Epilepsy Center and Division of Neurology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Epilepsia Open. 2021 Jan 29;6(1):38-44. doi: 10.1002/epi4.12466. eCollection 2021 Mar.
Literature review of patients with developmental and epileptic encephalopathy (-DEE) reveals, based on 16 reports including 139 patients, a clinical phenotype that includes age- and disease-specific stereotyped seizures. The typical seizure type of -DEE, focal tonic, starts within 0-5 days of life and is readily captured by video-electroencephalography VEEG for clinical and genetic diagnosis. After initial identification, -DEE seizures are clinically apparent and can be clearly identified without the use of EEG or VEEG. Therefore, we propose that the 2019 recommendations from the International League against Epilepsy (ILAE), the Pediatric Epilepsy Research Consortium (PERC), for capturing and recording seizures for clinical trials (, 4, 2019, 537) are suitable for use in -DEE‒associated antiseizure medicine (ASM) treatment trials. The ILAE/PERC consensus guidance states that a caregiver-maintained seizure diary, completed by caregivers who are trained to recognize seizures using within-patient historical recordings, accurately captures seizures prospectively in a clinical trial. An alternative approach historically endorsed by the Food and Drug Administration (FDA) compares seizure counts captured on VEEG before and after treatment. A major advantage of the ILAE/PERC strategy is that it expands the numbers of eligible patients who meet inclusion criteria of clinical trials while maintaining accurate seizure counts (, 4, 2019, 537). Three recent phase 3 pivotal pediatric trials investigating ASMs to treat syndromic seizures in patients as young as 2 years of age (, 17, 2017, 699; , 21, 2020, 2243; , 17, 2018, 1085); and ongoing phase 2 open-label pediatric clinical trial that includes pediatric epileptic syndromes as young as 1 month of age (, 176, 2018, 773), have already used caregiver-maintained seizure diaries successfully. For determining the outcome of a -DEE ASM treatment trial, the use of a seizure diary to count seizures by trained observers is feasible because the seizures of -DEE are clinically apparent. This strategy is supported by successful precedent in clinical trials in similar age groups and has the endorsement of the international pediatric epilepsy community.
对患有发育性和癫痫性脑病（-DEE）的患者的文献回顾显示，基于包括 139 例患者在内的 16 项报告，存在一种临床表型，包括年龄和疾病特异性刻板性发作。-DEE 的典型发作类型为局灶性强直，在生命的 0-5 天内开始，并可通过视频脑电图（VEEG）进行临床和遗传诊断。在最初识别后，-DEE 发作在临床上是明显的，无需使用 EEG 或 VEEG 即可清晰识别。因此，我们建议国际抗癫痫联盟（ILAE）、儿科癫痫研究联盟（PERC）于 2019 年发布的用于捕获和记录临床试验中发作的建议（,, 2019, 537）适用于与 -DEE 相关的抗癫痫药物（ASM）治疗试验。ILAE/PERC 共识指南指出，由经过培训以使用患者内部历史记录识别发作的护理人员维护的发作日记，可以准确地前瞻性捕获临床试验中的发作。食品和药物管理局（FDA）过去认可的替代方法是比较治疗前后 VEEG 上捕获的发作次数。ILAE/PERC 策略的一个主要优势是，它扩大了符合临床试验纳入标准的合格患者数量，同时保持了准确的发作次数（,, 2019, 537）。三项最近的针对 2 岁及以上患者综合征性发作的 3 期关键性儿科试验（,, 2017, 699；, 21, 2020, 2243；, 17, 2018, 1085），以及正在进行的包括 1 个月龄及以上儿童癫痫综合征的 2 期开放标签儿科临床试验（, 176, 2018, 773），已经成功使用了护理人员维护的发作日记。为了确定 -DEE ASM 治疗试验的结果，使用训练有素的观察者来计算发作次数的发作日记是可行的，因为 -DEE 的发作在临床上是明显的。这种策略在类似年龄组的临床试验中已经取得了成功，得到了国际儿科癫痫界的认可。
