Follow‐Up Study of Children with a History of a Febrile Convulsion.

Although adrenocorticotropic hormone (ACTH) has long been the therapy of choice in infantile spasms, frequent side effects occur during ACTH therapy. In addition, previous studies have shown a disappointing outcome in mental development in patients with symptomatic infantile spasms treated with ACTH. Therefore an improved treatment is required. We report the results of a new treatment for infantile spasms. Twenty-one patients (14 boys and seven girls, aged 4-31 months; mean, 9.8 months) who had symptomatic infantile spasms between November 1986 and October 1992 were enrolled in this study. The etiologic factors were perinatal asphyxia in four, neonatal intracranial hemorrhage in three, brain atrophy in three, brain infarction in one, purulent meningitis in one, encephalomeningocele in one, ectopic gray matter in one, phacomatosis in one, and unknown in six (patients with developmental delay before onset and no significant history). Initially, all of the patients were administered pyridoxal phosphate orally at a dosage of 20-30 mglkglday followed by an increase to 40-50 mglkglday. When seizures did not disappear completely, ACTH (zinc hydroxide suspension of tetracosactide) was then combined with pyridoxal phosphate. ACTH was administered at a dosage of 0.01 mglkg (0.4 IUIkg of natural ACTH) in daily injections for the first 2 weeks. The frequency of the injections was then gradually reduced over a 3to 6-week period. An excellent response was defined as total cessation of seizures at 1 month after discontinuation of ACTH. Pyridoxal phosphate therapy was continued as long as a good, sustained effect with the first course of ACTH was seen. If the infantile spasms recurred or the EEG returned to a hypsarrhythmic pattern (or both), a short course of ACTH therapy (0.01 mg/kg/day for 1 week) was added to the treatment regimen. If other antiepileptic drugs (AEDs) were required because of poor control or the occurrence of other types of seizures, follow-up was ended, and the final evaluation of developmental outcome was performed. Pyridoxal phosphate alone produced excellent seizure control in two of the 21 patients. ACTH was added to the regimen in 19 patients, excluding the two patients who had an excellent response to pyridoxal phosphate alone. At 1 month after discontinuation of ACTH, 15 (79%) of the 19 patients had excellent seizure responses. The mean interval until achievement of seizure control was 4.4 days. Outcomes have been monitored in 15 patients, excluding the two responders to pyridoxal phosphate alone and the four nonresponders to combination therapy. The mean follow-up time was 32.7 months (range, 2-104 months). Infantile spasms relapsed after a seizure-free period in six (40%) of the 15 patients. Normal development was observed in five (33%) of the 15 patients. Combination therapy seemed to provide a better outcome in mental development than has been observed in previous studies, in which development was normal in only 5-7% of patients with symptomatic infantile spasms. Moreover, our combination therapy stopped the spasms more rapidly than did other ACTH regimens. In view of these findings, vitamin B, may have played an important role in controlling seizures by as yet to be clarified mechanisms. In addition, it has been shown that ACTH itself may have an adverse effect on the developing brain. Thus it is reasonable to recommend that the dose of ACTH be minimized to avoid potential risk to the developing brain. At present, in view of its therapeutic efficacy and low total ACTH dose, combination therapy with high-dose pyridoxal phosphate and low-dose ACTH should be regarded as the best available method of treating infantile spasms.