Localized shape abnormalities in the thalamus and pallidum are associated with secondarily generalized seizures in...

Mesial temporal lobe epilepsy (mTLE) is a common type of drug-resistant epilepsy and secondarily generalized tonic-clonic seizures (sGTCS) have devastating consequences for patients' safety and quality of life. To probe the mechanism underlying the genesis of sGTCS, we investigated the structural differences between patients with and without sGTCS in a cohort of mTLE with radiologically defined unilateral hippocampal sclerosis. We performed voxel-based morphometric analysis of cortex and vertex-wise shape analysis of subcortical structures (the basal ganglia and thalamus) on MRI of 39 patients (21 with and 18 without sGTCS). Comparisons were initially made between sGTCS and non-sGTCS groups, and subsequently made between uncontrolled-sGTCS and controlled-sGTCS subgroups. Regional atrophy of the ipsilateral ventral pallidum (cluster size=450 voxels, corrected p=0.047, Max voxel coordinate=107, 120, 65), medial thalamus (cluster size=1128 voxels, corrected p=0.049, Max voxel coordinate=107, 93, 67), middle frontal gyrus (cluster size=60 voxels, corrected p<0.05, Max voxel coordinate=-30, 49.5, 6), and contralateral posterior cingulate cortex (cluster size=130 voxels, corrected p<0.05, Max voxel coordinate=16.5, -57, 27) was found in the sGTCS group relative to the non-sGTCS group. Furthermore, the uncontrolled-sGTCS subgroup showed more pronounced atrophy of the ipsilateral medial thalamus (cluster size=1240 voxels, corrected p=0.014, Max voxel coordinate=107, 93, 67) than the controlled-sGTCS subgroup. These findings indicate a central role of thalamus and pallidum in the pathophysiology of sGTCS in mTLE.