Purpose: A prospective randomized controlled study was conducted for the purpose of identifying the lowest effective ACTH dose, with the fewest adverse effects, for the treatment of West syndrome (WS).
Subjects and methods: Twenty-five subjects with cryptogenic (CWS, n = 9) or symptomatic (SWS, n = 16) WS were enrolled in this study. They were randomly assigned to receive either low-dose (0.005 mg/kg per day = 0.2 IU/kg per day) or high-dose (0.025 mg/kg per day = 1 IU/kg per day) synthetic ACTH therapy. ACTH was administered every morning for 2 weeks and tapered to zero over the subsequent 2 weeks. Both effectiveness and adverse effects were compared between the two treatment regimens in each type of WS.
Result: After completion of the treatment protocol in the CWS group, spasms and hypsarrhythmia were completely suppressed in 3/4 (75%) given the low-dose and 5/5 (100%) given the high-dose treatment. In the SWS group, the spasms and hypsarrhythmia disappeared in 6/8 (75%) in each dose group. There were no significant differences in initial responses between the low-dose and high-dose treatments for either type of WS (P > 0.05). Long-term seizure and developmental outcomes, assessed in the 17 responders who were followed up for longer than 1 year after the completion of ACTH therapy, were also essentially the same. We did not recognize differences in side effect profiles between the two treatment regimens with the exceptions of sleepiness and brain shrinkage estimated by CT scan, both of which were significantly milder in the low-dose than in the high-dose group (P < 0.05).
Conclusion: Unexpectedly, this prospective randomized controlled study demonstrated the dose of ACTH required for spasm cessation and disappearance of the hypsarrhythmic EEG pattern to be lower than previously believed. A low-dose regimen should thus be considered for CWS, and for SWS associated with significant cerebral atrophy.