this competitive revision application, we propose to pair our infrastructure (predictive modeling and genomic expertise) with institutional resources (Cleveland Clinic COVID-19 Registry and Biobank) to advance the epidemiological and mechanistic understanding of neurological complications of COVID-19, particularly epilepsy, stroke, and delirium, and to generate nomograms and online risk calculators for the relevant neurological COVID-19 complications. The objectives of this revised proposal are to characterize the incidence and manifestation phenotype of new onset seizures, stroke, and delirium in all patients diagnosed as COVID+ (3,177 as of May 7) in our healthcare system, to build and validate prediction models to identify individuals at risk of neurological complications, and to identify systematically disease modules (molecular determinants of disease pathobiology/physiology) for COVID-19 that can reveal novel underlying mechanisms for SARS-CoV-2 associated neurological manifestations. Older age, smoking, diabetes, hypertension, cardiovascular disease, kidney disease, chronic lung disease, and cancer correlate with progression to severe disease in patients hospitalized with COVID-19. We hypothesize that these factors are similarly associated with a higher risk of neurological complications. However, these “risk factors” are not specific, occur in various combinations, and have limited value as isolated indicators of specific neurological complications. Our team's expertise will be used to generate nomograms and online risk calculators for the relevant neurological complications observed in the CCHS COVID-19 registry cohort, to explore underlying mechanisms of these neurological complications using innovative human protein-protein analyses, and to generate tools that can guide decisions in clinical care.