Dynamics of Epileptiform Activity and the Efficacy and Tolerance of Valproic Acid Formulations in Adolescents and Adults with Newly Diagnosed Epilepsy

Abstract

Objectives. To assess the dynamics of the index of epileptiform activity (IEA) as indicator of the efficacy and tolerance of treatment with valproic acid formulations in patients with new diagnoses of generalized and focal epilepsy. Materials and Methods. The study included 93 patients (53 men, 38 women) with focal (n = 27) and idiopathic generalized (n = 66) epilepsy. Patients with idiopathic and age-dependent focal epilepsy were not included in the study. Video EEG monitoring was run at each visit and diffuse and generalized epileptiform activity in waking to sleep, during sleep, after sleep, and during fragmentary waking was evaluated, with assessment of the quantitative IEA, at the beginning of treatment and at 1, 3, 6, and 12 months. Therapeutic drug monitoring was run by titrating drug at one month of treatment or at treatment adjustment. Treatment efficacy was assessed in terms of the absence of seizures and decreases in seizure frequency by more than 50% (responders) and less than 50% (inadequate effect). Adverse events were evaluated on the SIDAED scale. Results. The highest IEA values were seen in both subgroups of patients – with focal and idiopathic generalized epilepsy – before valproic acid treatment initiation. Total IEA in patients with idiopathic generalized epilepsy (52.8 ± 7.8) was significantly greater, while during waking to sleep (3.4 ± 0.8) and during sleep (4.3 ± 0.8) IEA was significantly lower than in patients with focal epilepsy, where the index was 27.1 ± 5.5 (p = 0.027) and 10.5 ± 5.5 (p = 0.003), 8.9 ± 3.7 (p = 0.046), respectively. Valproic acid displayed high efficacy and good tolerance in the treatment of idiopathic generalized and focal epilepsy: by the end of 12 months of observations, remission was obtained in 69 patients (74.2%) and decreases in seizures by more than 50% were seen in 22 patients (23.7%); inadequate effects were obtained in only two subjects (2.1%). Adverse events were recorded in a few cases. Conclusions. Valproic acid remains one of the drugs of choice for the treatment of idiopathic generalized and focal epilepsy. IEA may provide an additional objective criterion in difficult cases to discriminate idiopathic generalized from focal epilepsy in terms of total IEA, IEA before sleep, IEA during sleep, and IEA during fragmentary waking in the first months of treatment (1–3 months), objectively reflecting the dynamics of valproic acid treatment efficacy,