Abstracts

Rationale: Focal cortical dysplasia (FCD) type II is a prevalent epileptogenic developmental malformation related to abnormal neuroglial proliferation and migration with likely a strong genetic underpinning. Clinical observations point to a preferential location in the frontal lobe and at sulcal bottoms (Besson et al., 2008; Blumcke et al., 2017). Our purpose was to study the anatomical distribution of FCD and its relation to sulcal pits, the putative first cortical folds thought to be genetically-determined (Le Guen et al., 2017). Methods: We studied 85 consecutive FCD patients (44 males; age: 26.4±10.4 years) and 88 healthy controls (41 males; age: 30.8±9.2) with high-resolution 3D T1-weighted MRI (T1w). Images were linearly registered to MNI152 space and classified into tissue types. The CLASP algorithm (Kim et al., 2005) preprocessed T1w to generate models of the cortical interfaces. FCD lesions were manually segmented, including the transmantle sign (61% of cases). We intersected labels with surface models to generate group-level lesional probability maps and identified sulcal pits as the deepest point of sulcal basins (Le Guen et al., 2017). After smoothing pit maps with a surface kernel of 5 mm,  we measured their density across the brain as the number of pit per kernel unit. A surface-based linear model compared the density map of patients to controls, co-varying for age. A post hoc analysis in clusters of findings assessed sulco-gyral morphology, including depth, number of branches and curvature.  Results: Fig 1 shows the statistical parametric map of FCD lesions and the transmantle sign overlaid on cortical and ventricular surfaces, respectively. FCD topography followed a rostral-to-caudal gradient, with a peak concentration in the frontal lobe (68%), specifically in the superior frontal gyrus, followed by the parietal lobe (23%). High frontal prevalence persisted when controlling for surface-area. Transmantle sign locations followed a similar topography (64% frontal, 15% parietal, 11% temporal, 6% insula, 4% occipital). Compared to controls, FCD patients showed increased sulcal pit density in the frontal lobe (p_FWE<0.05), mostly near the highest FCD concentration (Fig 2A, B). In these regions, multivariate analysis (Hoteling T² test: p<0.02) showed abnormally deep sulci with an increased number of branches and more complex folding patterns (Fig 2C). Conclusions: Anatomical proximity of FCD lesions with areas of increased sulcal pit density supports disrupted mechanical properties and possible implications of genetic cues. The predominant frontal lobe aggregation of lesions and transmantle signs suggest a morphogenetic link between the site of abnormal neuronal proliferation in the ventricular zone and the overlying cortex harboring the FCD. Funding: Canadian Institutes of Health Research, Canadian League Against Epilepsy, Savoy Epilepsy Foundation