Generalized tonic-clonic seizures (GTCS) comprise a common subsyndrome of idiopathic generalized epilepsy (IGE). Previous studies found that patients with GTCS had structural abnormalities in a few specific brain regions. However, the underlying clinical cause leading to these abnormalities remains unclear. The present study aimed to explore the relationship between changes in gray-matter (GM) volume and duration of epilepsy, based on GM volume differences observed between GTCS patients and healthy controls.

Voxel-based morphometry (VBM) analysis with DARTEL (diffeomorphic anatomical registration through exponential Lie algebra) was used to investigate GM volume differences in 31 GTCS patients compared with 37 age- and gender-matched healthy controls. Voxel-based correlation analysis was used to explore the relationship between GM volume and duration of epilepsy in GTCS patients.

Compared with healthy controls, GTCS patients showed significant decreases in GM volume in the bilateral thalami, frontal lobe, insula and cerebellum. In addition, GM volume in the bilateral thalami and left medial frontal gyrus had a negative correlation with duration of epilepsy.

GM volume changes in the thalamus and frontal lobe were associated with progressive epileptic seizures. The results indicate the presence of an abnormal thalamocortical network, which may reflect an underlying pathophysiological mechanism of GTCS.