Abstracts

Rationale: Infantile spasms (IS) is a severe epileptic encephalopathy. Early identification of IS and timely, appropriately chosen treatment are necessary to achieve seizure remission and reduce negative impact on development. Trisomy 21 is one of the most common genetic etiologies of IS. The objective of this study was to evaluate the clinical characteristics, time to diagnosis and response to treatment in a large cohort of children with IS secondary to Trisomy 21. Methods: We identified children with Trisomy 21 and IS from the National Infantile Spasms Consortium (NISC), enrolled prospectively from 2012 to 2017. This selected group was studied for descriptive characteristics, time to diagnosis of IS, choice of treatment, and response to initial treatment. Response to initial treatment was defined as the impact of the first drug on IS at 2 weeks or later. Results: Out of 579 children in the NISC database, 41 were identified as having IS secondary to Trisomy 21 (based on clinical diagnosis and/or genetic testing); 28 (68%) were male. Mean onset of IS was 7.2 months (range 3.5-12.7 months), with mean age of diagnosis of 9 months (range 4-18 months). The median time to diagnosis was 26 days (IQR 6-61).  None had other unprovoked seizure types prior to the onset of IS; only one had a complex febrile seizure prior to IS diagnosis. Presentation of all 41 children was clinically consistent with West Syndrome, with all initial EEGs interpreted as hypsarrhythmia or modified hypsarrhythmia.First line therapy was ACTH for 21 (71% responded), oral steroids for 10 (60% responded), vigabatrin for 6 (50% responded), and non-standard treatment for 3 (oxcarbazepine, topiramate, and zonisamide; none responded).  First line therapy data was not available for 1. Among the 22 infants who required a second therapy for IS: 6 received ACTH (83% responded), 4 oral steroids (50% responded), 6 vigabatrin (83% responded). Follow-up data were incomplete for infants treated with other drugs as second line treatment; the single infant with follow up data did not show a response.  Conclusions: In this cohort of children with Trisomy 21 and IS, there is a long lag to diagnosis and treatment. As the presentation was rarely preceded by other seizures, and the presentation was uniformly consistent with West Syndrome, the index of suspicion for IS should be high in children with Trisomy 21 with paroxysmal events. Preemptive counseling by primary care physicians for parents of infants with Trisomy 21 may be the best approach to prevent delays in diagnosis, which may minimize the impact on development in this at-risk population of children with IS.  As with IS from other etiologies, ACTH appears to provide the best response.  Funding: None