Valproate reduces spontaneous generalized spikes and waves but not photoparoxysmal reactions in patients with idiopathic generalized epilepsies

Purpose: Patients with idiopathic generalized epilepsies (IGEs) often present with interictal spike-wave discharges (SWDs) at rest (spontaneous SWDs), during hyperventilation, and in response to photic stimulation (photoparoxysmal response or PPR). Valproic acid (VPA) is a first-line antiepileptic drug for therapy of patients with IGE. Herein we investigated the effect of VPA on all three types of SWDs in children and adolescents with IGE. Methods: Routine electroencephalography (EEG) during wakefulness, which was recorded before VPA monotherapy and up to four times during the first year of the VPA treatment, was analyzed retrospectively. For the analysis of the VPA effect on spontaneous SWDs and SWDs under hyperventilation, the number and duration of SWDs were counted. SWDs under intermittent photo stimulation (IPS) were classified according to the extent of propagation (grading). Response to VPA treatment (rest/hyperventilation) was defined as a disappearance of SWDs within the year after VPA introduction. Key Findings: Eighty-four patients (37 male and 47 female, mean age 9.5 +/- 4.1 years) exhibited spontaneous SWDs or SWDs under hyperventilation. From this sample, 34 patients exhibited the PPR (7 male and 27 female, mean age 10.1 +/- 3.9 years). A significant reduction in the number and duration of spontaneous SWDs and SWDs under hyperventilation was observed in the first 6 weeks of treatment (p <= 0.001, corrected, 87.3% responders). This effect remained stable over the 1 year observation period. Concerning PPR, only 4 (12.9%) of 31 patients were classified as responders. The difference between groups of patients with spontaneous/induced SWDs and PPR according to the number of responders was significant (p < 0.001). Significance: This study provides evidence that the effect of VPA on SWDs differs dependent on the types of SWDs. In the majority of patients, spontaneous SWDs and SWDs induced by hyperventilation disappeared, whereas the PPR mostly remained under VPA treatment. These results point to different pathogenetic mechanisms underlying the spontaneous and the evoked generalized epileptic activity in the EEG.