Abstracts

Rationale: Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reduction in patients with temporal lobe epilepsy (TLE). Methods: We used radial atrophy mapping (RAM) to measure hippocampal atrophy in 40 patients with unilateral TLE, established by ictal video-electroencephalographic monitoring, with or without a history of febrile seizures and depression. Thirty-eight subjects had 1.5-Tesla (T) GE Medical Systems, Milwaukee, WI, U.S.A.), and two had 3.0 T (Phillips Achieva, Netherlands) 3D spoiled gradient recalled MRI scans. All images were loaded onto a linux-based system and visualized using MEDx (Medical Numerics, Germantown, MD, USA). We resliced images into the axial plane and used non-parametric non-uniform intensity normalization to correct for artifactual differences in intensity inhomogeneity. Images were normalized by linear (12 parameter) transformation to a default MNI template with Statistical Parametric Mapping (SPM2) software (www.fil.ion.ucl.ac.uk/spm) and resliced into 1 mm x 1 mm x 1 mm voxels. RAM calculates the radial distance (the 3D distance from a medial curve through the centroid of the hippocampus to the surface) at uniformly spaced points. These distance maps are averaged across groups and visualized on a hippocampal surface map. Multiple linear regression was used to single out the effects of covariates on local atrophy. The study was approved by the NINDS/NIDCD Institutional Review Board. Results: Subjects with a history of febrile seizures (FS +, n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures. Atrophy in the hippocampus ipsilateral to seizure focus (IHC) was more diffuse than contralateral atrophy in FS + patients. Regressing out epilepsy duration, gender, seizure focus hemisphere, and BDI reduced IHC but not CHC atrophy. Subjects classified as depressed by the Beck Depression Inventory (BDI-II) (n = 11) had atrophy in the supero-anterior portion of the CHC compared to non-depressed subjects (n = 29). IHC atrophy was not significantly greater in depressed versus non-depressed subjects. We found a significant negative correlation between duration of epilepsy and volume of the hippocampus ipsilateral to seizure focus (r = -0.49, p < 0.01). Conclusions: Our results indicate that a history of febrile seizures, and depression, have independent effects on the hippocampus contralateral as well as ipsilateral to the seizure focus in patients with TLE.