Abstract：
OBJECTIVE: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters.
METHODS: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed.
RESULTS: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h.
CONCLUSIONS: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.
METHODS: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed.
RESULTS: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h.
CONCLUSIONS: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction.
摘要：
目的：癫痫发作需要及时的药物治疗，以尽量减少进展为癫痫持续状态的可能，增加医疗保健使用，以及对日常生活的干扰。孤立性癫痫发作可能表现出周期性模式，包括昼夜节律和更长的节奏。然而,对癫痫发作群中的周期性模式知之甚少。这种事后分析的数据来自长期，阶段3，开放标签，地西泮鼻喷雾剂的重复剂量安全性研究模拟了治疗的癫痫发作集群的周期性。
方法：混合效应余弦分析评估昼夜节律，和使用12和24小时的单组分余弦用于计算余弦参数(例如，节奏的中线统计，波浪安培，andacrophase[peak]).对完整队列和一致队列的参与者进行了分析，这些参与者在四个中的每一个中都有两个或更多个癫痫发作集群，3个月期间。还分析了癫痫类型对cosinor参数的影响。
结果：在24小时内绘制的癫痫发作簇事件显示出双峰分布，顶相（峰）在〜06:30和〜18:30。12小时的图显示在~06:30有一个单峰。Cosinor分析了完整且一致的队列，两种模型的顶体期均可在24小时量表上的〜23:30和12小时量表上的〜07:30预测癫痫发作活动的峰值。一致的队列与基线和峰值癫痫发作簇活动的增加有关。按癫痫类型进行的分析确定了不同的趋势。局灶性癫痫组的癫痫发作群在晚上达到高峰（顶期19:19），而全身性癫痫组的事件在早晨达到高峰（顶期04:46）。它们共同构成了在24小时内观察到的双峰聚类。
结论：对使用地西泮鼻喷雾剂治疗的癫痫群集的分析显示，癫痫群集在12小时和24小时的时间范围内周期性发生，与孤立性癫痫的报告相似。进一步阐明这些模式可能为患者护理提供重要信息，从改善以患者为中心的结果到癫痫发作群集预测。
方法：混合效应余弦分析评估昼夜节律，和使用12和24小时的单组分余弦用于计算余弦参数(例如，节奏的中线统计，波浪安培，andacrophase[peak]).对完整队列和一致队列的参与者进行了分析，这些参与者在四个中的每一个中都有两个或更多个癫痫发作集群，3个月期间。还分析了癫痫类型对cosinor参数的影响。
结果：在24小时内绘制的癫痫发作簇事件显示出双峰分布，顶相（峰）在〜06:30和〜18:30。12小时的图显示在~06:30有一个单峰。Cosinor分析了完整且一致的队列，两种模型的顶体期均可在24小时量表上的〜23:30和12小时量表上的〜07:30预测癫痫发作活动的峰值。一致的队列与基线和峰值癫痫发作簇活动的增加有关。按癫痫类型进行的分析确定了不同的趋势。局灶性癫痫组的癫痫发作群在晚上达到高峰（顶期19:19），而全身性癫痫组的事件在早晨达到高峰（顶期04:46）。它们共同构成了在24小时内观察到的双峰聚类。
结论：对使用地西泮鼻喷雾剂治疗的癫痫群集的分析显示，癫痫群集在12小时和24小时的时间范围内周期性发生，与孤立性癫痫的报告相似。进一步阐明这些模式可能为患者护理提供重要信息，从改善以患者为中心的结果到癫痫发作群集预测。
