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Treatment of intractable childhood epilepsy with high-dose valproate
Y Ohtsuka1, R Amano, M Mizukawa
1Department of Child Neurology, Okayama University Medical School, Japan.
Insights
High-dose valproate (VPA) therapy effectively controlled seizures in children with refractory epilepsy, particularly West syndrome. While side effects like hypofibrinogenemia occurred, they were reversible.
Area of Science:
- Pediatric Neurology
- Epileptology
Background:
- Refractory epilepsy in children presents significant treatment challenges.
- Valproate (VPA) is a commonly used antiepileptic drug.
Purpose of the Study:
- To evaluate the efficacy and safety of high-dose valproate (VPA) therapy in pediatric refractory epilepsy.
- To assess VPA's impact on seizure control and EEG findings.
Main Methods:
- Forty-six children with refractory epilepsy received high-dose VPA (serum levels >100 µg/mL).
- Treatment involved monotherapy or dual-drug therapy.
- Seizure control and EEG changes were monitored.
Main Results:
- Initial seizure control was achieved in 32.6% and improvement in 26.1% of patients.
- Long-term follow-up showed sustained control in 30.4% and improvement in 23.9%.
- High-dose VPA was particularly effective for West syndrome and epilepsy with continuous spike-waves during slow-wave sleep.
Conclusions:
- High-dose valproate therapy is an effective treatment option for refractory epilepsy in children.
- VPA demonstrated notable efficacy in specific epilepsy syndromes like West syndrome.
- Reversible side effects such as hypofibrinogenemia and thrombocytopenia were observed.
Abstract:
Forty-six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high-dose (serum level above 100 micrograms/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 micrograms/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow-up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow-up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High-dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike-waves during slow-wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.