IDH-mutant gliomas are characterized by unique metabolic alterations, particularly the accumulation of d-2-hydroxyglutarate (d-2-HG), which has been implicated in promoting epileptogenesis. Mortazavi et al. demonstrated that d-2-HG leads to metabolic disruptions in surrounding cortical neurons, resulting in increased seizure activity. Their study utilized in vitro neuron-glial cultures and human cortical tissue from patients, revealing a direct link between d-2-HG levels and mTOR hyperactivation, which is known to influence neuronal excitability (ref: Mortazavi doi.org/10.1093/neuonc/). Furthermore, Qin et al. explored the role of ATRX, a chromatin remodeler, in gliomas, finding that ATRX loss leads to dysregulation of cell-cycle phase transition and increased sensitivity to radiation therapy. Their findings suggest that ATRX interacts with regulatory elements of cell-cycle genes, impacting the response of glioma cells to treatment (ref: Qin doi.org/10.1016/j.celrep.2021.110216/). Additionally, a meta-analysis by Schulten et al. assessed the expression profiles associated with IDH1 and IDH2 mutations across various tumor types, highlighting the complexity of these mutations and their variable oncogenic effects (ref: Schulten doi.org/10.1038/s41598-021-04214-7/). Together, these studies underscore the importance of understanding molecular mechanisms in IDH-mutant gliomas for developing targeted therapies and improving patient outcomes.

Imaging techniques play a crucial role in the diagnosis and classification of gliomas, particularly in distinguishing between IDH-mutant and IDH-wildtype tumors. Mancini et al. investigated the utility of chemical exchange saturation transfer (CEST) MRI, finding that specific biomarkers derived from CEST metrics could aid in the classification of treatment-naïve gliomas, with IDH-wildtype tumors showing higher amide/amine ratios compared to IDH-mutant tumors (ref: Mancini doi.org/10.1007/s00259-022-05676-1/). Li et al. further contributed to this field by identifying key radiological features, such as the hyperintense FLAIR rim, that are associated with IDH-mutant non-codeleted lower-grade gliomas, emphasizing the importance of specific imaging characteristics in diagnosis (ref: Li doi.org/10.1007/s00330-021-08500-w/). Moreover, Sun et al. demonstrated the effectiveness of mean apparent propagator-MRI in evaluating glioma grade and IDH-1 mutation status, revealing significant differences in MRI metrics between IDH-mutant and wild-type gliomas (ref: Sun doi.org/10.1007/s00330-021-08522-4/). These advancements in imaging techniques not only enhance diagnostic accuracy but also provide insights into tumor biology, facilitating more personalized treatment approaches.

The clinical management of gliomas is increasingly informed by molecular and histopathological characteristics, which can guide treatment strategies. Cevik et al. proposed using information theory to improve diagnostic workflows in surgical neuropathology, emphasizing the need for robust clinical aids to enhance the classification of CNS tumors in resource-limited settings (ref: Cevik doi.org/10.1111/bpa.13050/). This approach aims to integrate clinical, histological, and molecular data to optimize patient care. In parallel, Qin et al. highlighted the implications of ATRX loss in gliomas, which not only affects tumor biology but also enhances sensitivity to radiation therapy, suggesting that ATRX status could be a potential biomarker for tailoring treatment (ref: Qin doi.org/10.1016/j.celrep.2021.110216/). Additionally, Ashraf et al. explored the relationship between glioblastoma multiforme and the subventricular zone, providing insights into tumor behavior and potential therapeutic targets (ref: Ashraf doi.org/10.1080/02688697.2021.2024144/). Collectively, these studies underscore the importance of integrating molecular insights into clinical practice to refine treatment strategies and improve patient outcomes.

Histopathological features are critical for the classification and understanding of gliomas, particularly in the context of molecular characteristics. Bitar et al. conducted a retrospective analysis to determine the frequency of focal cortical dysplasia-like features adjacent to adult-type diffuse gliomas, revealing that such findings are not uncommon and may influence diagnostic considerations (ref: Bitar doi.org/10.1093/jnen/). This study highlights the need for careful histological evaluation in glioma diagnosis. Cevik et al. also emphasized the integration of histological and molecular data to enhance diagnostic workflows, suggesting that simple information theory calculations can aid in the classification of CNS tumors (ref: Cevik doi.org/10.1111/bpa.13050/). Furthermore, Marker et al. investigated the dominant TP53 hotspot mutations in IDH-mutant astrocytomas, providing valuable insights into the molecular landscape of these tumors and their implications for classification and treatment (ref: Marker doi.org/10.1093/noajnl/). Together, these studies illustrate the evolving landscape of glioma classification, driven by advancements in histopathological and molecular analysis.

Epileptogenesis in gliomas, particularly those with IDH mutations, is a significant concern impacting patient quality of life. Mortazavi et al. explored the mechanisms underlying seizures in IDH-mutant gliomas, proposing that d-2-hydroxyglutarate (d-2-HG) contributes to metabolic disruptions in cortical neurons, leading to increased seizure activity (ref: Mortazavi doi.org/10.1093/neuonc/). Their findings suggest a direct link between tumor metabolism and neurological symptoms, highlighting the need for targeted interventions. Additionally, Cevik et al. discussed the importance of integrating clinical and molecular data to improve diagnostic workflows in surgical neuropathology, which could enhance the identification of patients at risk for seizures and other neurological symptoms (ref: Cevik doi.org/10.1111/bpa.13050/). This integration of molecular insights into clinical practice is essential for developing personalized treatment strategies that address both tumor biology and associated neurological symptoms.