Abstracts

Rationale: Infantile spasms (IS) are seizures often associated with poor developmental outcome. There is no consensus on the optimal treatment for IS and medication dosing regimens vary. The National Infantile Spasms Consortium (NISC) is a US multicenter initiative to improve IS outcomes through prospective data collection. The aim of this study was to assess response to initial treatments and our ability to standardize treatment regimens across centers. Methods: Thirty five US pediatric epilepsy centers enrolled infants with newly diagnosed IS aged two months to two years. ACTH, oral corticosteroids (OC) and vigabatrin were designated as "first line" initial treatments. Recommendations for dosing regimens for ACTH and OC were provided by NISC to participating centers based on best available evidence and expert consensus. Remission was defined as resolution of IS and absence of hypsarrhythmia at 2 weeks and sustained at 3 months. Results: From June, 2012 to June, 2014, 35 centers enrolled 238 infants. Mean age at IS onset was 7.4 months and mean age at diagnosis was 8.4 months; 54% male. Initial treatment was documented in 230 cases: ACTH 99 (43%); OC 50 (22%); vigabatrin 41 (18%); topiramate 21 (9%); levetiracetam 7 (3%); two each of zonisamide, oxcarbazepine, clobazam, and phenobarbital; one ketogenic diet. Clinicians followed NISC dosing recommendations in 84/99 (85%) of ACTH treated patients and 34/50 (68%) of OC treated patients. Three month outcome data was available for 205 children (87 ACTH, 48 OC, 34 vigabatrin, 36 other non-first line treatments). ACTH led to remission in 42 (48%), 2 additional late responders, and 7 relapses. OC led to remission in 13 (27%), 3 late responders, and 9 relapses. Vigabatrin led to remission in 13 (38%), no late responders, and 1 relapse. Of the children who received other treatments, only 2 (5%) achieved remission. The rate of remission with ACTH occurred significantly more often than with OC (p=0.02) or with non-first line treatments (p<0.001) but not significantly more than with vigabatrin (p=0.32). There was no significant difference in the rate of remission between initial treatment with prednisone compared to vigabatrin (p=0.29) Conclusions: In a large prospective cohort of patients with IS, ACTH is associated with better short term outcomes compared to OC and non-first line treatments but not compared to vigabatrin. While standardization of dosage in our group was higher than previously reported (Mytinger et al. J Child Neurol. 2012; 1289-94), further improving standardization between centers may strengthen our findings. The observational nature of this study may introduce clinician bias in treatment decisions and randomized clinical trials are needed to confirm best treatment practices.