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Despite being uncommon, postoperative vasospasm (PoVS) present notably high morbidity and mortality rates. Our aim was to identify prognostic factors associated with this condition and introduce a scoring system to improve subsequent clinical and radiological surveillance strategies. We conducted a retrospective analysis of our institutional database covering patients aged over 18 who underwent craniotomic or transsphenoidal surgery for elective tumor removal at the Neurosurgical Unit of our institution between January 2016 and August 2023. A comprehensive search was conducted using the Cochrane Database of Systematic Reviews and PubMed database to identify the most correlated risk factors. Literature review included a final group of 32 studies (52 patients) and identified SAH, vessel encasement or vessel manipulation, hypothalamic disfunction, meningitis, younger age, tumor size > 3 cm, and long operative time as predictive factors for PoVS. Our cohort included 2132 patients, with only 13 individuals (0.61%) presenting PoVS. To predict the occurrence of PoVS, we developed a logistic multivariate regression model that identified thick (defined as Fisher grade ≥ 3) subarachnoid hemorrhage (coeff. 6.7, p < 0.001), intraparenchymal hemorrhage (coeff. 3.44, p < 0.001), lesion located in the parasellar region (coeff. 2.1, p = 0.064), and lesion size ≥ 4 cm (coeff. 2.0, p = 0.069) as potential independent predictors of PoVS. Based on statistical model for these variables was assigned a score: thick SAH 7 points, intraparenchymal hemorrhage 3 points, parasellar lesion site 2 points, and lesion size ≥ 4 cm 2 points. The cumulative scores ranged from 0 to 14. PoVS is a rare complication but its association with significant morbidity and mortality underscores the importance of early identification and treatment. In our study we proposed a stratified risk score to identify high risk patients. However, due to rarity of this condition, our score proposal should be considered as a training set a to be validated in future studies with a multicenter setting., Competing Interests: Declarations. Ethical approval: This is an observational study. No ethical approval is required. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Choroid plexus tumors (CPT) are rare entities, and even rarer in adulthood., Methods: A retrospective consecutive series of 24 adult CPT patients was reviewed., Results: We described 24 adult CPTs. Clinical onset included cerebellar signs (n = 11, 45.8%), intracranial hypertension signs (n = 8, 33.4%), cranial nerves impairment (n = 5, 20.8%), incidental findings (n = 4, 16.6%), seizures (n = 1, 4.2%), spinal signs (n = 1, 4.2%). At first diagnosis, CPT was mostly located in the ventricular system, but other locations can occur, including the spine (one case); meningeal involvement was present in one, pre-surgical hydrocephalus in one case only. CPT histological grade ranged from grade 1 (n = 17), grade 2 (n = 6), and grade 3 (n = 1). TERTp mutation was detected in 17.6% (n = 3/17). TP53 mutation in 5.9% (n = 1/17). Gross Total, Subtotal, Partial resection and Biopsy were achieved in 17 (70.8%), 3 (12.5%), 3 (12.5%) and 1 (4.2%) of patients, respectively. 76% of cases (n = 16/21) experienced clinical worsening suddenly after surgery for different reasons, and mostly gradually recovered. For three cases no data was available. Adjuvant therapy was performed only for grades 2 and 3. At recurrence, surgery, radiosurgery, radiotherapy and chemotherapy were considered. The median Overall Survival from surgery was 219.25 months (95% CI, 188.83-249.67)., Conclusions: We confirm that CPT can occur in adults and are mostly grade 1 tumors located in the ventricular system. The surgical approach is the gold standard, although 76% of clinical worsening occurred, often transient. Adjuvant treatment was limited to higher grade CPT; however, no consensus has already been achieved about adjuvant therapy., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the local Ethical Committee. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Fondazione IRCCS Istituto Neurologico “Carlo Besta” research committee (Ref. 2015-034) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All individual participants included in the study signed informed consent; the consent included the possibility of publishing data, photos, exams in anonymized form. Competing interests: The authors declare that they have no conflict of interest., (© 2024. The Author(s).)

Objective: To compare the elastographic patterns of high-grade gliomas (HGGs) solid portions and those of adjacent healthy brain parenchyma, on intraoperative ultrasound, with magnetic resonance image (MRI) characteristics., Methods: Clinical records and images of HGGs patients, operated between June and December 2018, were retrospectively reviewed. Fusion images were used to compare preoperative gadolinium-enhanced T1-weighted MRI/fluid-attenuated inversion recovery images (Gd-T1 MRI/FLAIR) to intraoperative strain elastography (SE). FLAIR/Gd-T1 MRI images were used to define enhancement patterns (absent/whole lesion/peripheral) and lesions' characteristics (primary and secondary pattern, further subdivided in solid/necrotic/cystic/infiltrating). HGGs SE patterns were categorized as homogeneous/inhomogeneous, while lesions' primary and secondary patterns as stiff/intermediate/elastic. The SE motive of neighboring healthy brain parenchyma was defined similarly., Results: Eighteen patients (M:F, 11:7; mean age: 53 years) harboring 14 glioblastomas (77.8%) and 4 anaplastic astrocytomas (22.2%) were compared. Glioblastomas typically enhanced peripherally and had a primary necrotic pattern (78.6% and 64.3%, respectively), while anaplastic astrocytomas did not enhance and were solid (75% both) at T1-Gd MRI and FLAIR images. At SE anaplastic astrocytomas had a homogeneous stiff primary pattern, whereas the majority of glioblastomas primary patterns were heterogeneous (85.7%) and intermediate (78.6%)., Conclusions: Three major SE patterns defined HGGs and adjacent healthy brain parenchyma. SE patterns varied according to HGG histotypes and Gd-T1 MRI/FLAIR characteristics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2-3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas.

Circulating cell-free nucleic acids are considered a promising source of biomarkers for diseases and cancer. Liquid biopsy biomarkers for brain tumours represent a major, still unmet, clinical need. In plasma, nucleic acids can be free or be associated with extracellular vesicles (EVs). Here we report an easy and reproducible method to analyse cell-free nucleic acids in plasma and EVs by conventional flow cytometry easy to translate into the clinics. Nucleic acids associated with the EVs or present in plasma samples are stained by Pyronin Y, which is a fluorescent dye that is preferably binding double-stranded nucleic acids. Fluorescent staining of EVs isolated from cell-conditioned media is suitable for DNA and RNA detection by flow cytometry. The nucleic acids are partially protected from degradation by the EVs' membrane. Additionally, DNA and RNA can be stained in plasma samples and plasma-derived EVs. Remarkably, analysis of plasma from patients and healthy individuals reveals a difference in their nucleic acid profiles. Taken together, our results indicate that the proposed methodology, which is based on conventional direct flow cytometry, is a promising easy tool for plasma nucleic acid analysis., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Background: Invasive treatments like radiofrequency stereotactic lesioning or deep brain stimulation of the globus pallidus internus can resolve drug-resistant status dystonicus (SD). However, these open procedures are not always feasible in patients with SD., Objective: The aim was to report the safety and efficacy of simultaneous asleep bilateral transcranial magnetic resonance-guided focused ultrasound (MRgFUS) pallidotomy for life-threatening SD., Methods: We performed bilateral simultaneous MRgFUS pallidotomy under general anesthesia in 2 young patients with pantothenate kinase-associated neurodegeneration and GNAO1 encephalopathy. Both patients had medically refractory SD and severe comorbidities contraindicating open surgery., Results: SD resolved at 4 and 12 days after MRgFUS, respectively. Adverse events (intraoperative hypothermia and postoperative facial paralysis) were mild and transient., Conclusion: Bilateral simultaneous MRgFUS pallidotomy under general anesthesia is safe and may be a valid alternative therapeutic option for fragile patients. Further studies are needed to assess long-term efficacy of the procedure., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background and Objectives: Traditional and well-established transcranial approaches to the spheno-orbital region and middle cranial fossa guarantee optimal intracranial exposure, and additional orbital and zygomatic osteotomies provide further control over extracranial components to be resected; however, these techniques come at the cost of additional morbidity. The introduction of minimally invasive endoscopic approaches and the conceptualization of the so-called "multiportal" paradigm might provide an alternative route. This preliminary study investigates the feasibility of the combined Biportal Endoscopic TransOrbital and transMaxillary Approach (bETOMA) approach to the spheno-orbital and middle cranial fossa regions., Methods: Using 4 silicon-injected adult cadaver heads (8 sides; 16 approaches), we systematically dissected through superior eyelid ETOA and endoscopic TMA approaches. The analysis focused on pterygopalatine, infratemporal, anterior and middle cranial fossae, Meckel cave, and cavernous sinus access. We evaluated the feasibility of bETOMA using linear distances, angles of attack, and exposure areas. We also introduced volume of operative maneuverability, its standardized derivative (sVOM), target distance, visuo-operative angle, and working zone volume as novel metrics., Results: The analysis revealed comparable angles of attack between approaches. ETOA and TMA exposure areas were 918.38 ± 223.93 mm2 and 257.07 ± 86.07 mm2, respectively. TMA showed a larger VOM in the greater sphenoid wing, but ETOA offered superior distal maneuverability (sVOM: 5.39 ± 1.94 vs 2.54 ± 0.79 cm3) and closer intracranial space access (27.45 vs 50.83 mm). The combined approaches yielded a mean working zone volume of 13.75 ± 3.73 cm3 in the spheno-orbital interface., Conclusion: The bETOMA approach provides adequate neurovascular exposure and maneuverability to the spheno-orbital region, infratemporal, and anterior and middle cranial fossae, addressing significant limitations of previously investigated monoportal techniques (ie, optic nerve decompression, hyperostotic bone resection, and infratemporal exposure). This combined minimally invasive approach might help manage lesions harbored within the cranio-orbital interface region invading the extracranial space., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Introduction: Surgical training traditionally adheres to the apprenticeship paradigm, potentially exposing trainees to an increased risk of complications stemming from their limited experience. To mitigate this risk, augmented and virtual reality have been considered, though their effectiveness is difficult to assess., Research Question: The PASSION study seeks to investigate the improvement of manual dexterity following intensive training with neurosurgical simulators and to discern how surgeons' psychometric characteristics may influence their learning process and surgical performance., Material and Methods: Seventy-two residents were randomized into the simulation group (SG) and control group (CG). The course spanned five days, commencing with assessment of technical skills in basic procedures within a wet-lab setting on day 1. Over the subsequent core days, the SG engaged in simulated procedures, while the CG carried out routine activities in an OR. On day 5, all residents' technical competencies were evaluated. Psychometric measures of all participants were subjected to analysis., Results: The SG demonstrated superior performance (p < 0.0001) in the brain tumour removal compared to the CG. Positive learning curves were evident in the SG across the three days of simulator-based training for all tumour removal tasks (all p-values <0.05). No significant differences were noted in other tasks, and no meaningful correlations were observed between performance and any psychometric parameters., Discussion and Conclusion: A brief and intensive training regimen utilizing 3D virtual reality simulators enhances residents' microsurgical proficiency in brain tumour removal models. Simulators emerge as a viable tool to expedite the learning curve of in-training neurosurgeons., Competing Interests: 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., (© 2024 The Authors.)

Objective: The aim of this study was to provide a quantitative synthesis of the survival outcomes for patients with skull base chordomas, focusing on the role of 1) the extent of resection (gross-total [GTR] vs non-GTR), 2) the type of surgery (primary vs revision), 3) tumor histology, and 4) the different use of adjuvant therapies (proton beam radiotherapy [PBRT], photon radiotherapy [RT], or none)., Methods: A systematic review with a meta-analysis was conducted following the 2020 PRISMA guidelines. Observational studies describing adult and pediatric patient cohorts harboring skull base chordomas were included. The primary outcome measures were represented by the 5-year overall survival (OS) and progression-free survival (PFS) rates. The main intervention effects were represented by the extent of resection (GTR vs non-GTR), type of surgical excision (primary vs revision surgeries), tumor histology, and the different use of adjuvant therapies (PBRT, RT, or none). The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the Joanna Briggs Institute checklist for case series., Results: Six hundred forty-four studies were identified through a database and register search. After study selection, 51 studies and 3871 patients were included in the meta-analysis. The overall 5-year OS rate was 73%, which increased to 84% among patients undergoing GTR. The overall 5-year PFS rate was 52%, increasing to 74% for patients receiving GTR. The 5-year OS and PFS rates for patients undergoing PBRT were 86% and 71%, compared with 71% and 54% for patients receiving RT, and 55% and 25% when no adjuvant treatments were used. Patients undergoing their first surgery had 2.13-fold greater chances of being disease-free and 1.4-fold greater chances of being alive at 5 years follow-up compared with patients who received a revision surgery. Patients harboring chondroid chordomas had 1.13- and 1.9-fold greater chances of being alive at 5 years compared with patients with conventional and de-differentiated chordomas, respectively. The overall risk of bias was low in the included studies., Conclusions: The results of this comprehensive meta-analysis highlight the tremendous impact of GTR and adjuvant PBRT on improving OS and PFS of patients harboring skull base chordomas, with better survival rates demonstrated for patients with chondroid tumors. Even in experienced hands, the rate of surgical morbidity remains high. Proper management in high-volume centers is mandatory to reach the expected resection goal at the first surgical attempt and to reduce surgical morbidity. The introduction of the endoscopic endonasal approach was related to improved surgical and functional outcomes.

Five-year glioblastoma (GBM) survivors (LTS) are the minority of the isocitrate dehydrogenase (IDH)-wild-type GBM patients, and their molecular fingerprint is still largely unexplored. This multicenter retrospective study analyzed a large LTS-GBM cohort from nine Italian institutions and molecularly characterized a subgroup of patients by mutation, DNA methylation (DNAm) and copy number variation (CNV) profiling, comparing it to standard survival GBM. Mutation scan allowed the identification of pathogenic variants in most cases, showing a similar mutational spectrum in both groups, and highlighted TP53 as the most commonly mutated gene in the LTS group. We confirmed DNAm as a valuable tool for GBM classification with a diagnostic refinement by using brain tumor classifier v12.5. LTS were more heterogeneous with more cases classified as diffuse pediatric high-grade glioma subtypes and having peculiar CNVs. We observed a global higher methylation in CpG islands and in gene promoters of LTS with methylation levels of distinct gene promoters correlating with prognosis., Competing Interests: Declaration of competing interest The authors declared that have no competing interest., (Copyright © 2024. Published by Elsevier B.V.)

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rinaldo, Cilia, Leta, Gammone, Andreasi, Colucci, Braccia, Telese, Poli, Levi, Romito, Ghilemetti, De Martin, Fumagalli, Epifani, Prioni, Amami, Piacentini, Elia, Devigili, Nazzi, Ciceri, Stanziano, Grisoli, Caldiera, Catotti, DiMeco, Moreschi and Eleopra.)

The angle of exposure (AnE) represents a metric that is particularly useful for analyzing circular bony structures during skull base dissections. The authors aimed to develop and validate a neuronavigation-based method to measure the AnE. A formula based on vectorial geometry and the coordinates of three points collected with a neuronavigation system was developed to measure the AnE. The method was validated using a plexiglass phantom head. To demonstrate its applicability, the authors measured the AnE in 6 cadaveric specimens after exposure of the hypoglossal canal using a far-medial approach (FMA) and a far-lateral transtubercular approach (FLTA) and in 6 different specimens after exposure of the jugular foramen using an FLTA and a retrosigmoid approach (RSA). The mean angles measured at 45°, 90°, and 180° using a goniometer during the validation test were 44.8° ± 1.1°, 90.8° ± 1.2°, and 179.7° ± 0.8° using the novel formula (p > 0.05). In the first illustrative application, the mean AnEs for the FMA and FLTA were 129° ± 0.9° and 243° ± 1.9°, respectively. In the second scenario, the mean AnEs were 192° ± 1.3° for the FTLA and 143° ± 2.1° for the RSA. The neuronavigation-based technique described is a highly accurate method to measure the AnE.

Fluorescein-mediated sonodynamic therapy (FL-SDT) is an extremely promising approach for glioma treatment, resulting from the combination of low-intensity focused ultrasound (FUS) with a sonosensitizer. In the present study, we evaluated the efficacy and immunomodulation of SDT with fluorescein as the sonosensitizer in immunocompetent GL261 glioma mice for the first time. In vitro studies demonstrated that the exposure of GL261 cells to FL-SDT induced immunogenic cell death and relevant upregulation of MHC class I, CD80 and CD86 expression. In vivo studies were then performed to treat GL261 glioma-bearing mice with FL-SDT, fluorescein alone, or FUS alone. Perturbation of the glioma-associated macrophage subset within the immune microenvironment was induced by all the treatments. Notably, a relevant depletion of myeloid-derived suppressor cells (MDSCs) and concomitant robust infiltration of CD8+ T cells were observed in the SDT-FL-treated mice, resulting in a significant radiological delay in glioma progression and a consequent improvement in survival. Tumor control and improved survival were also observed in mice treated with FL alone (median survival 41.5 days, p > 0.0001 compared to untreated mice), reflecting considerable modulation of the immune microenvironment. Interestingly, a high circulating lymphocyte-to-monocyte ratio and a very low proportion of MDSCs were predictive of better survival in FL- and FL-SDT-treated mice than in untreated and FUS-treated mice, in which elevated monocyte and MDSC frequencies correlated with worse survival. The immunostimulatory potential of FL-SDT treatment and the profound modulation of most immunosuppressive components within the microenvironment encouraged the exploration of the combination of FL-SDT with immunotherapeutic strategies.

The lack of early detection and a high rate of recurrence/progression after surgery are defined as the most common causes of a very poor prognosis of Gliomas. The developments of quantification systems with special regards to artificial intelligence (AI) on medical images (CT, MRI, PET) are under evaluation in the clinical and research context in view of several applications providing different information related to the reconstruction of imaging, the segmentation of tissues acquired, the selection of features, and the proper data analyses. Different approaches of AI have been proposed as the machine and deep learning, which utilize artificial neural networks inspired by neuronal architectures. In addition, new systems have been developed using AI techniques to offer suggestions or make decisions in medical diagnosis, emulating the judgment of radiologist experts. The potential clinical role of AI focuses on the prediction of disease progression in more aggressive forms in gliomas, differential diagnosis (pseudoprogression vs. proper progression), and the follow-up of aggressive gliomas. This narrative Review will focus on the available applications of AI in brain tumor diagnosis, mainly related to malignant gliomas, with particular attention to the postoperative application of MRI and PET imaging, considering the current state of technical approach and the evaluation after treatment (including surgery, radiotherapy/chemotherapy, and prognostic stratification).

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug-resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal., Objectives: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET., Methods: Ten patients with DT and 35 with ET who consecutively underwent MRgFUS thalamotomy were followed for 12 months. Although in both groups the initial surgical planning coordinates corresponded to the ventralis intermediate (Vim), the final target could be modified intraoperatively based on clinical response., Results: Tremor significantly improved in both groups. The thalamic lesion was significantly more anterior in DT than ET. Considering both ET and DT groups, the more anterior the lesion, the lower the odds ratio for adverse events., Conclusions: MRgFUS thalamotomy is safe and effective in DT and ET. Compared to classical Vim coordinates used for ET, more anterior targeting should be considered for DT., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)