Abstracts

Rationale: MRI-based morphometric studies have shown widespread reductions in cortical thickness and volume in unilateral temporal lobe epilepsy (TLE). Although this volume loss is presumably related to duration of illness, the few studies that examined this hypothesis produced mixed results, possibly due to small sample sizes, age confounds, and suboptimal morphometric methods.  Methods: High-resolution T1 MRI data were acquired in 137 patients being evaluated for surgical treatment of unilateral left TLE as determined by video EEG and imaging studies (mean age 36.9, range 18-70). Duration of epilepsy (mean 16.2 years, range 0.8-51.3) was calculated as the number of years from the onset of recurring seizures to the date of MRI. MRI data were analyzed with FreeSurfer v6, which produces an automated parcellation of the cortical surface based on sulcal folding patterns. Grey matter volumes were computed for each of the 66 cortical regions (33 per hemisphere) in the Desikan-Killiany parcellation, as well as hippocampus, thalamus, and basal ganglia, and correlated with epilepsy duration. Because epilepsy duration is partly confounded with age of the patient (which has known effects on grey matter volume in healthy people), duration was residualized against age by linear regression to examine effects of duration independent of age. Given the large number of tests performed, only correlations significant at p < .01 are reported, and correlations that remained significant after Holm-Bonferroni correction are noted. Results: Widespread bilateral brain regions showed reduction of grey matter volume with increasing age. After removing effects of age, duration of epilepsy was negatively correlated with grey matter volume in 8 regions: left hippocampus (r = -.381, p < .001), left temporal pole (r = -.284, p < .001), left entorhinal cortex (r = -.280, p < .001), right entorhinal cortex (r = -.258, p =.001), left thalamus (r = -.244, p =.002), left parahippocampus (r = -.228, p =.004), right hippocampus (r = -.209, p =.007), and right temporal pole (r = -.199, p =.01). Left hippocampus, temporal pole, and entorhinal cortex remained significant after correction for multiple comparisons. Conclusions: Longer duration of TLE is associated with progressive loss of grey matter volume in medial and anterior temporal lobe structures bilaterally, independent of effects of advancing age. The effects were only modestly more pronounced on the side of the seizure focus. The progressive nature of grey matter volume loss in TLE underscores the importance of early surgical treatment in medically refractory patients. Funding: Supported by NINDS R01 NS35929