Pannexin-1 channel inhibition blocks seizure activity in brain slices from epileptic patients and reduces spontaneous seizures in a mouse model of pharmacoresistant epilepsy.

Summary: Purpose: Failure of anterior temporal lobectomy for temporal lobe epilepsy has raised the question of insular cortex involvement in these seizures. Because of difficulties in exploring the insula with invasive electroencephalography (EEG) recordings, only few studies have been performed and this question remains unanswered.Methods: Here, we studied 17 patients who underwent surgery for drug‐resistant temporal lobe epilepsy, explored with intracerebral electrodes, with at least one electrode coplanar to the insula. We analyzed seizure propagation patterns from temporal lobe structures to the insula, and their effect on outcome. We used an objective measure of the epileptogenicity of the insula for individual cases and group analysis between patients who were seizure‐free after surgery and the others.Key Findings: All temporal lobe seizures propagated to the insular cortex, with a shorter propagation delay in the case of mesiolateral temporal lobe seizures, thus supporting the existence of a perilimbic network. Epileptogenicity of the insular cortex was not a prognostic factor for outcome after surgery.Significance: Insular involvement in temporal lobe seizure is not per se a prognostic factor for surgical outcome. Prognosis may be correlated with larger epileptogenic zones that our stereoelectroencephalography spatial sampling could have underestimated.

BACKGROUND AND PURPOSE: The severity of Moyamoya disease is generally scaled with conventional angiography and nuclear medicine. Arterial spin-labeling MR imaging is now acknowledged for the noninvasive quantification of cerebral blood flow. This study aimed to analyze CBF modifications with statistical parametric mapping of arterial spin-labeling MR imaging in children undergoing an operation for Moyamoya disease. MATERIALS AND METHODS: We included 15 children treated by indirect cerebral revascularization with multiple burr-holes between 2011 and 2013. Arterial spin-labeling MR imaging and T1 sequences were then analyzed under SPM8, according to the general linear model, before and after the operation (3 and 12 months). Voxel-based analysis was performed at the group level, comparing all diseased hemispheres with all normal hemispheres and, at the individual level, comparing each patient with a control group. RESULTS: Group analysis showed statistically significant preoperative hypoperfusion in the MCA territory in the Moyamoya hemispheres and a significant increase of cerebral perfusion in the same territory after revascularization (P < .05 family-wise error–corrected). Before the operation, individual analysis showed significant hypoperfusion for each patient co-localized with the angiographic defect on DSA. All except 1 patient had improvement of CBF after revascularization, correlated with their clinical status. CONCLUSIONS: SPM analysis of arterial spin-labeling MR imaging offers a noninvasive evaluation of preoperative cerebral hemodynamic impairment and an objective assessment of postoperative improvement in children with Moyamoya disease.

Diffuse midline gliomas (DMG) are pediatric tumors with negligible 2-year survival after diagnosis characterized by their ability to infiltrate the central nervous system. In the hope of controlling the local growth and slowing the disease, all patients receive radiotherapy. However, distant progression occurs frequently in DMG patients. Current clues as to what causes tumor infiltration circle mainly around the tumor microenvironment, but there are currently no known determinants to predict the degree of invasiveness. In this study, we use patient-derived glioma stem cells (GSCs) to create patient-specific 3D avatars to model interindividual invasion and elucidate the cellular supporting mechanisms. We show that GSC models in 3D mirror the invasive behavior of the parental tumors, thus proving the ability of DMG to infiltrate as an autonomous characteristic of tumor cells. Furthermore, we distinguished 2 modes of migration, mesenchymal and ameboid-like, and associated the ameboid-like modality with GSCs derived from the most invasive tumors. Using transcriptomics of both organoids and primary tumors, we further characterized the invasive ameboid-like tumors as oligodendrocyte progenitor-like, with highly contractile cytoskeleton and reduced adhesion ability driven by crucial over-expression of bone morphogenetic pathway 7 (BMP7). Finally, we deciphered MEK, ERK, and Rho/ROCK kinases activated downstream of the BMP7 stimulation as actionable targets controlling tumor cell motility. Our findings identify 2 new therapeutic avenues. First, patient-derived GSCs represent a predictive tool for patient stratification in order to adapt irradiation strategies. Second, autocrine and short-range BMP7-related signaling becomes a druggable target to prevent DMG spread and metastasis.