Diffuse IDH-mutant astrocytomas are brain tumors typically diagnosed as low-grade but capable of progressing to higher grades. They exhibit three cellular states resembling astrocytes, oligodendrocytes, and neural progenitor (NPC) cells. Understanding their biology has been limited by the scarcity of relevant in vitro models. Here, we established and extensively characterized four astrocytoma cell lines (LGG275, LGG336, LGG85, LGG349) derived from IDH-mutant astrocytomas of different grades and analyzed them using multi-omics approaches. These lines display growth rates in vitro and in vivo consistent with tumor grade and recapitulate some key molecular alterations observed in patient tumors, including IDH1, ATRX, and TP53 mutations, ALT (alternative lengthening of telomeres) activation and, in more aggressive lines, MET and PDGFRA alterations. Single-cell RNA sequencing revealed three major transcriptional states (astrocyte-like, oligodendrocyte-like, and NPC-like), consistent with those described in patient tumors. A hallmark of higher-grade-derived lines (LGG85, LGG349) is the persistence of NPC-like populations without growth factors possibly reflecting tumor progression. The LGG275 line most accurately mirrors slow-growing astrocytomas. Using CD44 and GLAST, we isolated astrocyte-like (CD44⁺/GLAST⁺) cells from LGG275 that preferentially adopt a quiescent state yet retain remarkable plasticity, generating oligodendrocyte-like cells (CD44⁻/GLAST⁻). Transcriptomic and proteomic analyses revealed that astrocyte-like and oligodendrocyte-like cells populations resemble, respectively, quiescent and activated neural stem (NSC) cells from the adult subventricular zone (SVZ). Finally, we provide evidence that NOTCH signaling contributes to the regulation of cell state balance, promoting transitions toward an astrocyte-like transcriptional program while DLL3, an anti-Notch protein, expressed by oligodendrocyte-like cells, modulates both proliferation and phenotype. These cell lines represent valuable resources for dissecting lineage dynamics, heterogeneity, and progression mechanisms in IDH-mutant astrocytomas.
L. Garcia, C. Granotier-Beckers, D. Pineau et al.· Acta Neuropathologica Commun...· 0 citations
Complete resection of the epileptogenic zone offers the best chance of seizure control in patients with drug-resistant epilepsy. However, surgical management remains challenging when the epileptogenic zone is located within or adjacent to eloquent brain regions. Awake craniotomy (AC), combined with intraoperative functional mapping, has the potential to maximize resection while preserving neurological function. Despite its increasing use, evidence regarding its safety and efficacy in epilepsy surgery remains limited. This study aimed to systematically evaluate the feasibility, reported safety, and reported seizure outcomes of awake craniotomy in patients undergoing surgery for drug-resistant non-oncological epilepsy.
A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases in accordance with PRISMA guidelines.
Seven retrospective studies comprising 231 patients from six countries were included; 120 patients underwent AC. Four studies (57.1%) included mixed adult and pediatric populations and three (42.9%) included adults only; however, none provided age-stratified seizure or complication outcomes, precluding separate pediatric analysis. Reported seizure duration ranged from 2 to 39 years. The frontal lobe was the most frequently involved region (
n
= 52; 43.3%), followed by the temporal lobe (
n
= 27; 22.5%), and cortical dysplasia was the most common underlying pathology (
n
= 30; 25.0%). Language and sensorimotor functions were the most commonly mapped eloquent areas, each reported in five studies (71.4%). Seizure outcomes were predominantly assessed using the Engel classification. Complete seizure freedom (Engel class I) was reported in 69 of 120 AC patients (57.5%); a random-effects single-arm synthesis estimated an Engel I proportion of 59.3% (95% CI: 46.3–71.2%; I2 = 31.9%). Comparisons with surgery under general anesthesia (GA) were available in only two non-randomized studies and should be interpreted cautiously. No study reported conversion from AC to GA. Postoperative neurological deficits were largely transient, with a low reported incidence of permanent morbidity. Owing to substantial differences in patient selection, surgical indications, and study design, these findings should be considered exploratory and should not be interpreted as demonstrating comparable seizure outcomes or treatment effectiveness.
In carefully selected patients with drug-resistant non-tumor epilepsy involving or adjacent to eloquent cortex, AC with intraoperative functional mapping appears feasible and may help preserve neurological function while enabling tailored resection. The current evidence base remains limited by retrospective designs, heterogeneous populations and techniques, inconsistent outcome reporting, and sparse comparative data; therefore, efficacy and equivalence with surgery under general anesthesia should not be inferred.
M. Mofatteh, M. Mashayekhi, Sho Giersztein et al.· BMC Surgery· 0 citations
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