Search

Gliomas are the most common primary malignant brain tumours in adults. Despite decades of research into novel therapeutic approaches, the prognosis remains poor. PARP1-2 are critical for DNA repair, cell survival and genomic stability and PARP inhibition (PARPi) may be a promising therapeutic approach for gliomas. Inhibition of PARP activity leads to homologous recombination deficiency (HRD), which, in combination with DNA damage, results in cell death. This review summarises the current knowledge and future perspectives of PARPi in glioma. The available literature was reviewed using PubMed, recent major international oncology congresses were consulted, and ongoing clinical trials were searched using ClinicalTrials.gov. In translational research, PARPi have demonstrated a strong scientific rationale for their use in the treatment of glioma. They have been evaluated both alone and in combination with radiotherapy, temozolomide, anti-angiogenic agents, immunotherapy and other new drugs in newly diagnosed or recurrent glioma. Most studies were open-label, non-randomised, dose-escalation phase I-II trials. Early results show promising anti-tumour activity, and key challenges include identifying predictive biomarkers, elucidating synergistic effects in combination therapies, addressing the development of resistance, and managing hematological toxicity. In conclusion, early phase studies have shown promising anti-tumour activity of PARPi that should be confirmed in larger prospective and randomised trials. In addition, the development of novel PARPi with improved blood brain barrier (BBB) penetration and PARP inhibitor activity with new synergistic treatment combinations seems promising and needs to be further explored., Competing Interests: Declaration of Competing Interest Ahmed Idbaih reports a relationship with Research grants from Carthera, Transgene, Sanofi, Air Liquide, Servier, Nutritheragene, advisory board for Leo Pharma, Novocure and Boehringer Ingelheim Int, travel funding from Novocure, Carthera and Leo Pharma. Michael Weller reports a relationship with research grants from Novartis, Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Anheart, Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Pfizer, Philogen, Roche and Servier. Matteo Simonelli reports a relationship with honoraria for lectures or advisory board participation or consulting from Incyte, Bristol Myers Squibb, Servier, GlaxoSmithKline, Sanofi and travel funding from Roche, Pfizer, Sanofi. Giuseppe Lombardi reports a relationship with consulting or advisory role funding from ABBVIE, Bayer, Novartis, Orbus Therapeutics, BrainFarm, Celgene, CureTeq, GlaxoSmithKline, Health4U, Braun, Janssen, BioRegio Stern, Servier, Novocure, and travel funding from Roche and Bayer, Servier. Matthias Preusser has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Böhringer-Ingelheim, Telix, Medscape, OncLive., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gliomas are the most common primary brain tumors, representing approximately 28% of all central nervous system tumors. These tumors are characterized by rapid progression and show a median survival of approximately 18 months. The therapeutic options consist of surgical resection followed by radiotherapy and chemotherapy. Despite the multidisciplinary approach and the biomolecular role of targeted therapies, the median progression-free survival is approximately 6-8 months. The incomplete tumor compliance with treatment is due to several factors such as the presence of the blood-brain barrier, the numerous pathways involved in tumor transformation, and the presence of intra-tumoral mutations. Among these, the interaction between the mutations of genes involved in tumor bio-energetic metabolism and the functional response of the tumor has become the protagonist of numerous studies. In this scenario, the main role is played by mitochondria, cellular organelles delimited by a double membrane and containing their own DNA (mtDNA), which participates in numerous cellular processes such as the regulation of cellular metabolism, cellular proliferation, and apoptosis and is also the main source of cellular energy production. Therefore, it is understood that the mitochondrion, specifically its functional alteration, is a leading figure in tumor transformation, including brain tumors. The acquisition of mutations in the mitochondrial DNA of tumor cells and the subsequent identification of the so-called mitochondria-related genes (MRGs), both functional (mutation of Complex I) and structural (mutations of Complex III/IV), have been seen to play an important role in metabolic reprogramming with increased proliferation, resistance to apoptosis, and the progression of tumorigenesis. This demonstrates that these mitochondrial alterations could have a role not only in the intrinsic tumor biology but also in the extrinsic one associated with the therapeutic response. We aim to summarize the main mitochondrial dysfunction interactions present in gliomas and how they might impact prognosis.

Purpose: Patients diagnosed with High Grade Gliomas (HGG) generally tend to have a relatively negative prognosis with a high risk of early tumor recurrence (TR) after post-operative radio-chemotherapy. The assessment of the pre-operative risk of early versus delayed TR can be crucial to develop a personalized surgical approach. The purpose of this article is to predict TR using MRI radiomic analysis., Methods: Data were retrospectively collected from a database. A total of 248 patients were included based on the availability of 6-month TR results: 188 were used to train the model, the others to externally validate it. After manual segmentation of the tumor, Radiomic features were extracted and different machine learning models were implemented considering a combination of T1 and T2 weighted MR sequences. Receiver Operating Characteristic (ROC) curve was calculated with relative model performance metrics (accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)) at the best threshold based on the Youden Index., Results: Models performance were evaluated based on test set results. The best model resulted to be the XGBoost, with an area under ROC curve of 0.72 (95% CI: 0.56 - 0.87). At the best threshold, the model exhibits 0.75 (95% CI: 0.63 - 0.75) as accuracy, 0.62 (95% CI: 0.38 - 0.83) as sensitivity 0.80 (95% CI: 0.66 - 0.89 as specificity, 0.53 (95% CI: 0.31 - 0.73) as PPV, 0.88 (95% CI: 0.72 - 0.94) as NPV., Conclusion: MRI radiomic analysis represents a powerful tool to predict late HGG recurrence, which can be useful to plan personalized surgical treatments and to offer pertinent patient pre-operative counseling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pignotti, Ius, Russo, Bagatto, Beghella Bartoli, Boccia, Boldrini, Chiesa, Ciardi, Cusumano, Giordano, La Rocca, Mazzarella, Mazzucchi, Olivi, Skrap, Tran, Varcasia, Gaudino and Sabatino.)

Background: Glioblastoma (GBM) is an extremely aggressive brain tumor that has few available treatment options and a dismal prognosis. Recent research has highlighted the potential of extracellular vesicles (MSC-EVs) produced from mesenchymal stem cells as a potential treatment approach for GBM. MSC-EVs, including exosomes, microvesicles, and apoptotic bodies, perform a significant function in cellular communication and have shown promise in mediating anti-tumor effects., Purpose: This systematic literature review aims to consolidate current findings on the therapeutic potential of MSC-EVs in GBM treatment., Methods: A systematic search was conducted across major medical databases (PubMed, Web of Science, and Scopus) up to September 2024 to identify studies investigating the use of MSC-derived EVs in GBM therapy. Keywords included "extracellular vesicles", "mesenchymal stem cells", "targeted therapies", "outcomes", "adverse events", "glioblastoma", and "exosomes". Inclusion criteria were studies published in English involving GBM models both in vivo and in vitro and those reporting on therapeutic outcomes of MSC-EVs. Data were extracted and analyzed based on EV characteristics, mechanisms of action, and therapeutic efficacy., Results: The review identified several key studies demonstrating the anti-tumor effects of MSC-EVs in GBM models. A total of three studies were included, focusing on studies conducted between 2021 and 2023. The review included three studies that collectively enrolled a total of 18 patients. These studies were distributed across two years, with two trials published in 2023 (66.7%) and one in 2021 (33.3%). The mean age of the participants ranged from 37 to 57 years. In terms of gender distribution, males were the predominant group in all studies. Prior to receiving MSC-EV therapy, all patients had undergone standard treatments for GBM, including surgery, chemotherapy (CT), and, in some cases, radiation therapy (RT). In all three studies, the targeted treatment involved the administration of herpes simplex virus thymidine kinase (HSVtk) gene therapy delivered to the tumor site, then 14 days of ganciclovir treatment. Outcomes across the studies indicated varying levels of efficacy for the MSC-EV-based therapy. The larger 2023 study reported fewer encouraging outcomes, with a median PFS of 11.0 months (95% CI: 8.3-13.7) and a median OS of 16.0 months (95% CI: 14.3-17.7). Adverse effects were reported in only one of the studies, the 2021 trial, where patients experienced mild-to-moderate side effects, including fever, headache, and cerebrospinal fluid leukocytosis. A total of 11 studies on preclinical trials, using in vitro and in vivo models, were included, covering publications from 2010 to 2024. The studies utilized MSCs as delivery systems for various therapeutic agents (interleukin 12, interleukin 7, doxorubicin, paclitaxel), reflecting the versatility of these cells in targeted cancer therapies., Conclusions: MSC-derived EVs represent a promising therapeutic approach for GBM, offering multiple mechanisms to inhibit tumor growth and enhance treatment efficacy. Their ability to deliver bioactive molecules and modulate the tumor microenvironment underscores their potential as a novel, cell-free therapeutic strategy. Future studies should optimize EV production and delivery methods and fully understand their long-term effects in clinical settings to harness their therapeutic potential in GBM treatment.

Background: Incidentally discovered low-grade gliomas (iLGGs) are very rare and little is still known about their associated functional imaging activation patterns, white-matter status, and plasticity potential. Recent studies shed light on several clinical factors responsible for the good clinical status observed in these patients versus those with their symptomatic counterpart (sLGGs), including small volume. Comparisons were typically carried out by comparing iLGGs with the wider and more heterogeneous sLGG group. In this study, we investigated whether iLGGs affect the brain differently from comparably small sLGGs., Method: Starting from a sample of 13 patients with iLGG, in the current comparative cross-sectional study, we identified a group of patients with sLGGs, primarily matched by lesion volume. We looked for potential differences between the two groups in language-related functional and structural parameters (the fMRI network associated with naming and white-matter fascicles)., Results: The t -test did not show significant differences in the fMRI network, but these emerged when performing masking. No significant differences were observed at the white-matter level., Conclusions: Given that small volumes characterized both groups and that demographic variables were comparable, too, we hypothesized that differences between the two groups could be attributed to alternative lesion-related parameters. We discussed these findings from clinical and neurosurgical perspectives.

Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory disease control, making the progression of the disease inevitable. Currently, there is a lack of therapeutic options to control tumor growth after the diagnosis of recurrence. The rarity of these tumors, their distinct behavioral characteristics, and the limited availability of tumor tissue necessary for the development of prognostic and predictive biomarkers contribute to the absence of a standardized approach for treating recurrent brainstem gliomas. A salvage radiotherapy (RT) retreatment could represent a promising approach for recurrent brainstem gliomas. However, to date, it has been mainly evaluated in pediatric cases, with few experiences available to assess the most appropriate RT dose, safety, and clinical responses in adult patients. This comprehensive review aims to identify instances of adult patients with recurrent brainstem gliomas subjected to a secondary course of RT, with a specific focus on the analysis of treatment-related toxicity and outcomes. Through this investigation, we endeavor to contribute valuable insights into the viability and efficacy of salvage RT retreatment in managing recurrent brainstem gliomas in the adult population.

Patients affected by glioma frequently experience epileptic discharges; however, the causes of brain tumor-related epilepsy (BTRE) are still not completely understood. We investigated the mechanisms underlying BTRE by analyzing the effects of exosomes released by U87 glioma cells and by patient-derived glioma cells. Rat hippocampal neurons incubated for 24 hours with these exosomes exhibited increased spontaneous firing, while their resting membrane potential shifted positively by 10-15 mV. Voltage clamp recordings demonstrated that the activation of the Na+ current shifted toward more hyperpolarized voltages by 10-15 mV. To understand the factors inducing hyperexcitability, we focused on exosomal cytokines. Western blot and ELISAs showed that TNF-α was present inside glioma-derived exosomes. Remarkably, incubation with TNF-α fully mimicked the phenotype induced by exosomes, with neurons firing continuously, while their resting membrane potential shifted positively. Real-time PCR revealed that both exosomes and TNF-α induced overexpression of the voltage-gated Na+ channel Nav1.6, a low-threshold Na+ channel responsible for hyperexcitability. When neurons were preincubated with infliximab, a specific TNF-α inhibitor, the hyperexcitability induced by exosomes and TNF-α was drastically reduced. We propose that infliximab, an FDA-approved drug to treat rheumatoid arthritis, could ameliorate the conditions of glioma patients with BTRE.

The management of meningioma in elderly patients (MEP) presents a complex and evolving challenge. Data available offer conflicting information on treatment options and complications. This survey aimed to examine the current approach to MEP, comparing the national profile to data in the current literature. A survey addressing the treatments options and management of meningioma in elderly was designed on behalf of SINch® (Società Italiana di Neurochirurgia) and sent via email to all Chiefs of Neurosurgical Departments. The survey remained open for responses from May 5th, 2022, until November 21st, 2022. A search of the literature published between January 2000 and March 2023, in accordance to PRISMA guidelines, was included. A total of 51 Neurosurgical centers participated in the survey. The caseload profile of each center influences the choice of treatment selection (Stereotactic Radiosurgery versus open surgery) (p = 0.01) and the consolidated practice of discussing cases within a multidisciplinary group (p = 0.02). The pooled meta-analysis demonstrated a significant increased risk in the elderly group for permanent deficits (p < 0.00001), postoperative infections (p = 0.0004) and hemorrhage (p = 0.0001), perioperative mortality (p < 0.00001), and medical complications (p < 0.00001) as compared to the young population. This study presents the initial comprehensive analysis of the existing trends in the surgical management of MEP in Italy. The significant variation in practices primarily stems from the absence of standardized guidelines. While most centers have adopted an integrated approach, there is a need to promote a multidisciplinary care model. Prospective studies are needed to gather robust evidence in this clinical setting., (© 2024. The Author(s).)

Gliomas' aggressive nature and resistance to therapy make them a major problem in oncology. Gliomas continue to have dismal prognoses despite significant advancements in medical science, and traditional treatments like surgery, radiation (RT), and chemotherapy (CT) frequently prove to be ineffective. After glioma stem cells (GSCs) were discovered, the traditional view of gliomas as homogeneous masses changed. GSCs are essential for tumor growth, treatment resistance, and recurrence. These cells' distinct capacities for differentiation and self-renewal are changing our knowledge of the biology of gliomas. This systematic literature review aims to uncover the molecular mechanisms driving glioma progression associated with GSCs. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. The first literature search was performed on 1 March 2024, and the search was updated on 15 May 2024. Employing MeSH terms and Boolean operators, the search focused on molecular mechanisms associated with GCSs-mediated glioma progression. Inclusion criteria encompassed English language studies, preclinical studies, and clinical trials. A number of 957 papers were initially identified, of which 65 studies spanning from 2005 to 2024 were finally included in the review. The main GSC model distribution is arranged in decreasing order of frequency: U87: 20 studies (32.0%); U251: 13 studies (20.0%); A172: 4 studies (6.2%); and T98G: 2 studies (3.17%). From most to least frequent, the distribution of the primary GSC pathway is as follows: Notch: 8 studies (12.3%); STAT3: 6 studies (9.2%); Wnt/β-catenin: 6 studies (9.2%); HIF: 5 studies (7.7%); and PI3K/AKT: 4 studies (6.2%). The distribution of molecular effects, from most to least common, is as follows: inhibition of differentiation: 22 studies (33.8%); increased proliferation: 18 studies (27.7%); enhanced invasive ability: 15 studies (23.1%); increased self-renewal: 5 studies (7.7%); and inhibition of apoptosis: 3 studies (4.6%). This work highlights GSC heterogeneity and the dynamic interplay within the glioblastoma microenvironment, underscoring the need for a tailored approach. A few key pathways influencing GSC behavior are JAK/STAT3, PI3K/AKT, Wnt/β-catenin, and Notch. Therapy may target these pathways. This research urges more study to fill in knowledge gaps in the biology of GSCs and translate findings into useful treatment approaches that could improve GBM patient outcomes.

Despite the implementation of multimodal treatments after surgery, glioblastoma (GBM) remains an incurable disease, posing a significant challenge in neuro-oncology. In this clinical setting, local therapy (LT), a developing paradigm, has received significant interest over time due to its potential to overcome the drawbacks of conventional therapy options for GBM. The present review aimed to trace the historical development, highlight contemporary advances and provide insights into the future horizons of LT in GBM management. In compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols criteria, a systematic review of the literature on the role of LT in GBM management was conducted. A total of 2,467 potentially relevant articles were found and, after removal of duplicates, 2,007 studies were screened by title and abstract (Cohen's κ coefficient=0.92). Overall, it emerged that 15, 10 and 6 clinical studies explored the clinical efficiency of intraoperative local treatment modalities, local radiotherapy and local immunotherapy, respectively. GBM recurrences occur within 2 cm of the radiation field in 80% of cases, emphasizing the significant influence of local factors on recurrence. This highlights the urgent requirement for LT strategies. In total, three primary reasons have thus led to the development of numerous LT solutions in recent decades: i) Intratumoral implants allow the blood-brain barrier to be bypassed, resulting in limited systemic toxicity; ii) LT facilitates bridging therapy between surgery and standard treatments; and iii) given the complexity of GBM, targeting multiple components of the tumor microenvironment through ligands specific to various elements could have a synergistic effect in treatments. Considering the spatial and temporal heterogeneity of GBM, the disease prognosis could be significantly improved by a combination of therapeutic strategies in the era of precision medicine., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Ius et al.)

Background: Several risk stratification scores have been suggested to aid prognostication and guide treatment strategies for brain metastases (BMs). However, the current scores do not focus on the specific neurosurgical population, therefore not predicting short-term mortality and postoperative performance status., Methods: This retrospective observational study of 362 consecutive patients treated with surgery for BMs aims to identify the factors associated with post-surgical outcomes and propose a surgery-specific prognostic score for patients with BMs candidate for open surgery., Results: Factors significantly associated with OS and performance status in multivariate analysis were age, KPS, surgical site, synchronous debut of BM, number, tumor volume, seizure, extra-cranial metastases, and deep-seated location. The variables were incorporated into the Anamnestic Radiological Metastases Outcome Surgical score (ARMO-S). The values range between 0 and 10. Patients were divided into two groups (low-risk and high-risk) based on each significant subgroup's median survival and performance status with an optimal cutoff value determined as 4. The two groups have significant differences in OS (9.6 versus 14 months, p = 0.0048) postoperative KPS (90 versus 70, p = 0.012) and KPS at last follow-up evaluation (75 versus 30, p < 0.001) CONCLUSION: ARMO-S is a simple and comprehensive score for BM patients selected for neurosurgery, as it incorporates the main factors of the most important prognostic scores, implementing them with more surgery-specific predictive elements such as tumor location and volume, presence of seizures at onset, and involvement of eloquent brain areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The most common primary brain tumor is glioblastoma (GBM), yet the current therapeutic options for this disease are not promising. Although immunotherapeutic techniques have shown poor success in GBM thus far despite efforts, new developments provide optimism. One of these developments is chimeric antigen receptor (CAR)-T cell treatment, which includes removing and genetically modifying autologous T cells to produce a receptor that targets a GBM antigen before reintroducing the cells into the patient's body. A number of preclinical studies have produced encouraging results, which have led to the start of clinical trials assessing these CAR-T cell treatments for GBM and other brain tumors. Although results in tumors such as diffuse intrinsic pontine gliomas and lymphomas have been promising, preliminary findings in GBM have not produced any clinical benefits. The paucity of particular antigens in GBM, their inconsistent expression patterns, and the possible immunoediting-induced loss of these antigens after antigen-targeted therapy are some possible causes for this discrepancy. The goal of this systematic literature review is to assess potential approaches for creating CAR-T cells that are more effective for this indication, as well as the clinical experiences that are already being had with CAR-T cell therapy in GBM. Up until 9 May 2024, a thorough search was carried out across the three main medical databases: PubMed, Web of Science, and Scopus. Relevant Medical Subject Heading (MeSH) terms and keywords associated with "glioblastoma", "CAR-T", "T cell therapy", "overall survival", and "progression free survival" were employed in the search approach. Preclinical and clinical research on the application of CAR-T cells as a therapeutic approach for GBM are included in the review. A total of 838 papers were identified. Of these, 379 articles were assessed for eligibility, resulting in 8 articles meeting the inclusion criteria. The included studies were conducted between 2015 and 2023, with a total of 151 patients enrolled. The studies varied in CAR-T cell types. EGFRvIII CAR-T cells were the most frequently investigated, used in three studies (37.5%). Intravenous delivery was the most common method of delivery (62.5%). Median OS ranged from 5.5 to 11.1 months across the studies. PFS was reported in only two studies, with values of 7.5 months and 1.3 months. This systematic review highlights the evolving research on CAR-T cell therapy for GBM, emphasizing its potential despite challenges. Targeting antigens like EGFRvIII and IL13Rα2 shows promise in treating recurrent GBM. However, issues such as antigen escape, tumor heterogeneity, and immunosuppression require further optimization. Innovative delivery methods, combination therapies, and personalized approaches are crucial for enhancing CAR-T cell efficacy. Ongoing research is essential to refine these therapies and improve outcomes for GBM patients.

Background: Generative Adversarial Networks (GANs) are a class of artificial neural networks capable of generating content such as images, text, and sound. For several years already, artificial intelligence algorithms have shown promise as tools in the medical field, particularly in oncology. Generative Adversarial Networks (GANs) represent a new frontier of innovation, as they are revolutionizing artificial content generation, opening opportunities in artificial intelligence and deep learning. Purpose: This systematic review aims to investigate what the stage of development of such technology is in the field of head and neck surgery, offering a general overview of the applications of such algorithms, how they work, and the potential limitations to be overcome in the future. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in conducting this study, and the PICOS framework was used to formulate the research question. The following databases were evaluated: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, ClinicalTrials.gov, ScienceDirect, and CINAHL. Results: Out of 700 studies, only 9 were included. Eight applications of GANs in the head and neck region were summarized, including the classification of craniosynostosis, recognition of the presence of chronic sinusitis, diagnosis of radicular cysts in panoramic X-rays, segmentation of craniomaxillofacial bones, reconstruction of bone defects, removal of metal artifacts from CT scans, prediction of the postoperative face, and improvement of the resolution of panoramic X-rays. Conclusions: Generative Adversarial Networks may represent a new evolutionary step in the study of pathology, oncological and otherwise, making the approach to the disease much more precise and personalized.

We retrospectively analyzed data from 15 patients, with a normal pre-operative cognitive performance, undergoing awake surgery for left fronto-temporal low-grade glioma. We combined a pre-surgical measure (fMRI maps of motor- and language-related centers) with intra-surgical measures (MNI-registered cortical sites data obtained during intra-operative direct electrical stimulation, DES, while they performed the two most common language tasks: number counting and picture naming). Selective DES effects along the precentral gyrus/inferior frontal gyrus (and/or the connected speech articulation network) were obtained. DES of the precentral gyrus evoked the motor speech arrest, i.e., anarthria (with apparent mentalis muscle movements). We calculated the number of shared voxels between the lip-tongue and overt counting related- and silent naming-related fMRI maps and the Volumes of Interest (VOIs) obtained by merging together the MNI sites at which a given speech disturbance was observed, normalized on their mean the values (i.e., Z score). Both tongue- and lips-related movements fMRI maps maximally overlapped (Z = 1.05 and Z = 0.94 for lips and tongue vs. 0.16 and -1.003 for counting and naming) with the motor speech arrest seed. DES of the inferior frontal gyrus, pars opercularis and the rolandic operculum induced speech arrest proper (without apparent mentalis muscle movements). This area maximally overlapped with overt counting-related fMRI map (Z = -0.11 and Z = 0.09 for lips and tongue vs. 0.9 and 0.0006 for counting and naming). Interestingly, our fMRI maps indicated reduced Broca's area activity during silent speech compared to overt speech. Lastly, DES of the inferior frontal gyrus, pars opercularis and triangularis evoked variations of the output, i.e., dysarthria, a motor speech disorder occurring when patients cannot control the muscles used to produce articulated sounds (phonemes). Silent object naming-related fMRI map maximally overlapped (Z = -0.93 and Z = -1.04 for lips and tongue vs. -1.07 and 0.99 for counting and naming) with this seed. Speech disturbances evoked by DES may be thought of as selective interferences with specific recruitment of left inferior frontal gyrus and precentral cortex which are differentiable in terms of the specific interference induced., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Paragangliomas (PG) are rare neoplasms of neuroendocrine origin that tend to be highly vascularized, slow-growing, and usually sporadic. To date, common treatment options are surgical resection (SR), with or without radiation therapy (RT), and a watch-and-wait approach., Aim: To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT (FSRT) treatment in unresectable PG (uPG)., Methods: We retrospectively evaluated patients with uPG (medically inoperable or refused SR) treated with FSRT with a Cyberknife System (Accuray Incorporated, Sunnyvale, California). Toxicity and initial efficacy were evaluated., Results: From May 2009 to January 2023, 6 patients with a median age of 68 (range 20-84) were treated with FSRT. The median delivered dose was 21 Gy (range 20-30 Gy) at a median isodose line of 75.5% (range 70%-76%) in 4 fractions (range 3-5 fractions). The median volume was 13.6 mL (range 12.4-65.24 mL). The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively. Site of origin involved were the timpa-nojugular glomus (4/6), temporal bone, and cervical spine. In 1 of the 6 patients, the follow-up was insufficient; 5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%. We observed negligible toxicities during and after RT. The majority of patients showed stable symptoms during follow-up. Only 1 patient developed spine metastases., Conclusion: Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Incidentally discovered low-grade gliomas (iLGGs) represent a rare neurological condition, which is associated with a good clinical status and usually preserved - or borderline - cognitive functions; only recently, knowledge has increased on their development and clinical features. Better understanding these aspects is fundamental to set up the most appropriate clinical protocol., Methods: We used fMRI to conduct an exploratory investigation of the effects of iLGG growth on the brain and the potential occurrence of early rearrangement in the functional network associated with object naming. We compared this group of 13 patients with an iLGG in the left hemisphere (maximum lesion overlap in the left inferior frontal gyrus and median tumor volume 12 cm 3 ) and with preserved naming skills with that of a healthy control group., Results: No significant differences were observed in the functional activations between the two groups, but a cluster in the controls vs. patients contrast mainly located in the right lateral visual cortex. As this region is unspecific for object naming and no significant changes emerged when checking for covariates, we concluded that iLGG growth did not affect the functional network and plasticity-related reorganization did not occur yet. We attributed this finding to iLGG features, such as small tumor size at the diagnosis and lack or minimal infiltration., Conclusions: These findings are preliminary, and we recommend future investigation to replicate them and test generalizability to other functional networks. Understanding the potential functional effects of iLGG growth is fundamental for the choice of the most appropriate treatment.

Background: Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity., Aim: To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms., Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including "glioma stem cells", "radiotherapy", "chemotherapy", "resistance", and "targeted therapies". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR)., Results: In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors ( e.g., LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies ( e.g., cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies., Conclusion: GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Multiple radiomics models have been proposed for grading glioma using different algorithms, features, and sequences of magnetic resonance imaging. The research seeks to assess the present overall performance of radiomics for grading glioma., Methods: A systematic literature review of the databases Ovid MEDLINE PubMed, and Ovid EMBASE for publications published on radiomics for glioma grading between 2012 and 2023 was performed. The systematic review was carried out following the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analysis., Results: In the meta-analysis, a total of 7654 patients from 40 articles, were assessed. R-package mada was used for modeling the joint estimates of specificity (SPE) and sensitivity (SEN). Pooled event rates across studies were performed with a random-effects meta-analysis. The heterogeneity of SPE and SEN were based on the χ2 test. Overall values for SPE and SEN in the differentiation between high-grade gliomas (HGGs) and low-grade gliomas (LGGs) were 84% and 91%, respectively. With regards to the discrimination between World Health Organization (WHO) grade 4 and WHO grade 3, the overall SPE was 81% and the SEN was 89%. The modern non-linear classifiers showed a better trend, whereas textural features tend to be the best-performing (29%) and the most used., Conclusions: Our findings confirm that present radiomics' diagnostic performance for glioma grading is superior in terms of SEN and SPE for the HGGs vs. LGGs discrimination task when compared to the WHO grade 4 vs. 3 task., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background : Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. Methods : A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. Results : Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral ( n = 8, 44.4%), followed by clivus ( n = 7, 38.9%) and lumbar spine ( n = 3, 16.7%). Primary treatments preceding targeted therapies included surgery ( n = 10, 55.6%), RT ( n = 9, 50.0%), and systemic treatments ( n = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). Conclusions : This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.

Background/Objectives : Tuberculum sellae meningiomas (TSMs) constitute 5-10% of intracranial meningiomas, often causing visual impairment. Traditional microsurgical transcranial approaches (MTAs) have been effective, but the emergence of innovative surgical trajectories, such as endoscopic endonasal approaches (EEAs), has sparked debate. While EEAs offer advantages like reduced brain retraction, they are linked to higher cerebrospinal fluid leak (CSF leak) risk. This meta-analysis aims to comprehensively compare the efficacy and safety of EEAs and MTAs for the resection of TSMs, offering insights into their respective outcomes and complications. Methods : A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on TSMs treated with either EEA or MTA until 2024. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications. Results : A total of 291 papers were initially identified, of which 18 studies spanning from 2000 to 2024 met the inclusion criteria. The exclusion of 180 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and a lack of details on method/results. The 18 studies comprised a total sample of 1093 patients: 444 patients who underwent EEAs and 649 patients who underwent MTAs for TSMs. Gross total resection (GTR) rates ranged from 80.9% for EEAs to 79.8% for MTAs. The rate of visual improvement was 86.6% in the EEA group and 65.4% in the MTA group. The recurrence rate in the EEA group was 6.9%, while it was 5.1% in MTA group. The postoperative complications analyzed were CSF leak, infections, dysosmia, intracranial hemorrhage (ICH), and endocrine disorders. The rate of CSF leak was 9.8% in the EEA group and 2.1% in MTA group. The rate of infections in the EEA group was 5.7%, while it was 3.7% in the MTA group. The rate of dysosmia ranged from 10.3% for MTAs to 12.9% for EEAs. The rate of ICH in the EEA group was 0.9%, while that in the MTA group was 3.8%. The rate of endocrine disorders in the EEA group was 10.8%, while that in the MTA group was 10.2%. No significant difference was detected in the rate of GTR between the EEA and MTA groups (OR 1.15, 95% CI 0.7-0.95; p = 0.53), while a significant benefit in visual outcomes was shown in EEAs (OR 3.54, 95% CI 2.2-5.72; p < 0.01). There was no significant variation in the recurrence rate between EEA and MTA groups (OR 0.92, 95% CI 0.19-4.46; p = 0.89). While a considerably increased chance of CSF leak from EEAs was shown (OR 4.47, 95% CI 2.52-7.92; p < 0.01), no significant difference between EEA and MTA groups was detected in the rate of infections (OR 1.92, 95% CI 0.73-5.06; p = 0.15), the rate of dysosmia (OR 1.25, 95% CI 0.31-4.99; p = 0.71), the rate of ICH (OR 0.61, 95% CI 0.20-1.87; p = 0.33), and the rate of endocrine disorders (OR 1.16, 95% CI 0.69-1.95; p = 0.53). Conclusions : This meta-analysis suggests that both EEAs and MTAs are viable options for TSM resection, with distinct advantages and drawbacks. The EEAs demonstrate superior visual outcomes in selected cases while GTR and recurrence rates support the overall effectiveness of MTAs and EEAs. Endoscopic endonasal approaches had a higher chance of CSF leaks, but there are no appreciable variations in other complications. These results provide additional insights regarding patient outcomes in the intricate clinical setting of TSMs.

Glioblastoma is the most common malignant primary tumor of the CNS. The prognosis is dismal, with a median survival of 15 months. Surgical treatment followed by adjuvant therapies such as radiotherapy and chemotherapy characterize the classical strategy. The WNT pathway plays a key role in cellular proliferation, differentiation, and invasion. The DKK3 protein, capable of acting as a tumor suppressor, also appears to be able to modulate the WNT pathway. We performed, in a series of 40 patients, immunohistochemical and Western blot evaluations of DKK3 to better understand how the expression of this protein can influence clinical behavior. We used a statistical analysis, with correlations between the expression of DKK3 and overall survival, age, sex, Ki-67, p53, and MGMT and IDH status. We also correlated our data with information included in the cBioPortal database. In our analyses, DKK3 expression, in both immunohistochemistry and Western blot analyses, was reduced or absent in many cases, showing downregulation. To date, no clinical study exists in the literature that reports a potential correlation between IDH and MGMT status and the WNT pathway through the expression of DKK3. Modulation of this pathway through the expression of DKK3 could represent a new tailored therapeutic strategy in the treatment of glioblastoma.

Background: The aim of this study was to understand the impact of SARS-COV-2 disease on neurosurgeons and our profession; specifically, to trace the role of women, in particular young neurosurgeons, in addressing this health emergency., Methods: This cross-sectional study evaluated the impact of SARS-COV-2 disease on Italian neurosurgeons stratified by gender (44 [49.9%] males and 49 [52.1%] females) enrolled through a questionnaire-based online survey., Results: Ninety-three Italian neurosurgeons were included in this study. The percentage of female participants was 52.1% (49) and 53% (50) were younger than 40 years. Men were significantly more affected than women by complications (14 versus 3), while there was no gender difference in the COVID-19 infection rate. Furthermore, the social impact of the pandemic was the same between men and women., Conclusions: Our analysis did not show significant differences between the two genders in the susceptibility, and mortality from COVID-19. The possible and immediate implementation of anti-COVID-19 measures and devices, associated with a lower risk of transmission in the treatment of neurosurgical pathologies, has likely, moderated and disregarded the socio-psychological "gender gap" of the Covid-19 pandemic.

Adult brainstem gliomas (BSGs) are a group of rare central nervous system tumors with varying prognoses and controversial standard treatment strategies. To provide an overview of current trends, a systematic review using the PRISMA guidelines, Class of evidence (CE) and strength of recommendation (SR), was conducted. The review identified 27 studies. Surgery was found to have a positive impact on survival, particularly for focal lesions with CE II SR C. Stereotactic image-guided biopsy was recommended when resective surgery was not feasible with CE II and SR B. The role of systemic treatments remains unclear. Eight studies provided molecular biology data. This review gathers crucial literature on diagnosis and management of adult BSGs. It provides evidence-based guidance with updated recommendations for diagnosing and treating, taking into account recent molecular and genetic advancements. The importance of brain biopsy is emphasized to optimize treatment using emerging genetic-molecular findings and explore potential targeted therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of both upper and lower motor neurons, resulting in clinical features such as muscle weakness, paralysis, and ultimately, respiratory failure. Nowadays, there is not effective treatment to reverse the progression of the disease, that leads to death within 3-5 years after the onset. Nevertheless, the induced pluripotent stem cells (iPS) technology could be the answer, providing disease modelling, drug testing, and cell-based therapies for this pathology. The aim of this work was to conduct a literature review of the past 5 years about the role of iPS in ALS, to better define the neurobiological mechanisms involved in the pathogenesis and the potential future therapies. The review also deals with advanced and currently available technologies used to reprogram cell lines and generate human motor neurons in vitro , which represent the source to study the pathological processes, the relationship between phenotype and genotype, the disease progression and the potential therapeutic targets of these group of disorders. Specific treatment options with stem cells involve Advance Gene Editing Technology, neuroprotective agents, and cells or exosomes transplantation, aimed to replace dead or damaged nerve cells. In summary, this review comprehensively addresses the role of human pluripotent stem cells (hPSCs) in motor neuron diseases (MND), with a focus on physiopathology, diagnostic and prognostic implications, specific and potential future treatment options. Understanding the biological mechanisms and practical implications of hPSCs in MND is crucial for advancing therapeutic strategies and improving outcomes for patients affected by these devastating diseases., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: Previous assessments of stem cell therapy for spinal cord injuries (SCI) have encountered challenges and constraints. Current research primarily emphasizes safety in early-phase clinical trials, while systematic reviews prioritize effectiveness, often overlooking safety and translational feasibility. This situation prompts inquiries regarding the readiness for clinical adoption., Aim: To offer an up-to-date systematic literature review of clinical trial results con cerning stem cell therapy for SCI., Methods: A systematic search was conducted across major medical databases [PubMed, Embase, Reference Citation Analysis (RCA), and Cochrane Library] up to October 14, 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "spinal cord", "injury", "clinical trials", "stem cells", "functional outcomes", and "adverse events". Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI., Results: In a comprehensive review of 66 studies on stem cell therapies for SCI, 496 papers were initially identified, with 237 chosen for full-text analysis. Among them, 236 were deemed eligible after excluding 170 for various reasons. These studies encompassed 1086 patients with varying SCI levels, with cervical injuries being the most common (42.2%). Bone marrow stem cells were the predominant stem cell type used (71.1%), with various administration methods. Follow-up durations averaged around 84.4 months. The 32.7% of patients showed functional impro vement from American spinal injury association Impairment Scale (AIS) A to B, 40.8% from AIS A to C, 5.3% from AIS A to D, and 2.1% from AIS B to C. Sensory improvements were observed in 30.9% of patients. A relatively small number of adverse events were recorded, including fever (15.1%), headaches (4.3%), muscle tension (3.1%), and dizziness (2.6%), highlighting the potential for SCI recovery with stem cell therapy., Conclusion: In the realm of SCI treatment, stem cell-based therapies show promise, but clinical trials reveal potential adverse events and limitations, underscoring the need for meticulous optimization of transplantation conditions and parameters, caution against swift clinical implementation, a deeper understanding of SCI pathophysiology, and addressing ethical, tumorigenicity, immunogenicity, and immunotoxicity concerns before gradual and careful adoption in clinical practice., Competing Interests: Conflict-of-interest statement: All the author declare no conflict of interests for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium score as a surrogate marker of the coronary calcium score in 32 patients with lung cancer. Subsequently, we assessed the impact of the ICA calcium score on overall survival in GBM patients treated with radio-chemotherapy. Results: We analysed 50 GBM patients. At the univariate analysis, methyl-guanine-methyltransferase gene (MGMT) promoter methylation ( p = 0.048), gross total tumour resection ( p = 0.017), and calcium score ( p = 0.011) were significant prognostic predictors in patients with GBM. These three variables also maintained statistical significance in the multivariate analysis. Conclusions: the ICA calcium score could be a promising prognostic biomarker in GBM patients.

Background: Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance., Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects., Results: Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%)., Conclusions: The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.

Background: The blood-brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery., Methods: A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "lipid nanoparticles", "intranasal administration", "neuro-oncological diseases", and "neurodegenerative disorders". This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases., Results: Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer's disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications., Conclusions: This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial.

Objectives: To characterize a profile for patients with tumor-related epilepsy presenting olfactory auras., Materials and Methods: We conducted a monocentric, retrospective study on patients who underwent surgery in the Neurosurgery Unit of Udine University Hospital (Udine, Italy), between the 1st of January 2010 and the 1st of January 2019, for primary brain tumors (PBTs) involving the temporal lobe and the insula. All patients were affected by tumor-related epilepsy; the study group presented olfactory auras as well. We collected neuroradiological, neuropsychological and neurophysiological data from patients' medical charts., Results: The subtraction analysis of MRI data shows maximum lesion overlay in left olfactory cortex, left and right hippocampus, left amygdala, right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus. The presence of olfactory auras did not influence seizure outcome (p = 0.500) or tumor recurrence after surgery (p = 0.185). The type of auras (elementary vs. complex), also, did not influence seizure control (p = 0.222)., Discussion: In presence of olfactory auras, anterior and mesial temporal regions are mainly involved, such as olfactory cortex, amygdala, and anterior hippocampus, together with right rolandic operculum, right inferior frontal gyrus and right middle temporal gyrus, suggesting their possible role in the genesis of olfactory auras. Post-surgical seizure outcome and disease relapse are not influenced by neither the presence nor the type of olfactory auras., Conclusions: Olfactory auras are rare event, however they may be often underestimated by the patients and under-investigated by the clinicians, even when their occurrence can represent a useful localizing tool., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT), chemotherapy (CMT), and surgical resection. Despite the progress made in traditional treatments, the outlook for patients with HGGs remains bleak. Tumor metabolism is emerging as a potential target for glioma therapies, a promising approach that harnesses the metabolism to target tumor cells. However, the efficacy of therapies targeting the metabolism of HGGs remains unclear, compelling a comprehensive review. This study aimed to assess the outcome of present trials on HGG therapies targeting metabolism. A comprehensive search of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted until November 2023. The search method used pertinent Medical Subject Heading (MeSH) terminologies and keywords referring to "high-grade gliomas", "metabolism", "target therapies", "monoclonal antibodies", "overall survival", and "progression-free survival". The review analyzed studies that focused on therapies targeting the metabolism of HGGs in human subjects. These studies included both randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs). Out of 284 articles identified, 23 trials met the inclusion criteria and were thoroughly analyzed. Phase II trials were the most numerous (62%). Targeted metabolic therapies were predominantly used for recurrent HGGs (67%). The most common targeted pathways were the vascular endothelial growth factor (VEGF, 43%), the human epidermal growth factor receptor (HER, 22%), the platelet-derived growth factor (PDGF, 17%), and the mammalian target of rapamycin (mTOR, 17%). In 39% of studies, the subject treatment was combined with CMT (22%), RT (4%), or both (13%). The median OS widely ranged from 4 to 26.3 months, while the median PFS ranged from 1.5 to 13 months. This systematic literature review offers a thorough exploration of the present state of metabolic therapies for HGGs. The multitude of targeted pathways underscores the intricate nature of addressing the metabolic aspects of these tumors. Despite existing challenges, these findings provide valuable insights, guiding future research endeavors. The results serve as a foundation for refining treatment strategies and enhancing patient outcomes within the complex landscape of HGGs.

Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.

We explored the functional outcome following awake surgery and Real-Time Neuropsychological Testing (RTNT) in the left insula. We carried out a longitudinal investigation by comparing the patients' language profile, and, in particular, the object-naming skills and the associated fMRI network, of pre-surgery and follow-up (i.e., a few months after surgery) in a group of 23 patients harboring a left-sided low grade glioma centered to the insulo-temporal area. Tumor resection, performed while continuously monitoring patients' performance by RNTN, was high (median = 92 %). From the neuropsychological viewpoint, almost all patients displayed preserved naming and language skills in general, both before surgery and at follow-up, when they recovered from a transient impairment recorded immediately after surgery. From the functional imaging viewpoint, the naming networks of the two assessment times were almost equivalent, with non-parametric analyses showing brain remodeling involving perilesional areas preoperatively and the contralesional, healthy, insula at follow-up. We discussed the anatomo-functional mechanisms that contributed to the preservation of the functional and cognitive pattern as observed in this longitudinal study, with a particular focus on the promising plasticity potential of the left insular area. In particular, we commented that, at least in our patient series and by applying an optimized surgical procedure, surgery in the insula was safe and generally contributed to the preservation of the language functions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Plasticity could take place as a compensatory process following brain glioma growth. Only a few studies specifically explored plasticity in patients affected by a glioma invading the left insula; even more, plasticity of the insular cortex in task-based functional language network is almost unexplored. In the current study, we explored potential plasticity in a consecutive series of 22 patients affected by a glioma centered to the left insula, by comparing their preoperative object-naming functional network with that of a group of healthy controls. After having controlled for demographic variables, fMRI results showed that patients vs. controls activated a cluster in the right, contralesional pars triangularis including the Broca's area. On the other hand, controls did not significantly activate any brain region more than patients. At behavioral level, patients retained a generally preserved naming performance as well as a proficient language processing profile. These findings suggest that involvement of language-specific areas in the healthy hemisphere could help compensate for the left, affected insula, thus allowing preservation of the naming functions. Results are commented in relation to lesion site, naming performance, and potential relevance for neurosurgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Optic neuritis (ON) is an inflammatory condition affecting the optic nerve, leading to vision impairment and potential vision loss. This manuscript aims to provide a comprehensive review of the current understanding of ON, including its definition, epidemiology, physiology, genetics, molecular pathways, therapy, ongoing clinical studies, and future perspectives. ON is characterized by inflammation of the optic nerve, often resulting from an autoimmune response. Epidemiological studies have shown a higher incidence in females and an association with certain genetic factors. The physiology of ON involves an immune-mediated attack on the myelin sheath surrounding the optic nerve, leading to demyelination and subsequent impairment of nerve signal transmission. This inflammatory process involves various molecular pathways, including the activation of immune cells and the release of pro-inflammatory cytokines. Genetic factors play a significant role in the susceptibility to ON. Several genes involved in immune regulation and myelin maintenance have been implicated in the disease pathogenesis. Understanding the genetic basis can provide insights into disease mechanisms and potential therapeutic targets. Therapy for ON focuses on reducing inflammation and promoting nerve regeneration. Future perspectives involve personalized medicine approaches based on genetic profiling, regenerative therapies to repair damaged myelin, and the development of neuroprotective strategies. Advancements in understanding molecular pathways, genetics, and diagnostic tools offer new opportunities for targeted therapies and improved patient outcomes in the future.

Objectives: Dural based Marginal Zone MALT-type B-Cell Lymphoma (MZBCL) is an intracranial tumor that can mimicking meningioma both from a clinical and a radiological point of view. A standard treatment protocol is still lacking. Aim of the present work is to provide an update of the present literature regarding this rare neoplasia., Patients and Methods: We report the case of a patient with a dural-based lesion mimicking a meningioma of the tentorium. After surgical treatment, the diagnosis was of MZBCL. A literature review is performed to highlight the typical characteristics of this rare intracranial lesion and to define the best therapeutic approach., Results: Literature review included 38 articles describing 126 cases of intracranial dural-based MZBCL. No clinical trial has been found. Clinical and histopathological features are properly collected to provide a guide for future cases. Different treatment options have been attempted. Combination of surgery with adjuvant radiation therapy is the most used option., Conclusions: MZBCL should be considered in differential diagnosis for dural-based intracranial lesion. Surgery followed by radiation therapy is the most reported treatment. As a consequence of the rarity of this disease, of its indolent progression and of the lack of adequate follow-up, it is not possible to define it is the best treatment option.

Given the increasingly important role that the use of artificial intelligence algorithms is taking on in the medical field today (especially in oncology), the purpose of this systematic review is to analyze the main reports on such algorithms applied for the prognostic evaluation of patients with head and neck malignancies. The objective of this paper is to examine the currently available literature in the field of artificial intelligence applied to head and neck oncology, particularly in the prognostic evaluation of the patient with this kind of tumor, by means of a systematic review. The paper exposes an overview of the applications of artificial intelligence in deriving prognostic information related to the prediction of survival and recurrence and how these data may have a potential impact on the choice of therapeutic strategy, making it increasingly personalized. This systematic review was written following the PRISMA 2020 guidelines.

The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy.

Background: Meckel's cave is a challenging surgical target due to its deep location and proximity to vital neurovascular structures. Surgeons have developed various microsurgical transcranial approaches (MTAs) to access it, but there is no consensus on the best method. Newer endoscopic approaches have also emerged. This study seeks to quantitatively compare these surgical approaches to Meckel's cave, offering insights into surgical volumes and exposure areas., Methods: Fifteen surgical approaches were performed bilaterally in six specimens, including the pterional approach (PTA), fronto-temporal-orbito-zygomatic approach (FTOZA), subtemporal approach (STA), Kawase approach (KWA), retrosigmoid approach (RSA), retrosigmoid approach with suprameatal extension (RSAS), endoscopic endonasal transpterygoid approach (EETPA), inferolateral transorbital approach (ILTEA) and superior eyelid approach (SEYA). All the MTAs were performed both with 10 mm and 15 mm of brain retraction, to consider different percentages of surface exposure. A dedicated navigation system was used to quantify the surgical working volumes and exposure of different areas of Meckel's cave (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Microsurgical transcranial approaches were quantified with two different degrees of brain retraction (10 mm and 15 mm). Statistical analysis was performed using a mixed linear model with bootstrap resampling., Results: The RSAS with 15 mm of retraction offered the maximum exposure of the trigeminal stem (TS). If compared to the KWA, the RSA exposed more of the TS (69% vs. 46%; p = 0.01). The EETPA and ILTEA exposed the Gasserian ganglion (GG) mainly in the anteromedial portion, but with a significant 20% gain in exposure provided by the EETPA compared to ILTEA (42% vs. 22%; p = 0.06). The STA with 15 mm of retraction offered the maximum exposure of the GG, with a significant gain in exposure compared to the STA with 10 mm of retraction (50% vs. 35%; p = 0.03). The medial part of the three trigeminal branches was mainly exposed by the EETPA, particularly for the ophthalmic (66%) and maxillary (83%) nerves. The EETPA offered the maximum exposure of the medial part of the mandibular nerve, with a significant gain in exposure compared to the ILTEA (42% vs. 11%; p = 0.01) and the SEY (42% vs. 2%; p = 0.01). The FTOZA offered the maximum exposure of the lateral part of the ophthalmic nerve, with a significant gain of 67% ( p = 0.03) and 48% ( p = 0.04) in exposure compared to the PTA and STA, respectively. The STA with 15 mm of retraction offered the maximum exposure of the lateral part of the maxillary nerve, with a significant gain in exposure compared to the STA with 10 mm of retraction (58% vs. 45%; p = 0.04). The STA with 15 mm of retraction provided a significant exposure gain of 23% for the lateral part of the mandibular nerve compared to FTOZA with 15 mm of retraction ( p = 0.03)., Conclusions: The endoscopic approaches, through the endonasal and transorbital routes, can provide adequate exposure of Meckel's cave, especially for its more medial portions, bypassing the impediment of major neurovascular structures and significant brain retraction. As far as the most lateral portion of Meckel's cave, MTA approaches still seem to be the gold standard in obtaining optimal exposure and adequate surgical volumes.

Background: Virtual surgical planning allows surgeons to meticulously define surgical procedures by creating a digital replica of patients' anatomy. This enables precise preoperative assessment, facilitating the selection of optimal surgical approaches and the customization of treatment plans. In neck surgery, virtual planning has been significantly underreported compared to craniofacial surgery, due to a multitude of factors, including the predominance of soft tissues, the unavailability of intraoperative navigation and the complexity of segmenting such areas. Augmented reality represents the most innovative approach to translate virtual planning for real patients, as it merges the digital world with the surgical field in real time. Surgeons can access patient-specific data directly within their field of view, through dedicated visors. In head and neck surgical oncology, augmented reality systems overlay critical anatomical information onto the surgeon's visual field. This aids in locating and preserving vital structures, such as nerves and blood vessels, during complex procedures. In this paper, the authors examine a series of patients undergoing complex neck surgical oncology procedures with prior virtual surgical planning analysis. For each patient, the surgical plan was imported in Hololens headset to allow for intraoperative augmented reality visualization. The authors discuss the results of this preliminary investigation, tracing the conceptual framework for an increasing AR implementation in complex head and neck surgical oncology procedures.

Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "glioblastomas," "immunotherapies," and "treatment." The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.

Background: Spheno-orbital meningiomas (SOMs) are rare tumors arising from the meninges surrounding the sphenoid bone and orbital structures. Surgical resection is the primary treatment approach for SOMs. Several surgical approaches have been described during the decades, including microsurgical transcranial (MTAs), endoscopic endonasal (EEAs), endoscopic transorbital (ETOAs), and combined approaches, and the choice of surgical approach remains a topic of debate., Purpose: This systematic review and meta-analysis aim to compare the clinical and surgical outcomes of different surgical approaches used for the treatment of SOMs, discussing surgical techniques, outcomes, and factors influencing surgical decision making., Methods: A comprehensive literature review of the databases PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted for articles published on the role of surgery for the treatment of SOMs until 2023. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analysis was performed to estimate pooled event rates and assess heterogeneity. Fixed- and random-effects were used to assess 95% confidential intervals (CIs) of presenting symptoms, outcomes, and complications., Results: A total of 59 studies comprising 1903 patients were included in the systematic review and meta-analysis. Gross total resection (GTR) rates ranged from 23.5% for ETOAs to 59.8% for MTAs. Overall recurrence rate after surgery was 20.7%. Progression-free survival (PFS) rates at 5 and 10 years were 75.5% and 49.1%, respectively. Visual acuity and proptosis improvement rates were 57.5% and 79.3%, respectively. Postoperative cranial nerve (CN) focal deficits were observed in 20.6% of cases. The overall cerebro-spinal fluid (CSF) leak rate was 3.9%, and other complications occurred in 13.9% of cases. MTAs showed the highest GTR rates (59.8%, 95%CI = 49.5-70.2%; p = 0.001) but were associated with increased CN deficits (21.0%, 95%CI = 14.5-27.6%). ETOAs had the lowest GTR rates (23.5%, 95%CI = 0.0-52.5%; p = 0.001), while combined ETOA and EEA had the highest CSF leak rates (20.3%, 95%CI = 0.0-46.7%; p = 0.551). ETOAs were associated with better proptosis improvement (79.4%, 95%CI = 57.3-100%; p = 0.002), while anatomical class I lesions were associated with better visual acuity (71.5%, 95%CI = 63.7-79.4; p = 0.003) and proptosis (60.1%, 95%CI = 38.0-82.2; p = 0.001) recovery. No significant differences were found in PFS rates between surgical approaches., Conclusion: Surgical treatment of SOMs aims to preserve visual function and improve proptosis. Different surgical approaches offer varying rates of GTR, complications, and functional outcomes. A multidisciplinary approach involving a skull base team is crucial for optimizing patient outcomes.

The 2021 WHO (World Health Organization) classification of brain tumors incorporated the rapid advances in the molecular, genetic, and pathogenesis understanding of brain tumor pathogenesis, behavior, and treatment response. It revolutionized brain tumor classification by placing great emphasis on molecular types and completely splitting adult-type and pediatric-type diffuse gliomas. Brainstem gliomas (BSGs) are the leading primary tumors of the brainstem, although they are quite uncommon in adults compared with the pediatric population, representing less than 2% of adult gliomas. Surgery is not always the treatment of choice since resection is rarely feasible and does not improve overall survival, and biopsies are not generally performed since the location is treacherous. Therefore, MRI (Magnetic Resonance Imaging) without and with gadolinium administration represents the optimal noninvasive radiological technique to suggest brainstem gliomas diagnosis, plan a multidisciplinary treatment and for follow-up evaluations. The MRI protocol encompasses morphological sequences as well as functional and advanced sequences, such as DWI/ADC (Diffusion-Weighted Imaging/Apparent Diffusion Coefficient), DTI (Diffusion Tensor Imaging), PWI (Perfusion-Weighted Imaging), and MRS (Magnetic Resonance Spectroscopy), which improve the accuracy of the diagnosis of BSGs by adding substantial information regarding the cellularity, the infiltrative behavior toward the v fiber tracts, the vascularity, and the molecular changes. Brainstem gliomas have been divided into four categories on the basis of their MRI radiological appearance, including diffuse intrinsic low-grade gliomas, enhancing malignant gliomas, localized tectal gliomas, and other forms. The aim of our review is to provide insight into the role of advanced MRI sequences in the diagnosis and follow-up of adult brainstem gliomas.