Sodium valproate use is associated with reduced parietal lobe thickness and brain volume

Abstract

Objective: We hypothesized that total brain volume, white matter volume, and lobar cortical thickness would be different in epilepsy patients. We studied valproate relative to nonvalproate by using patients with epilepsy and healthy controls.

Methods: Patients with focal intractable epilepsy from a tertiary epilepsy center were the primary group for analysis. A confirmatory analysis was carried out in an independent group of subjects imaged as part of a community-based study of childhood-onset epilepsy. Total brain volume; white matter volume; and frontal, parietal, occipital, and temporal lobe thickness were measured by processing whole-brain T1-weighted MRI using FreeSurfer 5.1.

Results: Total brain volume, white matter volume, and parietal thickness were reduced in the valproate group relative to controls and nonvalproate users (valproate, n = 9; nonvalproate, n = 27; controls, n = 45; all male). These findings were confirmed in an independent group (valproate, n = 7; nonvalproate, n = 70; controls, n = 20; all male).

Conclusions: Sodium valproate use in epilepsy is associated with parietal lobe thinning, reduced total brain volume, and reduced white matter volume.

Level of evidence: This study provides Class IV evidence that use of valproate in epilepsy is associated with reduced parietal lobe thickness, total brain volume, and white matter volume.

Figure 1. Antiepileptic drug combinations in intractable focal epilepsy

Antiepileptic drug combinations in intractable focal epilepsy cases (group A). Valproate cases are shown in orange, and nonvalproate cases are shown in gray. A line between the 2 drugs indicates the individual was taking the drugs as polytherapy. The “other” category includes nonantiepileptic medications.

Figure 2. Volume and cortical thickness in valproate epilepsy cases, nonvalproate epilepsy cases, and controls

Epilepsy patients taking valproate (+VPA) have reduced brain volume, white matter volume, and parietal lobe cortical thickness relative to epilepsy patients not on valproate (−VPA) and healthy controls. The figure shows brain volume measurements and average lobar thickness in controls, nonvalproate epilepsy cases (−VPA), and valproate-taking epilepsy cases (+VPA). Group A are presurgical focal epilepsy cases from a tertiary epilepsy center; group B are childhood-onset epilepsy cases. The error bars represent standard errors on the mean. Statistically significant differences are marked with an asterisk (**p < 0.001; *p < 0.05; †p < 0.1).

Figure 3. Valproate-related cortical thickness decreases in focal epilepsy

Spatial distribution of cortical thickness decreases in subjects with focal epilepsy taking valproate relative to subjects with epilepsy not taking valproate (group A). The intensity of the color overlay indicates the magnitude of the thickness decrease. Hotter colors indicate reduced cortical thickness in subjects taking valproate.