Abstracts

Rationale: Medically intractable mesial temporal lobe epilepsy (TLE) is associated with MRI detectable hippocampal atrophy (TLE-HA) in 70% of patients. About 30% of TLE patients have normal hippocampal volumes (TLE-NV). On the other hand, entorhinal cortex atrophy is found in both groups (Bernasconi et al., Neurology 2001; 56(10):1335-9). With respect to neocortical pathology, many studies have shown widespread atrophy in TLE-HA, but little is known about TLE-NV. A previous voxel-based morphometry (VBM) study failed to find any cortical atrophy in TLE-NV (Müller et al., Epilepsia 2006; 47(5):900-7). Measuring cortical thickness is a more direct and biologically meaningful method to quantify atrophy than VBM as it allows analyzing continuous changes of the convoluted cortical surface. Our purpose was to study neocortical pathology in patients with TLE-NV by comparing them to healthy controls and to patients with TLE-HA. Methods: We performed cortical thickness analysis in 98 patients with intractable TLE and 48 age- and sex-matched controls using an unbiased automatic surface-based deformation algorithm on high-resolution MRI (Kim et al., NeuroImage 2005; 27(1):210-21). Based on the EEG lateralization and hippocampal volumetry, we classified patients into four groups: left TLE-HA (n=25), right TLE-HA (n=25), left TLE-NV (n=25) and right TLE-NV (n=23). We performed the following analyses using one-tailed t-tests: i) comparison of each TLE group to healthy controls, ii) comparison between TLE-NV and TLE-HA. Vertex-wise significances were thresholded using random field theory. Results: Compared to controls, in left TLE-NV, clusters of cortical thinning were found in the ipsilateral superior frontal, inferior frontal and lateral temporal as well as in the contralateral posterior temporo-occipital regions (Figure, upper panel). In left TLE-HA, atrophy was found in bilateral superior frontal, medial frontal, central, and ipsilateral hippocampal areas (Figure, lower panel). In RTLE, the pattern of changes was similar, but less widespread. Vertex-wise comparison of cortical thickness between TLE-HA and TLE-NV revealed a significant difference only in the hippocampal region. Conclusions: TLE-NV is associated with neocortical atrophy similar in topography to that found in TLE-HA, but less extensive, suggesting that these two entities are part of the same pathological spectrum. Common pathophysiological mechanisms such as seizure spread are likely to contribute to neocortical atrophy in TLE-NV and TLE-HA.