Kalinowska-Doman Adrianna, Strzelczyk Adam, Paprocka Justyna
Pediatric Neurology Department, Medical University of Silesia, Faculty of Medical Sciences, Katowice, Poland.
Goethe-University Frankfurt, Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, University Medicine Frankfurt, Frankfurt am Main, Germany.
Seizure. 2025 Sep;131:391-396. doi: 10.1016/j.seizure.2025.08.002. Epub 2025 Aug 6.
Background Cyclin-dependent kinase-like 5 deficiency disorder (CDD) is a disease belonging to the group of developmental and epileptic encephalopathies (DEE), characterized by drug-resistant epilepsy, delayed psychomotor development, premature mortality, and movement disorders. Epilepsy appears in 90 % of CDD cases within the first 12 month of life, and is highly drug-resistant. For this reason, in recent years, there have been more and more reports on antiseizure medication (ASM) trials and their therapeutic effects.
This review aims to summarize the reports and studies on the effectiveness of ASMs therapeutic options developed in recent years, including new generation drugs such as ganaxolone or cannabidiol.
A search of open-access PubMed database was conducted for studies published from January 2019 to October 2024, using the keywords "cdkl5", and "cdkl5 deficiency disorder". Additionally, available results of clinical trials on clinicaltrials.gov were searched with the same keywords. The reviewer independently screened the literature according to inclusion and exclusion criteria followed by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
Treating epilepsy in CDKL5 deficiency disorder remains difficult. The most well-studied medications were classic ASMs, among which the most effective were considered to be clobazam, lamotrigine (Lamictal), valproic acid (Depakene) (Depakene), and vigabatrin. Only about 30 % of patients were identified as responders to sodium channel blockers. Ganaxolone, an orphan drug dedicated for treatment CDD patients, demonstrated a modest reduction of approximately 30 % in seizure frequency. Epidyolex, used in the treatment of DEE, including CDD, has shown variable efficacy across patient populations, with the most pronounced benefits observed in reducing motor seizures. Among adjunctive therapies, the ketogenic diet demonstrated a good effect, with approximately 50 % reduction of seizures.
Because low number of patients studied worldwide, information on treatment options and outcomes is limited. Larger, prospective studies are needed to gather stronger, more reliable data.
背景 细胞周期蛋白依赖性激酶样5缺乏症（CDD）是一种属于发育性和癫痫性脑病（DEE）的疾病，其特征为耐药性癫痫、精神运动发育迟缓、过早死亡和运动障碍。90%的CDD病例在出生后的头12个月内出现癫痫，且具有高度耐药性。因此，近年来，关于抗癫痫药物（ASM）试验及其治疗效果的报道越来越多。
本综述旨在总结近年来开发的ASM治疗方案有效性的报告和研究，包括加奈索酮或大麻二酚等新一代药物。
使用关键词“cdkl5”和“cdkl5缺乏症”，在开放获取的PubMed数据库中搜索2019年1月至2024年10月发表的研究。此外，使用相同关键词搜索clinicaltrials.gov上的临床试验可用结果。 reviewer根据纳入和排除标准独立筛选文献，随后遵循PRISMA（系统评价和Meta分析的首选报告项目）指南。
治疗CDKL5缺乏症中的癫痫仍然困难。研究最多的药物是经典的ASM，其中最有效的被认为是氯巴占、拉莫三嗪（利必通）、丙戊酸（德巴金）和氨己烯酸。只有约30%的患者被确定为对钠通道阻滞剂有反应。加奈索酮是一种专门用于治疗CDD患者的孤儿药，其癫痫发作频率适度降低了约30%。用于治疗包括CDD在内的DEE的 Epidyolex在不同患者群体中的疗效各不相同，在减少运动性癫痫发作方面观察到最显著的益处。在辅助治疗中，生酮饮食显示出良好的效果，癫痫发作减少了约50%。
由于全球范围内研究的患者数量较少，关于治疗选择和结果的信息有限。需要进行更大规模的前瞻性研究，以收集更有力、更可靠的数据。
