PDF(Pubmed)
Abstract：
CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy. Ganaxolone, a neuroactive steroid, reduces the frequency of major motor seizures in children with CDD. This analysis explored the effect of ganaxolone on non-seizure outcomes. Children (2-19 years) with genetically confirmed CDD and ≥ 16 major motor seizures per month were enrolled in a double-blind randomized placebo-controlled trial. Ganaxolone or placebo was administered three times daily for 17 weeks. Behaviour was measured with the Anxiety, Depression and Mood Scale (ADAMS), daytime sleepiness with the Child Health Sleep Questionnaire, and quality of life with the Quality of Life Inventory-Disability (QI-Disability) scale. Scores were compared using ANOVA, adjusted for age, sex, number of anti-seizure mediations, baseline 28-day major motor seizure frequency, baseline developmental skills, and behaviour, sleep or quality of life scores. 101 children with CDD (39 clinical sites, 8 countries) were randomized. Median (IQR) age was 6 (3-10) years, 79.2 % were female, and 50 received ganaxolone. After 17 weeks of treatment, Manic/Hyperactive scores (mean difference 1.27, 95%CI -2.38,-0.16) and Compulsive Behaviour scores (mean difference 0.58, 95%CI -1.14,-0.01) were lower (improved) in the ganaxolone group compared with the placebo group. Daytime sleepiness scores were similar between groups. The total change in QOL score for children in the ganaxolone group was 2.6 points (95%CI -1.74,7.02) higher (improved) than in the placebo group but without statistical significance. Along with better seizure control, children who received ganaxolone had improved behavioural scores in select domains compared to placebo.
摘要：
CDKL5缺乏症（CDD）是一种罕见的发育性和癫痫性脑病。加奈索酮,一种神经活性类固醇,减少儿童的主要运动性癫痫发作的频率。本分析探讨了加奈索酮对非癫痫结局的影响。在一项双盲随机安慰剂对照试验中，儿童（2-19岁）具有遗传证实的CDD和每月≥16次主要运动性癫痫发作。加奈索酮或安慰剂每天给药3次，共17周。行为是用焦虑来衡量的，抑郁和情绪量表（ADAMS）白天嗜睡与儿童健康睡眠问卷，和生活质量的生活质量量表-残疾(QI-残疾)量表。使用方差分析比较分数，根据年龄调整，性别,抗癫痫调解的数量，基线28天主要运动性癫痫发作频率，基线发展技能，和行为，睡眠或生活质量评分。101名儿童CDD（39个临床站点，8个国家）被随机分配。年龄中位数（IQR）为6（3-10）岁，79.2%为女性，50人接受了加奈索酮。经过17周的治疗，与安慰剂组相比，加奈索酮组的躁狂/多动评分（平均差1.27，95CI-2.38，-0.16）和强迫行为评分（平均差0.58，95CI-1.14，-0.01）较低（改善）。两组白天嗜睡评分相似。加奈索酮组儿童QOL评分的总变化比安慰剂组高2.6分(95CI-1.74,7.02)(改善),但无统计学意义。随着更好的癫痫发作控制，与安慰剂相比,接受加奈索酮治疗的儿童在特定领域的行为评分有所改善.
