Therapy of Infantile Spasms with Valproate: Results of a Prospective Study

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Abstract
In a prospective study, 22 children with recently manifested infantile spasms (18 patients with symptomatic and 4 with idiopathic infantile spasms) were treated with sodium valproate (VPA). Before VPA was instituted, a loading test was performed to exclude abnormal patterns of VPA metabolites by gas chromatography and mass spectroscopy of serum and urine. This test was repeated during VPA therapy; an abnormal pattern of VPA metabolites was not observed. VPA was started in increasing dosage until infantile spasms were controlled or a maximum dose of 100 mg/kg/day was reached. If VPA did not control seizures or at least reduce frequency significantly after a trial of 4-6 weeks, dexamethasone was added to VPA. If focal seizures occurred in association with localized epileptogenic EEG discharges, carbamazepine (CBZ) was added to VPA. After 4 weeks of VPA monotherapy, infantile spasms were controlled in 11 children. After 3 months of therapy, 16 children were free of seizures (14 patients VPA monotherapy), and 4 children had reduction of seizure frequency to < 25%. VPA doses varied between 40 and 100 mg/kg/day (mean 74). The mean plasma concentration was 113 .mu.g/ml (range 46-177). After 6 months of therapy, total seizure control was achieved in 20 of 22 patients (16 children VPA monotherapy). The mean observation time was 16 1/2 months (range 6-36 months). There were seven relapses in six children during the first 7 months of therapy. Assessment of the developmental status of the children after 1 and 2 years of therapy showed no or slight retardation in .apprx. 35%, moderate retardation in .apprx. 40%. The four children with infantile spasms were seizure free within 5 weeks; they showed no relapse, and their development was within normal limits or only slightly retarded. Adverse effects included initial transient symptoms of gastrointestinal distress and/or sedation. A remarkable side effect was muscle hypotonia in nearly all children. Thrombocytopenic purpura occurred in seven children, mostly in association with an upper respiratory tract infection, and disappeared after dose reduction. This study shows that VPA monotherapy in high doses is effective in the treatment of infantile spasms.