Valproate use associated with frontal and cerebellar gray matter volume reductions: A voxel‐based morphometry study

Abstract

AbstractRecent morphometric magnetic resonance imaging (MRI) studies suggested the possibility that valproate (VPA) use is associated with parieto‐occipital cortical thinning in patients with heterogeneous epilepsy syndromes. In this study, we examined the effect of VPA on the brain volume using a large number of homogenous patients with idiopathic generalized epilepsy. Voxel‐based morphometry was used to compare regional gray matter (GM) volume between 112 patients currently taking VPA (VPA+ group), 81 patients not currently taking VPA (VPA– group), and 120 healthy subjects (control group). The VPA+ group showed a significant GM volume reduction in the bilateral cerebellum, hippocampus, insula, caudate nucleus, medial frontal cortex/anterior cingulate cortex, primary motor/premotor cortex, medial occipital cortex, and anteromedial thalamus, as compared to the control group. The VPA– group showed a significant GM volume reduction in the anteromedial thalamus and right hippocampus/temporal cortex, as compared to the control group. Compared to the VPA– group, the VPA+ group had a significant GM volume reduction in the bilateral cerebellum, primary motor/premotor cortex, and medial frontal cortex/anterior cingulate cortex. We have provided evidence that VPA use could result in GM volume reductions in the frontal cortex and cerebellum. Our findings should be acknowledged as a potential confounding factor in morphometric MRI studies that include subjects taking VPA.