The Current Diagnostic Performance of MRI-Based Radiomics for Glioma Grading: A Meta-Analysis.

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.

A Systematic Review of the Metabolism of High-Grade Gliomas: Current Targeted Therapies and Future Perspectives.

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.

Non-surgical management of chronic subdural hematoma: insights and future perspectives from an international survey including neurosurgeons from 90 countries worldwide.

BACKGROUND: Chronic subdural hematoma (cSDH) is one of the most common neurosurgical conditions. Although surgical evacuation is still the gold standard for treatment, recent advances have led to the development of other management strategies, such as medical therapies and endovascular middle meningeal artery (MMA) embolization. Through this international survey, we investigated the global trends in cSDH management, focusing on medical and endovascular treatments. DESIGN AND PARTICIPANTS: A 14-question, web-based, anonymous survey was distributed to neurosurgeons worldwide. RESULTS: Most responders do not perform MMA embolization (69.5%) unless for specific indications (29.6%). These indications include residual cSDH after surgical evacuation (58.9%) or cSDH in patients on antiplatelet medications to avoid surgical evacuation (44.8%). Survey participants from teaching versus non-teaching hospitals (p = 0.002), public versus private hospitals (p = 0.022), and Europe versus other continents (p < 0.001) are the most users of MMA embolization. A large number of participants (51%) declare they use a conservative/medical approach, mainly to avoid surgery in patients with small cSDH (74.8%). CONCLUSIONS: This survey highlights the current trends of cSDH management, focusing on conservative and MMA embolization treatment strategies. Most responders prefer a conservative approach for patients with small cSDHs not requiring surgical evacuation. However, in higher-risk scenarios such as residual hematomas after surgery or patients on antiplatelet medications, MMA embolization is regarded as a reasonable option by participants. Future studies should clarify the indications of MMA embolization, including appropriate patient selection and efficacy as a stand-alone procedure.

Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements.

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.

Surgical treatment of previously embolized craniocervical junction dural arteriovenous fistula.

Craniocervical junction dural arteriovenous fistulas (dAVFs) are rare vascular lesions with a potentially dangerous natural history due to the onset of neurological deficit secondary to intracranial hemorrhage or myelopathy due to venous congestion. Despite advances in endovascular techniques, many dAVFs located in this area continue to require surgical treatment as embolization is often not feasible or safe. In this video, the authors illustrate a patient with a symptomatic craniocervical junction dAVF who had undergone attempted Onyx embolization at another institution. Because of persistent filling of the fistula and worsening myelopathy after the previous attempt, the patient was referred to the authors' clinic for definitive surgical treatment. The video illustrates the typical location of the early draining vein in most craniocervical junction dAVFs immediately below the emergence of the vertebral artery from the dura. The patient underwent successful definitive clip ligation of the fistula, which was exposed through a lateral suboccipital craniotomy.The video can be found here: https://youtu.be/Bvg6VKLgwO0.

The Transorbital Approach: A Comprehensive Review of Targets, Surgical Techniques, and Multiportal Variants.

The transorbital approach (TOA) is gaining popularity in skull base surgery scenarios. This approach represents a valuable surgical corridor to access various compartments and safely address several intracranial pathologies, both intradurally and extradurally, including tumors of the olfactory groove in the anterior cranial fossa (ACF), cavernous sinus in the middle cranial fossa (MCF), and the cerebellopontine angle in the posterior cranial fossa (PCF). The TOA exists in many variants, both from the point of view of invasiveness and from that of the entry point to the orbit, corresponding to the four orbital quadrants: the superior eyelid crease (SLC), the precaruncular (PC), the lateral retrocanthal (LRC), and the preseptal lower eyelid (PS). Moreover, multiportal variants, consisting of the combination of the transorbital approach with others, exist and are relevant to reach peculiar surgical territories. The significance of the TOA in neurosurgery, coupled with the dearth of thorough studies assessing its various applications and adaptations, underscores the necessity for this research. This extensive review delineates the multitude of target lesions reachable through the transorbital route, categorizing them based on surgical complexity. Furthermore, it provides an overview of the different transorbital variations, both standalone and in conjunction with other techniques. By offering a comprehensive understanding, this study aims to enhance awareness and knowledge regarding the current utility of the transorbital approach in neurosurgery. Additionally, it aims to steer future investigations toward deeper exploration, refinement, and exploration of additional perspectives concerning this surgical method.

Radiomics for differentiation of gliomas from primary central nervous system lymphomas: a systematic review and meta-analysis.

Background and objective: Numerous radiomics-based models have been proposed to discriminate between central nervous system (CNS) gliomas and primary central nervous system lymphomas (PCNSLs). Given the heterogeneity of the existing models, we aimed to define their overall performance and identify the most critical variables to pilot future algorithms. Methods: A systematic review of the literature and a meta-analysis were conducted, encompassing 12 studies and a total of 1779 patients, focusing on radiomics to differentiate gliomas from PCNSLs. A comprehensive literature search was performed through PubMed, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus databases. Overall sensitivity (SEN) and specificity (SPE) were estimated. Event rates were pooled using a random-effects meta-analysis, and the heterogeneity was assessed using the χ2 test. Results: The overall SEN and SPE for differentiation between CNS gliomas and PCNSLs were 88% (95% CI = 0.83 - 0.91) and 87% (95% CI = 0.83 - 0.91), respectively. The best-performing features were the ones extracted from the Gray Level Run Length Matrix (GLRLM; ACC 97%), followed by those obtained from the Neighboring Gray Tone Difference Matrix (NGTDM; ACC 93%), and shape-based features (ACC 91%). The 18F-FDG-PET/CT was the best-performing imaging modality (ACC 97%), followed by the MRI CE-T1W (ACC 87% - 95%). Most studies applied a cross-validation analysis (92%). Conclusion: The current SEN and SPE of radiomics to discriminate CNS gliomas from PCNSLs are high, making radiomics a helpful method to differentiate these tumor types. The best-performing features are the GLRLM, NGTDM, and shape-based features. The 18F-FDG-PET/CT imaging modality is the best-performing, while the MRI CE-T1W is the most used.

Clustering Functional Magnetic Resonance Imaging Time Series in Glioblastoma Characterization: A Review of the Evolution, Applications, and Potentials.

In this paper, we discuss how the clustering analysis technique can be applied to analyze functional magnetic resonance imaging (fMRI) time-series data in the context of glioblastoma (GBM), a highly heterogeneous brain tumor. The precise characterization of GBM is challenging and requires advanced analytical approaches. We have synthesized the existing literature to provide an overview of how clustering algorithms can help identify unique patterns within the dynamics of GBM. Our review shows that the clustering of fMRI time series has great potential for improving the differentiation between various subtypes of GBM, which is pivotal for developing personalized therapeutic strategies. Moreover, this method proves to be effective in capturing temporal changes occurring in GBM, enhancing the monitoring of disease progression and response to treatment. By thoroughly examining and consolidating the current research, this paper contributes to the understanding of how clustering techniques applied to fMRI data can refine the characterization of GBM. This article emphasizes the importance of incorporating cutting-edge data analysis techniques into neuroimaging and neuro-oncology research. By providing a detailed perspective, this approach may guide future investigations and boost the development of tailored therapeutic strategies for GBM.

PET imaging for a very early detection of rapid eye movement sleep behaviour disorder and Parkinson's disease - A model-based cost-effectiveness analysis.

Parkinson's disease (PD) is the second most prevalent neurodegenerative condition after Alzheimer's disease and it represents one of the fastest emerging neurological diseases worldwide. PD is usually diagnosed after the third decade of life with symptoms like tremors at rest and muscle stiffness. Rapid Eye Movement sleep behavioral disorder (RBD) is another disorder that is caused by a loss of typical muscle relaxation during sleep with a lot of motor activity. Usually, RBD is strongly associated with PD. Recent studies have demonstrated that PD reduces the life expectancy of patients to 10 and 20 years after being diagnosed. In addition, delayed diagnosis and treatment of these neurological disorders have significant socio-economic impacts on patients, their partners and on the general public. Often, it is not clear about PD associated financial burdens both in low and high-income countries. On the other hand, PD triggers neurological variations that affect differences in the dopamine transporter (DAT) and in glucose metabolism. Therefore, positron emission tomography (PET) using specific DAT radiotracers and fluorine-18 labeled desoxyglucose (FDG) has being considered a key imaging technique that could be applied clinically for the very early diagnosis of RBD and in PD. However, a few myths about PET is that it is very expensive. Here, we looked at the cost of treatment of PD and RBD in relation to early PET imaging. Our finding suggests that PET imaging might also be a cost sparing diagnostic option in the management of patients with PD and RBD, not only for first world countries as it is the case now but also for the third world countries. Therefore, PET is a cost-effective imaging technique for very early diagnostic of RBD and PD.

Current and Future Applications of Arterial Spin Labeling MRI in Cerebral Arteriovenous Malformations.

Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic workup of AVMs and their variants in both adult and pediatric populations is proposed. Evaluation after treatments, whether endovascular or microsurgical, was similarly examined. ASL, with its endogenous tracer and favorable safety profile, offers functional assessment and arterial feeder identification. ASL has demonstrated strong performance in identifying feeder arteries and detecting arteriovenous shunting, although some studies report inferior performance compared with digital subtraction angiography (DSA) in delineating venous drainage. Challenges include uncertainties in sensitivity for specific AVM features. Detecting AVMs in challenging locations, such as the apical cranial convexity, is further complicated, demanding careful consideration due to the risk of underestimating total blood flow. Navigating these challenges, ASL provides a noninvasive avenue with undeniable merits, but a balanced approach considering its limitations is crucial. Larger-scale prospective studies are needed to comprehensively evaluate the diagnostic performance of ASL in AVM assessment.

The oculomotor cistern and pituitary adenomas: anatomical and clinical study.

OBJECTIVE: The oculomotor cistern (OMC) is a meningeal cuff filled with CSF that contains the oculomotor nerve (cranial nerve [CN] III) at the level of the lateral wall of the cavernous sinus. Only a few studies have investigated the involvement of the OMC by pituitary adenomas (pituitary neuroendocrine tumors [PitNETs]), mainly with relatively small case series. The aim of this study was to perform a histomorphological description of the OMC and systematically analyze its involvement by PitNETs from radiological, clinical, and surgical perspectives. METHODS: Ten hemisellae from formalin-fixed specimens were studied with 3-µm sections. Digital image analysis software was used for morphological and quantitative assessments. Clinical, radiological, surgical, and histological data of patients undergoing endoscopic transsphenoidal surgery for PitNETs at the University of Brescia, Italy, between 2014 and 2021 were recorded. OMC involvement was graded as not compressed, compressed, and invaded. The same surgical team operated on all patients. RESULTS: The OMC had an elliptical shape with an average area of 3.1 mm2 and a length of 5.5 mm. No cisternal points of weakness were recognized in the histomorphological study. Of 315 patients, 246 had complete data: apoplexy and CN III palsy were documented in 6.9% and 8.5%, respectively. OMC compression and invasion were recorded in 106 (43.1%) and 23 (9.3%) patients. Significant associations between OMC involvement and PitNET dimensions (p < 0.001), Knosp grade (p < 0.001), preoperative oculomotor palsy (p < 0.001), Ki-67 percentage (p = 0.009), and recurrence/progression of residual tumor (p = 0.008) were found. A new postoperative CN III palsy was evident in 2%: transient in 4 cases, and persistent in 1 patient treated for a recurrent PitNET who experienced a local infection complication. Preoperative CN III palsy improved in 10 cases. CONCLUSIONS: Significant OMC involvement by PitNETs might be underrecognized, but it can be treated using the endoscopic transsphenoidal approach, and it affects patient outcomes.

The benefit of antibiotic-combined Mg-hydroxyapatite bone graft substitute over autologous bone for surgical site infection prevention in posterolateral spinal fusion: a retrospective cohort study.

Retrospective cohort study. Objective: The authors' goal was to clarify whether a bone substitute combined with antibiotics might gain a hold in spinal surgery as a preventive treatment for early infections (EIs). Background: A relatively infrequent but severe complication in spinal surgery is the occurrence of EIs. Methods: The authors retrospectively compared a population undergoing posterolateral fusion with Mg-enriched hydroxyapatite paste mixed with 60 mg rifampicin powder, with a matched population treated with autologous bone without antibiotics. A total of 30 patients from 2020 to 2021 were included in our study. We estimated EI's relative risk and the number needed to treat. Statistical analyses were performed using the R statistical package v3.4.1 (http://www.r-project.org). Results: No early infections occurred in the population treated with antibiotic-combined bone substitutes, compared with 6.7% of patients treated with autologous bone without antibiotics. The relative risk of EIs was 0.33 (P=.49; 95% CI=0.01-7.58) and the number needed to treat was 15. Conclusions: The results support the hypothesis that combining bone substitutes with antibiotics may decrease the risk of EIs and could be a viable option to improve spinal surgery outcomes. However, a larger sample size would be needed to confirm the benefit of rifampicin-combined Mg-enriched hydroxyapatite substitutes over autologous bone for surgical site infection prevention. Level of Evidence: Level 3.

Brain Arteriovenous Malformations and Pregnancy: A Systematic Review of the Literature.

BACKGROUND: The bleeding risk and outcome of pregnant women harboring intracranial arteriovenous malformations are still unclear, and no consensus has been achieved on management timing and strategy. METHODS: We searched PubMed, MEDLINE, and EMBASE from 1990 to 2022 for studies evaluating the bleeding risk and the outcome of women with intracranial arteriovenous malformations. Our primary end point was the hemorrhage rate. The secondary end points were pregnancy outcome and treatment safety for the mother and the fetus. RESULTS: Nine studies reporting on 2426 women were included. The overall hemorrhage rate in untreated women was 2.6%. The rate of first bleeding during pregnancy and postpartum was greater than the respective fertile period in unpregnant women (11% vs. 6.7%). The risk of first bleeding was greater in the II and III trimesters (4.5% and 2.9%), while was lower during delivery and puerperium (0.1% and 0.2%). The majority of the women did not report any complications after pregnancy and early postpartum death occurred in 4.1% of cases. The overall miscarriage rate was 12.4%. CONCLUSIONS: Women harboring intracranial arteriovenous malformations appear to have a greater risk of hemorrhage during pregnancy. There is an increased bleeding risk in the later stages of gestation, whereas delivery and puerperium are less risky phases. Outcomes are relatively good for the mother, with low rates of mortality and unfavorable sequelae, but there is a risk of miscarriage for the fetus. Intervention should be undertaken prophylactically before pregnancy or during early gestation if possible. For pregnant women who deferred treatment, multidisciplinary management is advised.

Advancements in Glioma Care: Focus on Emerging Neurosurgical Techniques.

BACKGROUND: Despite significant advances in understanding the molecular pathways of glioma, translating this knowledge into effective long-term solutions remains a challenge. Indeed, gliomas pose a significant challenge to neurosurgical oncology because of their diverse histopathological features, genetic heterogeneity, and clinical manifestations. Relevant sections: This study focuses on glioma complexity by reviewing recent advances in their management, also considering new classification systems and emerging neurosurgical techniques. To bridge the gap between new neurosurgical approaches and standards of care, the importance of molecular diagnosis and the use of techniques such as laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) are emphasized, exploring how the integration of molecular knowledge with emerging neurosurgical approaches can personalize and improve the treatment of gliomas. CONCLUSIONS: The choice between LITT and FUS should be tailored to each case, considering factors such as tumor characteristics and patient health. LITT is favored for larger, complex tumors, while FUS is standard for smaller, deep-seated ones. Both techniques are equally effective for small and superficial tumors. Our study provides clear guidance for treating pediatric low-grade gliomas and highlights the crucial roles of LITT and FUS in managing high-grade gliomas in adults. This research sets the stage for improved patient care and future developments in the field of neurosurgery.

Radiomics for Differentiation of Pediatric Posterior Fossa Tumors: A Meta-Analysis and Systematic Review of the Literature.

PURPOSE: To better define the overall performance of the current radiomics-based models for the discrimination of pediatric posterior fossa tumors. METHODS: A comprehensive literature search of the databases PubMed, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus was designed and conducted by an experienced librarian. We estimated overall sensitivity (SEN) and specificity (SPE). Event rates were pooled across studies using a random-effects meta-analysis, and the χ2 test was performed to assess the heterogeneity. RESULTS: Overall SEN and SPE for differentiation between MB, PA, and EP were found to be promising, with SEN values of 93% (95% CI = 0.88-0.96), 83% (95% CI = 0.66-0.93), and 85% (95% CI = 0.71-0.93), and corresponding SPE values of 87% (95% CI = 0.82-0.90), 95% (95% CI = 0.90-0.98) and 90% (95% CI = 0.84-0.94), respectively. For MB, there is a better trend for LR classifiers, while textural features are the most used and the best performing (ACC 96%). As for PA and EP, a synergistic employment of LR and NN classifiers, accompanied by geometrical or morphological features, demonstrated superior performance (ACC 94% and 96%, respectively). CONCLUSIONS: The diagnostic performance is high, making radiomics a helpful method to discriminate these tumor types. In the forthcoming years, we expect even more precise models.

Cigarette Smoking and Intracranial Aneurysms: A Pilot Analysis of SNPs in the CYP2A6 Gene in the Italian Population.

BACKGROUND: Cigarette smoking is a modifiable risk factor associated with formation and rupture of intracranial aneurysms (IAs). Cytochrome P450 2A6 (CYP2A6) is the main enzyme implied in catabolism of nicotine and xenobiotics, giving rise to oxidative stress products. Our study investigated the associations between specific single-nucleotide polymorphisms (SNPs) in the CYP2A6 gene and the presence of sporadic IAs in a cluster of Italian patients, as well as their rupture regarding cigarette smoking habit. METHODS: Three hundred and thirty-one Italian patients with sporadic IAs were recruited in a single institution. We recorded data on clinical onset with subarachnoid hemorrhage (SAH) and smoking habit. Genetic analysis was performed with a standard procedure on peripheral blood samples: CYP2A6 ∗1B2, CYP2A6 ∗2, and CYP2A6 ∗14 SNPs were analyzed in the study group along with 150 healthy control subjects. Statistical analysis was conducted according to genetic association study guidelines. RESULTS: In the patient cohort, the frequency of aSAH was significantly higher in current smokers (P < 0.001; OR=17.45), regardless of the pattern of CYP2A6 SNPs. There was a correlation between IA rupture and cigarette smoking in patients with the heterozygous CYP2A6 ∗1B2 allele (P < 0.001; OR=15.47). All patients carrying the heterozygous CYP2A6 ∗14 allele had an aSAH event (100%), regardless of smoking habit, although this correlation was not statistically significant (P = 1). CONCLUSIONS: According to our findings, a cigarette smoker carrying a fully active CYP2A6 enzyme (heterozygous ∗1B2 allele) may have an increased risk of IA rupture compared to those with functionally less active variants: further investigation on a larger sample is needed to verify this result. The role of the heterozygous CYP2A6 ∗14 allele in aSAH is yet to be clarified.

Developmental venous anomaly associated with dural arteriovenous fistula: Etiopathogenesis and hemorrhagic risk.

Introduction: Developmental venous anomalies (DVAs) have traditionally been defined as non-pathological congenital lesions. Compared to isolated DVAs, the association of DVAs with arteriovenous shunts seems to have a more adverse clinical connotation. In this review, we describe the association between DVA and dAVF and discuss the hemorrhagic risk. We also advance a hypothesis about the potential de novo formation of a DVA and challenge the dogma about their "developmental" or "congenital" nature. Methods: A systematic review of the literature on the association of DVA and dAVF was performed in accordance with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. Results: A number of 678 papers was initially identified, but only 9 studies were included in the final qualitative analysis. Most of the patients presented with bleeding (56%), with a median GCS of 14 (range 10-15). In 56% of the cases the DVA had a supratentorial location. Supratentorial DVAs mostly drained in the superior sagittal sinus (80%), while all of infratentorial/combined DVAs drained in deep ependymal veins of the 4th ventricle. All the supratentorial dAVFs drained into the superior sagittal sinus, while the infratentorial/combined dAVFs mostly drained in the jugular bulb, Vein of Rosenthal, or transverse-sigmoid sinuses (75%). Most of the dAVFs were classified as Cognard type IIa + b (67%), while in a smaller number of cases type I (22%) and type V (11%). The dAVF was the target of treatment in each case and most patients underwent endovascular treatment (78%). The dAVF was completely occluded in 78% of cases and no periprocedural complications were reported. Conclusion: The clinical presentation, radiological findings, and treatment outcomes of DVAs and associated dAVFs have been discussed. Despite the general opinion that DVAs are benign congenital lesions, increasing epidemiological and radiological evidence supports a potential acquired origin, and the venous system seem to play a pivotal role in their post-natal genesis and development.

Tumor Microenvironment and Glioblastoma Cell Interplay as Promoters of Therapeutic Resistance.

The invasive nature of glioblastoma is problematic in a radical surgery approach and can be responsible for tumor recurrence. In order to create new therapeutic strategies, it is imperative to have a better understanding of the mechanisms behind tumor growth and invasion. The continuous cross-talk between glioma stem cells (GSCs) and the tumor microenvironment (TME) contributes to disease progression, which renders research in this field difficult and challenging. The main aim of the review was to assess the different possible mechanisms that could explain resistance to treatment promoted by TME and GSCs in glioblastoma, including the role of M2 macrophages, micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) from exosomes from the TME. A systematic review of the literature on the role of the TME in developing and promoting radioresistance and chemoresistance of GBM was performed according to PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. A dedicated literature review search was also performed on the immunotherapeutic agents against the immune TME. We identified 367 papers using the reported keywords. The final qualitative analysis was conducted on 25 studies. A growing amount of evidence in the current literature supports the role of M2 macrophages and non-coding RNAs in promoting the mechanisms of chemo and radioresistance. A better insight into how GBM cells interact with TME is an essential step towards comprehending the mechanisms that give rise to resistance to standard treatment, which can help to pave the way for the development of novel therapeutic strategies for GBM patients.

Quantitative Anatomical Studies in Neurosurgery: A Systematic and Critical Review of Research Methods.

BACKGROUND: The anatomy laboratory can provide the ideal setting for the preclinical phase of neurosurgical research. Our purpose is to comprehensively and critically review the preclinical anatomical quantification methods used in cranial neurosurgery. METHODS: A systematic review was conducted following the PRISMA guidelines. The PubMed, Ovid MEDLINE, and Ovid EMBASE databases were searched, yielding 1667 papers. A statistical analysis was performed using R. RESULTS: The included studies were published from 1996 to 2023. The risk of bias assessment indicated high-quality studies. Target exposure was the most studied feature (81.7%), mainly with area quantification (64.9%). The surgical corridor was quantified in 60.9% of studies, more commonly with the quantification of the angle of view (60%). Neuronavigation-based methods benefit from quantifying the surgical pyramid features that define a cranial neurosurgical approach and allowing post-dissection data analyses. Direct measurements might diminish the error that is inherent to navigation methods and are useful to collect a small amount of data. CONCLUSION: Quantifying neurosurgical approaches in the anatomy laboratory provides an objective assessment of the surgical corridor and target exposure. There is currently limited comparability among quantitative neurosurgical anatomy studies; sharing common research methods will provide comparable data that might also be investigated with artificial intelligence methods.

Surgical Treatment of Spheno-Orbital Meningiomas: A Systematic Review and Meta-Analysis of Surgical Techniques and Outcomes.

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.