Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first-line therapies.
Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first-line therapies.
复制标题
CDKL5 缺乏症中的癫痫痉挛：治疗延迟且对一线治疗反应不佳。
作者：
Olson,HeatherE;Demarest,Scott;Pestana-Knight,Elia;Moosa,AhsanN;Zhang,Xiaoming;Pérez-Pérez,JoséR;Weisenberg,Judy;O'ConnorPrange,Erin;Marsh,EricD;Rajaraman,RajsekarR;Suter,Bernhard;Katyayan,Akshat;Haviland,Isabel;Daniels,Car
我们的目的是评估婴儿发作性癫痫痉挛（ES）在CDKL 5缺乏症（CDD）与其他病因的治疗反应。MethodsWe评估了ES患者从CDKL 5卓越中心和国家婴儿痉挛协会（NISC），发病2个月至2年，治疗促肾上腺皮质激素（ACTH），口服皮质类固醇，氨己烯酸，和/或生酮饮食。我们排除了患有结节性硬化症、21三体综合征或病因不明但发育正常的儿童，因为已知有不同的治疗反应。我们比较了两个队列的治疗时间和ES缓解在14天和3 months.ResultsWe评估了59个人与CDD（79%的女性，中位ES发病6个月）和232个人从NISC数据库（46%的女性，中位发病7个月）。在CDD队列中，ES之前的癫痫发作很常见（88%），34%的患者在ES发作时出现高度心律失常及其变体。CDD队列中27/59例（46%）和NISC队列中182/232例（78%）在ES发作1个月内开始ACTH、口服皮质类固醇或氨己烯酸的初始治疗（p<0.0001）。CDD组ES的14天临床缓解率（26%，7/27）低于NISC队列（58%，106/182，p= .0002）。在3个月时，27例CDD患者中有1例（4%）出现持续ES缓解，而NISC队列中182例患者中有96例（53%）出现持续ES缓解（p<0.0001）。在较长的前置时间（≥1个月）或既往治疗中观察到相当的结果。生酮饮食，在3个月内使用的ES发病，导致ES缓解1个月，持续3个月，在至少2个13（15%）的个人与CDD。SignificanceCompared广泛的一组婴儿ES，儿童与ES在CDD的设置往往经历较长的前置时间治疗和标准治疗反应差。需要开发治疗慢性阻塞性肺病ES的替代治疗方法。
ObjectiveWe aimed to assess the treatment response of infantile‐onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies.MethodsWe evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months.ResultsWe evaluated 59 individuals with CDD (79% female, median ES onset 6 months) and 232 individuals from the NISC database (46% female, median onset 7 months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1 month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (p< .0001). Fourteen‐day clinical remission of ES was lower for the CDD group (26%, 7/27) than for the NISC cohort (58%, 106/182,p= .0002). Sustained ES remission at 3 months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (p< .0001). Comparable results were observed with longer lead time (≥1 month) or prior treatment. Ketogenic diet, used within 3 months of ES onset, resulted in ES remission at 1 month, sustained at 3 months, in at least 2 of 13 (15%) individuals with CDD.SignificanceCompared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed.