• Saud Alhusaini, Colin P Doherty, Cathy Scanlon, Lisa Ronan, Sinead Maguire, Gabor Borgulya, Paul Brennan, Norman Delanty, Mary Fitzsimons, and Gianpiero L Cavalleri.
• Department of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin 2, Ireland.
• Epilepsy Res. 2012 Mar 1;99(1-2):156-66.

PurposeApplying a cross-sectional design, we set out to further characterize the significance of extrahippocampal brain atrophy in a large sample of 'sporadic' mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). By evaluating the influence of epilepsy chronicity on structural atrophy, this work represents an important step towards the characterization of MRI-based volumetric measurements as genetic endophenotypes for this condition.MethodsUsing an automated brain segmentation technique, MRI-based volume measurements of several brain regions were compared between 75 patients with 'sporadic' MTLE+HS and 50 healthy controls. Applying linear regression models, we examined the relationship between structural atrophy and important clinical features of MTLE+HS, including disease duration, lifetime number of partial and generalized seizures, and history of initial precipitating insults (IPIs).ResultsSignificant volume loss was detected in ipsilateral hippocampus, amygdala, thalamus, and cerebral white matter (WM). In addition, contralateral hippocampal and bilateral cerebellar grey matter (GM) volume loss was observed in left MTLE+HS patients. Hippocampal, amygdalar, and cerebral WM volume loss correlated with duration of epilepsy. This correlation was stronger in patients with prior IPIs history. Further, cerebral WM, cerebellar GM, and contralateral hippocampal volume loss correlated with lifetime number of generalized seizures.ConclusionOur findings confirm that multiple brain regions beyond the hippocampus are involved in the pathogenesis of MTLE+HS. IPIs are an important factor influencing the rate of regional atrophy but our results also support a role for processes related to epilepsy chronicity. The consequence of epilepsy chronicity on candidate brain regions has important implications on their application as genetic endophenotypes.Copyright © 2011 Elsevier B.V. All rights reserved.

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