SUMMARYObjective: To evaluate white matter (WM) integrity of distinct groups of patients with antiepileptic drug (AED)-resistant localization-related epilepsies. Methods: We used diffusion tensor imaging (DTI) fiber-tractography and voxel-based morphometry (VBM) to investigate differences of WM micro-and macrostructural integrity in patients with different drug-resistant localization-related epilepsies: 17 with temporal lobe epilepsy with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 17 with TLE and normal MRI (TLE-NL), 14 with frontal lobe epilepsy and subtle MRI signs of focal cortical dysplasia (FLE-FCD), and 112 healthy controls. We performed fiber-tractography using a semiautomatic deterministic method to yield average fractional anisotropy (FA), axial (AD), and radial (RD) diffusivity ipsilateral and contralateral to the epileptogenic zone of the following tracts based on their functional and anatomic relevance: body of fornix (BoF), body of cingulum (BoC), inferior frontal occipital (IFO), and uncinate fasciculi (UF). In addition, we performed VBM of the WM maps to assess macrostructural integrity differences among groups. Results: TLE-HS had ipsilateral and contralateral decreased FA and increased RD for all tracts. VBM showed WM alterations mainly in the ipsilateral parahippocampal region and contralateral superior temporal gyrus. FLE-FCD showed bilateral FA decreases only in the BoC and ipsilateral RD increases also in the BoC. VBM showed WM reduction mainly in the ipsilateral precuneus and posterior and anterior cingulum. No significant WM alterations were found in the TLE-NL in DTI or VBM analysis. Significance: WM abnormalities differ in distinct AED-resistant localization-related epilepsies. The diverse distribution of the WM damage in these patients suggests that the localization of the epileptic networks may play a role in the WM burden. However, the distinct degree of this damage, more accentuated in TLE-HS, also suggests that the underlying cause of the epilepsy is probably an additional factor to explain this WM damage. KEY WORDS: Frontal lobe epilepsy, Temporal lobe epilepsy, Diffusion tensor imaging, Voxel-based morphometry.

SUMMARYObjective: Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy. Methods: We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. Results: We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. Significance: These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology.

Our findings indicate a role for retrograde and anterograde neurodegeneration in GM atrophy in NMOSD. However, the presence atrophy encompassing almost all lobes suggests that additional pathomechanisms might also be involved.

Objective: Drug-resistant temporal lobe epilepsy (TLE) often requires thorough investigation to define the epileptogenic zone for surgical treatment. We used simultaneous interictal scalp EEG-fMRI to evaluate its value for predicting longterm post-surgical outcome.Methods: 30 patients undergoing pre-surgical evaluation and proceeding to temporal lobe (TL) resection were studied.Interictal epileptiform discharges (IEDs) were identified on intra-MRI EEG and used to build a model of hemodynamic changes. In addition, topographic electroencephalographic correlation maps were calculated between the average IED during video-EEG and intra-MRI EEG and used as a condition. This allowed the analysis of all data irrespective of the presence of IED on intra-MRI EEG. Mean follow-up after surgery was 46 months. ILAE outcomes 1 and 2 were considered good and 3 to 6 poor surgical outcome. Hemodynamic maps were classified according to the presence (Concordant) or absence (Discordant) of BOLD change in the TL overlapping with the surgical resection. Results:The proportion of patients with good surgical outcome was significantly higher (13/16; 81%) in Concordant than in Discordant group (3/14; 21%) (Chi-squared test, Yates correction, p=0.003) and multivariate analysis showed that Concordant BOLD maps were independently related to good surgical outcome (p=0.007). Sensitivity and specificity of EEG-fMRI results to identify patients with good surgical outcome were 81% and 79%, respectively and positive and negative predictive values were 81% and 79%, respectively.

In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.