Diffusion tensor imaging in patients with focal epilepsies: comparative analyses of microstructural damage and anatomical connectivity between temporal and frontal lobe epilepsies with different etiology, seizure focus, and pharmacoresponse

Author(s)

Hebel Oziel Urquia Osorio

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2021-03-26

Examining board members

Fernando Cendes; Marcondes Cavalcante Franca Junior; Ana Carolina Coan; Luiz Eduardo Betting; Luiz Henrique Martins Castro

• Advisor: Fernando Cendes

Abstract

Introduction. The analysis of cerebral white matter integrity in epilepsy has increased rapidly in the last years. Several studies have shown diffuse changes in deep white matter (DWM) in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and frontal lobe epilepsy with focal cortical dysplasia (FLE-FCD). However, the study of superficial white matter (SWM) - immediately under the cortex remains unclear. Objective. To evaluate SWM/DWM integrity and identify distinctive patterns of microstructural abnormalities in focal epilepsies of diverse etiology, ictal onset and, type of pharmacoresponse. Methods. We included diffusion-weighted MRI data for 113 healthy controls and 113 patients with focal epilepsies: 51 pharmacoresistant and 27 pharmacoresponsive patients with MTLE-HS (with MRI signs of hippocampal sclerosis only: rMTLE-HS and gMTLE-HS, respectively), 15 with temporal and, 20 with frontal lobe epilepsy with MRI signs of focal cortical dysplasia (fFCD/tFCD [both pharmacoresistant]). To assess the white matter (WM) microstructure, we used the diffusion tensor imaging - DTI multi-atlas approach. We applied Kruskal-Wallis with Dunn-Bonferroni post hoc comparisons to examine fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) differences ipsi- and contralateral to the epileptogenic zone in 84 regions-of-interest (ROI). All analyses were corrected for multiple comparisons. Results. MTLE-HS groups presented more widespread SWM/DWM significant diffusion anomalies than FCD groups. DWM abnormalities were more widespread, and bilateral in both MTLE-HS groups and less diffuse in the FCD groups (mainly in the projection and commissural fibers). Concerning SWM, MTLE-HS groups showed multilobular ipsi- and contralateral abnormalities, with less extensive distribution in pharmacoresponsive patients. Both MTLE-HS groups presented with pronounced effects in similarly frontotemporal ROIs in all DTI metrics. Conversely, patients with tFCD and fFCD showed almost exclusively diffusion changes in temporal and frontal structures, respectively. Conclusion. Our findings add further evidence of widespread impairment in WM diffusion metrics in patients with MTLE-HS compared to other types of focal epilepsies. Notably, we demonstrate more restricted peri-ictal SWM microstructural damage in FCD patients, while MTLE- HS groups showed more robust effect sizes and overlapping changes of ipsilateral frontotemporal predominance. These findings suggest the potential of SWM analysis for the better biological understanding of focal epilepsies, identification of dysfunctional networks, and their relationship with the clinical-pathological phenotype. (AU)

• FAPESP's process: 16/05985-3 - Voxel-based diffusion tensor imaging in patients with focal epilepsies: comparative analyses of microstructural damage and anatomical connectivity between benign and refractory mesial temporal lobe epilepsy and frontal lobe epilepsy
• Grantee: Hebel Oziel Urquia Osorio
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)