Epilepsia, 46(10):1642–1645, 2005 Blackwell Publishing, Inc. C  2005 International League Against Epilepsy Subcortical Nuclei Volumetry in Idiopathic Generalized Epilepsy ∗ Margitta Seeck, ∗ Sylvain Dreifuss, †Goran Lantz, †Pierre Jallon, ‡Giovanni Foletti, §Paul-Andre Despland, ‖Jacqueline Delavelle, and ‖Francois Lazeyras ∗ Presurgical Epilepsy Evaluation Unit, “Functional Neurology and Neurosurgery” Program of the University Hospitals Lausanne and Geneva, †Department of Neurology, University Hospital of Geneva (HUG), ‡Insitution de Lavigny, §Department of Neurology, University Hospital of Lausanne (CHUV), and ‖Department of Radiology, HUG; Switzerland Summary: Purpose: The exact anatomic and neurophysio- logic correlates of idiopathic generalized epilepsy (IGE) in hu- mans are still not well understood, although the thalamus has frequently been invoked as the crucial structure in the genera- tion of primary generalized seizures. The few in vivo magnetic resonance (MR)-based studies in IGE patients suggest an al- tered cortical/subcortical gray matter ratio, but with no evidence of structural alterations of the thalamus. In this study, we sought to determine the volumes of the other subcortical structures. Methods: The volumes of the caudate nucleus, putamen, pal- lidum as well as the thalamus were each determined in both hemispheres in 11 patients with various IGE syndromes, nor- malized for whole-brain volumes and then compared with 15 age-matched controls. Results: No differences were noted in thalamic volumes, con- firming previous reports. However, smaller subcortical volumes were noted in the IGE patients (p < 0.009), mainly due to smaller putamen bilaterally (p ≤ 0.015). Conclusions: It is speculated that the presence of discrete frontal dysfunction, as noted in neuropsychological studies in IGE patients, indirectly supports our results because the putamen projects predominantly to the frontal cortex. Larger studies with more homogeneous patient populations are needed to determine the robustness of these findings and whether they are specific for particular IGE syndromes. Key Words: MRI—Idiopathic gen- eralized epilepsy—Volumetry—Human—Caudate nucleus— Thalamus—Pallidum—Putamen—Striatum—Basal ganglia. The significant role of subcortical structures in seizure generation and propagation in idiopathic generalized epilepsy (IGE) has been suspected on the basis of a number of human and animal studies (1). Depth electrode studies in epilepsy patients revealed active participation of the striatum and thalamus in seizure spread, even though no evidence was found for an independent subcortical focus (2). Thalamic dysfunction has been suggested by some positron emission tomography (PET) studies in patients with various IGE syndromes showing increased activity in these structures (3), although other PET studies did not find evidence of subcortical abnormalities (4). Neuronal dysfunction in the thalamus also has been indicated by MR spectroscopy (5). However, not only the thalamus, but also other subcor- tical structures seemed to be implicated in seizure propa- gation or even control. In support, electrical stimulation of the caudate nucleus has been found to decrease epileptic Accepted May 23, 2005. Address correspondence and reprint requests to Dr. M. Seeck at Laboratory of Presurgical Epilepsy, Department of Neurology, 24 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: margitta.seeck@hcuge.ch discharges in animals and humans (6). Only one MRI- based volumetric study of subcortical structures, which was limited to the thalamus, in a heterogeneous group of patients with IGE, found no difference versus normal con- trols (7). This finding contrasts with another MRI-based study in patients with IGE, in which subcortical structures (without further differentiation) appeared to be smaller in IGE patients as compared with healthy controls (8). We were interested to determine whether specific subcortical structures other than the thalamus, such as the caudate nu- cleus, pallidum, and putamen, showed abnormal volumes in this patient group compared with nonepileptic controls. METHODS Subjects The volumes of the caudate nucleus, putamen, pal- lidum, and thalamus were determined in both hemispheres of 11 subjects with various IGE syndromes (Table 1). Fif- teen age-matched healthy volunteers served as controls. All patients were seizure free (one patient was lost to follow-up), except one who experienced rare seizures be- cause of poor drug compliance. All but two received drug 1642