Abstracts

Rationale: Focal cortical dysplasia (FCD) accounts for up to 25% of patients undergoing resective surgery for medically refractory epilepsy (Sisodiya et al., 2009). Quantitative image analyses have suggested structural changes distant to the primary lesion, however, with the exception of one study (Colliot et al., 2006), previous work has included patients with various of malformations (Sisodiya et al., 1995, Woermann et al., 1999), and a consistent pattern of cortical pathology has not been established. Our purpose was to investigate whole-brain cortical integrity in patients with FCD using MRI-based cortical thickness measurements. Methods: We studied 30 patients (11 males, 30 10 years) with FCD and drug-resistant epilepsy. Mean duration of epilepsy was 23 10 years. In patients who underwent surgery (18/30), classification (Palmini et al., 2004) of the resected tissue revealed balloon cell FCD in 12 and non-balloon cell FCD in 6. The control group consisted of 42 age- and sex-matched individuals (16 males, 30 9 years). We measured cortical thickness using the CLASP algorithm (Kim et al., 2005) on 1.5 T MRI (3D T1-fast field echo sequence TR=18 ms; TE=10 ms, voxel size=1mm3). Two observers manually segmented the FCD lesions on multi-contrast MRI. FCD lesions were located in the frontal (n=21), parietal (n=5), temporal (n=2) and sylvian regions (n=2). Lesion labels were projected to the cortical surfaces. Thickness data and lesion labels were blurred using a 15mm surface-based smoothing kernel prior to analysis. To assess cortical thickness in extra-lesional tissue, we excluded vertices that fell within the blurred lesion labels. We compared patients to controls using vertex-wise two-tailed t-tests. We also assessed the effects of duration of epilepsy and Palmini subtype using linear models. Vertex-wise significances were corrected using the false discovery rate procedure (Benjamini and Hochberg, 1995). Results: Vertex-wise group analysis (Fig. 1a) revealed bilateral cortical thinning in FCD patients in frontal lobe regions, including pericentral and opercular cortices. Additional areas were seen in supramarginal and temporo-occipital cortices. There were no regions of increased cortical thickness. In areas of cortical thinning, we found a negative correlation (Fig. 1b) between age and cortical thickness in FCD patients (t=3.2, p<0.01), but not in controls (t=0.2, p=0.4). Moreover, the thickness in these regions was negatively correlated with duration of epilepsy (t=2.3, p=0.02). There was no association between histopathological subtype and pattern of cortical thinning. Conclusions: Despite the histological heterogeneity and variable anatomical topography of the FCD lesions, our results show areas of cortical thinning common to all patients. Progressive cortical thinning with increasing age and disease duration suggests that extra-lesional atrophy is secondary to the cumulative effect of seizures, advocating for early surgery in these patients. The preponderance of frontal lobe involvement may explain some aspects of the cognitive deficits in FCD (Guerrini and Parrini, 2009).