Epilepsia, 46(3):420–430, 2005 Blackwell Publishing, Inc. C  2005 International League Against Epilepsy Ipsilateral and Contralateral MRI Volumetric Abnormalities in Chronic Unilateral Temporal Lobe Epilepsy and their Clinical Correlates ∗ Michael Seidenberg, ∗ Kiesa Getz Kelly, ∗ Joy Parrish, ∗ Elizabeth Geary, ∗ Christian Dow, †Paul Rutecki, and †Bruce Hermann ∗ Rosalind Franklin University of Medicine and Science, North Chicago, Illinois; and †University of Wisconsin, Madison, Wisconsin, U.S.A. Summary: Purpose: To assess the presence, extent, and clin- ical correlates of quantitative MR volumetric abnormalities in ipsilateral and contralateral hippocampus, and temporal and ex- tratemporal lobe regions in unilateral temporal lobe epilepsy (TLE). Methods: In total, 34 subjects with unilateral left (n = 15) or right (n = 19) TLE were compared with 65 healthy controls. Regions of interest included the ipsilateral and contralateral hip- pocampus as well as temporal, frontal, parietal, and occipital lobe gray and white matter. Clinical markers of neurodevelopmental insult (initial precipitating insult, early age of recurrent seizures) and chronicity of epilepsy (epilepsy duration, estimated number of lifetime generalized seizures) were related to magnetic reso- nance (MR) volume abnormalities. Results: Quantitative MR abnormalities extend beyond the ipsilateral hippocampus and temporal lobe with extratemporal (frontal and parietal lobe) reductions in cerebral white matter, especially ipsilateral but also contralateral to the side of seizure onset. Volumetric abnormalities in ipsilateral hippocampus and bilateral cerebral white matter are associated with factors related to both the onset and the chronicity of the patients’ epilepsy. Conclusions: These cross-sectional findings support the view that volumetric abnormalities in chronic TLE are associated with a combination of neurodevelopmental and progressive ef- fects, characterized by a prominent disruption in ipsilateral hip- pocampus and neural connectivity (i.e., white matter volume loss) that extends beyond the temporal lobe, affecting both ip- silateral and contralateral hemispheres. Key Words: Temporal lobe epilepsy—Quantitative MRI. Quantitative volumetric magnetic resonance imaging (MRI) studies in temporal lobe epilepsy (TLE) have fo- cused on the hippocampus because of its role in the initia- tion and propagation of seizures and the degree of seizure relief obtained after its resection. Volumetric abnormali- ties have been identified consistently in the hippocampus ipsilateral to side of seizure onset (1–4), with reduced hip- pocampal volumes highly correlated with histopathologic findings of hippocampal sclerosis and favorable surgical outcomes (4,5). It is now appreciated that MR volumetric abnormalities may extend beyond the hippocampus to ad- jacent structures including the amygdala (6,7), fornix (8), entorhinal cortex and parahippocampal region (6,9,10), thalamus (11,12), basal ganglia (13), more distal tempo- ral lobe regions such as the temporal pole (14,15), and distant structures such as the cerebellum (16–18). Accepted October 31, 2004. Address correspondence and reprint requests to Dr. M. Seidenberg at Department of Psychology, Rosalind Franklin University, 3333 Green Bay Road, North Chicago, Illinois 60064, U.S.A. E-mail: Michael.Seidenberg@rosalindfranklin.edu Of interest are a small number of reports suggesting the presence of generalized and diffuse cortical volume reductions in TLE (19,20). However, few of these studies have examined segmented (gray and white matter) vol- umes throughout the lobar regions of the cortex to char- acterize the nature of this broader impact. Marsh et al. (21) reported bilateral frontoparietal gray and white mat- ter volume loss in a small sample of 14 male TLE pa- tients compared with controls. Lee et al. (19) reported re- duced whole brain volume in 27 patients with TLE, but did not examine volumes of gray and white matter. Sisodiya et al. (22) described widespread occult structural abnor- malities occurring in visually normal-appearing MRIs in 27 patients with hippocampal sclerosis. Theodore et al. (23) reported that patients with localization-related epilepsy and temporal lobe onset with a history of complex febrile convulsions had significantly reduced total cerebral volume compared with that in patients without such a his- tory. Our own prior investigation (24) reported whole brain volumetric abnormalities in TLE, most evident in cerebral white matter, but a very limited number of ictal-monitored 420