Abstracts

Rationale: The relative efficacy of hormonal therapies in the treatment of infantile spasms (IS) is unclear. Although high-dose ACTH (150 IU/m2/day x 2 weeks) is more effective than traditionally high-dose prednisone (2 mg/kg/day), very high-dose prednisolone (PRED) (4-8 mg/kg/day) may yield similar response rates as compared to high-dose ACTH. This study was conducted to evaluate the short-term efficacy of PRED to achieve clinical and electroencephalographic resolution of IS, and to avoid the use of ACTH and its requisite delay in therapy initiation (1-2 days), pain (intramuscular injections), and cost. Methods: A standardized treatment protocol for IS was instituted based on previously reported efficacy and side effect profile. 22 subjects with video-EEG confirmed IS whose treatment conformed to the protocol were retrospectively identified. Very high dose PRED (8 mg/kg/day divided TID, with a max dose of 60 mg/day) was the initial therapy. After 2 weeks, all patients with cessation of spasms were admitted for video-EEG to confirm a complete response (absence of both spasms and hypsarrhythmia). Subjects with a complete response were tapered off PRED over 2 weeks. All subjects with incomplete response were immediately transitioned to high dose ACTH (150 IU/m2/day divided BID) and PRED was discontinued without tapering. Response was again evaluated by video-EEG two weeks after ACTH initiation. Results: Mean age of IS onset was 9.4 months (SD 7.5), and mean age at PRED initiation was 15.3 months (SD 11.6). Etiology of IS was cryptogenic (n=3) or symptomatic (identified cause, n=13; unidentified cause, n=6). Only 3 patients were completely treatment-naive and patients failed a mean of 1.8 medications prior to PRED treatment. Only 2 patients exhibited normal development prior to onset of IS. 50% (11/22) of patients had a complete response to PRED. Of the remaining 11 patients, 4 exhibited a partial response to PRED (continued spasms but resolution of hypsarrhythmia). 2 weeks after transition to ACTH, 36% (4/11) of these patients completely responded. After 4 weeks, a cumulative 68% (15/22) of patients completely responded to therapy. One PRED-responder and one ACTH-responder were lost to follow-up after protocol completion. Among the 20 subjects with follow-up (mean 21 months), 27% (4/15) of responders exhibited a relapse of IS between 2 and 9 months after initial response. For the patients with known developmental outcome at age 2 years (n=13) and 4 years (n=6), all exhibited at least mild developmental delay. Although hypertension was common, there were no adverse events during treatment that required discontinuation of PRED or ACTH. Conclusions: Among this cohort of infants with IS who were relatively old, and for whom hormonal therapy was generally delayed, very high dose oral PRED appears to be an effective alternative to intramuscular ACTH. Still, A randomized trial comparing high-dose ACTH (150 IU/m2/day) to very high-dose PRED (4-8 mg/kg/day) is required to determine the best hormonal therapy for IS. In the absence of a definitive trial, the treatment protocol presented here is a reasonable option.