Glioblastoma is a highly aggressive primary brain tumour marked by extensive genomic and epigenomic alterations, cellular heterogeneity, and therapeutic resistance. Despite maximal surgical resection followed by chemoradiotherapy, median survival remains approximately 15 months, reflecting the tumour’s invasive behaviour and adaptability. Advances in molecular oncology have revealed two promising therapeutic directions: epigenetic reprogramming and neurogenetic modulation. Glioblastoma exhibits widespread epigenetic dysregulation that disrupts transcriptional control, enhances cellular plasticity, and drives tumour progression. Concurrently, glioma cells aberrantly reactivate developmental programmes, acquiring neural stem cell-like states governed by transcription factors and signalling networks such as SOX2, OLIG2, Notch, and Wnt. These pathways collectively sustain stemness, lineage mimicry, and therapy resistance. This review proposes a focused conceptual framework centred on epigenetic and neurogenetic modulation as two core regulatory layers shaping glioblastoma plasticity and adaptive resistance. We highlight how DNA methylation, histone modifications, and chromatin remodelling contribute to transcriptional dysregulation, and how neurodevelopmental signalling reinforces malignant plasticity. Emerging preclinical and clinical studies combining epigenetic inhibitors with differentiation- or reprogramming-based therapies are discussed. By uniting mechanistic insights from chromatin biology, neurodevelopment, and cancer therapeutics, this integrative conceptual framework offers a structured lens for targeting key vulnerabilities underlying glioblastoma plasticity. The integration of these complementary strategies offers potential to enhance therapeutic responsiveness and improve disease management in this devastating malignancy.

Background Insular surgery remains technically demanding because of the region’s deep location and intimate relationships with the middle cerebral artery complex and surrounding white matter pathways. Safe resection requires precise understanding of vascular landmarks and subcortical functional boundaries. Methods Eight formalin-fixed adult cadaveric heads (16 hemispheres) underwent bilateral two-piece orbitozygomatic (OZ) transsylvian (TS) dissections. Endoscopic assistance (0° and 30°) was used selectively to enhance visualization of deep and anatomically concealed regions. Following cortical exposure, approach-oriented subinsular fiber separation and dedicated hemispheric Klingler fiber dissections were performed to define operative surgical boundaries and characterize the three-dimensional organization of the peri-insular white matter. Results The OZ–TS corridor provided wide anterior and anteroinferior exposure of the insula, allowing early identification of the M2 trunks, M3 opercular branches, and lenticulostriate arteries, thereby clarifying the medial vascular limit. Endoscopic assistance provided complementary visualization of the limen insulae, anterior perforated substance, and deep perforators while maintaining the established operative corridor. Layered subinsular dissection consistently revealed the extreme capsule, claustrum, external capsule with its uncinate fasciculus and inferior fronto-occipital fasciculus (IFOF), followed by the putamen and internal capsule. The IFOF formed a critical medial boundary in anterior resections, whereas the posterior limb of the internal capsule and optic radiation defined posteromedial and posterior functional limits. Conclusion Endoscope-assisted OZ–TS exposure combined with a structured fiber-separation strategy provides an integrated anatomical perspective of the insular region. Early identification of vascular landmarks and systematic progression along intrinsic white matter planes facilitate anatomical definition of subcortical surgical boundaries.

Objective: To delineate the anatomical spectrum, frequency, and neurosurgical relevance of anterior inferior cerebellar artery (AICA) variations through combined radiological and microsurgical cadaveric analysis, and to explore potential associations between AICA anomalies and posterior circulation aneurysms. Material and Methods: Computed tomography angiography (CTA) scans of 400 patients (212 males, 188 females; mean age 55.9 years) were retrospectively reviewed for AICA anomalies, aneurysms, and other vascular variations. Cadaveric dissections of two formalin-fixed adult heads (four sides) were performed through retrosigmoid and far-lateral approaches under microscope magnification, with attention to cranial nerve relationships and labyrinthine artery origin. Results: AICA variations were identified in 26 patients (6.5%), totaling 27 variant arteries. The most common anomaly was AICA-PICA common trunk (2.5%), followed by early bifurcation (1.5%) and duplication (1.0%). Hypoplasia (0.75%), double origin (0.5%), aplasia (0.25%), and fenestration (0.25%) were less frequent. Posterior circulation aneurysms were present in 17 patients (4.25%); 11.5% of patients with AICA variations harbored aneurysms versus 3.7% without variations, suggesting a potential anatomical predisposition to aneurysm formation. Cadaveric dissection confirmed AICA origin from the basilar artery, looping around the CN VII–VIII complex, and consistent relationship with the labyrinthine artery and flocculus. Conclusion: AICA variations occur in ~6.5% of individuals, most commonly as an AICA-PICA common trunk or early bifurcation, and show a higher association with posterior circulation aneurysms. Accurate preoperative identification and understanding of microsurgical anatomy are essential, as these variants increase surgical complexity and potential complications in skull base and vascular procedures.

BACKGROUND AND OBJECTIVES: Access to the orbit, cavernous sinus, Meckel cave (MC), and infratemporal fossa (ITF) remains challenging due to the complex 3-dimensional anatomy and proximity to critical neurovascular structures. An extradural endoscopic orbitozygomatic (OZ) approach has the potential to provide a direct surgical corridor across these compartments while minimizing the limitations of compartment-specific corridors. METHODS: Five formalin-fixed, silicone-injected cadaveric heads (10 sides) were dissected using an extradural OZ approach under operative microscopy supplemented with 0° and 30° rigid endoscopes. After a two-piece OZ craniotomy, extradural dissection was performed toward the superior orbital fissure and foramen rotundum/ovale, combined with anterior petrosectomy and opening of MC. Anatomic exposure, corridor continuity, and visualization of key neurovascular structures were qualitatively assessed. RESULTS: The extradural endoscopic OZ approach created a direct working corridor from the lateral orbit to the ITF and petroclival region. Endoscopic augmentation enhanced visualization of the lateral cavernous sinus wall, trigeminal divisions (V ₁ -V ₃ ), cavernous internal carotid artery, medial orbital apex, deep infratemporal recesses, and the petroclival region. Anterior petrosectomy extended exposure toward the upper clivus and ventrolateral brainstem. Limitations included restricted microscopic visualization of the medial orbit and inferior ITF, which were partially mitigated by angled endoscopy. CONCLUSION: This cadaveric study demonstrates that the extradural OZ–anterior petrosectomy approach establishes a continuous anatomic corridor integrating the orbit, cavernous sinus/MC, ITF, and petroclival region, while defining its boundaries, areas of optimal exposure, and inherent limitations. As a qualitative study, the findings are descriptive in nature and do not include quantitative morphometric analysis.

Background/Objectives: Invasive intracranial pressure (ICP) monitoring is standard in pediatric neurocritical care, but the potential of non-invasive near-infrared spectroscopy (NIRS) and the bedside drivers of ICP remain under-explored. We evaluated the association between cerebral NIRS (rSO₂), pain and agitation, systemic hemodynamics, inflammatory markers, and invasive ICP in critically ill children. Methods: In this prospective pilot study, children undergoing external ventricular-drain-based ICP monitoring were followed with repeated measurements. Linear Mixed Models (LMM) with a random patient intercept were used to assess the NIRS–ICP association, adjusting for hemodynamic (mean arterial pressure (MAP), heart rate) and clinical variables. The Mann–Whitney U test compared parameters across a 20 mmHg ICP threshold, and the Kruskal–Wallis test compared ICP burden across etiology and outcome subgroups. Inflammatory markers (CRP, WBC, procalcitonin) were evaluated separately. Results: A total of 596 measurements from 21 patients were analyzed. Cerebral NIRS was the strongest independent predictor of ICP, showing a significant inverse association (estimate −0.609, p < 0.001). Agitation was independently associated with higher ICP (estimate 0.856, p < 0.001), and this effect was significantly modified by the patient’s behavioral state, being attenuated during sleep and calm wakefulness compared with agitated wakefulness (sleep × agitation interaction, p = 0.002). MAP retained an independent positive association with ICP (estimate 0.044, p = 0.019), whereas pain score did not. After adjustment for etiology and sex, these associations remained unchanged; etiology was itself an independent predictor of ICP (p = 0.001), whereas sex was not. Serum CRP independently predicted ICP (t = 2.382, p = 0.018), whereas WBC and procalcitonin did not. ICP burden differed by etiology, with intracranial masses and leukemia showing the highest loads (p < 0.001), but not across clinical-outcome groups (p = 0.192). Conclusions: Cerebral NIRS-derived rSO₂ was an independent inverse correlate of invasive ICP, and agitation was independently associated with ICP in a state-dependent manner, with its effect attenuated during sleep and calm wakefulness. CRP and etiology further shaped ICP burden. These findings support integrating non-invasive cerebral oximetry into multimodal pediatric neuromonitoring and highlight the value of managing distress to mitigate intracranial hypertension.

Surgical exposure of the ventral petroclival region remains technically challenging because of the complex three-dimensional relationships among the middle cranial fossa, petroclival junction, cavernous sinus, brainstem, and surrounding neurovascular structures. The orbitozygomatic (OZ) approach, anterior transpetrosal approach (ATPA), and pretemporal corridor are well-established approaches that provide complementary anatomical perspectives. This study aimed to define the continuous ventral petroclival corridor created by integrating extradural OZ–ATPA exposure with the intradural pretemporal corridor under endoscopic assistance. Five silicone-injected human cadaveric heads (10 sides) underwent standardized OZ craniotomy followed by extradural ATPA. The dissection was sequentially extended through a pretemporal intradural corridor and supplemented with 0° and 30° endoscopic inspection to evaluate anatomical continuity beyond the microscopic line of sight. Stepwise dissections were performed to characterize anatomical visualization during the sequential dissection along the ventral petroclival axis. Following anterior petrosectomy and dural opening, the ventrolateral brainstem between the dorsum sellae and the internal auditory canal (IAC) was visualized. Through the combined OZ–pretemporal trajectory, the optic tract, crural cistern, interpeduncular cistern, and mammillary bodies were identified from an inferior-to-superior perspective. Endoscopic inspection demonstrated deep and contralateral petroclival structures, including the contralateral abducens nerve and petrous apex, as well as inferior structures toward the cerebellopontine angle beyond the IAC. These findings document qualitative anatomical visualization; surgical freedom and the safety of instrument manipulation around the inferior and contralateral structures were not assessed. Stepwise integration of extradural OZ–ATPA exposure with the intradural pretemporal corridor and endoscopic inspection provides complementary anatomical views from the mammillary bodies to the cerebellopontine angle. This framework may support three-dimensional anatomical orientation and operative planning, but endoscopic visualization does not establish a safe working corridor to all visualized structures.