The relationship between dose of ACTH and the initial effect and long-term prognosis was investigated in 41 children with infantile spasms at the Department of Pediatrics, Kyoto University, Kyoto, Japan. ACTH therapy began at 2-13 months of age (mean: 11.8 months) and the average treatment lag was 4.5 months. All patients were treated with Vitamin B6, valproate, and other anticonvulsants without benefit before ACTH therapy was begun. All patients had hypsarrhythmia on the EEG. The cause was acquired in 30 patients, unknown in 8 and associated with developmental delay, and idiopathic in 3 patients whose development was normal. The doses in 16 patients was 0.5 mg (20 IU) for those older than one year of age and 0.25 mg (10 IU) for those less than one year; daily injections were given for two weeks, every other day for two weeks, and twice weekly for a total of 30 injections. One-half of these doses were used in 14 patients and doses were calculated on the basis of body weight (0.01-0.015 mg) (0.4-0.6 IU)/kg in 11 patients. More than 0.015 mg (0.6 IU)/kg/day of ACTH was needed for a good initial response of seizures and EEG abnormalities. Doses lower than 0.015 mg/kg/day provided less seizure control at the end of treatment and less EEG improvement. ACTH in a dose of 1.6-2.4 IU/kg/ day and a total dose of 44-60 IU/kg resulted in better mental development than smaller doses, but side effects increased with larger daily doses or larger total doses. Seizures were controlled in 71-89% with doses above 0.6 IU/kg/day. ACTH-induced cerebral atrophy increased with the total dose of ACTH but was not seen when daily doses were 2.4 IU/kg/day or less and total dose was 60 IU/kg. [1]

COMMENT. The authors recommend that ACTH doses based on body weight or body surface area should be used in future studies to compare the results obtained at different institutions. The doses used in this study from Japan were relatively small and ranged from 7.3-47.6 IU/m2/day whereas those recommended in some recent publications have been much higher and usually 150 U/m2/day. Snead OC [2] advocated 150 U/m2/day for one week, 75 U/m2/day in the second week, and 75 U/m2 on alternate days for the third week. Bobele GB, Bodensteiner JB from the University of Oklahoma and Morgantown, West Virginia University, (Neurologic Clinics August 1990, W. B. Saunders, Philadelphia) recommend 150 U/m2/day for a total of 6-8 weeks and the same dosage on alternate days for a further 6-8 weeks followed by tapering for a total treatment period of 4-6 months. These larger doses are associated with an increased frequency of serious side effects from ACTH. My own preference has favored the more conservative treatment with smaller doses and the experience in Japan tends to support the recommendation of doses of 1-2 IU/kg/day and a total ACTH dose of approximately 50 IU/kg.