Abstracts

Rationale: Patients with pharmacoresistant cryptogenic focal epilepsy (cFE), where conventional MRI does not show any structural lesion are potential candidates for epilepsy surgery. The absence of a visible surgical target challenges presurgical evaluation and requires complementary diagnostic methods to guide further investigations, especially intracranial EEG recordings. Here we present a new diagnostic approach, based on Diffusion Tensor Imaging (DTI) and the quantification of regional u-fibers to identify specific microstructural abnormalities in the epileptogenic zone of patients with cFE. Methods: 55 patients with cFE and 60 healthy controls were investigated. DTI data was acquired on a 3T GE Signa HDx MRI Scanner with 64 diffusion weighted directions, and a b-value of 1000 s/mm. Whole brain tractography was performed, and tracts representing subcortical u-fibers were selected, based on length, curvature and shape. Tract density images were created, specifying the number of tracts passing through any voxel. These u-fiber tract density images (ufTDI) were spatially normalized to MNI-space and every single patient's ufTDI was statistically compared against the control population, using SPM software. Clusters of significant reductions in ufTDI were determined, thresholding at a minimum size of 5 cm and a p-value < 0.001. Localization of ufTDI reductions was compared with clinical data from the presurgical evaluation. Results: All patients had normal conventional 3T MRI, using a specific epilepsy protocol. In 43 patients, a conclusive hypothesis on the epileptogenic zone could be derived, based on ictal and interictal EEG, seizure semiology, FDG-PET and ictal SPECT imaging. Only those 43 patients were included in the final analysis, in the remaining 12, clinical data was inconclusive, preventing final validation of their ufTDI alterations. Clusters of significant ufTDI reductions were found in 91% of the patients and 78 % of these reductions were consistent with the clinical localization of the epileptogenic zone. Twelve patients underwent intracranial EEG recording with depth electrodes, confirming seizure onset in 74% of the detected ufTDI reductions. Eight patients had resective surgery and the most frequent histopathological finding was mild malformation of cortical development (MCD) with blurred gray-white matter border and ectopic neurons in the white matter. Conclusions: Quantitative ufTDI has proven sensitive and specific to detect microstructural alterations in patients with cFE. MCD is a frequent cause of cFE and typically affects the gray-white matter border, where u-fibers are located, spanning between neighboring gyri, directly underneath the cortex. We hypothesize that ectopic neurons disrupt the microstructural order of subcortical white matter, thereby reducing the number of reconstructed u-fibers in this region. ufTDI has become a routine diagnostic method in our center for all patients with cFE and is now regularly used to guide implantation of intracranial electrodes. Funding: Fridrich-Baur-Stiftung