Abstracts

Rationale: Natural adrenocorticotropic hormone (ACTH) is the most commonly used treatment for infantile spasms (IS) in the United States. The 2004 AAN and CNS practice parameter could not recommend an ACTH dose or duration for IS due to lack of evidence (Neurology 2004;62(10):1668-81). In a single study using a high-dose, 4-week ACTH protocol, all 13 responders achieved clinical remission within 7 days with electrographic remission confirmed >2 weeks after starting ACTH (Pediatrics 1996;97(3):375-9). Studies using longer ACTH protocols have not evaluated the precise timing to remission. Knowledge regarding the typical timing of remission could help to inform decisions about earlier changes in treatment when ACTH is deemed ineffective. Shorter treatment courses may minimize the side effects of ACTH. We hypothesized that successful treatment with ACTH is determined within 2 weeks of initiation. The purpose of this study is to help elucidate the optimal ACTH treatment duration by determining the time to clinical remission among ACTH responders.Methods: We conducted a retrospective chart review of all IS patients managed at our institution from January, 2009 to June, 2013. Subjects were identified using an EEG database (search terms: hypsarrhythmia and infantile spasms ) and hospital discharge codes (345.60, 345.61). Patients who did not receive ACTH were excluded. Two high-dose ACTH protocols were used during our study period. Prior to September, 2012 a long course (typically 12-weeks) was used and after this date the protocol was modified to a short course (typically 4-weeks). We defined ACTH response as remission of clinical IS sustained for 28 days. For ACTH responders, the diagnostic and post-ACTH EEG tracings were reviewed for improvement to determine electroclinical remission (EEG tracing available for review in 19/22 responders). The Mann-Whitney U, Pearson chi-square and Fischer exact tests were used to compare continuous and categorical variables between the long and short course groups.Results: Of 85 IS patients identified, 40 were treated with ACTH. A single patient was excluded from analysis because the response to ACTH could not be determined. Of the remaining 39 patients, 22 responded to ACTH. The mean time to clinical remission was 5.7 days (median 5 days, range 1-20 days). The patient with clinical remission at 20 days did so only after a second course of high dose (150 U/m2/day) ACTH was started 19 days into treatment. If this patient is removed, the mean time to remission becomes 5 days (median 5 days, range 1-12 days). There were no differences between remission rates (p=0.14), days to remission (p=0.08), post-ACTH EEG grade (p=0.33) or the rates of relapse (3 in the long course group, 1 in the short course group, p=0.61) between protocols.Conclusions: This study provides Class IV evidence that among IS patients the response to ACTH is determined early in the treatment course. Clinicians should consider an alternative treatment if clinical remission does not occur within 2 weeks of starting ACTH. Large prospective studies are needed to determine the optimal duration of ACTH for IS.