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Hippocampal and thalamic atrophy in mild temporal lobe epilepsy

A VBM study

From the Institute of Neurology (A.L., A.G., A.Q.), University Magna Græcia, Catanzaro; Institute of Neurological Sciences (A.L., A.C., A.G., A.Q.), National Research Council, Piano Lago–Mangone, Cosenza; Regional Epilepsy Center (U.A.), Hospital of Reggio Calabria, Reggio Calabria; and Department of Neurosciences, Psychiatry and Anaesthesiology (A.C.), University of Messina, Italy.

Address correspondence and reprint requests to Prof. Antonio Gambardella, Cattedra ed U.O. di Neurologia, Università degli Studi "Magna Graecia," Campus Universitario Germaneto, Viale Europa, 88100 Catanzaro, Italy a.gambardella{at}isn.cnr.it

Background: Patients with temporal lobe epilepsy (TLE) often have mild drug-responsive epilepsy which is frequently associated with MRI detectable mesial temporal sclerosis (MTS), indicating that MTS is not necessarily related to seizure severity. To better define the anatomic substrates associated with TLE, we applied voxel-based morphometry (VBM) analysis to patients with mild TLE.

Methods: Optimized VBM was applied to the MRI brain images of 95 consecutive unrelated patients who were diagnosed with mild TLE and to 37 healthy controls. We complemented the investigation by calculating the gray matter volume of regions of interest (ROIs) in the bilateral hippocampus. Standard MRI scans revealed evidence of MTS (pTLE) in 34 patients, and no evidence of MTS in the remaining 61 (nTLE).

Results: The VBM analysis provided evidence of a reduction in gray matter volume in the hippocampus and thalami. The gray matter volume reduction in the thalamic and hippocampal networks was significantly more severe in patients with pTLE than in the nTLE or the control groups (at a threshold of FWE-corrected p < 0.05). Patients with nTLE showed the same gray matter abnormalities at an uncorrected statistical threshold (p < 0.001) compared to normal controls. ROI analysis confirmed the ipsilateral hippocampal atrophy that was detected in routine MRI scans.

Conclusions: The structural abnormalities seen in patients with mild temporal lobe epilepsy (TLE) demonstrate that a temporo-limbic pathway, which includes the thalamus, plays a major role in the pathogenesis of TLE. It is likely that other factors, especially genetic ones, play a major role in the causation and severity of TLE.

GLOSSARY: ANCOVA = analysis of covariance; ANOVA = analysis of variance; FC = febrile convulsion; FWE = family-wise error; GM = gray matter; Hf = hippocampus; MTLE = mesial TLE; MTS = mesial temporal sclerosis; nTLE = patients with TLE without mesial temporal sclerosis; pTLE = patients with TLE with mesial temporal sclerosis; ROI = region of interest; TIV = total intracranial volume; TLE = temporal lobe epilepsy; VBM = voxel-based morphometry; WM = white matter.

Disclosure: The authors report no disclosures.

Received January 15, 2008. Accepted in final form June 23, 2008.

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