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

项目总结 癫痫猝死(SUDEP)是儿童期过早死亡的一个重要原因 癫痫。异常的脑、呼吸和心脏过程是SUDEP的候选机制。 支持心脏机制的是成人癫痫患者心脏骤停风险较高的发现， 发作间期和发作间期的心电图异常提示心脏 由心肌重塑引起的脆弱性。伴发作期高危心律失常的表现 低氧血症提示呼吸紊乱也可导致心脏异常。 癫痫。一项对儿童期癫痫发作的纵向、基于人群的研究表明， SUDEP的风险随着癫痫持续时间的增加而增加，这表明可能存在进行性变化 这会增加成年后的死亡风险。我们的主要假设是心脏电信号 重塑是癫痫持续时间的函数，并使心脏容易受到这样的压力 随着时间的推移，癫痫发作或呼吸紊乱，从而导致SUDEP。对于这项建议，我们 是否会前瞻性地跟踪一组没有已知离子通道病或心脏疾病的儿童癫痫患者 在第四个癫痫转诊中心使用心电研究作为替代标记物进行管理。 我们将获得每年一次的心电研究，并收集与每一次心电有关的临床和实验室数据。为 参加研究的儿童在研究期间因呼吸道疾病而住院，我们将 获取额外的心电图，并收集与住院相关的额外临床信息。vbl.使用 控制潜在混杂因素的多变量模型，如癫痫症状和发作频率、发作次数 抗癫痫药物，以及通过单因素分析确定的其他因素，我们将调查 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 评估并发呼吸道疾病是否是异常心电图的独立危险因素；以及 癫痫持续时间是否会改变并发呼吸期间出现异常心电图的可能性 生病了。

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.