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

Abstract

Recent morphometric 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 grey 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). VPA+ group showed a significant GM volume reduction in 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 control group. VPA– group showed a significant GM volume reduction in anteromedial thalamus and right hippocampus/temporal cortex, as compared to control group. Compared to VPA– group, VPA+ group had a significant GM volume reduction in 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.

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