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 and Objectives: Endoscope-assisted posterior fossa decompression with duraplasty (PFDD) is a minimally invasive alternative treatment for Chiari I malformation; however, its comparative effectiveness remains unclear. Therefore, this study aimed to compare the outcomes of conventional open decompression with those of endoscope-assisted minimally invasive decompression combined with duraplasty to assess the balance between limited surgical exposure and associated technical challenges. Materials and Methods: This retrospective single-center study compared 22 patients who underwent endoscope-assisted PFDD with a historical cohort of 16 patients treated with conventional open PFDD. Patients with C1–2 instability, prior craniovertebral surgery, or concomitant pathology requiring an alternative surgical strategy were excluded. The clinical outcomes, radiological findings, surgical variables, and complications were analyzed. Results: Clinical improvement, overall recovery, and 3-month Chicago Chiari Outcome Scale (CCOS) scores were comparable between the groups. The endoscopic group had higher CCOS scores at discharge. Syrinx resolution rates were similar, whereas postoperative cisterna magna expansion was more limited in the endoscopic cohort. The endoscopic approach was associated with a significantly shorter incision length and earlier mobilization. The rates of complications, including pseudomeningocele, cerebrospinal fluid fistula, and wound infection, did not differ significantly between the groups. Conclusions: Endoscope-assisted PFDD may be a less invasive alternative with comparable short-term clinical and radiological outcomes. Despite the technical challenges related to a limited working corridor, it can be considered a feasible option for selected patients.

Background and Objectives: Unplanned return to the operating room (URTOR) is a sensitive indicator of surgical quality; however, data in neurosurgery are limited. This retrospective study analyzed patients who underwent URTOR following neurosurgical procedures over an eight-year period to define early and late patterns, identify underlying causes, and evaluate the distribution of cases according to surgeon experience. Materials and Methods: Records of 18,258 consecutive surgeries including both elective and emergency procedures in adult and pediatric patients, performed at a single center between 2010 and 2018 were retrospectively reviewed. Unplanned reoperations within 30 days of the index surgery were defined as URTOR; those occurring within ≤7 days were classified as “early,” and those occurring between 8 and 30 days were classified as “late.” Demographic data, surgical characteristics, causes of URTOR, and surgeons’ seniority were examined. Results: Among 18,258 neurosurgical procedures, 324 URTORs (1.8%) were identified. The median patient age was 38 years; 37% were children. Early URTOR comprised 59% and was primarily associated with hemorrhagic–vascular complications, whereas late URTOR accounted for 41% and was dominated by cerebrospinal fluid-related and infectious complications. Late events prevailed in significantly younger cases and were disproportionately followed by ventriculo–peritoneal shunt or endoscopic third ventriculostomy index operations. Junior surgeons performed 74% of later operations requiring URTOR versus 30% of early failures. Sex, weekday/weekend timing, and surgeons’ experience did not affect the overall URTOR classification categories. The median interval was six days. Conclusions: Centers worldwide have begun to examine URTOR rates, which are directly associated with hospital quality measurements. These results may inform targeted education and prevention by identifying patient groups at higher reoperation risk within a specific timeframe.

The middle cerebral artery is the largest branch of the internal carotid artery and supplies extensive cortical and deep cerebral territories. Variations in its branching pattern are of considerable importance in microsurgical planning and may influence aneurysm development. This study aimed to evaluate the prevalence of middle cerebral artery variations, their microsurgical anatomy, and their relationship with anterior circulation aneurysms. Computed tomography angiography images of 500 patients were retrospectively reviewed to identify middle cerebral artery variations and anterior circulation aneurysms. Additionally, the microsurgical anatomy of the middle cerebral artery was demonstrated through dissections of two cadaveric heads. Descriptive statistical analyses were performed. Middle cerebral artery variations were identified in 62 patients (12.4%), with a total of 73 variations. The most frequent variants were trifurcation (n=35) and early cortical branch (n=24), followed by accessory middle cerebral artery (n=6), fenestration (n=6), and duplication (n=2). Eleven patients exhibited two concurrent variations. Anterior circulation aneurysms were detected in 118 patients, comprising 132 aneurysms in total. The most common locations were middle cerebral artery (n=53), posterior communicating artery (n=28), and anterior communicating artery (n=27). Fourteen patients harbored multiple anterior aneurysms. Aneurysms were present in 30.6% of patients with middle cerebral artery variations compared to 22.6% of those without variations. Among variation subtypes, trifurcation demonstrated the highest aneurysm rate (45.7%). Cadaveric dissections emphasized the surgical relevance of preserving early cortical branches and perforating arteries. Recognition of middle cerebral artery variations and their association with aneurysm distribution is essential for optimizing microsurgical strategy and improving neurovascular management.