Abstracts

Rationale: Structural asymmetry based on hippocampal volumetry using MRI has been used as a predictor of seizure laterality in drug resistant temporal lobe epilepsy (TLE). However, pathology studies have demonstrated more localized subfield-specific effects in TLE. Prior work on 4T MRI in lesional TLE found focal atrophy in CA1, CA2, CA3 and DG (dentate gyrus) in the hippocampus of seizure onset (1). In nonlesional TLE, this study showed no significant differences. Resting state functional connectivity of the default mode network, amygdala and entorhinal cortex and hippocampus in TLE are decreased ipsilateral to seizure onset. To our knowledge, there is no prior work looking at subfield functional connectivity in TLE. We sought to develop biomarkers of seizure onset laterality based upon hippocampal subfield volume measures and inter- and intra-hemispheric functional connectivity on 7T high-resolution MRI.Methods: Subjects were recruited from the Penn Epilepsy Center and had drug resistant TLE: 5 Nonlesional TLE (3 right, 2 left onset), 5 Lesional TLE (3 right, 2 left onset), 2 Bitemporal, 10 Controls. Imaging included 0.4x0.4x1.0 mm3 T2-MRI in which hippocampal subfields were labeled using a multi-atlas segmentation algorithm previously validated in 3T MRI. Connectivity between subfields was computed using linear correlation of residual time series extracted from 2 mm3 isotropic resting BOLD-fMRI after filtering out physiological noise.Results: Structural: When comparing lesional TLE to controls, total hippocampal volume, CA1 and DG were atrophied ipsilateral to seizure onset (p<0.05). When comparing nonlesional TLE to controls, total hippocampal volume, CA1 and DG were larger ipsilateral to seizure onset (only DG reached statistical significance, p<0.05). Comparison of Lesional TLE versus nonlesional TLE indicated total hippocampal volume, CA1, CA3, DG (p=0.07) atrophied in lesional TLE. Functional – resting BOLD (asymmetry ratio calculations): CA1 connectivity to the whole hippocampus, DG and hippocampal head were decreased ipsilateral to seizure onset in comparison to controls. Difference in CA1 connectivity to the hippocampal subfields on the contralateral side did not reach statistical significance. Inter-hemispheric asymmetry of CA1 connectivity were significantly different in both unilateral and bitemporal patients in comparison with controls.Conclusions: In lesional TLE on 7T high-resolutional MRI, CA1 and DG were atrophied ipsilateral to seizure onset. These results are similar to prior work in 4T MRI. In nonlesional TLE, CA1 and DG volumes were larger ipsilateral to seizure onset (DG reached statistical significance). Functional connectivity measures showed decreased connectivity of CA1 ipsilateral to seizure onset. 1. Mueller et al., Epilepsia, 2009: 50(1474-83)