From the Division of Epilepsy and Clinical Neurophysiology (C.J.Y., C.H.), Department of Neurology, Boston Children's Hospital, MA; Department of Pediatrics (J.R.M.), Division of Pediatric Neurology, Nationwide Children's Hospital, The Ohio State University, Columbus; Division of Child Neurology (F.M.B.), Department of Neurology, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology and ICCTR Biostatistics and Research Design Center (B.Z., S.L.), Boston Children's Hospital and Harvard Medical School, MA; Division of Child Neurology (D.S.), Department of Pediatrics, University of Arkansas for Medical Sciences, AR; Department of Pediatrics (S.A.H.), Division of Neurology, University of California, Los Angeles; Department of Neurology (E.G.Y.), Montefiore Medical Center, Bronx, NY; Jane and John Justin Neurosciences (C.G.K.), Cook Children's Hospital, Fort Worth, TX; Departments of Pediatrics and Neurology (C.J.), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora; Department of Pediatrics (R.K.S.), Division of Neurology, Atrium Health/Levine Children's, Charlotte, NC; Division of Pediatric Neurology (S. Bhatia), Department of Pediatrics, Medical University of South Carolina, Charleston; Department of Pediatrics (S. Bhalla), Division of Child Neurology, Emory University School of Medicine, Children's Healthcare of Atlanta, GA; and Department of Pediatrics (R.S.), Michigan Medicine, University of Michigan, Ann Arbor, MI.
Neurology. 2022 Nov 29;99(22):e2494-e2503. doi: 10.1212/WNL.0000000000201232. Epub 2022 Aug 29.
Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response.
The National Infantile Spasms Consortium prospectively followed children aged 2-24 months with new-onset infantile spasms at 23 US centers (2012-2018). We included children treated with standard therapy (ACTH, oral steroids, or vigabatrin). Sustained treatment response was defined as having the last clinically recognized infantile spasms on or before treatment day 14, absence of hypsarrhythmia on EEG 2-4 weeks after treatment, and persistence of remission to day 30. We analyzed the time to treatment response and assessed clinical characteristics to predict sustained treatment response.
Among 395 infants, clinical infantile spasms remission occurred in 43% (n = 171) within the first 2 weeks of treatment, of which 81% (138/171) responded within the first week of treatment. There was no difference in the median time to response across standard therapies (ACTH: median 4 days, interquartile range [IQR] 3-7; oral steroids: median 3 days, IQR 2-5; vigabatrin: median 3 days, IQR 1-6). Individuals without hypsarrhythmia on the pretreatment EEG (i.e., abnormal but not hypsarrhythmia) were more likely to have early treatment response than infants with hypsarrhythmia at infantile spasms onset (hazard ratio 2.23, 95% CI 1.39-3.57). No other clinical factors predicted early responders to therapy.
Remission after first infantile spasms treatment can be identified by treatment day 7 in most children. Given the importance of early and effective treatment, these data suggest that children who do not respond to standard infantile spasms therapy within 1 week should be reassessed immediately for additional standard treatment. This approach could optimize outcomes by facilitating early sequential therapy for children with infantile spasms.
标准治疗（促肾上腺皮质激素[ACTH]、口服类固醇或氨己烯酸）未能控制近一半婴儿痉挛症患儿的病情。早期识别无应答者可以实现序贯治疗的快速启动。我们旨在确定适当婴儿痉挛症治疗开始后达到临床缓解的时间，并确定婴儿痉挛症治疗应答时间的预测因素。
全国婴儿痉挛症联合会前瞻性地在 23 个美国中心（2012-2018 年）对 2-24 月龄新诊断为婴儿痉挛症的儿童进行了随访。我们纳入了接受标准治疗（ACTH、口服类固醇或氨己烯酸）的儿童。持续治疗应答定义为治疗第 14 天或之前最后一次临床确认婴儿痉挛发作，治疗后 2-4 周脑电图上无高波幅失律，且缓解状态持续至第 30 天。我们分析了治疗应答时间，并评估了临床特征以预测持续治疗应答。
在 395 例婴儿中，43%（n=171）在治疗的前 2 周内出现临床婴儿痉挛缓解，其中 81%（138/171）在治疗的第 1 周内应答。标准治疗的中位应答时间无差异（ACTH：中位 4 天，四分位距[IQR]3-7；口服类固醇：中位 3 天，IQR 2-5；氨己烯酸：中位 3 天，IQR 1-6）。无痉挛发作起始时高波幅失律的脑电图（即异常但非高波幅失律）的个体比有高波幅失律的婴儿更早出现治疗应答（风险比 2.23，95%CI 1.39-3.57）。其他临床因素均不能预测治疗的早期应答者。
大多数儿童在首次婴儿痉挛症治疗后第 7 天可确定缓解。鉴于早期和有效治疗的重要性，这些数据表明，在 1 周内对标准婴儿痉挛症治疗无应答的儿童应立即重新评估以接受额外的标准治疗。这种方法可以通过为婴儿痉挛症儿童实现早期序贯治疗来优化结局。
