Search Results (74)

Precision neurosurgery is rapidly evolving as a medical specialty by merging genomic medicine, multi-omics technologies, and artificial intelligence (AI) technology, while at the same time, society is shifting away from the traditional, anatomic model of care to consider a more precise, molecular model of care. The general purpose of this review is to contemporaneously reflect on how these advances will impact neurosurgical care by providing us with more precise diagnostic and treatment pathways. We hope to provide a relevant review of the recent advances in genomics and multi-omics in the context of clinical practice and highlight their transformational opportunities in the existing models of care, where improved molecular insights can support improvements in clinical care. More specifically, we will highlight how genomic profiling, CRISPR-Cas9, and multi-omics platforms (genomics, transcriptomics, proteomics, and metabolomics) are increasing our understanding of central nervous system (CNS) disorders. Achievements obtained with transformational technologies such as single-cell RNA sequencing and intraoperative mass spectrometry are exemplary of the molecular diagnostic possibilities in real-time molecular diagnostics to enable a more directed approach in surgical options. We will also explore how identifying specific biomarkers (e.g., IDH mutations and MGMT promoter methylation) became a tipping point in the care of glioblastoma and allowed for the establishment of a new taxonomy of tumors that became applicable for surgeons, where a change in practice enjoined a different surgical resection approach and subsequently stratified the adjuvant therapies undertaken after surgery. Furthermore, we reflect on how the novel genomic characterization of mutations like DEPDC5 and SCN1A transformed the pre-surgery selection of surgical candidates for refractory epilepsy when conventional imaging did not define an epileptogenic zone, thus reducing resective surgery occurring in clinical practice. While we are atop the crest of an exciting wave of advances, we recognize that we also must be diligent about the challenges we must navigate to implement genomic medicine in neurosurgery—including ethical and technical challenges that could arise when genomic mutation-based therapies require the concurrent application of multi-omics data collection to be realized in practice for the benefit of patients, as well as the constraints from the blood–brain barrier. The primary challenges also relate to the possible gene privacy implications around genomic medicine and equitable access to technology-based alternative practice disrupting interventions. We hope the contribution from this review will not just be situational consolidation and integration of knowledge but also a stimulus for new lines of research and clinical practice. We also hope to stimulate mindful discussions about future possibilities for conscientious and sustainable progress in our evolution toward a genomic model of precision neurosurgery. In the spirit of providing a critical perspective, we hope that we are also adding to the larger opportunity to embed molecular precision into neuroscience care, striving to promote better practice and better outcomes for patients in a global sense. Full article

Intracranial tumors such as gliomas, meningiomas, and brain metastases induce complex alterations in brain function beyond their focal presence. Modern connectomic and neuroimaging approaches, including resting-state functional MRI (rs-fMRI) and diffusion MRI, have revealed that these tumors disrupt and reorganize large-scale brain networks in heterogeneous ways. In adult patients, diffuse gliomas infiltrate neural circuits, causing both local disconnections and widespread functional changes that often extend into structurally intact regions. Meningiomas and metastases, though typically well-circumscribed, can perturb networks via mass effect, edema, and diaschisis, sometimes provoking global “dysconnectivity” related to cognitive deficits. Therefore, this review synthesizes interdisciplinary evidence from neuroscience, oncology, and neuroimaging on how intracranial tumors disrupt functional brain connectivity pre- and post-surgery. We discuss how functional heterogeneity (i.e., differences in network involvement due to tumor type, location, and histo-molecular profile) manifests in connectomic analyses, from altered default mode and salience network activity to changes in structural–functional coupling. The clinical relevance of these network effects is examined, highlighting implications for pre-surgical planning, prognostication of neurocognitive outcomes, and post-operative recovery. Gliomas demonstrate remarkable functional plasticity, with network remodeling that may correlate with tumor genotype (e.g., IDH mutation), while meningioma-related edema and metastasis location modulate the extent of network disturbance. Finally, we explore future directions, including imaging-guided therapies and “network-aware” neurosurgical strategies that aim to preserve and restore brain connectivity. Understanding functional heterogeneity in brain tumors through a connectomic lens not only provides insights into the neuroscience of cancer but also informs more effective, personalized approaches to neuro-oncologic care. Full article

Background High-grade gliomas (HGGs) are aggressive brain tumors with poor prognoses. Maximizing the extent of resection (EOR) is a critical surgical goal. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has been proposed to enhance tumor visualization and resection. MethodsWe retrospectively analyzed 141 patients with histologically confirmed HGGs who underwent either 5-ALA-guided (n = 71) or conventional white-light (n = 70) resection between 2018 and 2023. Propensity score matching and multivariate Cox regression models were used to assess the impact of 5-ALA on surgical outcomes and survival. Results: Gross total resection (GTR) was significantly more common in the 5-ALA group than the conventional white-light group (28.17% vs. 12.86%, p = 0.0245). Kaplan–Meier analysis showed no statistically significant difference in overall survival between groups after matching (log-rank p = 0.6371). However, patients with GTR had significantly improved survival compared to those with subtotal resection (log-rank p = 0.0423). Multivariate Cox regression identified radiotherapy (HR = 0.291, 95% CI: 0.166–0.513, p < 0.001), higher Karnofsky Performance Status (HR = 0.962, 95% CI: 0.942–0.982, p = 0.0003), and GTR (HR = 0.476, 95% CI: 0.272–0.834, p = 0.0091) as independent predictors of improved survival. 5-ALA usage was not an independent predictor (HR = 0.885, 95% CI: 0.554–1.413, p = 0.612). Radiotherapy and chemotherapy were more frequently administered in the conventional white-light group (p = 0.0404 and p = 0.0085, respectively). Conclusions 5-ALA fluorescence-guided surgery significantly increases the rate of gross total resection in high-grade glioma patients but does not independently confer a survival advantage. Survival outcomes are primarily influenced by the extent of resection, adjuvant therapy, and functional status. Integration of 5-ALA within a comprehensive oncological framework may enhance its clinical utility. Full article

Background: The tubular retractor-assisted minimally invasive parafascicular approach (trMIPS) is a transsulcal approach to deep-seated brain tumours. It is a safe surgical approach but its impact on the microvascular dynamics of the retracted cortex and its clinical implications are unknown. Methods: This was a single-centre prospective study including patients with deep-seated brain tumours operated on with a trMIPS (BrainPath Nico System^©). All patients underwent pre- and post-cannulation indocyanine green study using a FLOW 800 module in a KINEVO Zeiss^© microscope. Speed, delay, time-to-peak (TtP) rise-in-time and cerebral blood flow index (CBFI) metrics were assessed. Results: Thirty-five patients were included, with 144 regions-of-interest (ROIs) selected. The majority of patients were diagnosed with glioblastoma (51.43%), and 37.14% of patients had a preoperative focal neurological deficit (FND) at presentation. A ROI-based analysis concluded that an increase in speed and CBFI was related with a worse neurological outcome when comparing the pre- and post-brain cannulation assessments (speed: deterioration = 43.12 ± 80.60% versus stable = −14.51 ± 57.80% versus improvement = 6.93 ± 31.33%, p < 0.0001; CBFI: deterioration = 50.40 ± 88.17% versus stable = −2.70 ± 67.54% versus improvement = −38.98 ± 26.17%, p = 0.0005). These findings were reproducible in a combined-ROI per patient analysis and confirmed after adjustment for confounding. Conclusion: Microvascular flow dynamics impact trMIPS outcomes as an increase in the speed and CBFI after decannulation was related with worse neurological outcome. Full article

Background: One-step cranioplasty combined with tumor removal is a recognized approach in neuro-oncology for patients with neoplastic skull invasion. The use of advanced technologies, including Mixed Reality (MR), has introduced new possibilities in surgical workflows. MR technology may provide additional benefits in preoperative planning, patient engagement, and intraoperative guidance. Can the proposed treatment algorithm, which includes Mixed Reality (MR) for preoperative planning and intraoperative navigation, demonstrate tangible utility and improve outcomes in the surgical management of skull-invasive tumors? Methods: A retrospective study was conducted on 14 patients treated at Cannizzaro Hospital, Catania, Italy, for skull-invasive tumors. The treatment algorithm incorporated tumor removal and one-step cranioplasty using custom-made titanium alloy meshes. Standard intraoperative navigation was compared with MR-based navigation. MR headsets and the Virtual Surgery Intelligence (VSI) platform were employed for preoperative planning, surgical guidance, and patient/family communication. Tumor types included nine meningiomas and five other tumor variants. Results: The integration of MR proved beneficial for preoperative planning, facilitating enhanced visualization of patient anatomy and aiding communication with patients and families. MR-assisted intraoperative navigation offered improved anatomical familiarity but demonstrated slightly lower accuracy compared with standard navigation. Postoperative outcomes were satisfactory across the cohort, with no significant complications reported. Conclusions: The study highlights the potential utility of the proposed treatment algorithm including MR technology in the surgical management of skull-invasive tumors. While MR provides enhanced visualization and preoperative engagement, standard navigation remains more precise during surgery. Nevertheless, MR serves as a valuable complementary tool, and its role in neuro-oncological workflows is expected to grow with technological advancements. Full article

Pediatric primary brain tumors pose significant therapeutic challenges due to their aggressive nature and the critical environment of the developing brain. Traditional modalities like surgery, chemotherapy, and radiotherapy often achieve limited success in high-grade gliomas and embryonal tumors. Tumor-treating fields (TTfields), a non-invasive therapy delivering alternating electric fields, has emerged as a promising approach to disrupt tumor cell division through mechanisms such as mitotic disruption, DNA damage, and tumor microenvironment modulation. TTfields are thought to selectively target dividing tumor cells while sparing healthy, non-dividing cells. While TTfields therapy is FDA-approved for the management of glioblastoma and other cancers, its application in pediatric brain tumors remains under investigation. Preclinical studies reveal its potential in medulloblastoma and ependymoma models, while observational data suggest its safety and feasibility in children. Current research focuses on optimizing TTfields’ efficacy through advanced technologies, including high-intensity arrays, skull remodeling, and integration with immunotherapies such as immune checkpoint inhibitors. Innovative device-based therapies like magnetic field-based technologies further expand the treatment possibilities. As clinical trials progress, TTfields and related modalities offer hope for addressing unmet needs in pediatric neuro-oncology, especially for tumors in challenging locations. Future directions include biomarker identification, tailored protocols, and novel therapeutic combinations to enhance outcomes in pediatric brain tumor management. Full article

Aim: The management of low-grade gliomas (LGGs) is evolving with new insights into disease biology. Furthermore, recently, the phase III INDIGO¹ study highlighted the benefits of an IDH inhibitor, vorasidenib, in treating residual or recurrent grade 2 IDH-mutant gliomas following surgery alone. We aimed to characterise the current patterns of care for patients with LGGs in Australia and New Zealand, including the role of vorasidenib. Methods: An online survey examining respondents’ practice setting, caseload, and preferred treatment approach to three clinical scenarios was distributed through the Cooperative Trials Group for Neuro-Oncology, New Zealand Aotearoa Neuro-Oncology Society, and the Australian and New Zealand Society for Neuropathology in December 2023 with three reminders in April, June, and September of 2024. Results: The survey response rate was 19.6% (57/291), 87.7% from Australia, and 12.3% from New Zealand, spanning medical oncology (45.7%), pathology (22.8%), radiation oncology (17.5%), and neurosurgery (14.0%). Case 1 examined an IDH-mutant grade 2 astrocytoma following gross total resection. Observation alone was recommended by 93%. Case 2 examined an incompletely resected IDH-mutant grade 2 astrocytoma. If feasible, 38% recommended further surgery and 83% adjuvant chemotherapy and radiotherapy. After 12 months of disease stability, 53% of the respondents preferred vorasidenib over the existing therapies. Case 3 examined an incompletely resected IDH-mutant grade 3 oligodendroglioma. No respondents recommended observation alone, with 26% recommending salvage surgery and 97% recommending further chemotherapy and radiotherapy. Conclusions: This study describes current management practices for LGGs in Australia and New Zealand, showing ongoing variation and a cautious approach to integrating IDH inhibitors. This highlights the critical role of multidisciplinary team-based decision-making in increasingly complex clinical situations. Full article

Introduction: Glioma Grade 4 (GG4) tumors, which include both IDH-mutated and IDH wild-type astrocytomas, are the most prevalent and aggressive form of primary brain tumor. Radiomics is gaining ground in neuro-oncology. The integration of this data into machine learning models has the potential to improve the accuracy of prognostic models for GG4 patients. Karnofsky Performance Status (KPS), an established preoperative prognostic factor for survival, is commonly used in these patients. In this study, we developed a nomogram to identify patients with improved functional performance as indicated by an increase in KPS after surgery by analyzing radiomic features from preoperative 3D MRI scans. Methods: Quantitative imaging features were extracted from the -3D T1 GRE sequence of 157 patients from a single center and were used to develop the machine learning (ML) model. To improve applicability and create a nomogram, multivariable logistic regression analysis was performed to build a model incorporating clinical characteristics and radiomics features. Results: We labeled 55 cases in which KPS was improved after surgery (35%, KPS-flag = 1). The resulting model was evaluated according to test series results. The best model was obtained by XGBoost using the features extracted by pyradiomics, with a Matthew coefficient score (MCC) of 0.339 (95% CI: 0.330–0.3483) in cross-validation. The out-of-sample evaluation on the test set yielded an MCC of 0.302. A nomogram evaluating the improvement of KPS post-surgery was built based on statistically significant variables from multivariate logistic regression including clinical and radiomics data (c-index = 0.760, test set). Conclusions: MRI radiomic analysis represents a powerful tool to predict postoperative functional outcomes, as evaluated by KPS. Full article

Brain tumors, both primary and metastatic, represent a significant global health burden due to their high incidence, mortality, and the severe neurological deficits they frequently cause. Gliomas, especially high-grade gliomas (HGGs), rank among the most aggressive and lethal neoplasms, with only modest gains in long-term survival despite extensive molecular research and established standard therapies. In neurosurgical practice, maximizing the extent of safe resection is a principal strategy for improving clinical outcomes. Yet, the infiltrative nature of gliomas often complicates the accurate delineation of tumor margins. Confocal laser endomicroscopy (CLE), originally introduced in gastroenterology, has recently gained prominence in neuro-oncology by enabling real-time, high-resolution cellular imaging during surgery. This technique allows for intraoperative tumor characterization and reduces dependence on time-consuming frozen-section analyses. Recent technological advances, including device miniaturization and second-generation CLE systems, have substantially improved image quality and diagnostic utility. Furthermore, integration with deep learning algorithms and telepathology platforms fosters automated image interpretation and remote expert consultations, thereby accelerating surgical decision making and enhancing diagnostic consistency. Future work should address remaining challenges, such as mitigating motion artifacts, refining training protocols, and broadening the range of applicable fluorescent probes, to solidify CLE’s role as a critical intraoperative adjunct in neurosurgical oncology. Full article

Current standard of care treatment for patients with spine tumors includes multidisciplinary approaches, including the following: (1) surgical tumor debulking, epidural spinal cord decompression, and spine stabilization techniques; (2) systemic chemo/targeted therapies; (3) radiation therapy; and (4) surveillance imaging for local disease control and recurrence. Titanium pedicle screw and rod fixation have become commonplace in the spine surgeon’s armamentarium for the stabilization of the spine following tumor resection and separation surgery. However, the high degree of imaging artifacts seen with titanium implants on postoperative CT and MRI scans can significantly hinder the accurate delineation of vertebral anatomy and adjacent neurovascular structures to allow for the safe and effective planning of downstream radiation therapies and detection of disease recurrence. Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) spine implants have emerged as a promising alternative to titanium due to the lack of artifact signals on CT and MRI, allowing for more accurate and safe postoperative radiation planning. In this article, we review the tenants of the surgical and radiation management of spine tumors and discuss the safety, efficacy, and current limitations of CFR-PEEK spine implants in the multidisciplinary management of spine oncology patients. Full article

Background and Objective: Access to high-quality patient-derived brain tumor tissues is instrumental for translational neuro-oncology research. Glioblastoma tumor material resected by ultrasonic aspiration (UA) during surgery offers an abundant source of material; however, it is generally not used for research experiments. We hypothesize that UA-derived tumor tissue represents a source of tissue that accurately reflects the immune infiltrates of glioblastomas. Methods: In this study, we have utilized UA-derived tissue and performed a head-to-head comparison with paired resection tissue from the vital tumor core of the same patient. A combination of 16 fluorochrome-conjugated antibodies was designed to identify tumor-infiltrating T, B, and NK lymphocytes and characterize the TILs by spectral flow cytometry. Furthermore, a 5-plex panel was designed to spatially characterize the T cells, macrophages, and tumor cells on the paired UA and resection tissues. Results: UA-obtained cells exhibited a comparable yield and viability, as well as an abundance of tumor-infiltrating T, B, and NK lymphocytes compared to resection sample-derived cells. Importantly, we observed that there is a high concordance with respect to expression intensities of immune checkpoints by T cells in both types of tissue samples. Conclusions: These findings underscore the feasibility and reliability of utilizing the immune infiltrates from ultrasonic aspiration-acquired glioblastoma tissue. Full article

Background: Oncological surgery of the parotid gland or of the temporal bone may require the contemporary sacrifice of the facial nerve (FN). In such cases, the immediate repair of the sacrificed FN is recommended. The aim of this study is to evaluate the impact of facial rehabilitation (FR) and, secondarily, of post-operative radiotherapy (PORT) on the FN outcome after FN sacrifice and reconstruction via cable graft. Methods: This is a multicentric retrospective study including patients affected by malignant tumors whose surgical excision required FN sacrifice and contextual FN reconstruction with a cable graft. Other FN reconstruction techniques were excluded. FN function was assessed using both House–Brackmann and Sunnybrook grading systems. Results: A total of 28 patients were included. Most of the patients underwent a total parotidectomy. The greater auricular nerve was the main donor for cable graft. FR and PORT were performed in 22 and 15 patients, respectively. In particular, 20 patients underwent neuro-muscular retraining (NMR). Patients who underwent FR had better FN outcomes compared to those who did not (p = 0.02 at 12 months and p = 0.0002 at 24 months). In contrast, there was no statistically significant difference between patients who underwent PORT and those who did not (p > 0.05). Pre-operative FN palsy is a risk factor of worse FN function outcomes after cable graft. Conclusions: Our study, even though it was limited to only 28 cases, may demonstrate that cable graft failure is not due to PORT, as widely believed among clinicians, but to the absence of a rehabilitation program. Moreover, we suggest that the key to obtaining the best possible FN function results after FN sacrifice is the association of a technically correct FN reconstruction with a proper and targeted FR. Full article

Central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children, with prognosis remaining dismal for some of these malignancies. Though the past two decades have seen advancements in surgery, radiation, and targeted therapy, major unresolved hurdles continue to undermine the therapeutic efficacy. These include challenges in suboptimal drug delivery through the blood–brain barrier (BBB), marked intra-tumoral molecular heterogeneity, and the elusive tumor microenvironment. Drug repurposing or re-tasking FDA-approved drugs with evidence of penetration into the CNS, using newer methods of intracranial drug delivery facilitating optimal drug exposure, has been an area of intense research. This could be a valuable tool, as most of these agents have already gone through the lengthy process of drug development and the evaluation of safety risks and the optimal pharmacokinetic profile. They can now be used and tested in clinics with an accelerated and different approach. Conclusions: The next-generation therapeutic strategy should prioritize repurposing oncologic and non-oncologic drugs that have been used for other indication, and have demonstrated robust preclinical activity against pediatric brain tumors. In combination with novel drug delivery techniques, these drugs could hold significant therapeutic promise in pediatric neurooncology. Full article

Advances in neuro-oncology have transformed the diagnosis and management of brain tumors, which are among the most challenging malignancies due to their high mortality rates and complex neurological effects. Despite advancements in surgery and chemoradiotherapy, the prognosis for glioblastoma multiforme (GBM) and brain metastases remains poor, underscoring the need for innovative diagnostic strategies. This review highlights recent advancements in imaging techniques, liquid biopsies, and artificial intelligence (AI) applications addressing current diagnostic challenges. Advanced imaging techniques, including diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS), improve the differentiation of tumor progression from treatment-related changes. Additionally, novel positron emission tomography (PET) radiotracers, such as ¹⁸F-fluoropivalate, ¹⁸F-fluoroethyltyrosine, and ¹⁸F-fluluciclovine, facilitate metabolic profiling of high-grade gliomas. Liquid biopsy, a minimally invasive technique, enables real-time monitoring of biomarkers such as circulating tumor DNA (ctDNA), extracellular vesicles (EVs), circulating tumor cells (CTCs), and tumor-educated platelets (TEPs), enhancing diagnostic precision. AI-driven algorithms, such as convolutional neural networks, integrate diagnostic tools to improve accuracy, reduce interobserver variability, and accelerate clinical decision-making. These innovations advance personalized neuro-oncological care, offering new opportunities to improve outcomes for patients with central nervous system tumors. We advocate for future research integrating these tools into clinical workflows, addressing accessibility challenges, and standardizing methodologies to ensure broad applicability in neuro-oncology. Full article

Objective: Navigated transcranial magnetic stimulation (nTMS) has seldom been used to study visuospatial (VS) circuits so far. Our work studied (I) VS functions in neurosurgical oncological patients by using repetitive nTMS (rnTMS), (II) the possible subcortical circuits underneath, and (III) the correspondence between nTMS and direct cortical stimulation (DCS) during awake procedures. Methods: We designed a monocentric prospective study, adopting a protocol to use rnTMS for preoperative planning, including VS functions for lesions potentially involving the VS network, including neurosurgical awake and asleep procedures. nTMS-based-DTI tractography allowed the visualization of subcortical circuits. Statistical analyses on nTMS/DCS points were performed. Clinical results were collected pre- and postoperatively. Results: Finally, 27 patients with primitive intra-axial brain lesions were enrolled between April 2023 and March 2024. Specific tests and an experimental integrated VS test (VISA) were used. The clinical evaluation (at 5 ± 7, 30 ± 10, 90 ± 10 days after surgery) documented 33% of patients with neglect in the left hemisphere four days after surgery and, during the 3-month follow-up, preservation of visuospatial function/clinical recovery (90.62% in MMSE, 98.86% in the bell test, 80% in the clock test, and 98% in the OCS test). The surgical strategy was modulated according to the nTMS map. Subcortical bundles were traced to identify those most involved in these functions: SFLII > SLFII > SLFI. A comparison of the nTMS and DCS points in awake surgery (n = 10 patients) documented a sensitivity (Se) of 12%, a specificity (Sp) of 91.21%, a positive predictive value (PPV) of 42%, a negative predictive value (NPV) of 66%, and an accuracy of ~63.7%. Conclusions: Based on our preliminary results, nTMS is advantageous for studying cognitive functions, minimising neurological impairment. Further analyses are needed to validate our data. Full article