Authors :
Jessica Barrios Martinez, MD – University of Pittsburgh; Thandar Aung, MD, MS – University of Pittsburgh Medical Center; David Fernandes-Cabral, MD – University of Pittsburgh Medical Center; Jorge Gonzalez-Martinez, MD, PhD – University of Pittsburgh Medical Center; Catherine Liegeois-Chauvel, PhD – University of Pittsburgh; Joseph Mettenburg, MD, PhD – University of Pittsburgh Medical Center; Fang-Cheng Yeh, MD, PhD – University of Pittsburgh
Rationale: Structural network effects on focal epilepsy are not well understood. Patients have been explored with Stereoelectroencephalography (sEEG) to determine the anatomical location of an epileptogenic focus, but symptoms displaying a more global cortical involvement justifies the opportunity to study connectivity of the entire brain. Studies have shown an increased in anisotropic diffusion (i.e., a measurement for connectivity at the voxel level) in epilepsy patients.[1] This in turn appears to be one of the disease hallmarks, especially in patients with more complex presentations such as generalized seizures and behavioral changes, implying that the disease is not limited to focal changes in connectivity, but a more global neuronal involvement is at play. To this end, we studied the connectivity of white matter tracts of the entire brain of ten patients with medical intractable focal epilepsy using Differential Tractography, [1] a technique that only tracts fibers and segments of white matter tracts displaying a change in connectivity when compared with a normal population.
Methods: In a prospective observational study, we compared diffusion data from ten patients with focal intractable epilepsy with an age and sex matched template constructed from a normal control population for each individual subject. Diffusion MRI was acquired as part of a battery of preoperative tests for sEEG. The data was reconstructed and processed using DSI Studio (
https://dsi-studio.labsolver.org/). Each subject was then compared to their corresponding age and sex matched constructed template, which evaluates connectivity at the voxel level. This allowed to perform fiber tracking of fibers with an increase in normalized quantitative anisotropy (nQA) above 20%. False discovery rates were calculated to determine the number of false positive findings.
Results: In total, ten patients (age: 22-68 years old; sex M/F=4/6) with diagnosis of focal and intractable epilepsy were studied. Differential tractography results showed all patients displaying a cortical enhancement of fibers with increased connectivity (nQA) above 20% in a superficial cortical distribution or ring pattern (Figure 1). A total of nine out of 10 patients showed a statistically significant false discovery rate (FDR < 0.05), and only one patient showed an FDR=0.2.