Short-term, low-dose ACTH therapy in West syndrome

Introduction: We investigated the effect of short-term, low-dose adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms.

Patients and methods: 105 previously untreated patients (57 boys and 48 girls) with infantile spasms were enrolled in an open-label, prospective study between 1984 and 2004. Age at onset of spasms ranged from 2–10 months in 95% children, 12–20 months in 4% children and a single patient was four years old. 95% patients showed typical flexor-extensor spasms and 5% suffered atypic seizures. Neuroimaging (CT, MRI) revealed: perinatal asphyxia (61%), other conditions (16%) including focal cortical dysplasia, malformations, brain atrophy, dysmyelinosis, leucomalacia, calcifications. In 23% of cases, the epilepsy was cryptogenic. In 97% cases the EEG characteristically demonstrated hypsarrhythmia. Synthetic ACTH was administered as the first and only anticonvulsive medication intramuscularly for 5 days (10–20 IU/m²). 8 further doses followed initially in 3-day intervals and later on in 5-day intervals over a total of 3–4 weeks.

Results: Complete cessation of spasms in the first 2 weeks was attained in 65% cases, EEG normalization was achieved during the first 3–4 weeks and no relapse occurred up to an observation period of 6–12 years. 22% showed minor improvement and in 13% major side-effects (hypertension, infections) appeared, that led to trial interruption. Cushing syndrome, irritability and mild cerebral shrinkage presented reversible side effects in several cases. 30% of children showed a normal mental development, while 70% presented moderate to severe mental retardation.

Conclusion: This study shows that low-dose short-term ACTH administration is effective in the treatment of infantile spasms and the resolution of hypsarrhythmia. As previously observed in other studies, cryptogenic patients had a better outcome, associated with prompt EEG normalization.