Abstracts

Rationale: Rationale: Infantile Spasms (IS) are a severe epileptic encephalopathy presenting in the first 2 years of life. Optimal first-line treatment of spasms continues to be debated. There is little data to inform clinicians whether baseline factors, such as developmental status at the time of diagnosis or underlying cause of spasms, influence the likelihood of clinical response.Methods: Methods: The National Infantile Spasms Consortium (NISC) established a prospective database enrolling infants with new diagnosis of infantile spasms, from June 2012 to July 2014. Children were identified as responders to treatment if there was a clinical remission and resolution of hypsarhythmia within 2 weeks of treatment initiation and sustained for 3 months. Standard treatments of ACTH, oral corticosteroids, and vigabatrin were considered individually, and all other non-standard therapies analyzed collectively. Developmental status (provider rating of motor and cognitive status) and etiology (determined by history, neuroimaging, and genetic/metabolic testing) were assessed. Infants were categorized into etiologic groups of genetic/metabolic, prior brain injury, malformation of cortical development/other structural, unknown with abnormal development, and unknown with normal development. Logistic regression was used to assess differences in prescribing patterns across etiologic and developmental groups. For multivariate analysis of response rates, etiologic groups were merged to reflect structural etiology, non-structural etiology, but infants with unknown etiology and prior normal development remained separate.Results: Results: 230 were included in the analysis. 53% were male, mean age of onset was 7 months (IQR 5, 9), and median time to treatment was 15 days (IQR 6, 37). 33% had a history of seizures prior to onset of spasms. There was non-random distribution of treatment choice when stratified by etiology (p<.001) and by development (p<.001). Infants with unknown etiology were more likely to be treated with ACTH, particularly if they had prior normal development. Infants with more severe developmental problems were less likely to be prescribed ACTH. Choosing ACTH as initial treatment was associated with higher response rates (p<0.001). In univariate analysis, having no or mild developmental issues was associated with increased response rate (p=0.025). There was a trend towards significance of higher response rates in infants with unknown etiology and prior normal development (p=.07). With multivariate analysis etiology (p=0.29) and development (p=0.24) were no longer significant predictors of treatment response.Conclusions: Conclusions: In a large multicenter cohort of children with IS, etiology and development affected treatment choice, but these factors were not significant predictors of response rate. Response does significantly vary by treatment choice, with greater responders among infants treated first with ACTH. Therefore, ACTH should be considered as possible first-line treatment in all infants, including those with impaired development or known structural or genetic/metabolic etiology.