Abstracts

Rationale: Although epileptogenic lesions are often detected by MRI, in many patients with drug-resistant seizures visual inspection of conventional imaging fails to pinpoint a surgical target ¹. Growing evidence, however, suggests that cryptogenic (MRI-negative) epilepsy is not necessarily non-lesional, the primary histopathological substrate being subtle cortical dysplasia ^2,3. Histologically, subtle dysplasia (ILAE Type I) is characterized by cortical thinning, and persistence of developmental radial microcolumns and loss of horizontal hexalaminar structure ⁴. These post-migrational cortical organization defects likely arise from abnormalities in neuronal rearrangement ⁵ and cortical network maturation ⁴. Importantly, during the dynamic process of cortical organization, differential growth of cortical layers and viscoelastic forces from axonal tension between interconnected areas ^6,7 are thought to lead to the formation of sulci and gyri. 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 cryptogenic epilepsy. Methods: We studied 37 patients (22 males, 30±8 years) with cryptogenic, drug-resistant extra-temporal epilepsy. Based on clinical and EEG data, the focus was pre-central (frontal or fronto-central) in 22 and post-central (centro-parietal, parietal or parieto-occipital) in 15 (left-sided in 21 and right-sided in 16). To quantify folding complexity, we obtained whole-brain surface-based measures of absolute mean cortical curvature ⁸ from 1.5 T MRI scans (3D T1-fast field echo sequence, TR=18 ms; TE=10 ms, voxel size=1mm³). Patients were compared to 41 age- and sex-matched healthy controls (males 16, 31±11) using vertex-wise t-tests. Prior to analysis, curvature measurements were blurred using a 20 mm surface-based diffusion kernel. In order to rule out potential confounds of cortical atrophy, we statistically corrected the curvature value at each vertex by the corresponding thickness measure. Results: Compared to controls, patients with cryptogenic epilepsy displayed increased folding complexity in the orbitofrontal cortex, bilaterally (p<0.04; Figure 1). We found no association between curvature changes and the location of seizure focus, or epilepsy duration. Conclusions: Cryptogenic epilepsy is associated with increased sulco-gyral complexity. These anomalies are independent of cortical atrophy and seizure focus location. Their distinct location suggests altered loco-regional connectivity. Increased folding complexity suggests morphological commonality with polymicrogyrias and reinforces the notion that cryptogenic epilepsy may belong to the recently-described group of cortical malformations that are secondary to abnormal post-migrational development ⁹ .