Sodium valproate is associated with cortical thinning of disease-specific areas in juvenile myoclonic epilepsy.

Background: Juvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME.

Methods: In this cross-sectional study, individuals with JME with and without valproate, with temporal lobe epilepsy (TLE) with valproate and controls were selected through propensity score matching. Participants underwent T1-weighted brain imaging and vertex-wise calculation of cortical thickness.

Results: We matched 36 individuals with JME on valproate with 36 individuals with JME without valproate, 36 controls and 19 individuals with TLE on valproate. JME on valproate showed thinning of the precentral gyri (left and right, p<0.001) compared with controls and thinning of the left precentral gyrus when compared with JME not on valproate (p<0.01) or to TLE on valproate (p<0.001). Valproate dose correlated negatively with the thickness of the precentral gyri, postcentral gyri and superior frontal gyrus in JME (left and right p<0.0001), but not in TLE.

Conclusions: Valproate was associated with JME-specific and dose-dependent thinning of the cortical motor regions. This suggests that valproate is a key modulator of cortical morphology in JME, an effect that may underlie its high efficacy in this syndrome.