The Impact of Lateral Ventricular Opening in the Resection of Newly Diagnosed High-Grade Gliomas: A Single Center Experience.

Given the importance of maximizing resection for prognosis in patients with HGG and the potential risks associated with ventricle opening, this study aimed to assess the actual increase in post-surgical complications related to lateral ventricle opening and its influence on OS and PFS. A retrospective study was conducted on newly diagnosed HGG, dividing the patients into two groups according to whether the lateral ventricle was opened (69 patients) or not opened (311 patients). PFS, OS, subependymal dissemination, distant parenchymal recurrences, the development of hydrocephalus and CSF leak were considered outcome measures. A cohort of 380 patients (154 females (40.5%) and 226 males (59.5%)) was involved in the study (median age 61 years). The PFS averaged 10.9 months (±13.3 SD), and OS averaged 16.6 months (± 16.3 SD). Among complications, subependymal dissemination was registered in 15 cases (3.9%), multifocal and multicentric progression in 56 cases (14.7%), leptomeningeal dissemination in 12 (3.2%) and hydrocephalus in 8 (2.1%). These occurrences could not be clearly justified by ventricular opening. The act of opening the lateral ventricles itself does not carry an elevated risk of dissemination, hydrocephalus or cerebrospinal fluid (CSF) leak. Therefore, if necessary, it should be pursued to achieve radical removal of the disease.

Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy.

Introduction: There are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research question: This study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methods: In this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. Results: The study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusions: In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.

Deep learning-based algorithm for postoperative glioblastoma MRI segmentation: a promising new tool for tumor burden assessment.

OBJECTIVE: Clinical and surgical decisions for glioblastoma patients depend on a tumor imaging-based evaluation. Artificial Intelligence (AI) can be applied to magnetic resonance imaging (MRI) assessment to support clinical practice, surgery planning and prognostic predictions. In a real-world context, the current obstacles for AI are low-quality imaging and postoperative reliability. The aim of this study is to train an automatic algorithm for glioblastoma segmentation on a clinical MRI dataset and to obtain reliable results both pre- and post-operatively. METHODS: The dataset used for this study comprises 237 (71 preoperative and 166 postoperative) MRIs from 71 patients affected by a histologically confirmed Grade IV Glioma. The implemented U-Net architecture was trained by transfer learning to perform the segmentation task on postoperative MRIs. The training was carried out first on BraTS2021 dataset for preoperative segmentation. Performance is evaluated using DICE score (DS) and Hausdorff 95% (H95). RESULTS: In preoperative scenario, overall DS is 91.09 (± 0.60) and H95 is 8.35 (± 1.12), considering tumor core, enhancing tumor and whole tumor (ET and edema). In postoperative context, overall DS is 72.31 (± 2.88) and H95 is 23.43 (± 7.24), considering resection cavity (RC), gross tumor volume (GTV) and whole tumor (WT). Remarkably, the RC segmentation obtained a mean DS of 63.52 (± 8.90) in postoperative MRIs. CONCLUSIONS: The performances achieved by the algorithm are consistent with previous literature for both pre-operative and post-operative glioblastoma's MRI evaluation. Through the proposed algorithm, it is possible to reduce the impact of low-quality images and missing sequences.

How Reliable Is Fluorescence-Guided Surgery in Low-Grade Gliomas? A Systematic Review Concerning Different Fluorophores.

BACKGROUND: Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade gliomas, while its role is less definitely assessed in low-grade gliomas. METHODS: A systematic review was conducted. 5-aminolevulinic acid, sodium fluorescein, indocyanine green and tozuleristide were taken into account. The main considered outcome was the fluorescence rate, defined as the number of patients in whom positive fluorescence was detected out of the total number of patients. Only low-grade gliomas were considered, and data were grouped according to single fluorophores. RESULTS: 16 papers about 5-aminolevulinic acid, 4 about sodium fluorescein, 2 about indocyanine green and 1 about tozuleristide were included in the systematic review. Regarding 5-aminolevulinic acid, a total of 467 low-grade glioma patients were included, and fluorescence positivity was detected in 34 out of 451 Grade II tumors (7.3%); while in Grade I tumors, fluorescence positivity was detected in 9 out of 16 cases. In 16 sodium fluorescein patients, seven positive fluorescent cases were detected. As far as indocyanine is concerned, two studies accounting for six patients (three positive) were included, while for tozuleristide, a single clinical trial with eight patients (two positive) was retrieved. CONCLUSIONS: The current evidence does not support the routine use of 5-aminolevulinic acid or sodium fluorescein with a standard operating microscope because of the low fluorescence rates. New molecules, including tozuleristide, and new techniques for fluorescence detection have shown promising results; however, their use still needs to be clinically validated on a large scale.

Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas.

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families). The tumorigenic potential of each GSC better correlates with its transcriptional profile than its genetic make-up, with classical GSCs being inherently more aggressive and mesenchymal more dependent on exogenous growth factors across multiple GBMs. These GSCs can segregate and recapitulate different histopathological aspects of the same GBM, as shown in a paradigmatic tumor with two histopathologically distinct components, including a conventional GBM and a more aggressive primitive neuronal component. This study provides a resource for investigating how GSCs with distinct genetic and/or phenotypic features contribute to individual GBM heterogeneity and malignant escalation.

Facial nerve outcome score: a new score to predict long-term facial nerve function after vestibular schwannoma surgery.

Introduction: Patients' quality of life (QoL), facial nerve (FN), and cochlear nerve (CN) (if conserved) functions should be pursued as final outcomes of vestibular schwannoma (VS) surgery. In regard to FN function, different morphologic and neurophysiological factors have been related to postoperative outcomes. The aim of the current retrospective study was to investigate the impact of these factors on the short- and long-term FN function after VS resection. The combination of preoperative and intraoperative factors resulted in designing and validating a multiparametric score to predict short- and long-term FN function. Methods: A single-center retrospective analysis was performed for patients harboring non-syndromic VS who underwent surgical resection in the period 2015-2020. A minimum follow-up period of 12 months was considered among the inclusion criteria. Morphological tumor characteristics, intraoperative neurophysiological parameters, and postoperative clinical factors, namely, House-Brackmann (HB) scale, were retrieved in the study. A statistical analysis was conducted to investigate any relationships with FN outcome and to assess the reliability of the score. Results: Seventy-two patients with solitary primary VS were treated in the period of the study. A total of 59.8% of patients showed an HB value < 3 in the immediate postoperative period (T1), reaching to 76.4% at the last follow-up evaluation. A multiparametric score, Facial Nerve Outcome Score (FNOS), was built. The totality of patients with FNOS grade A showed an HB value < 3 at 12 months, decreasing to 70% for those with FNOS grade B, whereas 100% of patients with FNOS grade C showed an HB value ≥ 3. The ordinal logistic regression showed three times increasing probability to see an HB value ≥ 3 at 3-month follow-up for each worsening point in FNOS score [Exp(B), 2,999; p < 0.001] that was even more probable [Exp(B), 5.486; p < 0.001] at 12 months. Conclusion: The FNOS score resulted to be a reliable score, showing high associations with FN function both at short- and long-term follow-up. Although multicenter studies would be able to increase its reproducibility, it could be used to predict the FN damage after surgery and the potential of restoring its function on the long-term period.

Updates in Glioblastoma Immunotherapy: An Overview of the Current Clinical and Translational Scenario.

Glioblastoma (GBM) is the most common and aggressive central nervous system tumor, requiring multimodal management. Due to its malignant behavior and infiltrative growth pattern, GBM is one of the most difficult tumors to treat and gross total resection is still considered to be the first crucial step. The deep understanding of GBM microenvironment and the possibility of manipulating the patient's innate and adaptive immune system to fight the neoplasm represent the base of immunotherapeutic strategies that currently express the future for the fight against GBM. Despite the immunotherapeutic approach having been successfully adopted in several solid and haematologic neoplasms, immune resistance and the immunosuppressive environment make the use of these strategies challenging in GBM treatment. We describe the most recent updates regarding new therapeutic strategies that target the immune system, immune checkpoint inhibitors, chimeric antigen receptor T cell therapy, peptide and oncolytic vaccines, and the relevant mechanism of immune resistance. However, no significant results have yet been obtained in studies targeting single molecules/pathways. The future direction of GBM therapy will include a combined approach that, in contrast to the inescapable current treatment modality of maximal resection followed by chemo- and radiotherapy, may combine a multifaceted immunotherapy treatment with the dual goals of directly killing tumor cells and activating the innate and adaptive immune response.

Liquid Biopsy of Cerebrospinal Fluid Enables Selective Profiling of Glioma Molecular Subtypes at First Clinical Presentation.

PURPOSE: Current glioma diagnostic guidelines call for molecular profiling to stratify patients into prognostic and treatment subgroups. In case the tumor tissue is inaccessible, cerebrospinal fluid (CSF) has been proposed as a reliable tumor DNA source for liquid biopsy. We prospectively investigated the use of CSF for molecular characterization of newly diagnosed gliomas. EXPERIMENTAL DESIGN: We recruited two cohorts of newly diagnosed patients with glioma, one (n = 45) providing CSF collected in proximity of the tumor, the other (n = 39) CSF collected by lumbar puncture (LP). Both cohorts provided tumor tissues by surgery concomitant with CSF sampling. DNA samples retrieved from CSF and matched tumors were systematically characterized and compared by comprehensive (NGS, next-generation sequencing) or targeted (ddPCR, droplet digital PCR) methodologies. Conventional and molecular diagnosis outcomes were compared. RESULTS: We report that tumor DNA is abundant in CSF close to the tumor, but scanty and mostly below NGS sensitivity threshold in CSF from LP. Indeed, tumor DNA is mostly released by cells invading liquoral spaces, generating a gradient that attenuates by departing from the tumor. Nevertheless, in >60% of LP CSF samples, tumor DNA is sufficient to assess a selected panel of genetic alterations (IDH and TERT promoter mutations, EGFR amplification, CDKN2A/B deletion: ITEC protocol) and MGMT methylation that, combined with imaging, enable tissue-agnostic identification of main glioma molecular subtypes. CONCLUSIONS: This study shows potentialities and limitations of CSF liquid biopsy in achieving molecular characterization of gliomas at first clinical presentation and proposes a protocol to maximize diagnostic information retrievable from CSF DNA.

Fluorescence-Guided Surgery in Glioblastoma: 5-ALA, SF or Both? Differences between Fluorescent Dyes in 99 Consecutive Cases.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor's borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. METHODS: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. RESULTS: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). CONCLUSIONS: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage.

Elderly Gliobastoma Patients: The Impact of Surgery and Adjuvant Treatments on Survival: A Single Institution Experience.

Introduction. Elderly glioblastoma (GBM) patients often show limited response to treatment and poor outcome. Here, we provide a case series of elderly GBM patients from our Institution, in whom we assessed the clinical characteristics, feasibility of surgical resection, response to adjuvant treatments, and outcome, along with the impact of comorbidities and clinical status on survival. Patients and Methods. We included patients ≥ 65-year-old. We collected information about clinical and molecular features, extent of resection, adjuvant treatments, treatment-related complications, and outcome. Results. We included 135 patients. Median age was 71 years. In total, 127 patients (94.0%) had a Karnofsky Performance Status (KPS) ≥70 and 61/135 (45.2%) a Charlson Comorbidity Score (CCI) > 3. MGMTp methylation was found in 70/135 (51.9%). Subtotal resections (STRs), gross-total resections (GTRs), and biopsies were 102 (75.6%), 10 (7.4%) and 23 (17.0%), respectively. Median progression-free survival and overall survival (mOS) were 8.0 and 10.5 months for the whole cohort. Notably, GTR and radio-chemotherapy with temozolomide in patients with MGMTp methylation were associated with significantly longer mOS (32.8 and 44.8 months, respectively). In a multivariable analysis, risk of death was affected by STR vs. GTR (HR 2.8, p = 0.002), MGMTp methylation (HR 0.55, p = 0.007), and KPS at baseline ≥70 (HR 0.43, p = 0.031). Conversely, CCI and post-surgical complications were not significant. Conclusions. Elderly GBM patients often have a dismal prognosis. However, it is possible to identify a subgroup with favourable clinical and molecular features, who benefit from GTR and radio-chemotherapy with temozolomide. A comprehensive prognostic score is needed to guide treatment modality and predict the outcome.

A Systematic Review of Amino Acid PET Imaging in Adult-Type High-Grade Glioma Surgery: A Neurosurgeon's Perspective.

Amino acid PET imaging has been used for a few years in the clinical and surgical management of gliomas with satisfactory results in diagnosis and grading for surgical and radiotherapy planning and to differentiate recurrences. Biological tumor volume (BTV) provides more meaningful information than standard MR imaging alone and often exceeds the boundary of the contrast-enhanced nodule seen in MRI. Since a gross total resection reflects the resection of the contrast-enhanced nodule and the majority of recurrences are at a tumor's margins, an integration of PET imaging during resection could increase PFS and OS. A systematic review of the literature searching for "PET" [All fields] AND "glioma" [All fields] AND "resection" [All fields] was performed in order to investigate the diffusion of integration of PET imaging in surgical practice. Integration in a neuronavigation system and intraoperative use of PET imaging in the primary diagnosis of adult high-grade gliomas were among the criteria for article selection. Only one study has satisfied the inclusion criteria, and a few more (13) have declared to use multimodal imaging techniques with the integration of PET imaging to intentionally perform a biopsy of the PET uptake area. Despite few pieces of evidence, targeting a biologically active area in addition to other tools, which can help intraoperatively the neurosurgeon to increase the amount of resected tumor, has the potential to provide incremental and complementary information in the management of brain gliomas. Since supramaximal resection based on the extent of MRI FLAIR hyperintensity resulted in an advantage in terms of PFS and OS, PET-based biological tumor volume, avoiding new neurological deficits, deserves further investigation.

The Relevant Role of Navigated Tractography in Speech Eloquent Area Glioma Surgery: Single Center Experience.

BACKGROUND: Gliomas are among the most challenging pathologies for neurosurgeons due to their infiltrative and recurrent nature in functionally relevant regions. Current knowledge confirms that gross total resection highly influence survival in patient with glioma. However, surgery performed in eloquent brain area, could seriously compromise the quality of life in patient with reduced life expectancy even more if it concerns the language function. METHODS: 18 right-handed patients with perisylvian gliomas on the left hemisphere were prospectively analyzed over a period of 12 months. Standardized preoperative Diffusion-Tensor-Imaging based tractography of the five main language Tracts (Arcuate Fasciculus, Frontal Aslant Tract, Inferior Fronto-Occipital Fasciculus, Inferior Longitudinal Fasciculus, Uncinate Fasciculus) was navigated during the surgical procedure. Using a validated method, correlations were made between the pre-operative fascicles and their possible infiltration and surgical damage. The language status was assessed using the Aachen Aphasia Test. RESULTS: In all nine patients who developed a permanent disorder there was pre-operative involvement of at least one fascicle and resection of at least one of these. In this way, areas of high risk of permanent language damage have emerged as a result of surgical injury: the temporoparietal junction, the middle portion of the FAT and the temporal stem. CONCLUSIONS: Navigated tractography has proven to be a user-friendly tool that can assess perioperative risk, guide surgical resection, and help the neurosurgeon to find that balance between tumor resection and function preservation.

Where We Mentalize: Main Cortical Areas Involved in Mentalization.

When discussing "mentalization," we refer to a very special ability that only humans and few species of great apes possess: the ability to think about themselves and to represent in their mind their own mental state, attitudes, and beliefs and those of others. In this review, a summary of the main cortical areas involved in mentalization is presented. A thorough literature search using PubMed MEDLINE database was performed. The search terms "cognition," "metacognition," "mentalization," "direct electrical stimulation," "theory of mind," and their synonyms were combined with "prefrontal cortex," "temporo-parietal junction," "parietal cortex," "inferior frontal gyrus," "cingulate gyrus," and the names of other cortical areas to extract relevant published papers. Non-English publications were excluded. Data were extracted and analyzed in a qualitative manner. It is the authors' belief that knowledge of the neural substrate of metacognition is essential not only for the "neuroscientist" but also for the "practical neuroscientist" (i.e., the neurosurgeon), in order to better understand the pathophysiology of mentalizing dysfunctions in brain pathologies, especially those in which integrity of cortical areas or white matter connectivity is compromised. Furthermore, in the context of neuro-oncological surgery, understanding the anatomical structures involved in the theory of mind can help the neurosurgeon obtain a wider and safer resection. Though beyond of the scope of this paper, an important but unresolved issue concerns the long-range white matter connections that unify these cortical areas and that may be themselves involved in neural information processing.

Let Me See: Correlation between 5-ALA Fluorescence and Molecular Pathways in Glioblastoma: A Single Center Experience.

BACKGROUND: Despite the aggressiveness of multimodal treatment, glioblastoma (GBM) is still a challenge for neurosurgeons, neurooncologists, and radiotherapists. A surgical approach is still a cornerstone in GBM therapeutic management, as the extent of resection is strongly related both to overall survival and progression-free survival. From this perspective, the use of photodynamic molecules could represent an interesting tool to achieve maximal and safe resection. Being able to trace the lesion's edges, indeed, could allow to improve the extent of resection and to minimize residual tumor while sparing normal tissue. The use of 5-aminolevulinic acid (5-ALA) as a photodynamic tracer is well established due to its strict correlation both with cellularity and metabolic activity of the GBM cell clones. OBJECTIVE: Our study aims to define whether a different molecular asset of GBM (especially investigating IDH 1/2 mutation, proliferation index, and MGMT promoter methylation) results in different fluorescence expression, possibly because of differences in metabolic pathways due to different genotypes. METHODS: Patients undergoing surgery for GBM removal at our Institute (Dep. Of Neurosurgery, Ospedale Città della Salute e della Scienza, University of Turin, Italy) were retrospectively reviewed. Patients with histological diagnosis confirmation and to whom 5-ALA was given before surgery were included. The whole surgical procedure was recorded and then analyzed by three different people (a medical student, a resident, and a senior surgeon with an interest in neurooncology and experience in using 5-ALA) and a score was assigned to the different degrees of intraoperative fluorescence. The degree of fluorescence was then matched with the genotype. RESULTS: A trend of grade 2 fluorescence (i.e., "strong") was observed in the IDH 1/2 wild-type (WT) genotype, suggesting a more intense metabolic activity in this particular subgroup, while, no or weak fluorescence was observed more often in the IDH 1/2 mutated tumors, suggesting a lower metabolic activity. No relations were found between fluorescence grade and MGMT promoter methylation or, interestingly, cellularity. As a secondary analysis, more epileptogenicity of the IDH 1/2 mutated GBM was noticed, similarly to other recent literature. CONCLUSION: Our results do not support the use of 5-ALA as a diagnostic tool, or a way to substitute the molecular profiling, but confirm 5-ALA as a powerful metabolic tracer, able to easily detect the pathological cells, especially in the IDH WT genotype, and in this perspective, further studies will be necessary to better describe the metabolic activity of GBM cells.

Fluorescence-Guided Surgery for High-Grade Gliomas: State of the Art and New Perspectives.

High-grade gliomas are aggressive tumors that require multimodal management and gross total resection is considered to be the first crucial step of treatment. Because of their infiltrative nature, intraoperative differentiation of neoplastic tissue from normal parenchyma can be challenging. For these reasons, in the recent years, neurosurgeons have increasingly performed this surgery under the guidance of tissue fluorescence. Sodium fluoresceine and 5-aminolevulinic acid represent the 2 main compounds that allow real-time identification of residual malignant tissue and have been associated with improved gross total resection and radiological outcomes. Though presenting different profiles of sensitivity and specificity and further investigations concerning cost-effectiveness are need, Sodium fluoresceine, 5-aminolevulinic acid and new phluorophores, such as Indocyanine green, represent some of the most important tools in the neurosurgeon's hands to achieve gross total resection.

Foramen Caecum Vein Involved in Dural Arteriovenous Fistula Fed by Sphenopalatine Arteries: A Case Report.

Anterior cranial fossa (ACF) dural arteriovenous fistulas (ACF DAVFs) are an infrequent subtype of cranial DAVFs that are usually fed by the anterior ethmoidal artery (AEA) and ophthalmic artery (OA) branches. Due to the lack of dural venous sinus in the ACF, they directly drain into cortical veins, resulting in high bleeding tendency. For this reason, ACF DAVFs have to be treated regardless of whether they are symptomatic or not. A 74-year-old man, with hypertension history, came to our attention because of ear pain, dizziness, and impaired hearing for 2 months. No other pathological conditions have been found in his medical history. The patient underwent brain magnetic resonance imaging (MRI) scan and subsequently second level diagnostic investigations with digital subtraction angiography (DSA), showing a foramen caecum (FC) patency and a persistent, enlarged, arterialized FC vein (FCV) involved in an incidental ACF DAVF (Cognard IV), fed mainly by sphenopalatine arteries (SPAs) branches bilaterally. The patient underwent open surgery performed by small high frontal craniotomy with DAVFs complete closure and without any complications. To the best of our knowledge, this is the first case ever described of FCV persistence with involvement in an intracranial vascular malformation. It has been managed by surgical intervention that can be considered, despite the large skin incision, a minimally invasive approach with an excellent cosmetic result and minimal risk of complications.

How Reliable Are Volumetric Techniques for High-Grade Gliomas? A Comparison Study of Different Available Tools.

BACKGROUND: Gliomas are the most common malignant primary brain tumors. Assessment of the tumor volume represents a crucial point in preoperative and postoperative evaluation. OBJECTIVE: To compare pre- and postoperative tumor volumes obtained with an automated, semi-automatic, and manual segmentation tool. Mean processing time of each segmentation techniques was measured. METHODS: Manual segmentation was performed on preoperative and postoperative magnetic resonance images with the open-source software Horos (Horos Project). "SmartBrush," a tool of the IPlan Cranial software (Brainlab, Feldkirchen, Germany), was used to carry out the semi-automatic segmentation. The open-source BraTumIA software (NeuroImaging Tools and Resources Collaboratory) was employed for the automated segmentation. Pearson correlation coefficient was used to assess volumetric comparison. Subsequently deviation/range and average discrepancy were determined. The Wilcoxon signed-rank test was used to assess statistical significance. RESULTS: A total of 58 patients with a newly diagnosed high-grade glioma were enrolled. The comparison of the volumes calculated with Horos and IPlan showed a strong agreement both on preoperative and postoperative images (respectively: "enhancing" ρ = 0.99-0.78, "fluid-attenuated inversion recovery" ρ = 0.97-0.92, and "total tumor volume" ρ = 0.98-0.95). Agreement between BraTumIA and the other 2 techniques appeared to be strong for preoperative images, but showed a higher disagreement on postoperative images. Mean time expenditure for tumor segmentation was 27 min with manual segmentation, 17 min with semi-automated, and 8 min with automated software. CONCLUSION: The considered segmentation tools showed high agreement in preoperative volumetric assessment. Both manual and semi-automated software appear adequate for the postoperative quantification of residual volume. The evaluated automated software is not yet reliable. Automated software considerably reduces the time expenditure.

Exploring the anatomy of negative motor areas (NMAs): Findings in awake surgery.

Positive motor responses have been used in neurosurgery for the identification of motor structures. With the term "negative motor responses" (NMRs) a complete inhibition of movement without loss of muscle tone or consciousness is meant. Papers already exist in the literature regarding cortical areas in which such NMRs are evoked, the so-called "negative motor areas" (NMAs), but their location and functional meaning are still poorly understood. This paper discusses the anatomy of the NMAs of the human brain, in light of our brain mapping experience. 21 patients underwent awake surgery and direct electrical stimulation (DES) was performed using bipolar electrodes. Excision was interrupted when functional responses were intraoperatively identified through DES. The labeled mapping sites were recorded by photography prior to and following tumor resection. Results depicting a probabilistic map of negative motor network anatomy were retrospectively analyzed. Our findings strongly support the fact that the precentral gyrus, classical site of the of the Primary Motor Areas, is also strongly involved in generating NMRs. The distribution of NMAs was noted not to be as rigid as previously described, ranging in different brain areas with a somatotopic arrangement. Presented anatomical results are consistent with the literature, but the exact functional meaning of NMAs and their subcortical connectivity is still far from being completely understood.

Radiological evaluation of ex novo high grade glioma: velocity of diametric expansion and acceleration time study.

BACKGROUND: One of the greatest neuro-oncological concern remains the lack of knowledge about the etiopathogenesis and physiopathology of gliomas. Several studies reported a strict correlation between radiological features and biological behaviour of gliomas; in this way the velocity of diametric expansion (VDE) correlate with lower grade glioma aggressiveness. However, there are no the same strong evidences for high grade gliomas (HGG) because of the lack of several preoperative MRI. PATIENTS AND METHODS: We describe a series of 4 patients affected by HGG followed from 2014 to January 2019. Two patients are male and two female; two had a pathological diagnosis of glioblastoma (GBM), one of anaplastic astrocytoma (AA) and one had a neuroradiological diagnosis of GBM. The VDE and the acceleration time (AT) was calculated for fluid attenuated inversion recovery (FLAIR) volume and for the enhancing nodule (EN). Every patients underwent sequential MRI study along a mean period of 413 days. RESULTS: Mean VDE evaluated on FLAIR volume was 39.91 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 282.7%. Median appearance time of EN after first MRI scan was 432 days. Mean VDE was 45.02 mm/year. Mean percentage ratio between peak values and mean value of acceleration was 257.52%. CONCLUSIONS: To our knowledge, this is the first report on VDE and acceleration growth in HGG confirming their strong aggressiveness. In a case in which we need to repeat an MRI, time between consecutive scans should be reduced to a maximum of 15-20 days and surgery should be executed as soon as possible.

Management of Extramedullary Intradural Spinal Tumors: The Impact of Clinical Status, Intraoperative Neurophysiological Monitoring and Surgical Approach on Outcomes in a 12-Year Double-Center Experience.

Objective: Intradural Extramedullary (IDEM) tumors are usually treated with surgical excision. The aim of this study was to investigate the impact on clinical outcomes of pre-surgical clinical conditions, intraoperative neurophysiological monitoring (IONM), surgical access to the spinal canal, histology, degree of resection and intra/postoperative complications. Methods: This is a retrospective observational study analyzing data of patients suffering from IDEM tumors who underwent surgical treatment over a 12 year period in a double-center experience. Data were extracted from a prospectively maintained database and included: sex, age at diagnosis, clinical status according to the modified McCormick Scale (Grades I-V) at admission, discharge, and follow-up, tumor histology, type of surgical access to the spinal canal (bilateral laminectomy vs. monolateral laminectomy vs. laminoplasty), degree of surgical removal, use and type of IONM, occurrence and type of intraoperative complications, use of Ultrasonic Aspirator (CUSA), radiological follow-up. Results: A total number of 249 patients was included with a mean follow-up of 48.3 months. Gross total resection was achieved in 210 patients (84.3%) mostly in Schwannomas (45.2%) and Meningiomas (40.4%). IONM was performed in 162 procedures (65%) and D-wave was recorded in 64.2% of all cervical and thoracic locations (99 patients). The linear regression diagram for McCormick grades before and after surgery (follow-up) showed a correlation between preoperative and postoperative clinical status. A statistically significant correlation was found between absence of worsening of clinical condition at follow-up and use of IONM at follow-up (p = 0.01) but not at discharge. No associations were found between the choice of surgical approach and the extent of resection (p = 0.79), the presence of recurrence or residual tumor (p = 0.14) or CSF leakage (p = 0.25). The extent of resection was not associated with the use of IONM (p = 0.91) or CUSA (p = 0.19). Conclusion: A reliable prediction of clinical improvement could be made based on pre-operative clinical status. The use of IONM resulted in better clinical outcomes at follow-up (not at discharge), but no associations were found with the extent of resection. The use of minimally invasive approaches such as monolateral laminectomy showed to be effective and not associated with worse outcomes or increased complications.