Department of Neurology and Division of Epilepsy, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Medical Genetics and Department of Pediatrics, Stanford University, Stanford, California.
Pediatr Neurol. 2018 Oct;87:48-56. doi: 10.1016/j.pediatrneurol.2018.04.012. Epub 2018 May 7.
No large-scale studies have specifically evaluated the outcomes of infantile spasms (IS) of unknown cause, previously known as cryptogenic or idiopathic. The Epilepsy Phenome/Genome Project aimed to characterize IS of unknown cause by phenotype and genotype analysis.
We undertook a retrospective multicenter observational cohort of 133 individuals within the Epilepsy Phenome/Genome Project database met criteria for IS of unknown cause with at least six months of follow-up data. Clinical medical records, imaging, and electroencephalography were examined.
Normal development occurred in only 15% of IS of unknown cause. The majority (85%) had clinically documented developmental delay (15% mild, 20% moderate, and 50% severe) at last assessment (median 2.7 years; interquartile interval 1.71-6.25 years). Predictors of positive developmental outcomes included no delay prior to IS (P < 0.001), older age of IS onset (median six months old), and resolution of IS after initial treatment (P < 0.001). Additional seizures after IS occurred in 67%, with predictors being seizures prior to IS (P = 0.018), earlier age of IS onset (median five months old), and refractory IS (P = 0.008). On a research basis, whole exome sequencing identified 15% with de novo variants in known epilepsy genes. Individuals with a genetic finding were more likely to have poor developmental outcomes (P = 0.035).
The current study highlights the predominately unfavorable developmental outcomes and that subsequent seizures are common in children with IS of unknown cause. Ongoing genetic evaluation of IS of seemingly unknown cause is likely to yield a diagnosis and provide valuable prognostic information.
目前尚无大型研究专门评估病因不明的婴儿痉挛症（IS）的结局，该病此前被称为隐源性或特发性。癫痫表型/基因组计划旨在通过表型和基因型分析来确定病因不明的 IS。
我们对癫痫表型/基因组计划数据库中符合病因不明的 IS 标准且至少有 6 个月随访数据的 133 名患者进行了回顾性多中心观察性队列研究。检查了临床病历、影像学和脑电图。
仅 15%的病因不明的 IS 患者有正常发育。大多数（85%）患者在最后一次评估时存在临床记录的发育迟缓（15%轻度、20%中度和 50%重度）（中位数 2.7 岁；四分位间距 1.71-6.25 岁）。阳性发育结局的预测因素包括 IS 前无发育迟缓（P < 0.001）、IS 发病年龄较大（中位数为 6 个月）和初始治疗后 IS 缓解（P < 0.001）。IS 后出现额外癫痫发作的比例为 67%，其预测因素为 IS 前有癫痫发作（P = 0.018）、IS 发病年龄较早（中位数为 5 个月）和难治性 IS（P = 0.008）。基于研究，外显子组测序发现 15%的患者有已知癫痫基因的新生变异。有基因发现的患者更有可能出现不良发育结局（P = 0.035）。
本研究强调了病因不明的 IS 患者主要存在不良发育结局，且随后发生癫痫发作较为常见。对看似病因不明的 IS 患者进行持续的遗传评估可能会得出诊断，并提供有价值的预后信息。
