Breakthrough Seizures in Children Receiving Valproate Therapy

接受丙戊酸盐治疗的儿童出现突破性癫痫发作

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Abstract

Introduction Breakthrough seizures in children diagnosed with epilepsy pose a significant clinical challenge. Though valproate is effective in managing seizures, a subset of patients can still experience breakthrough seizures. It can cause increased morbidity, reduce the quality of life, and increase anxiety among parents. There is insufficient data in the Indian population regarding the cause of breakthrough seizures and their association with serum valproate levels; hence, we carried out this study. Objective Primary Objective To study the clinical profile and drug levels in children presenting with breakthrough seizures while receiving valproate therapy. Secondary Objective To find out the association of the clinical, demographic, and etiological profile of breakthrough seizures with valproate levels. Methods A group of 100 children, 2-12 years old, receiving valproate therapy and presenting to the hospital within 24 hours of a breakthrough seizure were studied. Clinical and demographic profiles were recorded. Valproate levels were estimated using recombinant DNA technology using an autoanalyzer (reference level 50-100 mcg/ml). Phenytoin levels were estimated in 10 children receiving dual therapy (reference level 10-20 mcg/mL). Results The mean age was 81.6±31.9 months (59 M, 41 F). The mean dose of valproate was 24.8±8.4 mg. Syrup formulation was used in 73 and tablets in 27. Non-compliance was observed in 19, and fever was identified as a possible precipitating factor in 18. Compliance was not affected by age, sex, socioeconomic status, education of parents, or type of seizure (p > 0.05). Valproate levels were below the reference range in 44, within the reference range in 47, and above the reference range in 9. There was no statistically significant association between valproate levels (therapeutic or subtherapeutic) and age, sex, socioeconomic status, parental education, seizure type, or the presence of precipitating factors (p > 0.05). Similarly, mean valproate levels were also not affected by these factors. The levels did not vary with drug formulations. Conclusion Breakthrough seizures in children on valproate therapy were not related to valproate levels. Valproate levels were not affected by clinical or demographic profile, drug formulation, change in formulation, compliance, etc.

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