Longitudinal and cross-sectional analysis of atrophy in pharmacoresistant temporal lobe epilepsy

Abstract

Background: Whether recurrent epileptic seizures induce brain damage is debated. Disease progression in epilepsy has been evaluated only in a few community-based studies involving patients with seizures well controlled by medication. These studies concluded that epilepsy does not inevitably lead to global cerebral damage.

Objective: To track the progression of neocortical atrophy in pharmacoresistant temporal lobe epilepsy (TLE) using longitudinal and cross-sectional designs.

Methods: Using a fully automated measure of cortical thickness on MRI, we studied a homogeneous sample of patients with pharmacoresistant TLE. In the longitudinal analysis (n = 18), fixed-effect models were used to quantify cortical atrophy over a mean interscan interval of 2.5 years (range = 7 to 90 months). In the cross-sectional analysis (n = 121), we correlated epilepsy duration and thickness. To dissociate normal aging from pathologic progression, we compared aging effects in TLE to healthy controls.

Results: The longitudinal analysis mapped progression in ipsilateral temporopolar and central and contralateral orbitofrontal, insular, and angular regions. In patients with more than 14 years of disease, atrophy progressed more rapidly in frontocentral and parietal regions that in those with shorter duration. The cross-sectional study showed progressive atrophy in the mesial and superolateral frontal, and parietal cortices.

Conclusions: Our combined cross-sectional and longitudinal analysis in patients with pharmacoresistant temporal lobe epilepsy demonstrated progressive neocortical atrophy over a mean interval of 2.5 years that is distinct from normal aging, likely representing seizure-induced damage. The cumulative character of atrophy underlies the importance of early surgical treatment in this group of patients.

Figure 1 Cross-sectional analysis Effects of duration on (A) mean cortical thickness (black dots represent individual patients with temporal lobe epilepsy; the solid black line describes the linear regression model) and (B) thickness at each vertex. Significances have been thresholded at p < 0.005. Peak positions and resolution elements (i.e., resels) of significant clusters after random field theory correction are shown (cluster threshold t >3.2, cluster extent threshold 0.8 resels).

Figure 2 Longitudinal analysis Effect of interscan interval on (A) changes in mean hemispheric cortical thickness (gray lines connect the MR scans, indicated as black dots; the mixed-effects model is plotted as a solid black line); (B) vertex-wise mean annual rate of cortical thinning (in mm/year) in blue; (C) regions of vertex-wise progressive thinning (p < 0.005) in blue. Peak positions and resolution elements (i.e., resels) of significant clusters after random field theory correction are shown (cluster threshold t >3.5, cluster extent threshold 0.8 resels).

Figure 3 Longitudinal analysis Interaction between duration of epilepsy and disease progression. Superior view showing areas undergoing faster progression of atrophy (p < 0.005) in patients with longer disease duration (≥14 years). Peak positions and resolution elements (i.e., resels) of clusters after random field theory correction are shown (cluster threshold t >3.5, cluster extent threshold 0.8 resels).