Treatment of infantile spasms with very high dose prednisolone before high dose adrenocorticotropic hormone

Abstract

Purpose: This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms.

Methods: Twenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy.

Key findings: Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response.

Significance: Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.

Keywords: ACTHar; Corticosteroids; Corticotropin; Hypsarrhythmia; West syndrome.

Conflict of interest statement

Disclosure of Conflicts of Interest: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Dr. Hussain has served on the scientific advisory board for and received an honorarium from Questcor Pharmaceuticals, and has received research funding from Lundbeck, inc.

Dr. Shinnar has received personal compensation for consulting for Questcor and serving on a Scientific Advisory Board for Questcor.

Ms. Kwong reports no disclosures.

Dr. Lerner reports no disclosures.

Dr. Matsumoto reports no disclosures.

Dr. Wu has served on the professional advisory board for the Tuberous Sclerosis Alliance; has received honoraria from and has served on the scientific advisory board and speakers' bureau for Novartis Pharmaceutical Inc and Lundbeck; and has received research support from the Tuberous Sclerosis Alliance, Today's and Tomorrow's Children Fund, Novartis Pharmaceuticals Inc, Department of Defense/Congressionally Directed Medical Research Program, and the National Institutes of Health (R01 NS082649, K23 NS051637, P20 NS080199, U01 NS082320, and R34 MH089299).

Dr. Shields has received compensation as a consultant to Questcor, Lundbeck, GlaxoSmithKline, and Catalyst, and has received royalties from Lundbeck.

Dr. Sankar serves on scientific advisory boards for and has received honoraria and funding for travel from UCB Pharma, Sunovion, Upsher-Smith, Supernus, and Lundbeck Pharma; serves on speakers' bureaus for and has received speaker honoraria from UCB, GlaxoSmithKline, Cyberonics and Lundbeck. He receives funding from NIH NINDS NS065783 (coinvestigator), NS045911 (site PI CAE Study), P20 NS080181 (Epilepsy Research Centers without Walls) and from Pfizer (Lyrica pediatric partial seizures trial).

Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Figures

Figure 1

The UCLA Hormonal Therapy Protocol. aAll video-EEG evaluations were inpatient overnight studies. bResponse requires video-EEG confirmation of freedom from both spasms and hypsarrhythmia.