High-grade gliomas are aggressive, primary, central nervous system tumors with low survival rates due to recurrence and resistance to current therapy models. Recent studies have highlighted the importance between the interaction of glioma cancer cells and cells of the tumor microenvironment (TME). Cancer stem cells and immune cells play a critical role in the TME of gliomas. TMEs in glioma include the perivascular TME, hypoxic TME, and invasive TME, each of which have evolved as our understanding of the involved cellular players has improved. This review discusses the multidimensional aspects of the current targeted therapies and interactions between glioma cells and the TME with specific focus on targeted immunotherapies. Understanding the complexities of the TME and elucidating the various tumor-cell interactions will be critical for facilitating the development of novel precision strategies, ultimately enabling better patient outcomes.

Background/Objectives: Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare neuroectodermal malignancy of the nasal cavity characterized by aggressive local invasion and variable metastatic potential, with diverse clinical behavior, often presenting at advanced stages. ONB poses challenges for targeted therapeutic strategies, despite advances in surgical and multimodal treatment strategies, because of the rarity of this disease and the limited understanding of its molecular pathophysiology. Methods: A comprehensive review of genomic, multi-omic, and molecular studies was performed to integrate known targeted sites in ONB with the current understanding of its pathophysiology. Results: Recent genetic and molecular studies have identified significant epigenetic and signaling pathway alterations that are critical in pathogenesis and treatment resistance and may serve as potential therapeutic targets. Additionally, novel discovered immunohistochemical and transcriptomic markers, such as IDH2, NEUROD1, and OTX2, offer improved diagnostic specificity and prognostication. Multi-genomic platforms (i.e., multi-omics), involving the combined integration of transcriptomics, epigenetics, and proteomics findings, have led to several recent insights, including the subclassification of neural and basal genomic subtypes, the identification of key driver mutations, and new insights into disease development. This review synthesizes current knowledge on the molecular landscape of ONB, including its tumor origin, immune microenvironment, genetic alterations, and key molecular pathways involved in its pathogenesis. Conclusions: Future research may benefit from integrating these findings into precision medicine approaches, enabling earlier diagnosis and more accurate prognosis.

Background: Leptomeningeal disease (LMD) is challenging to diagnose and monitor given the poor sensitivity of current gold-standard diagnostics. Cerebrospinal fluid tumor cells (CSF-TCs) have been studied as a biomarker for disease management because oncogene amplification of the primary, metastatic, and CNS metastatic tumors can be heterogeneous. The CNSide platform enumerates CSF-TCs and analyzes oncogene expression via immunocytochemistry (ICC), fluorescent in situ hybridization (FISH), and next-generation sequencing (NGS). We report the utility of this combined enumerative and mutational testing for LMD diagnosis and disease monitoring. Methods: A multicenter, retrospective analysis of commercially ordered assays from two health systems between January 2020 and July 2023 included 613 tests on 218 individual patients with suspected or confirmed LMD. To date, this is the largest cohort of patients in LMD literature evaluated using CSF-TCs. Results: CSF-TCs were detected in 67% (412/613) of samples. The most analyzed cancer types were breast (n = 105) and lung (n = 65). In lung cancer, anaplastic lymphoma kinase (ALK) was detected in 14% (17/118), and c-MET was detected in 61% (78/128). In breast cancer, HER2 was detected in 39% (65/168), and estrogen receptor (ER) was detected in 26% (44/168). Sixty-six patients underwent 2+ longitudinal CSF draws; among these, there were 58 flips in oncogene detection over time, and 30% (20/66) of patients had at least one biomarker change in the CSF. Conclusions: Longitudinal combined ICC/FISH/NGS CSF testing demonstrates a wide range in CSF-TC enumeration, which may be correlated with clinical course, and furthermore identifies actionable tumor markers that frequently fluctuate over time. Utilization of this platform would enable timely, personalized LMD-specific chemotherapy.

Background: Intracranial atherosclerotic disease (ICAD) remains a major global cause of ischemic stroke—particularly in Asian, Black, and Hispanic populations—and is characterized by high recurrence rates despite advances in intensive medical management. Objectives: This review synthesizes current evidence on surgical and endovascular approaches for ICAD, including extracranial–intracranial bypass, encephaloduroarteriosynangiosis, angioplasty, and hybrid revascularization strategies. Methods: We performed a structured narrative literature search of PubMed and Scopus. Searches were conducted up to 1 October 2025 using combinations of subject headings and keywords, including “intracranial atherosclerotic disease”, “ICAD”, “intracranial stenosis”, “bypass”, “encephaloduroarteriosynangiosis”, “angioplasty”, “stenting”, “revascularization”, and “stroke”. We also scanned reference lists of key articles and relevant reviews. Non-English language articles were excluded. Results: While randomized trials such as SAMMPRIS, VISSIT, and CASSISS reaffirm intensive medical management as first-line therapy, emerging data suggest that surgical revascularization may benefit select patients with hemodynamic compromise refractory to medical therapy. Recent studies incorporating physiologic imaging—such as PET, SPECT, and perfusion MRI—have refined patient selection, reducing perioperative risk and improving long-term outcomes. Innovations in indirect revascularization, hybrid procedures, and intraoperative imaging continue to expand therapeutic possibilities. However, evidence remains heterogeneous, underscoring the need for well-powered randomized trials integrating modern surgical techniques, objective hemodynamic endpoints, and AI-enhanced imaging analytics. Conclusions: While intensive medical management remains the first-line standard of care, select patients with refractory, hemodynamically significant ICAD may benefit from direct, indirect, or hybrid surgical revascularization. Future directions emphasize personalized, physiology-based management frameworks that combine medical, surgical, and technological advances to optimize stroke prevention and long-term vascular outcomes in ICAD.

The discovery of the glymphatic system (GS) transformed understanding of central nervous system homeostasis by revealing a brain-wide network that facilitates cerebrospinal and interstitial fluid exchange along perivascular pathways. This system clears metabolic waste and maintains the precise ionic environment required for neuronal function through the coordinated action of astrocytic aquaporin-4 channels and intact perivascular architecture. Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, alters physiological barriers through pathological angiogenesis, compression of perivascular spaces, depolarization of aquaporin-4 at astrocytic endfeet, and obstruction of venous and lymphatic drainage. This narrative review synthesizes current experimental and clinical literature identified through targeted searches of PubMed and Scopus to examine interactions between glioblastoma, glymphatic system dysfunction, and tumor microenvironmental changes. To minimize selection bias, studies were categorized according to evidence source and experimental design. Evidence from rodent models and advanced imaging demonstrates as tumor growth impairs glymphatic function, the resulting dysfunction promotes tumor progression by enabling accumulation of pro-tumorigenic growth factors, inflammatory mediators, and acidic metabolites, while elevated interstitial fluid pressure limits drug delivery. Impaired antigen drainage further diminishes immune surveillance, contributing to the immunosuppressive microenvironment that limits immunotherapy efficacy. A critical evaluation of these mechanisms highlights how the glymphatic system influences disease progression and suggests novel avenues for diagnostic imaging and therapeutic intervention. Although significant challenges remain in modeling human fluid dynamics, understanding these hidden networks offers a promising frontier for strategies aimed at restoring cerebral clearance and improving clinical outcomes.

Introduction: Severe traumatic brain injury (sTBI) frequently coexists with polytrauma and often necessitates damage control neurosurgery (DCNS), where rapid decompression and temporary stabilization take precedence over definitive reconstruction. Within this context, anesthetic management must balance cerebral protection with ongoing resuscitation, yet high-quality DCNS-specific evidence remains limited. Materials and Methods: A comprehensive search of PubMed, Scopus, and Google Scholar (2015–2025) was conducted using MeSH terms and keywords related to neurotrauma, anesthesia, intracranial pressure, and perioperative management. Studies were included if they examined anesthetic or hemodynamic strategies in severe TBI or DCNS and reported relevant clinical or physiologic outcomes. Results: Nineteen articles addressing perioperative strategies for optimizing DCNS outcomes were analyzed. Discussion: Preoperative care emphasizes hemodynamic stabilization and permissive hypertension, damage control resuscitation including massive transfusion protocols, optimization of cerebral perfusion pressure (CPP) and neuromonitoring, and the use of hyperosmolar therapy. Transexamic acid can be used in sTBI safely but with unclear improvement in outcomes. Intraoperatively, propofol-based total intravenous anesthesia is generally preferred over volatile agents due to favorable effects on intracranial pressure (ICP), cerebral blood flow (CBF), autoregulation, and emergence. While historically contraindicated, ketamine and etomidate are now increasingly used as hemodynamically protective induction agents. Analgesic and sedative strategies prioritize dexmedetomidine and carefully titrated opioids to minimize respiratory depression and reduce postoperative complications. CPP and ICP-directed management relies on individualized blood pressure targets, vasopressor selection, lung-protective ventilation, and strict temperature control. Conclusions: Emerging evidence has suggested the benefit of DCNS for patient survival. Overall, perioperative care is guided largely by physiology and extrapolation, highlighting the need for standardized protocols.