Abstracts

Rationale: Infantile spasms (IS) are a severe epileptic encephalopathy presenting in the first two years of life. Longer time to treatment and no response to treatment have been identified as risk factors for poor outcomes. There are three medications with greater than Class IV evidence to support their use for infantile spasms. However, there is very little data to guide clinicians on the choice of an alternative therapy if the initial treatment is ineffective.Methods: The National Infantile Spasms Consortium (NISC) database was used to assess response to second treatment. This database enrolls children with new onset infantile spasms in a prospective manner with information including date IS onset, dates and doses of treatment, development at onset, and etiology. Response was recorded as resolution of clinical IS and hypsarhythmia. Information from June 2012 to July 2014 was used for this study. Children in whom initial treatment failed to provide remission were assessed and only those started on a second treatment were analyzed. Treatment, etiology, development, and response to second medication were assessed. We considered two classes of standard medications: hormonal (ACTH and oral corticosteroids) and vigabatrin. Other non-standard medications included topiramate, clobazam, levetiracetam, ketogenic diet, oxcarbazepine, zonisamide, rufinamide, and valproate. We assessed the relationship of demographic and clinical characteristics with choice of second treatment and response to second treatment using Chi-square tests.Results: 118 children were included in the analysis: 54% were male, median gestational age at birth was 39 weeks (IQR 37, 40), 78% were born at > 37 weeks gestation and 39% had a history of prior seizures. Median age at spasm onset was 6 months (IQR 4, 8), median time from spasms onset to initial treatment was 14 days (IQR 5,36), and median time from first treatment to second treatment was 25 days (IQR 17, 36). There were no significant differences in second medication choice related to etiology. Children with severe development delay at onset were less likely to receive vigabatrin as a second medication. Overall response rate to a second medication after failing an initial treatment was 37%. Children receiving an initial treatment for IS within 4 weeks were more likely to respond to second treatment (p=0.04) but time to the second treatment was not related to outcome (p=0.17). Medication chosen for second treatment was related to response (p=0.049). Children treated with a standard medication that had a different mechanism of action than the initial medication were more likely to respond to second medication. (See table)Conclusions: Greater than one third of children with IS will respond to a second medication. Rapid initial treatment increases the likelihood of response to the second treatment. In addition, choosing a standard medication (ACTH, oral corticosteroids or vigabatrin) that has a different mechanism of action is more likely to be effective.