Abstracts

Rationale: To assess based on etiology the response of infantile spasms and hypsarrhythmia to vigabatrin as first line therapy with an early switch to ACTH in refractory children. This study is part of a larger randomized double blind clinical trial looking at the long-term developmental and epilepsy outcome of infantile spasms with an add-on calcium channel blocker.Methods: We recruited 69 children with new onset infantile spasms over a 2-year period. Children were randomized to conventional treatment with flunarizine or placebo. Conventional treatment consisted of 150 mg/kg vigabatrin and 200 mg vitamin B6. After 2 weeks, responders defined as no spasm and no hypsarrhythmia on a 6-hour video-EEG remained on the same treatment for 6 months. For non-responders ACTH 150 IU/m2 was added with a slow taper over a 12-week course. Additional EEGs were performed at 4 and 24 weeks. Children who failed ACTH after 2 weeks were put on high-dose topiramate.Results: 45 out of 69 children had a favorable outcome on vigabatrin at 2 weeks, for a 65% success rate. 5/5 with tuberous sclerosis, 4/4 children with cortical dysplasia, 2/2 with periventricular leukomalacia, 2/2 with meningoencephalitis, 2/3 with trisomy 21, 2/4 with metabolic disorders, 1/1 with schizencephaly, and 1/1 with shaken baby syndrome responded. For the cryptogenic spasms, 21/28 showed a complete response (75%) at 2 weeks, 2 had persistent hypsarrhythmia at 2 weeks, two had recurrences of spasms on vigabatrin and 5 showed no response. In total, 5 patients had a recurrence of spasms on vigabatrin. More importantly, certain etiologies were more likely to be refractory including 3/3 with neonatal strokes, 5/7 with diffuse atrophy, 4/6 with severe HIE, and 1/1 with NF1. Of the 29 who received ACTH, 23 responded within 2 weeks for a 80% response rate to refractory spasms. This included 3 out of the 5 with severe HIE that failed vigabatrin. The other 4 who failed ACTH included a child with trisomy 21, one with recurrent spasms due to meningoencephalitis, one child with recurrent cryptogenic spasms, and one with atrophy who developed hemispasms on ACTH that responded to topiramate. No responder at the end of the 12-week regimen recurred after. At 6 months, only 4 of 63 patients (6%) had persistent spasms and 12 (19%) had partial epilepsy. In addition to 4 deaths due to the underlying etiology, two patients are excluded from the 6-month analysis because they did not want to continue the add-on treatment as they were seizure free. Adverse events were reported in 12/69 children with vigabatrin. No child required to stop treatment. While 19 out of 29 ACTH patient had adverse events with 3 children having to stop ACTH with no recurrence of spasms. Conclusions: In our population in light of this new prospective data, vigabatrin remains the first choice medication for infantile spasms with the possible exception of children with severe neonatal vascular insults. A two-week delay does not appear to reduce the efficacy of ACTH. Supported by grants from CIHR and CURE