# Association of valproate use and hippocampal atrophy in idiopathic generalized epilepsy

## TL;DR

This study found that valproate use is linked to reduced hippocampal volume in patients with idiopathic generalized epilepsy.

## Contribution

The study identifies valproate's association with hippocampal atrophy in IGE using HippUnfold segmentation.

## Key findings

- Bilateral hippocampal volumes were reduced in IGE compared to healthy controls.
- Valproate use was associated with significant hippocampal volume reductions in IGE patients.
- Right hippocampus and subfield reductions were observed in generalized tonic–clonic seizures alone.

## Abstract

•HippUnfold was applied to segment hippocampus.•The volumes of bilateral hippocampi were reduced in idiopathic generalized epilepsy compared with healthy controls.•Subgroup analysis showed significant volume reductions in right hippocampus and its subfields in generalized tonic–clonic seizures alone.•Valproate use was associated with hippocampal atrophy in IGE patients.

HippUnfold was applied to segment hippocampus.

The volumes of bilateral hippocampi were reduced in idiopathic generalized epilepsy compared with healthy controls.

Subgroup analysis showed significant volume reductions in right hippocampus and its subfields in generalized tonic–clonic seizures alone.

Valproate use was associated with hippocampal atrophy in IGE patients.

Recent studies revealed the effect of valproate (VPA) on brain structural changes in idiopathic generalized epilepsy (IGE). We aimed to investigate the volume of the entire hippocampus and subfields in patients with IGE, and explored their associations with VPA use.

A total of 211 patients with IGE and 97 healthy controls (HCs) were enrolled in this study. All participants underwent T1-weighted images. Each hippocampus was segmented into seven subfields using HippUnfold. The volumes of bilateral hippocampi and each hippocampal subfield were evaluated. Spearman correlation analyses were performed to identify VPA use related abnormalities in IGE. Subgroup analyses for juvenile myoclonic epilepsy (JME), epilepsy with generalized tonic–clonic seizures alone (GTCA), and absence epilepsy (AE) were conducted.

The volumes of bilateral hippocampi were reduced in IGE compared with HCs. Subgroup analysis showed significant volume reductions in right hippocampus and its subfields in GTCA. Additionally, significant volume reductions were detected in bilateral hippocampal volumes and subfields in IGE patients currently taking VPA compared with HCs. A negative correlation was observed between the left CA2 volume and the age of onset.

Our study revealed volume reductions in bilateral hippocampi in IGE, as well as in the right hippocampus and its subfields in GTCA. Abnormalities in both subfields and the whole hippocampus were associated with VPA use. These findings suggest that VPA may have more extensive neuroanatomical effects in IGE, potentially accounting for the heterogeneity observed in neuroimaging studies.