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Purpose: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. Methods: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. Results: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). Conclusions: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

Background: The COVID-19 pandemic and its impact on hospitals' activity and organization has imposed a vast change in standard neurosurgical oncology practice to accommodate for shifting resources. Aims: This investigation aims to analyse the nationwide capability in reorganizing the surgical neuro-oncological activity during the COVID-19 pandemic to evaluate whether COVID-19-pandemic influenced the surgical management in these patients. Method: A web-based dataset model organized by the Italian Neurosurgical Society (SINCh) was sent to all the Italian neurosurgical departments in May 2021, requesting to report the types and numbers of surgical procedures performed in the pre-pandemic period (from March 9th 2019 to March 9th 2020) compared to the pandemic period (from March 10th 2020 to March 10th 2021). Results: This multicentre investigation included the surgical activity of 35 Italian Neurosurgical Departments in a pre-pandemic year versus a pandemic year. During the COVID period, 699 fewer neuro-oncological patients were operated on than in the pre-COVID period. We noted a slight increase in urgency and a more severe decrease in elective and benign pathology. None of these differences was statistically significant. Surgically treated patients who tested positive for SARS-CoV-2 were 36, of which 11 died. Death was found to be COVID-related only in 2 cases. Conclusion: The reorganization of the Italian Neurosurgical Departments was able to guarantee a redistribution of the CNS tumors during the inter-pandemic periods, demonstrating that patients even in the pandemic era could be treated without compromising the efficacy and safety of the surgical procedure.

Purpose: The management of brain tumors during pregnancy is challenging. The clinical rarity and prognostic heterogeneity of such condition makes it difficult to develop standardized guidelines of treatment. The aim of this study was to assess the treatment options used in pregnant women with brain tumors that are currently used in Italy, considering the management of these patients reported in current literature in this field. Methods: A survey addressing the treatments options and management of brain tumors during pregnancy was designed on behalf of an ad-hoc task-force Neuro-Oncology committee of the Società Italiana di Neurochirurgia (SINch) to analyze the management of pregnant patients with brain tumors. We conducted a search of the literature published between January 2011 and September 2021, using MEDLINE (PubMed) in accordance to PRISMA guidelines. Data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. Results: A total of 18 Neurosurgical centers participated in the survey. A total of 31 pregnant women were included in this retrospective study. Meningiomas and gliomas were the two most common types of brain tumors diagnosed during pregnancy. An emergency surgical procedure was required in 12.9% of cases. Conclusion: A multidisciplinary and tailored approach is fundamental. In women showing clinical stability, neurosurgical options should preferably be delayed if possible, and considered during the second trimester or after delivery. In patients with acute neurological symptoms or tumor progression, medical abortion in the first trimester or a C-section in the second and third trimester need to be considered.

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%

We address existing controversies regarding neuroanatomical substrates of reading-aloud processes according to the dual-route processing models, in this particular instance in a series of 49 individuals with brain tumors who performed several reading tasks of real-time neuropsychological testing during surgery (low- to high-grade cerebral neoplasms involving the left hemisphere). We explored how reading abilities in individuals with brain tumors evolve during and after surgery for a brain tumor, and we studied the reading performance in a sample of 33 individuals in a 4-month follow-up after surgery. Impaired reading performance was seen pre-surgery in 7 individuals with brain tumors, intra-surgery in 18 individuals, at immediate post-surgery testing in 26 individuals, and at follow-up in 5 individuals. We classified their reading disorders according to operational criteria for either phonological or surface dyslexia. Neuroimaging results are discussed within the theoretical framework of the dual-route model of reading. Lesion-mask subtraction analyses revealed that areas selectively related with phonological dyslexia were located—along with the left hemisphere dorsal stream—in the Rolandic operculum, the inferior frontal gyrus, the precentral gyrus, the supramarginal gyrus, the insula (and/or the underlying external capsule), and parts of the superior longitudinal fasciculus, whereas lesions related to surface dyslexia involved the ventral stream, that is, the left middle and inferior temporal gyrus and parts of the left inferior longitudinal fasciculus.

Introduction: Seizures are the most common clinical manifestation of low-grade glioma (LGG). Many papers hypothesized an influence of epilepsy on glioma progression. To our knowledge, no clinical study demonstrated a direct relationship between persistence of epileptic seizures after surgery and overall survival (OS) in LGG patients. The present study aims at investigating the correlation between post-operative seizure outcome and survival in tumor-related epilepsy (TRE) patients. Methods: We performed a retrospective analysis of adult patients affected by TRE who underwent surgery for resection of LGG in a single high-volume neurosurgical center. Seizure outcome was assessed 1 year after surgery and categorized according to Engel classification. Clinical, molecular and radiological features were evaluated in univariate and multivariate analyses to investigate the correlation with OS. Results: A total of 146 patients met the inclusion criteria. Histopathological diagnosis was Diffuse Astrocytoma isocitrate dehydrogenase (IDH) wild type in 16 patients (11%), Diffuse astrocytoma IDH mutated in 89 patients (61%) and oligodendroglioma IDH mutated, 1p 19q codeleted in 41 patients (28%). 1 year after surgery, 103 (70.6%) patients were in Engel class 1. Median duration of follow-up period was 69.5 months. Median OS was 79.3 (72.2–86.4) months in the whole population, while it was 86.8 (78.4–95.2), 63.9 (45.7–82), 63.7 (45.2–82.2) and 47.5 (18.3–76.6) months for patients in Engel class 1, 2, 3 and 4, respectively. In a univariate analysis, Engel class evaluated 1 year after surgery significantly influenced OS (p < 0.01). Multivariate analysis showed that OS was independently associated with extent of resection (p = 0.02), molecular class (p < 0.01) and Engel class (p = 0.04). Conclusions: Seizure control 1 year after surgery significantly predicted survival of patients affected by LGG-related epilepsy in a large monocentric retrospective serie

Objective: Ability to thrive after invasive and intensive treatment is an important parameter to assess in patients with glioblastoma multiforme (GBM). Karnofsky Performance Status (KPS) is used to identify those patients suitable for postoperative radiochemotherapy. The aim of the present study is to investigate whether machine learning (ML)-based models can reliably predict patients' KPS 6 months after surgery. Methods: A cohort of 416 patients undergoing surgery for a histopathologically confirmed GBM were collected from a multicentric database and split into a training and hold-out test set in an 80:20 ratio. Worsening of KPS at 6 months after surgery (compared with preoperative KPS) occurred in 138 patients (33.2%). Relevant preoperative, intraoperative, and immediately postoperative variables were selected by a recursive features selection algorithm (Boruta) and used to build 2 ML-based predictive models. Results: A random forest classifier and a random forest regressor were trained to predict 6 months postoperative KPS as a categorical (worsening vs. stable/improving) and continuous variables; they achieved, respectively, an area under the curve of 0.81 (95% confidence interval, 0.76–0.84) and a mean absolute error of 4.4 (95% confidence interval, 4.0–4.7). Leveraging the predictive value resulting from the combination of independent variables, the random forest classifier outperformed conventional statistics (area under the curve improvement of +21%). Conclusions: Two robust ML-based prediction models were successfully trained and internally validated. Considerable effort remains to improve the interpretation of the results when these predictions are used in a patient-centered care context.

Surgical management of Diffuse Low-Grade Gliomas (DLGGs) has radically changed in the last 20 years. Awake surgery (AS) in combination with Direct Electrical Stimulation (DES) and real-time neuropsychological testing (RTNT) permits continuous intraoperative feedback, thus allowing to increase the extent of resection (EOR). The aim of this study was to evaluate the impact of the technological advancements and integration of multidisciplinary techniques on EOR. Two hundred and eighty-eight patients affected by DLGG were enrolled. Cases were stratified according to the surgical protocol that changed over time: 1. DES; 2. DES plus functional MRI/DTI images fused on a NeuroNavigation system; 3. Protocol 2 plus RTNT. Patients belonging to Protocol 1 had a median EOR of 83% (28–100), while those belonging to Protocol 2 and 3 had a median EOR of 88% (34–100) and 98% (50–100) respectively (p = 0.0001). New transient deficits with Protocol 1, 2 and 3 were noted in 38.96%, 34.31% and 31,08% of cases, and permanent deficits in 6.49%, 3.65% and 2.7% respectively. The average follow-up period was 6.8 years. OS was influenced by molecular class (p = 0.028), EOR (p = 0.018) and preoperative tumor growing pattern (p = 0.004). Multimodal surgical approach can provide a safer and wider removal of DLGG with potential subsequent benefits on OS. Further studies are necessary to corroborate our findings.

a B s T r a c T in 2018, the siNch (italian society of Neurosurgery) Neuro-oncology section, aiNo (italian association of Neuro-oncology) and siN (italian association of Neurology) Neuro-oncology section formed a collaborative Task force to look at the diagnosis and treatment of low-grade gliomas (lggs). The Task force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up.

OBJECTIVE: Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients. METHODS: Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score. RESULTS: Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell's c-index of 0.75 (95% CI 0.76–0.81). CONCLUSIONS: The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly

The glioblastoma microenvironment plays a substantial role in glioma biology. However, few studies have investigated its spatial heterogeneity. Exploiting 5-ALA Fluorescence Guided Surgery (FGS), we were able to distinguish between the tumor core (ALA+), infiltrating area (ALAPALE) and healthy tissue (ALA-) of the glioblastoma, based on the level of accumulated fluorescence. The aim of this study was to investigate the properties of the microenvironments associated with these regions. For this purpose, we isolated glioma-associated stem cells (GASC), resident in the glioma microenvironment, from ALA+, ALA-PALE and ALA-samples and compared them in terms of growth kinetic, phenotype and for the expression of 84 genes associated with cancer inflammation and immunity. Differentially expressed genes were correlated with transcriptomic datasets from TCGA/GTEX. Our results show that GASC derived from the three distinct regions, despite a similar phenotype, were characterized by different transcriptomic profiles. Moreover, we identified a GASC-based genetic signature predictive of overall survival and disease-free survival. This signature, highly expressed in ALA+ GASC, was also well represented in ALA PALE GASC. 5-ALA FGS allowed to underline the heterogeneity of the glioma microenvironments. Deepening knowledge of these differences can contribute to develop new adjuvant therapies targeting the crosstalk between tumor and its supporting microenvironment.

Despite recent discoveries in genetics and molecular fields, glioblastoma (GBM) prognosis still remains unfavorable with less than 10% of patients alive 5 years after diagnosis. Numerous studies have focused on the research of biological biomarkers to stratify GBM patients. We addressed this issue in our study by using clinical/molecular and image data, which is generally available to Neurosurgical Departments in order to create a prognostic score that can be useful to stratify GBM patients undergoing surgical resection. By using the random forest approach [CART analysis (classification and regression tree)] on Survival time data of 465 cases, we developed a new prediction score resulting in 10 groups based on extent of resection (EOR), age, tumor volumetric features, intraoperative protocols and tumor molecular classes. The resulting tree was trimmed according to similarities in the relative hazard ratios amongst groups, giving rise to a 5-group classification tree. These 5 groups were different in terms of overall survival (OS) (p < 0.000). The score performance in predicting death was defined by a Harrell’s c-index of 0.79 (95% confidence interval [0.76–0.81]). The proposed score could be useful in a clinical setting to refine the prognosis of GBM patients after surgery and prior to postoperative treatment.

Background: One of the most valuable innovations in high-grade glioma surgery is 5-aminolevulinic acid (5-ALA). Fluorescence is a specific and sensitive indicator of metabolically active tumor tissue. In the published literature, the main focus has been placed on false-negative cases, with only a few articles addressing false positivity. The aim of the article was to highlight settings in which 5-ALA fluorescence does not necessarily mean tumor and to point out conditions in which intraoperative 5-ALA fluorescence has to be critically interpreted. Methods: Using PubMed, a review of pertinent literature was done to specifically investigate all conditions, including non-neoplastic and other metabolically active lesions, that can mimic high-grade gliomas and cause a misleading intraoperative diagnosis. In addition, an institutional case characterized by strong 5-ALA fluorescence in radionecrosis is presented. Results: Literature results were grouped in 2 main categories according to the field of application: oncologic setting (9 articles and 1 institutional case) and nononcologic settings (5 articles). Conclusions: As reported, 5-ALA-induced fluorescence is not limited to glioma but is also evident in nonglioma and non-neoplastic conditions. Critical interpretation of intraoperative fluorescence is therefore mandatory in recurrences and in atypical cases that might hinder alternative diagnoses.

Achieving a safe and extensive neoplasm resection can be considered the main goal of brain tumor surgery. This paper is first aimed at providing an overview of the evolution of those tools serving the purpose. From the dawn of neurosurgery to the present days, major innovations have followed one another. However, those techniques may frequently lack of an instant biological feedback on the true extension and the infiltration of the tumor. Intraoperative fluorescence modalities could indeed fill this gap. Fluorescence guided surgery will be therefore introduced and discussed in this context. Our focus will be on the most common fluorescence techniques used in neurosurgery, namely 5-aminolevulinic acid, sodium fluorescein and in indocyanine green. Mode of action, strengths and weaknesses and level of evidence of each modality will be discussed.

BACKGROUND: Increasing the extent of resection (EOR) is considered a main goal in high grade glioma (HGG) surgery. Significant advancements have been recently made to assist surgery: namely the use of 5-aminolevulinic acid (5ALA) and the application of contrast-enhanced ultrasound (CEUS) embody two of the most recently introduced tools in the neuro-oncology field. A combined approach including the two techniques has been suggested in literature. Our primary aim is to identify in which conditions CEUS final survey has a real impact in a 5-ALA guided context and assess which preoperative tumor characteristics, with specific attention to working corridors can predict strains of the fluorescence guided procedure and hence recommend the use of the combined technique. METHODS: Forty-nine HGG glioma surgeries were performed at our institution with the abovementioned protocol between January 2016 and June 2016. Based on preoperative MRI, we stratified glioma characteristics according to three determinants: localization (deep versus superficial), size (<3.5 versus >3.5 cm) and shape (regular versus irregular). RESULTS: CEUS modified 5-ALA guided resection in 11 cases (22.45%): this appeared to be associated with statistically significance to deep tumor localization (P=0.04) and irregular/multi-lobulated margins (P=0.003). On the other hand, tumor size alone did not appear as a statistically significant determinant. CONCLUSIONS: When dark corridors are presents or when overlying brain parenchyma hinders illumination, drawbacks to the 5-ALA assistance can be expected, hence CEUS final survey has a crucial role of 'refinement'. In those selected cases, an integrated 5ALA+CEUS protocol was shown as advisable in EOR improvement.

Indocyanine green video angiography (ICG-VA) is a non-invasive, easy to use and very useful tool for various neurosurgical procedures. The first application was in neurovascular surgery, because it was born as an intravascular tracer for vessels visualization; this has been really useful in aneurysms, atero-venous malformations (AVMs) and dural fistulas surgery where identification, obliteration or patency of vessels is essential. introduced in vascular neurosurgery since 2003, icg-Va applications have broadened over time, both in vascular and in other neurosurgical fields. In 2003 Raabe et al. have been the first to describe the use of ICG-VA for intraoperative assessment of cerebral vascular flow, enabling visualization of vessel patency and aneurysm occlusion during aneurysm surgery. ICG-VA applications in vascular neurosurgery have significantly increased over time including complex aneurysms, bypass, atero-venous malformations (AVM) artero-venous fistulas (AVF), evaluation of cortical perfusion. The procedure can be easily repeated after 5-10 minutes. adverse reactions are comparable to those of other types of contrast media, with frequencies of 0.05% (hypotension, arrhythmia, or, more rarely, anaphylactic shock) to 0.2% (nausea, pruritus, syncope, or skin eruptions. The aim of the present study was to systematically analyze ICG-VA applications in vascular neurosurgery, highlighting the reported advantages and disadvantages, and discussing future perspectives.