Infantile Spasms of Unknown Cause: Who Can Have a Good Outcome?

Infantile spasms of unknown cause: predictors of outcome and genotype-phenotype correlation Yuskaitis CJ, Ruzhnikov MRZ, Howell KB, et al. Pediatr Neurol. 2018;87:48-56. doi:10.1016/j.pediatrneurol.2018.04.012. Epub 2018 May 7.

backgroundNo 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 (EPGP) aimed to characterize IS of unknown cause by phenotype and genotype analysis.

methodsWe undertook a retrospective multicenter observational cohort of 133 individuals within the EPGP database met criteria for IS of unknown cause with at least 6 months of follow-up data. Clinical medical records, imaging, and electroencephalography were examined.

resultsNormal 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 < .001), older age of IS onset (median 6 months old), and resolution of IS after initial treatment ( P < .001). Additional seizures after IS occurred in 67%, with predictors being seizures prior to IS ( P = .018), earlier age of IS onset (median 5 months old), and refractory IS ( P = .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 = .035).

conclusionsThe 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.