Search Results (1,029)

Technological advances in optical imaging and artificial light technologies have substantially transformed modern neurosurgical practice by improving intraoperative visualization and surgical precision. This narrative review evaluates current applications of fluorescence-guided surgery, optical navigation systems, near-infrared imaging, augmented visualization platforms, and artificial intelligence-assisted intraoperative imaging in neurosurgery. Particular attention is given to clinically established fluorophores, including 5-aminolevulinic acid, fluorescein sodium, and indocyanine green, which are increasingly used for tumor delineation, vascular assessment, and real-time tissue perfusion analysis. Emerging technologies such as Raman spectroscopy, multispectral imaging, holographic navigation, and nerve-specific fluorescent probes are also discussed in the context of precision and minimally invasive neurosurgery. Current evidence demonstrates that advanced optical systems improve surgical orientation, maximize extent of resection, and support preservation of critical neurovascular structures, particularly in neuro-oncology, vascular neurosurgery, and skull base surgery. However, limitations related to fluorescence specificity, standardization, cost, and technological accessibility remain significant challenges. The continued integration of multimodal optical imaging, computational navigation, and AI-assisted visualization is expected to further enhance intraoperative decision-making, surgical safety, and postoperative outcomes, contributing to the future development of precision image-guided neurosurgery. Full article

Small-molecule kinase inhibitors offer a compelling therapeutic strategy for glioblastoma, yet their clinical efficacy remains severely limited by blood–brain barrier penetration and active efflux transporter extrusion. This review evaluates current medicinal chemistry approaches and translational paradigms to overcome these drug delivery and biological constraints. A critical analysis of the literature reveals that direct structural optimization faces a multidimensional balancing act; next-generation design must prioritize macrocyclization, structural rigidification, and bioisosteric capping to lower polar surface area and evade P-glycoprotein and BCRP efflux. Furthermore, carrier-mediated prodrugs targeting the LAT1 transporter provide a viable rescue strategy for highly potent scaffolds. Reviewing recent clinical failures, such as paxalisib and osimertinib, underscores that single-node monotherapies fail due to compensatory pathway hyperactivation and clonal heterogeneity, whereas multi-targeted agents or rational dual-node combinations prevent rapid tumor adaptation. Additionally, combining kinase inhibitors with DNA damage repair inhibitors, immune checkpoint modulation, or MR-guided focused ultrasound could provide powerful synergistic networks. Finally, bridging the translational gap requires complementing conventional serum-cultured cell lines with patient-derived glioma stem cells and orthotopic xenografts to better recapitulate the cellular architecture of the disease. Ultimately, overcoming the therapeutic challenges in glioblastoma demands a fundamental pivot toward rigorous neuro-pharmacological design and multi-lineage network oncology. Full article

Background/Objectives: Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, characterized by inevitable recurrence, extensive inter-and intratumoral heterogeneity, and resistance to current therapies. A defining feature of GBM is the dynamic interplay between malignant cells and a diverse tumor microenvironment (TME), which together drive disease progression, therapeutic adaptation, and relapse. Understanding these complex cellular ecosystems has therefore become a major focus of glioblastoma research. Recent advances in spatial omics technologies have transformed our ability to investigate GBM biology directly within intact tissue architectures. Over the past five years, an expanding array of spatial transcriptomic, proteomic, and multi-omic platforms has enabled high-dimensional characterization of cellular states, cell–cell interactions, and tissue niches while preserving spatial context. These approaches have generated unprecedented insights into tumor organization, cellular plasticity, immune landscapes, vascular niches, and treatment-induced ecosystem remodeling. Methods: In this review, we provide an overview of spatial omics applications in glioblastoma research so far. Results: We summarize the technologies employed, the types and numbers of patient samples analyzed, and the major biological and clinical insights generated. We compare the strengths and limitations of different spatial platforms, discuss key considerations for study design and data interpretation, and highlight emerging trends in multimodal and longitudinal analyses. Conclusions: By integrating both technological and biological perspectives, this review serves as a practical resource for researchers seeking to implement spatial omics approaches in glioblastoma studies and to advance precision neuro-oncology. Full article

Background: Brain tumor magnetic resonance imaging (MRI) reporting and tumor segmentation for treatment planning are time-consuming and variable. This retrospective fixed-sequence paired workflow study evaluates whether AI assistance is associated with changes in efficiency, consistency, and reproducibility. Methods: Thirty MRI cases (10 vestibular schwannomas, 10 meningiomas, 10 brain metastases) were assessed. Two neuroradiologists completed diagnostic reporting with and without AI assistance, and two physicians completed tumor delineation with and without AI-generated preliminary contours after a 3-week washout. Results: Reporting time decreased from 42.94 to 27.90 min for Reader A and from 101.04 to 80.47 min for Reader B, corresponding to median paired case-level reductions of 40.39% and 11.51%, respectively; only Reader A reached statistical significance. Sensitivity remained 97.73% and 100.00%, while precision was numerically higher after AI assistance (89.58% to 97.73% and 83.02% to 91.67%). Report-similarity metrics increased across ROUGE-L, BERTScore F1, and Sentence-BERT cosine similarity (all p < 0.001). Contouring time decreased from 54.63 to 4.93 min for Reader 1 and from 184.44 to 44.19 min for Reader 2, with median paired reductions of 100.00% and 87.11%. Dice coefficients were numerically higher after AI assistance (0.81 to 0.87 and 0.83 to 0.87). Conclusions: AI assistance was associated with shorter task-completion times, higher report-similarity metrics, and numerically higher contour-overlap measures. Prospective validation should determine whether these workflow efficiency gains translate into broader clinical benefit. Full article

Background: Clinical outcomes in isocitrate dehydrogenase (IDH)-wildtype grade 4 diffuse glioma remain highly heterogeneous despite standard multimodal therapy. We evaluated the prognostic significance of pretreatment platelet-to-albumin ratio (PAR) and compared its performance with established inflammatory biomarkers. Methods: This retrospective cohort study included 166 patients with histopathologically confirmed IDH-wildtype grade 4 diffuse glioma treated between 2017 and 2025. Pretreatment PAR, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune inflammation value (PIV), C-reactive protein-to-albumin ratio (CAR), and lactate dehydrogenase-to-albumin ratio (LAR) were evaluated. Discriminative performance was assessed using classical and inverse probability of censoring weighting (IPCW)-adjusted time-dependent receiver operating characteristic (ROC) analyses. Survival outcomes were evaluated using Kaplan–Meier analyses and predefined baseline-adjusted multivariable Cox proportional hazards regression models. Internal validation was performed using 1000 bootstrap resampling iterations. Results: PAR demonstrated the highest discriminative performance for 12-month overall survival (OS), with an area under the curve of 0.853. Using an optimal cutoff value of 79.459, patients with elevated PAR experienced significantly shorter OS (median, 6.2 vs. 16.7 months; p < 0.001) and progression-free survival (PFS) (median, 5.9 vs. 12.3 months; p < 0.001). In baseline-adjusted multivariable analyses, elevated pretreatment PAR remained independently associated with inferior OS (hazard ratio [HR], 3.287; 95% confidence interval [CI], 2.196–4.921; p < 0.001) and PFS (HR, 3.791; 95% CI, 2.501–5.749; p < 0.001). These findings were supported by sensitivity analyses and bootstrap internal validation. Conclusions: Pretreatment PAR was independently associated with survival outcomes and demonstrated favorable discriminative performance relative to other inflammatory biomarkers. PAR may represent an accessible biomarker reflecting tumor–host interactions in IDH-wildtype grade 4 diffuse glioma. The proposed PAR cutoff should be considered exploratory and requires external validation before routine clinical application. Full article

Introduction: A subependymal giant cell astrocytoma (SEGA) is a benign tumor typically associated with tuberous sclerosis complex (TSC), an autosomal dominant syndrome. Case report: The patient, a 15-year-old male, presented with headaches, nausea, and visual obscurations, consistent with increased intracranial pressure. Neuroimaging identified a mass in the anterior left lateral ventricle causing unilateral obstruction at the foramen of Monro. During microsurgery, smears showed a low-grade glial tumor with a biphasic mix of elongated astrocytes and large epithelioid-to-gemistocyte-like cells. Gross total resection was achieved. On permanent sections, a tumor with large polygonal, ganglioid, and gemistocytic-like cells was seen. Nuclear pleomorphism, a feature of SEGA, was present. On immunohistochemistry, the tumor was positive for glial fibrillary acidic protein (GFAP), S100, and CD34, and the cells also displayed nuclear staining for TTF-1. A diagnosis of SEGA in the absence of clinical features of TSC was established; however, definitive classification as sporadic remains limited by the lack of molecular data. Conclusions: This case highlights the importance of evaluating intraventricular masses through the integration of lineage-specific immunohistochemical panels to prevent misclassification of pleomorphic giant cells as high-grade gliomas. Full article

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by rapid progression, therapeutic resistance, and poor patient prognosis. Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in GBM pathogenesis, particularly through their interactions with RNA-binding proteins (RBPs). These interactions form complex regulatory networks that influence multiple GBM hallmarks, such as sustained proliferation, induction of angiogenesis, and immune evasion. Additionally, these interactions play a pivotal role in maintaining glioma stem-like cells, a subpopulation responsible for tumor recurrence and resistance to conventional therapies. Understanding the mechanistic basis of lncRNA-RBP interactions offers promising opportunities for therapeutic intervention. Targeting these networks could enable the development of novel and more effective treatment strategies. This review provides an in-depth analysis of the molecular mechanisms by which lncRNA-RBP complexes promote GBM development. Full article

Headache is a frequent and clinically relevant symptom in patients undergoing cranial radiotherapy, most often reflecting treatment-induced structural and inflammatory changes such as cerebral edema or radiation-related brain injury. Differentiating secondary headache from primary disorders, particularly migraine, is essential for appropriate management. This review aims to examine the pathophysiological mechanisms underlying headache following cranial radiotherapy, evaluate current pharmacological and complementary treatment strategies and highlight key aspects of differential diagnosis with migraine. Unlike existing literature that focuses primarily on radiological findings of radiation injury, this review adopts a symptom-driven approach, reframing headache as a critical clinical gateway for the early detection of structural complications. A structured narrative review of the literature was conducted using PubMed/MEDLINE, Scopus and Google Scholar to identify studies published between 2020 and 2025, focusing on cerebral edema, radiation-related complications, therapeutic approaches and migraine. Relevant clinical trials, systematic reviews and guidelines were included. Cerebral edema consistently emerges as the main mechanism of acute and subacute post-radiotherapy headache, whereas late-onset symptoms are most often linked to radiation necrosis. Corticosteroids remain first-line therapy, while bevacizumab has demonstrated benefit in steroid-refractory cerebral edema and radiation necrosis through inhibition of vascular endothelial growth factor (VEGF), thereby reducing vascular permeability and attenuating peritumoral edema. Its use in the context of cranial radiotherapy requires careful consideration, as the safety of concomitant administration with radiation has not been formally established, and headache itself is among its recognized adverse effects. Evidence for complementary therapies, including Boswellia serrata and plant-based compounds, remains limited. Migraine constitutes a distinct neurovascular disorder requiring careful differentiation from secondary headache in oncological patients. The review emphasizes headache as a clinically relevant indicator of underlying structural complications rather than an isolated symptom. Post-radiotherapy headache should be interpreted as a manifestation of underlying structural pathology. Accurate etiological diagnosis and individualized management are essential. Further research is needed to refine treatment strategies and clarify the role of complementary therapies. Full article

Osteopontin (OPN), encoded by the SPP1/Spp1 gene, is increasingly recognized as an extracellular matrix-associated immunoregulatory molecule in the central nervous system (CNS). In CNS-related contexts, OPN does not act as a uniformly protective or detrimental factor. Instead, its effects depend on the producing cell type, molecular form, receptor axis, disease stage, and lesion compartment. Accumulating evidence indicates that OPN may participate in reparative processes, including tissue preservation, debris clearance, vascular remodeling, and support of myelin-related repair, while sustained or ectopic OPN activity may contribute to synaptic injury, persistent glial reactivity, remyelination failure, and immunosuppressive tumor progression. In this review, we summarize the molecular basis of SPP1/Spp1 expression and OPN protein signaling, with emphasis on isoforms, proteolytic processing, receptor usage, and secreted versus intracellular OPN. We then discuss its roles in CNS development, chronic neurological diseases, acute CNS injury, and neuro-oncology, and highlight the need to distinguish biomarker associations, omics-based candidate pathways, and functionally validated mechanisms when considering OPN-related diagnostic or therapeutic strategies. Full article

Background/Objectives: Repetitive transcranial magnetic stimulation (rTMS) has been increasingly investigated as an adjunctive intervention in neurorehabilitation, particularly for motor recovery after stroke. However, conventional rTMS protocols remain limited by variability in target localization, inter-individual anatomical differences, lesion-related network reorganization, and limited reproducibility across treatment sessions. Neuronavigated repetitive transcranial magnetic stimulation (nrTMS) integrates structural neuroimaging with real-time coil tracking, enabling more precise and reproducible stimulation of patient-specific cortical targets. This approach may be especially relevant in patients with focal brain lesions, postoperative anatomical distortion, or functionally reorganized networks. Methods: This narrative review summarizes the biological rationale, current clinical evidence, practical workflow, and limitations of nrTMS in neurorehabilitation, with particular attention to the distinction between conventional rTMS and neuronavigated protocols. Results: The strongest evidence for rTMS-based rehabilitation remains in post-stroke motor recovery, although most studies have used non-navigated protocols. In contrast, postoperative neuro-oncological rehabilitation represents a clinically relevant but still investigational context for nrTMS, as preoperative functional mapping, postoperative deficits, and early rehabilitation can be integrated within a patient-specific therapeutic pathway. Early studies suggest feasibility when stimulation is combined with structured physiotherapy; however, the available evidence is based on small and heterogeneous cohorts, and clinically meaningful superiority over conventional rTMS or standard rehabilitation has not yet been established. Data in traumatic brain injury, multiple sclerosis, ataxias, and neurodegenerative disorders are still preliminary and heterogeneous. Conclusions: Neuronavigation should not be interpreted as an independent therapeutic breakthrough, but rather as a precision-enhancing component of rTMS-based rehabilitation. Its main potential value lies in improving targeting accuracy, session-to-session reproducibility, and integration with individualized neuroimaging and rehabilitation goals. Accordingly, nrTMS should currently be considered a precision-enhancing and hypothesis-generating framework rather than an established rehabilitation standard. Full article

The widespread adoption of prostate-specific membrane antigen (PSMA)-targeted PET/CT has profoundly reshaped molecular imaging in prostate cancer and has substantially reduced the routine use of radiolabeled choline tracers. However, the transition from choline to PSMA imaging should not be interpreted simply as the replacement of one radiopharmaceutical by another, but rather as part of a broader evolution from metabolism-based imaging toward receptor-targeted and biology-driven imaging strategies. This narrative review critically reassesses the residual and emerging role of choline PET/CT in the PSMA era, with particular attention to the biological rationale of choline uptake, selected prostate cancer scenarios, and extra-prostatic applications. In prostate cancer, PSMA PET/CT remains the dominant imaging modality because of its superior diagnostic performance, particularly in biochemical recurrence; nevertheless, choline PET/CT may provide complementary metabolic information in highly selected settings, including PSMA-low or heterogeneous disease, aggressive or dedifferentiated variants, neuroendocrine transformation, equivocal PSMA findings, and limited PSMA availability. These prostate cancer applications, however, are supported mainly by biological rationale, indirect evidence, and limited clinical data and should therefore be regarded as exploratory rather than established indications. By contrast, ¹⁸F-fluorocholine PET/CT has emerged as a clinically established imaging modality in primary hyperparathyroidism, particularly after negative or inconclusive conventional imaging, with prospective studies and meta-analyses demonstrating high detection rates and superior performance compared with conventional scintigraphic techniques. Additional applications in hepatocellular carcinoma and selected neuro-oncologic settings remain exploratory and require further validation. Overall, choline PET/CT should not be considered obsolete in the PSMA era, but selectively repositioned within biology-driven and multiparametric imaging strategies, with its strongest evidence currently supporting primary hyperparathyroidism and its other applications requiring cautious interpretation and further prospective validation. Full article

Accurate, automated delineation of adult diffuse gliomas from multi-parametric magnetic resonance imaging (mpMRI) is central to quantitative neuro-oncology. Volumetric 3D networks dominate the BraTS leaderboard but require expensive GPUs, long training cycles, and provide diminishing returns relative to their compute budget. Slice-wise 2D models, by contrast, discard inter-slice context that is informative for thin tumor rims and small enhancing foci. We introduce GDNet, a 2.5D multimodal MRI segmentation framework for adult glioma evaluated on the BraTS 2024 cohort. GDNet consumes a stack of three adjacent axial slices from the four standard BraTS modalities (T1, T1ce, T2, FLAIR) as a 12-channel input to a compact U-shaped encoder–decoder with Group Normalization and predicts whole tumor (WT), tumor core (TC), and enhancing tumor (ET) masks for the central slice. The training pipeline pairs the 2.5D backbone with: (i) Exponential Moving Average (EMA) of model weights with decay 0.999, (ii) mixed tumor-aware slice sampling (p_tumor = 0.50), (iii) a compound Cross-Entropy + Soft-Dice loss, and (iv) AdamW with warm-up plus cosine annealing under Automatic Mixed Precision. We performed a systematic, step-by-step ablation covering a 2D baseline, EMA + mixed sampling, tumor-centered crop fine-tuning, a GDNet-inspired architectural integration, a region-aware loss, 3-slice and 5-slice 2.5D inputs, and connected-component post-processing, and we report multi-seed results to quantify reproducibility. On the held-out BraTS 2024 test partition, the final 3-slice 2.5D GDNet achieved positive-only Dice scores of 0.791 ± 0.000 (WT), 0.736 ± 0.003 (TC), 0.654 ± 0.004 (ET), and a mean foreground positive-only Dice of 0.820 ± 0.000 across seeds; the all-slice mean foreground Dice exceeded 0.927 ± 0.000. Validation positive-only scores were 0.805 ± 0.002 (WT), 0.757 ± 0.004 (TC), 0.683 ± 0.009 (ET). The inter-seed standard deviation was small for every region (≤0.01 Dice points), indicating low inter-seed variance across the two seeds evaluated; with only two seeds, we regard this as preliminary evidence of training stability rather than a strong reproducibility claim. The ablation isolated EMA + mixed tumor sampling and the 2.5D context window as the dominant sources of improvement; notably, a GDNet-style architectural integration with a region-aware loss did not outperform the simpler 2.5D U-Net on positive-only WT/TC/ET, and light post-processing improved only all-slice Dice. A failure-mode audit found that the residual catastrophic predictions are concentrated on a small minority of diffuse, infiltrative tumors with mass effect. Conclusions: Carefully engineered training strategies, tumor-aware sampling, EMA stabilization, and a modest 2.5D context window recover a substantial fraction of the accuracy of much heavier 3D networks at a fraction of the compute, are reproducible across seeds, and outperform a heavier GDNet-inspired architectural variant on the same data. GDNet is therefore a practical and, pending external validation, potentially clinically deployable framework for multimodal glioma segmentation on workstation-class GPU hardware. Full article

Background: Glioblastoma (used to be called glioblastoma multiforme—GBM) is the most common and aggressive brain tumor, having the lowest overall survival rate. Initial focal neurological deficits are primarily attributable to surrounding edema; however, as tumor invasion progresses, these deficits become more pronounced and permanent. The standard treatment for newly diagnosed glioblastoma is represented by cytoreductive neurosurgery followed by the Stupp Protocol. Postoperative recovery of the patient with glioblastoma is a long-term process that should include, for overall more acceptable outcomes, neurorehabilitation. This review aims to bring together evidence from neuro-oncology, neurosurgery, and neurorehabilitation in order to better understand the factors associated with recovery, functional status, and quality of life (QoL) after glioblastoma surgery. Our work also aimed to update the related knowledge base and to attempt to optimize the related protocols in patients with operated cerebral glioblastoma. Methods: For these purposes, we conducted a systematic literature review to assess the current state of research referring to the above-mentioned topic. We have used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA—widely recognized internationally) methodology. We used, in this respect, specific keyword combinations/“syntaxes” for searching literature in the domain, in four international databases. Results: Following PRISMA screening, 14 studies met the predefined eligibility criteria. Additional manual reference screening and complementary searches identified further relevant publications, resulting in a total of 22 included articles. Together, the reviewed work addressed a diverse range of topics relevant to postoperative glioblastoma management, including the potential role of multidisciplinary rehabilitation, cognitive interventions, neuromodulation approaches, and functional assessment strategies in improving postoperative outcomes and QoL in glioblastoma patients, while emphasizing that this interdisciplinary domain warrants more extended approaches. Discussion and Conclusions: Despite the relatively limited and largely exploratory available information, neurorehabilitation may contribute to improved functional outcomes and QoL in patients with glioblastoma. Full article

Background: Neuromodulation is a rapidly developing field with growing interest in its application in neuro-oncology, particularly since the publication of the EF-14 trial which demonstrated a survival benefit conferred by tumour treating fields (TTF) in patients with glioblastoma. In addition, the emerging field of cancer neuroscience has postulated the role of neural–tumour communication in tumour aetiology, which is theoretically targetable by neuromodulation strategies. This scoping review therefore aims to comprehensively evaluate current or future applications of neuromodulation in managing patients with brain tumours, encompassing preclinical and clinical studies. Methods: The MEDLINE database was queried for all relevant articles from inception to 1 December 2024. A synthesis of findings was performed, broadly categorised to preclinical and clinical research. Findings: The database search returned 3296 results, from which 187 full-text articles were further assessed. A total of 79 studies met the inclusion and exclusion criteria and were included. The results from preclinical studies (n = 18) were stratified according to modality which included electrical therapy, electroporation, electromagnetic field (EMF) and deep brain stimulation (DBS). Similarly, clinical studies (n = 61) were classified to preoperative modalities such as transcranial magnetic stimulation (TMS) and transcranial direct stimulation (tDCS), and postoperative modalities such as TMS, TTF, EMF and spinal cord stimulation (SCS). Interpretation: The application of neuromodulation as adjunctive therapy in the context of neuro-oncology is an emerging field, with encouraging results in various modalities across a wide range of applications from surgical planning and functional rehabilitation, to its therapeutic potential. Further research is urgently needed to harness the potential of neuromodulation in improving patient outcomes. Full article

Introduction: Pituitary carcinoma (PC) is a rare, aggressive endocrine neoplasm characterized by metastasis and challenging clinical management. The transformation from pituitary adenoma (PA) to PC is poorly understood, and predictors of metastasis remain elusive. This study evaluates the clinical course, surgical outcomes, and molecular characteristics of PC. Methods: We retrospectively reviewed patients with PC treated at the M. D. Anderson Cancer Center between 1993 and 2023. Primary outcomes included metastasis-free survival and overall survival (OS). Clinical features, radiographic findings, surgical strategies and outcomes, immunohistochemical profiles, and MIB-1 were analyzed. Results: The cohort (n = 20) had a median age at PA and PC diagnosis of 33.9 and 43.3 years, respectively. The median metastasis-free interval was 7.4 years. GH- and ACTH-secreting tumors showed shorter times to PC diagnosis, while nonfunctioning PAs had longer metastasis-free survival. PAs with MIB-1 > 10% had shorter survival. Dura was the most common site of metastasis within the CNS, and bone was the most common outside the CNS. Leptomeningeal disease was seen in six patients. PAs became aggressive > five years after initial surgical resection (n = 13) or metastasized early within the first five years (n = 7). Median OS from PA diagnosis was 13.7 years, and 8.6 years from PC diagnosis. A total of 102 neurosurgical procedures were performed, with a median of five per patient; the median was similar in patients surviving longer than five years vs. those whose survival was shorter (5.0 vs. 4.5 procedures, p = 0.661). Most surgical interventions post-PC diagnosis were for optic decompression or metastasectomy. All long-term survivors (at least five years after PC diagnosis) received temozolomide-based therapy, with most also receiving radiotherapy. Conclusions: PC shows a variable clinical course, with some PAs progressing to PC after years, while others transform rapidly. All long-term survivors received temozolomide-based therapy, most in combination with radiotherapy and repeated surgical intervention, suggesting that aggressive multimodal management may be associated with prolonged survival. Future research will focus on identifying reliable predictors of metastasis at different time points in the complex clinical evolution of these tumors. Full article