Abstracts

Rationale: Infantile spasms (IS) is an age specific epileptic encephalopathy often seen with hypsarrhythmia and associated with heterogeneous etiology. Spasms resolve, but are frequently followed by poor developmental outcome and epilepsy. ACTH is often used for short-term treatment of IS, however there is insufficient evidence regarding the optimal dosage/duration of treatment. Based on a 2 week response rate of 87% to high-dose (HD) ACTH, many centers have implemented HD-ACTH (150 IU/m2/d, followed by taper) for treatment of IS. Administration of HD-ACTH in once-daily or split, twice-daily dosing in not standardized, although the latter has been suggested by the National Infantile Spasms Consortium. The aim of this study is to report our experience with once-daily HD-ACTH and compare the response rate to ACTH from published literature.Methods: Hospital discharge records were queried from January, 2013 through December, 2014 for infants between 2-12 months with IS, discharged on HD-ACTH as follows: 150units/m2 QD x 14 days, 30units/m2 x 3 days, 15units/m2 x3 days, 10units/m2 x3days, 10units/m2 every other day x3 days. Inclusion criteria: (i) clinical IS with abnormal EEG and (ii) treatment of IS with HD-ACTH. The primary outcome measures were (i) cessation of spasms by day 14 of treatment and resolution of hypsarrhythmia in the follow-up EEG, (ii) relapse as defined as recurrence of clinical IS after complete remission sustained for ≥ 28 days. Response and relapse rates with CI were determined. Adverse events were noted.Results: We found 31 eligible subjects. Median age at onset of IS was 5.5 mo. (IQR: 4.9-7.9). Symptomatic etiology was identified in 22 (71%). Pre-treatment EEG showed hypsarrhythmia/modified hypsarrhythmia 21 (68%) and the reminder with significant EEG abnormality. Seizures before IS were seen in 14 (45.2%). Median time to ACTH was 3.14 weeks (IQR: 1.29-10). Median duration of follow-up was 13.1 mo. (IQR: 9.23-21.7). Day 14 response could not be determined in 1 patient as the patient did not continue ACTH. Day 14 response was noted in 21 patients (70%, CI = 0.531-0.869), all showing resolution of hypsarrhythmia or improvement in the EEG. Time to ACTH treatment for day 14 responders was 2 weeks and 7.7 weeks in non-responders. Of the 21 day 14 responders, 2 recurred with IS between day 14-28. Relapse of clinical IS was noted in 3 patients after they were spasm free between 38-106 days. Overall, spasm freedom without relapse was seen in 16 (53%, CI-0.349-0.718) with a median follow-up 12.5 mo. No patients stopped or changed treatment due to adverse effect. One patient with lissencephaly with severe delay died after completing the course of ACTH from progressive encephalopathy. Family had decided not to intubate or resuscitate.Conclusions: High dose ACTH administered once a day was effective for treatment of IS. Day 14 response, relapse rates, and adverse events were no different from published reports.