Abstracts

Rationale: Converging evidence suggests that abnormalities of neocortical and hippocampal development may play a role in the pathogenesis of temporal lobe epilepsy (TLE). As sulco-gyral patterns are thought to be a footprint of cortical development, we set out to quantitatively map folding complexity across the neocortex in TLE. Additionally, we tested whether there was a relationship between cortical complexity and features of hippocampal maldevelopment, commonly referred to as malrotation. Methods: We acquired high-resolution (1x1x1mm) T1-weighted MRI scans at 1.5T in 43 drug-resistant TLE patients with unilateral hippocampal atrophy (22 left TLE, 21 right TLE, 19 males, mean age: 35 /-11 years), and 40 age- and sex-matched healthy controls (17 males, mean age: 33 /-11 years). We applied the Constrained Laplacian Anatomic Segmentation using Proximity (CLASP) algorithm (1) to generate a model of the inner (white matter) and outer (grey matter) surfaces. Absolute mean curvature was calculated on the mid-surface between the white and grey matter and smoothed at 10 and 30mm Full Width Half Maximum. Group t-statistic maps of absolute mean cortical curvature were generated to test for differences in cortical folding between healthy volunteers and left and right TLE patients, which were adjusted for changes in cortical thickness. In patients, the resulting difference maps were used to assess the relationship between changes in cortical curvature and 3D measures of hippocampal positioning created from manual segmentations as previously described (2). Surgical outcomes were available for 36 patients. At follow-up (4 /-3 years), 25 patients had achieved a Engel Class I outcome, while 11 had a Class II, III or IV outcome. Results: We found increased folding complexity in the temporo-limbic cortices encompassing parahippocampal, temporopolar, insular, and fronto-opercular regions (p<0.05, random field theory corrected). Increased complexity was observed ipsilateral to the seizure focus in patients with LTLE, whereas these changes were bilateral in RTLE patients. In both TLE groups, temporo-limbic complexity increases positively correlated with the degree of hippocampal malrotation (LTLE: R=0.45, p=0.034; RTLE: R=0.55, p=0.008). We found tendencies for increased complexity in bilateral posterior temporal cortices in LTLE and contralateral parahippocampal cortices in RTLE to be predictive of unfavorable seizure outcome after surgery. Conclusions: The anatomical distribution of increased cortical complexity overlapping with limbic seizure networks in TLE and its association with hippocampal malrotation are strong indicators that neurodevelopmental factors may play a role in the epileptogenic process of TLE. References: (1) Kim JS et al., (2005). NeuroImage 27:210-221 (2) Kim H et al., (2006). Epilepsia 47: 72-73