Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the EfnA5 locus and reinforces repression of selected target genes in a cellular context-dependent fashion. EfnA5 mediates Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide pre-clinical evidence of druggability of the EFNA5 signalling pathway in GBM xenografts overexpressing Bmi1.

Magnetic resonance-guided laser interstitial thermal therapy (MR-gLiTT) is a novel minimally invasive treatment approach for drug-resistant focal epilepsy and brain tumors. Using thermal ablation induced by a laser diode implanted intracranially in a stereotactic manner, the technique is highly effective and safe, reducing the risk associated with more traditional open surgical approaches that could lead to increased neurological morbidity. Indications for MR-gLiTT in pediatric epilepsy surgery include hypothalamic hamartoma, tuberous sclerosis complex, cavernoma-related epilepsy, SEEG-guided seizure onset zone ablation, corpus callosotomy, periventricular nodular heterotopia, mesial temporal lobe epilepsy, and insular epilepsy. We review the available literature on the topic and present our series of patients with drug-resistant epilepsy treated by MR-gLiTT. Our experience, represented by six cases of hypothalamic hamartomas, one case of tuberous sclerosis, and one case of dysembryoplastic neuroepithelial tumor, helps to confirm that MR-gLiTT is a highly safe and effective procedure for several epilepsy conditions in children.

The role of MR Arterial-Spin-Labeling Cerebral Blood Flow maps (ASL-CBF) in the assessment of pediatric focal epilepsy is still debated. We aim to compare the Seizure Onset Zone (SOZ) detection rate of three methods of evaluation of ASL-CBF: 1) qualitative visual (qCBF), 2) z-score voxel-based quantitative analysis of index of asymmetry (AI-CBF), and 3) z-score voxel-based cluster analysis of the quantitative difference of patient’s CBF from the normative data of an age-matched healthy population (cCBF). Interictal ASL-CBF were acquired in 65 pediatric patients with focal epilepsy: 26 with focal brain lesions and 39 with a normal MRI. All hypoperfusion areas visible in at least 3 contiguous images of qCBF analysis were identified. In the quantitative evaluations, clusters with a significant z-score AI-CBF ≤ −1.64 and areas with a z-score cCBF ≤ −1.64 were considered potentially related to the SOZ. These areas were compared with the SOZ defined by the anatomo-electro-clinical data. In patients with a positive MRI, SOZ was correctly identified in 27% of patients using qCBF, 73% using AI-CBF, and 77% using cCBF. In negative MRI patients, SOZ was identified in 18% of patients using qCBF, in 46% using AI-CBF, and in 64% using cCBF (p < 0.001). Quantitative analyses of ASL-CBF maps increase the detection rate of SOZ compared to the qualitative method, principally in negative MRI patients.