Valproate decreases EEG synchronization in a use-dependent manner in idiopathic generalized epilepsy

Abstract

In order to explore the mechanism of action of valproate (VPA) in idiopathic generalized epilepsy (IGE), the effect of VPA on cortical EEG activity was investigated. VPA decreases EEG synchronization in the delta and theta frequency bands in a use-dependent manner in IGE patients. First setting: EEG records of 17 untreated IGE patients (NAE group) were analyzed and compared to those of 15 healthy controls (NC group). Second setting: EEG recorded in the untreated condition (NAE) was compared to the EEG recorded in the treated condition (VPA) of the patient group. Technique and analysis: 2 min of eyes-closed, waking EEG background activity (without epileptiform potentials and artifacts) were analyzed. Absolute power (AP) and mean frequency (MF) were computed for 19 electrodes and four frequency bands (delta=1.5-3.5 Hz, theta=3.5-7.5 Hz, alpha=7.5-12.5 Hz, beta=12.5-25.0 Hz). Log-transformed data entered further analysis. Group differences were computed by means of parametric statistics including correction for multiple comparisons. The VPA-related changes (APvpa-APnae) were correlated with the degree of the baseline abnormality (APnae) and the daily dose/serum levels of VPA. Statistically significant (p<0.05, corrected) changes in the first setting: diffuse delta, theta, alpha AP increase, mainly right hemispheric beta AP increase was found in the NAE group, as compared to the NC group. Second setting: VPA decreased delta and theta AP. Strong correlation was demonstrated between the degree of the initial AP abnormality and the VPA-related AP decrease. AP decrease did not correlate with the daily dose and the serum level of the drug. The hypothesis that VPA decreased EEG synchronization in the delta and theta frequency bands in a use-dependent manner was supported. The findings contribute to the understanding of the action of VPA at the network level.