Assessing determinants of electrocardiographic alterations and identifying exacerbating factors in pediatric epilepsy

评估心电图改变的决定因素并确定小儿癫痫的恶化因素

• 批准号: 10302120
• 负责人: Yi-Chen Lai
• 金额: $ 36.96万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302120
• 关键词: Acute; Adult; Appearance; Arrhythmia; Blood gas; Cardiac; Cerebrum; Cessation of life; Child; Childhood; Chronic; Clinical; Data; Electrolytes; Enrollment; Epilepsy; Frequencies; Future; Health; Heart; Heart Abnormalities; Heart Arrest; Heart Diseases; Heart Rate; Hospitalization; Hypoxemia; Incidence; Individual; Ions; Laboratories; Lead; Longitudinal Studies; Measurement; Mechanical ventilation; Medical; Medicine; Modeling; Monitor; Morphology; Outcome; Oxygen; Pathology; Patients; Pediatric Hospitals; Pediatric cohort; Pharmaceutical Preparations; Play; Population Study; Process; Prospective Studies; Relative Risks; Reporting; Risk; Risk Factors; Role; Seizures; Stress; Surrogate Markers; Temperature; Texas; Time; Ventricular Remodeling; base; biomedical referral center; childhood epilepsy; clinical practice; comorbidity; demographics; follow-up; high risk; insight; modifiable risk; mortality; mortality risk; physiologic stressor; premature; primary outcome; prospective; respiratory; risk prediction; secondary outcome; sudden unexpected death in epilepsy; supplemental oxygen

PROJECT SUMMARY Sudden unexpected death in epilepsy (SUDEP) is a significant cause of premature death in childhood-onset epilepsy. Aberrant cerebral, respiratory and cardiac processes are candidate mechanisms underlying SUDEP. In support of cardiac mechanism are the findings of higher risk of sudden cardiac arrest in adults with epilepsy, and inter-ictal and peri-ictal electrocardiographic (ECG) abnormalities suggesting increased cardiac vulnerability that results from myocardial remodeling. The appearance of high-risk arrhythmias with peri-ictal hypoxemia suggests that respiratory derangements can also contribute to the cardiac abnormalities in epilepsy. A longitudinal, population-based study of childhood-onset epilepsy has shown that the cumulative SUDEP risk increases with increasing epilepsy duration, suggesting that there might be progressive changes that contribute to mortality risk in adulthood. Our overarching hypothesis is that cardiac electrical remodeling occurs as function of epilepsy duration and renders the heart vulnerable to stresses such as seizures or respiratory derangements over time, thereby contributing to SUDEP. For this proposal we will prospectively follow a cohort of pediatric epilepsy patients without a known ion channelopathy or cardiac disease, who are managed in a quaternary epilepsy referral center using ECG studies as a surrogate marker. We will obtain yearly ECG studies and collect clinical and laboratory data associated with each ECG. For children enrolled in the study who are hospitalized for a respiratory illness during the study period, we will obtain additional ECGs and collect additional clinical information relating to the hospitalizations. Using multivariable models controlling for potential confounders such as seizure semiology and frequency, number of anti-seizure medications, and other factors identified through univariate analyses, we will investigate whether epilepsy duration is an independent risk factor for abnormal ECG. Using an analogous approach, we will also evaluate whether an intercurrent respiratory illness is an independent risk factor for abnormal ECG, and whether epilepsy duration modifies the likelihood of having an abnormal ECG during an intercurrent respiratory illness.

项目概要 癫痫猝死（SUDEP）是儿童期过早死亡的一个重要原因 癫痫。异常的大脑、呼吸和心脏过程是 SUDEP 的潜在机制。 支持心脏机制的是成人癫痫患者发生心脏骤停的风险较高的发现， 发作间期和围发作期心电图 (ECG) 异常表明心脏功能增加 心肌重构导致的脆弱性。围发作期高危心律失常的出现 低氧血症表明呼吸紊乱也可能导致心脏异常 癫痫。一项针对儿童期癫痫的纵向、基于人群的研究表明，累积的 SUDEP 风险随着癫痫持续时间的增加而增加，表明可能存在进行性变化 这会增加成年期的死亡风险。我们的首要假设是心电 重塑随着癫痫持续时间的变化而发生，并使心脏容易受到压力，例如 随着时间的推移，如癫痫发作或呼吸紊乱，从而导致 SUDEP。对于这个提案我们 将前瞻性地跟踪一组没有已知离子通道病或心脏疾病的小儿癫痫患者 疾病，他们在第四纪癫痫转诊中心使用心电图研究作为替代标记进行管理。 我们将获得年度心电图研究并收集与每个心电图相关的临床和实验室数据。为了 参与研究的儿童在研究期间因呼吸系统疾病住院，我们将 获得额外的心电图并收集与住院相关的额外临床信息。使用 控制潜在混杂因素的多变量模型，例如癫痫症状学和频率、癫痫发作次数 抗癫痫药物以及通过单变量分析确定的其他因素，我们将调查是否 癫痫持续时间是心电图异常的独立危险因素。使用类似的方法，我们还将 评估并发呼吸系统疾病是否是心电图异常的独立危险因素，以及 癫痫持续时间是否会改变并发呼吸期间心电图异常的可能性 疾病。