Department of Biomedical Engineering, The University of Melbourne, Melbourne, VIC, Australia; Department of Medicine, St Vincent's Hospital, The University of Melbourne, Melbourne, VIC, Australia.
Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, MA, USA; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Lancet Neurol. 2018 Nov;17(11):977-985. doi: 10.1016/S1474-4422(18)30274-6. Epub 2018 Sep 12.
Epilepsy has long been suspected to be governed by cyclic rhythms, with seizure rates rising and falling periodically over weeks, months, or even years. The very long scales of seizure patterns seem to defy natural explanation and have sometimes been attributed to hormonal cycles or environmental factors. This study aimed to quantify the strength and prevalence of seizure cycles at multiple temporal scales across a large cohort of people with epilepsy.
This retrospective cohort study used the two most comprehensive databases of human seizures (SeizureTracker [USA] and NeuroVista [Melbourne, VIC, Australia]) and analytic techniques from circular statistics to analyse patients with epilepsy for the presence and frequency of multitemporal cycles of seizure activity. NeuroVista patients were selected on the basis of having intractable focal epilepsy; data from patients with at least 30 clinical seizures were used. SeizureTracker participants are self selected and data do not adhere to any specific criteria; we used patients with a minimum of 100 seizures. The presence of seizure cycles over multiple time scales was measured using the mean resultant length (R value). The Rayleigh test and Hodges-Ajne test were used to test for circular uniformity. Monte-Carlo simulations were used to confirm the results of the Rayleigh test for seizure phase.
We used data from 12 people from the NeuroVista study (data recorded from June 10, 2010, to Aug 22, 2012) and 1118 patients from the SeizureTracker database (data recorded from Jan 1, 2007, to Oct 19, 2015). At least 891 (80%) of 1118 patients in the SeizureTracker cohort and 11 (92%) of 12 patients in the NeuroVista cohort showed circadian (24 h) modulation of their seizure rates. In the NeuroVista cohort, patient 8 had a significant cycle at precisely 1 week. Two others (patients 1 and 7) also had approximately 1-week cycles. Patients 1 and 4 had 2-week cycles. In the SeizureTracker cohort, between 77 (7%) and 233 (21%) of the 1118 patients showed strong circaseptan (weekly) rhythms, with a clear 7-day period. Between 151 (14%) and 247 (22%) patients had significant seizure cycles that were longer than 3 weeks. Seizure cycles were equally prevalent in men and women, and peak seizure rates were evenly distributed across all days of the week.
Our results suggest that seizure cycles are robust, patient specific, and more widespread than previously understood. They align with the accepted consensus that most epilepsies have some diurnal influence. Variations in seizure rate have important clinical implications. Detection and tracking of seizure cycles on a patient-specific basis should be standard in epilepsy management practices.
Australian National Health and Medical Research Council.
长期以来，癫痫一直被怀疑受周期性节律支配，其发作频率在数周、数月甚至数年内呈周期性上升和下降。发作模式的超长周期似乎无法用自然原因解释，有时被归因于激素周期或环境因素。本研究旨在通过大样本癫痫患者的多项时间尺度，定量评估发作周期的强度和普遍性。
本回顾性队列研究使用了两个最全面的人类癫痫发作数据库（美国的 SeizureTracker 和澳大利亚墨尔本的 NeuroVista），并采用循环统计学的分析技术，分析癫痫患者的多时间尺度发作活动是否存在和发作周期的频率。NeuroVista 患者是基于难治性局灶性癫痫选择的；使用至少有 30 次临床发作的数据。SeizureTracker 参与者是自行选择的，数据不遵循任何特定标准；我们使用至少有 100 次发作的患者。使用均方根长度（R 值）来测量多个时间尺度上发作周期的存在。使用 Rayleigh 检验和 Hodges-Ajne 检验来检验圆的均匀性。使用蒙特卡罗模拟来确认 Rayleigh 检验在癫痫发作相位上的结果。
我们使用了 NeuroVista 研究中的 12 名参与者的数据（记录时间为 2010 年 6 月 10 日至 2012 年 8 月 22 日）和 SeizureTracker 数据库中的 1118 名患者的数据（记录时间为 2007 年 1 月 1 日至 2015 年 10 月 19 日）。在 SeizureTracker 队列中，至少 891 名（80%）1118 名患者和 NeuroVista 队列中的 11 名（92%）患者的发作频率存在昼夜（24 小时）调制。在 NeuroVista 队列中，患者 8 具有精确的 1 周周期。另外两名患者（患者 1 和 7）也有大约 1 周的周期。患者 1 和 4 有 2 周的周期。在 SeizureTracker 队列中，1118 名患者中，有 77 名（7%）至 233 名（21%）有强烈的 circaseptan（每周）节律，有明确的 7 天周期。有 151 名（14%）至 247 名（22%）患者的发作周期长于 3 周。发作周期在男性和女性中同样普遍，发作高峰频率均匀分布在一周中的每一天。
我们的结果表明，发作周期是稳定的、患者特有的，而且比以前所理解的更为广泛。它们与普遍接受的共识一致，即大多数癫痫都有一定的昼夜影响。发作频率的变化具有重要的临床意义。在患者基础上检测和跟踪发作周期应成为癫痫管理实践的标准。
澳大利亚国家健康与医学研究理事会。
