Background: Although many studies have found abnormalities in subcortical grey matter (GM) in patients with temporal lobe epilepsy or generalised epilepsies, few studies have examined subcortical GM in focal neocortical seizures. Using structural and tensor magnetic resonance imaging (MRI), we evaluated subcortical GM from patients with extratemporal lobe epilepsy without visible lesion on MRI. Our aims were to determine whether there are structural abnormalities in these patients and to correlate the extent of any observed structural changes with clinical characteristics of disease in these patients.Methods: Twenty-four people with epilepsy and 29 age-matched normal subjects were imaged with high-resolution structural and diffusion tensor MR scans. The patients were characterised clinically by normal brain MRI scans and seizures that originated in the neocortex and evolved to secondarily generalised convulsions. We first used whole brain voxel-based morphometry (VBM) to detect density changes in subcortical GM. Volumetric data, values of mean diffusivity (MD) and fractional anisotropy (FA) for seven subcortical GM structures (hippocampus, caudate nucleus, putamen, globus pallidus, nucleus accumbens, thalamus and amygdala) were obtained using a model-based segmentation and registration tool. Differences in the volumes and diffusion parameters between patients and controls and correlations with the early onset and progression of epilepsy were estimated.Results: Reduced volumes and altered diffusion parameters of subcortical GM were universally observed in patients in the subcortical regions studied. In the patient-control group comparison of VBM, the right putamen, bilateral nucleus accumbens and right caudate nucleus of epileptic patients exhibited a significantly decreased density Segregated volumetry and diffusion assessment of subcortical GM showed apparent atrophy of the left caudate nucleus, left amygdala and right putamen; reduced FA values for the bilateral nucleus accumbens; and elevated MD values for the left thalamus, right hippocampus and right globus pallidus A decreased volume of the nucleus accumbens consistently related to an early onset of disease. The duration of disease contributed to the shrinkage of the left thalamus.Conclusions: Patients with neocortical seizures and secondary generalisation had smaller volumes and microstructural anomalies in subcortical GM regions. Subcortical GM atrophy is relevant to the early onset and progression of epilepsy.