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Purpose: Magnetic resonance imaging (MRI) is the current standard for preoperative planning of glioblastoma (GBM) surgery. However, recent data on the use of 11C-methionine positron emission tomography (11[C]-MET PET) suggest its role in providing additional information beyond MRI. The purpose of this study is to establish if there is a correlation between anatomical and metabolic data. Methods: We retrieved all GBM cases treated at our institution from 2014 to January 2021. Preoperative MRI (Enhancing Nodule -EN-, FLAIR and Total Tumor Volume -TTV-) and PET volumes were evaluated to analyze potential correlations between anatomical and metabolic data. These findings were then correlated with pathological results obtained from the different radiological tumor regions. Results: 150 patients underwent surgery for GBM and 49 of these were also studied preoperatively with 11[C]-MET PET; PET volume was evaluated in 47 patients. In 33 patients (70.21%) preoperative 11[C]-MET PET volume > preoperative EN volume and in 11 (23.4%) preoperative 11[C]-MET PET volume > preoperative TTV. We found a significant correlation between preoperative TTVs and PET volumes (p = 0.016) as well as between preoperative EN volumes and PET volumes (p = Conclusion: In our series PET volumes correlated with EN and TTV on preoperative MRI, indicating that PET should be considered in the presurgical planning to achieve a supratotal resection.

It is generally accepted that Glioblastoma (GBM) arise from cancer stem cells (CSC), however, there is little evidence on their anatomical distribution. We investigated the expression and distribution of SOX-2-positive and CD133-positive CSCs both in the enhancing nodule (EN) of GBM and in the FLAIR hyperintensity zones on a surgical, histopathological series of 33 GBMs.The inclusion criterion was the intraoperative sampling of different tumor regions individualized thanks to Neuronavigation and positivity to intraoperative fluorescence with the use of 5-aminolevulinic acid (5-ALA). 33 patients (20 males and 13 females with a mean age at diagnosis of 56 years) met the inclusion criterion. A total of 109 histological samples were evaluated, 52 for ENs and 57 for FLAIR hyperintensity zone. Considering the quantitative distribution of levels of intensity of staining (IS), ES (extent score) and immunoreactivity score (IRS), no difference was found between ENs and FLAIR regions for both the SOX-2 biomarker (respectively, IS p=0.851, ES p=0.561, IRS p=1.000) and the CD133 biomarker (IS p=0.653, ES p=0.409, IRS p=0.881). This evidence suggests to recalibrate the target of surgery for FLAIRECTOMY and 5-ALA could improve the possibility to achieve this goal.

Ping-pong fractures have become less frequent, and no definite predictors to determine which fractures will elevate spontaneously and which should undergo surgical treatment have been clearly defined. Herein, the authors present a revision of the literature, in which 54 papers were included, with a total of 228 children studied. Patients who underwent surgery accounted for 30%; elevation through obstetrical vacuum or other aspiration systems was applied in 30%; and spontaneous resolution occurred in 40%; in 4 patients, percutaneous microscrew elevation was applied. Overall, in 96.4% of patients, the outcome was favorable because we found no significant increase in the incidence of post-traumatic seizures or neurologic sequelae with no significant differences between treated patients and spontaneous elevation. Statistical analysis showed no significant differences among the different treatment methods (P = 0.53). Our results suggest that simple compound ping-pong fractures without brain compression, hematomas, or dural tears could benefit from conservative management. In cases of nonspontaneous resolution after 6 months, operative strategies should be performed, considering that there is no evidence of differences between vacuum elevation and surgical elevation.

Cerebellar liponeurocytoma (CL) is an unusual tumor, histologically composed of a mixture of small to medium-sized, rounded neurocytic cells and a variable lipomatous component. Although CL was originally considered as a subtype of medulloblastoma, subsequent molecular studies demonstrated that this tumor was a distinct entity, exhibiting the tumor protein p53 gene (TP53) missense mutations in 20% of cases, chromosome 17 deletion, and the absence of mutations in the adenomatous polyposis coli gene (APC), the protein patched homolog gene (PTCH), the kinase insert domain receptor gene (KDR), and the β-catenin gene (CTNNB). Apart from these molecular features, little is known about the pathogenesis and the genetic landscape of CL to date. In order to characterize the mutational landscape of CL and identify alterations that are driving tumorigenesis, we report a series of three cases, including one recurrent tumor, analysed by next-generation sequencing (NGS), which identified a total of 22 variants, of which four were missense mutations, nine were synonymous variants, and nine were located on intronic regions. In particular, DNA sequencing identified missense mutations in APC, KDR, and TP53 that could be implicated in promoting tumor progression and angiogenesis of CL. Furthermore, the NGS analysis revealed that recurrent CL did not have additional genetic changes compared with the primary tumor. Moreover, the high frequencies of detected mutations suggested that the identified alterations are germline variants. Indeed, an additional NGS on the genomic DNA obtained from one of the three patients confirmed the presence of the variants in the germline DNA. In conclusion, the obtained data support the hypothesis that CL is a distinct pathological entity that does not show specific somatic alterations driving tumorigenesis.

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients’ prognosis and correct surgical/radiotherapy planning.

Post-traumatic orbital meningoencephaloceles related to orbital roof fractures are a challenging clinical entity because of their rarity and difficult differential diagnosis. We report a case of post-traumatic intra-orbital meningoencephalocele in a 69-year-old man, secondary to a likely trapdoor mechanism, treated with a modified one-piece orbitozygomatic craniotomy. We also performed an extensive literature review of traumatic Intra-Orbital Encephalocele related to Orbital Roof Fracture focused on adult patients on electronic databases including Scopus, MEDLINE/PubMed, and Google Scholar. Patient well recovered after surgery with immediate exophthalmos resolution and discharged without visual or neurological deficits. The literature review included 22 papers with a total of 28 patients: 22 males (78.6%) and 6 females (21.4%), with a median age of 34.7 years. Twenty-six patients (92.9%) reported ocular injuries, with associated intracranial complications in 16 cases (61.5%). Twenty-seven patients (96.4%) were surgically treated, 18 of those underwent unilateral or bilateral frontal approach. Most orbital roof fractures can be managed nanoperatively if asymptomatic. Indeed, when the intra-orbital volume decreases, for example due to an encephalocele, the intra-orbital pressure could increase and determine an orbital compartment syndrome. In our case, we performed a one-piece modified orbitozygomatic approach, which has several advantages in comparison to the frequent unilateral or bilateral frontal craniotomy like the better exposure of the brain and orbit and a minimum brain retraction.

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The involvement of non-coding RNAs (ncRNAs) in glioblastoma multiforme (GBM) pathogenesis and progression has been ascertained but their cross-talk within GBM cells remains elusive. We previously demonstrated the role of circSMARCA5 as a tumor suppressor (TS) in GBM. In this paper, we explore the involvement of circSMARCA5 in the control of microRNA (miRNA) expression in GBM. By using TaqMan® low-density arrays, the expression of 748 miRNAs was assayed in U87MG overexpressing circSMARCA5. Differentially expressed (DE) miRNAs were validated through single TaqMan® assays in: (i) U87MG overexpressing circSMARCA5; (ii) four additional GBM cell lines (A172; CAS-1; SNB-19; U251MG); (iii) thirty-eight GBM biopsies; (iv) twenty biopsies of unaffected brain parenchyma (UC). Validated targets of DE miRNAs were selected from the databases TarBase and miRTarbase, and the literature; their expression was inferred from the GBM TCGA dataset. Expression was assayed in U87MG overexpressing circSMARCA5, GBM cell lines, and biopsies through real-time PCR. TS miRNAs 126-3p and 515-5p were upregulated following circSMARCA5 overexpression in U87MG and their expression was positively correlated with that of circSMARCA5 (r-values = 0.49 and 0.50, p-values = 9 × 10−5 and 7 × 10−5, respectively) in GBM biopsies. Among targets, IGFBP2 (target of miR-126-3p) and NRAS (target of miR-515-5p) mRNAs were positively correlated (r-value = 0.46, p-value = 0.00027), while their expression was negatively correlated with that of circSMARCA5 (r-values = −0.58 and −0.30, p-values = 0 and 0.019, respectively), miR-126-3p (r-value = −0.36, p-value = 0.0066), and miR-515-5p (r-value = −0.34, p-value = 0.010), respectively. Our data identified a new GBM subnetwork controlled by circSMARCA5, which regulates downstream miRNAs 126-3p and 515-5p, and their mRNA targets IGFBP2 and NRAS.

Background:Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a rare neuropathological entity, recently introduced in neuro-oncology. These tumors, histologically similar to oligodendrogliomas, cause epilepsy, occurring in children and young adults. Only few cases of PLNTY have been described in literature and all reported cases invariably focused on the onset of these tumors in children and young adults.Case Description:We report the case of a 50-year-old woman suffering from epilepsy since the 1styear of her life. Computed tomography scan and magnetic resonance imaging of the brain documented the presence of a calcified mass involving left temporal lobe. The tumor was surgically excised and the histological examination showed a hypocellular and massively calcified neoplasm with morphological and immunohistochemical features consistent with the diagnosis of “PLNTY.”Conclusion:A review of the literature revealed that there are 31 cases of PLNTY reported in literature, most of which are children or young adults. The present case represents the second PLNTY diagnosed in a middle-aged adult to the best of our knowledge, suggesting that PLNTY should always be included in the differential diagnosis of low-grade brain tumors, also in adult patients.

The Inferior Fronto-Occipital fascicle (IFOF) is a multitasking white matter (WM) bundle bridging frontal, temporal, parietal and occipital lobe. Many papers describe its role in the physiology of language, attention and affective behavior but its anatomical components and cortical terminations remain unclear. We analyze the surgical anatomy of the IFOF in the light of our experience with awake surgery, anatomical dissection on 10 human adult hemispheres (Klingler method) and literature review. Dissecting the specimens from lateral to medial we can describe 3 segments: a vertical segment that runs along the frontal lobe; an horizontal segment that runs along frontal lobe; an horizontal segment that runs from the limen insulae, passes into to the temporal stem and arrives at the parietal and occipital lobes. We retrospectively analyzed also 23 awake surgeries. 2 responses were elicited at subcortical stimulation at the third segment of the IFOF; stimulation gave paraphasias on the first segment of the IFOF in one case. All IFOF responses were founded in the left hemisphere. Anatomical knowledge is the cornerstone of surgical orientation, it allows eloquent structures to be reached quickly and it is of primary importance in awake surgery to avoid patient fatigue with lack of concentration.

Glioblastoma multiforme (GBM) is the most frequent and deadly human brain cancer. Early diagnosis through non-invasive biomarkers may render GBM more easily treatable, improving the prognosis of this currently incurable disease. We suggest the use of serum extracellular vesicle (sEV)-derived circular RNAs (circRNAs) as highly stable minimally invasive diagnostic biomarkers for GBM diagnosis. EVs were isolated by size exclusion chromatography from sera of 23 GBM and 5 grade 3 glioma (GIII) patients, and 10 unaffected controls (UC). The expression of two candidate circRNAs (circSMARCA5 and circHIPK3) was assayed by droplet digital PCR. CircSMARCA5 and circHIPK3 were significantly less abundant in sEVs from GBM patients with respect to UC (fold-change (FC) of −2.15 and −1.92, respectively) and GIII (FC of −1.75 and −1.4, respectively). Receiver operating characteristic curve (ROC) analysis, based on the expression of sEV-derived circSMARCA5 and circHIPK3, allowed us to distinguish GBM from UC (area under the curve (AUC) 0.823 (0.667–0.979) and 0.855 (0.704 to 1.000), with a 95% confidence interval (CI), respectively). Multivariable ROC analysis, performed by combining the expression of sEV-derived circSMARCA5 and circHIPK3 with preoperative neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR) and lymphocyte to monocyte (LMR) ratios, three known diagnostic and prognostic GBM markers, allowed an improvement in the GBM diagnostic accuracy (AUC 0.901 (0.7912 to 1.000), 95% CI). Our data suggest sEV-derived circSMARCA5 and circHIPK3 as good diagnostic biomarkers for GBM, especially when associated with preoperative NLR, PLR and LMR.

Cellular composition and molecular signatures of the glioma core compared with infiltrative margins are different, and it is well known that the tumor edge is enriched in microglia. In this review of the literature, we summarize the role of the peritumoral area in high-grade gliomas (HGGs) from surgical and biological points of view. There is evidence on the dual role of microglia in HGGs—a scavenger-tumoricidal role when microglia are activated in an M1 phenotype and a role favoring tumor growth and infiltration/migration when microglia are activated in an M2 phenotype. Microglia polarization is mediated by complex pathways involving cross-talk with glioma cells. In this scenario, extracellular vesicles and their miRNA cargo seem to play a central role. The switch to a specific phenotype correlates with prognosis and the pathological assessment of a specific microglial setting can predict a patient’s outcome. Some authors have designed an engineered microglial cell as a biologically active vehicle for the delivery of intraoperative near-infrared fluorescent dye with the aim of helping surgeons detect peritumoral infiltrated areas during resection. Furthermore, the pharmacological modulation of microglia-glioma cross-talk paves the way to more effective therapies.

Background Extent of tumor resection (EOTR) in glioblastoma surgery plays an important role in improving survival. Objective To analyze the efficacy, safety and reliability of fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images used to guide glioblastoma resection (FLAIRectomy) and to volumetrically measure postoperative EOTR, which was correlated with clinical outcome and survival. Methods A total of 68 glioblastoma patients (29 males, mean age 65.8) were prospectively enrolled. Hyperintense areas on FLAIR images, surrounding gadolinium-enhancing tissue on T1-weighted MR images, were screened for signal changes suggesting tumor infiltration and evaluated for supramaximal resection. The surgical protocol included 5-aminolevulinic acid (5-ALA) fluorescence, neuromonitoring, and intraoperative imaging tools. 5-ALA fluorescence intensity was analyzed and matched with the different sites on navigated MR, both on postcontrast T1-weighted and FLAIR images. Volumetric evaluation of EOTR on T1-weighted and FLAIR sequences was compared. Results FLAIR MR volumetric evaluation documented larger tumor volume than that assessed on contrast-enhancing T1 MR (72.6 vs 54.9 cc); residual tumor was seen in 43 patients; postcontrast T1 MR volumetric analysis showed complete resection in 64 cases. O6-methylguanine-DNA methyltransferase promoter was methylated in 8/68 (11.7%) cases; wild type Isocytrate Dehydrogenase-1 (IDH-1) was found in 66/68 patients. Progression free survival and overall survival (PFS and OS) were 17.43 and 25.11 mo, respectively. Multiple regression analysis showed a significant correlation between EOTR based on FLAIR, PFS (R2 = 0.46), and OS (R2 = 0.68). Conclusion EOTR based on FLAIR and 5-ALA fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium-enhancing, T1-based resection.

Objectives We present a challenging case of a 61-year-old male patient with a double meningioma. The first one was located on the right side of foramen magnum and the second one was located on left anterolateral side of C1–C2. Background Patient referred at our institution for a progressive spastic paraparesis from approximately 1 year with a recent onset of numbness in right hand. Neuroradiological imaging showed an extra-axial enhancing tumor with a dural tail on the right border of foramen magnum and another contralateral extra-axial enhancing lesion at C1–C2 level (Fig. 1). Results We have chosen a park bench position. Neurophysiological monitoring was used during both positioning and surgery. A linear skin incision in the occipital region extended to C7 was performed and a suboccipital craniotomy with the laminectomy of C1–C3 was performed (Fig. 2). Videofluroangiography was performed to the best visualization of the vertebral artery position during microsurgical dissection and exposure of craniovertebral junction region. An Y-shape dural opening was executed and two meningiomas was resected with the classical four D steps (devascularize, detach, debulking, and dissect). All anatomical structures were respected and there were no changes at neuromonitoring. Patient was discharged after 10 days in good neurological condition. Conclusion a single approach for multiple meningiomas of the craniovertebral junction and upper cervical spine region is feasible and effective. Videofluoroangiography as a way to achieve better visualization and control of the vertebral artery, and neurophysiological monitoring are crucial tools to reduce the morbidity of this surgical challenge.The link to the video can be found at: https://youtu.be/4w9HCfQZkgg.

Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential.

OBJECTIVENo consensus exists on the best treatment for recurrent high-grade glioma (HGG), particularly in terms of surgical indications, and scant data are available on the integrated use of multiple technologies to overcome intraoperative limits and pitfalls related to artifacts secondary to previous surgery and radiotherapy. Here, the authors report on their experience with the integration of multiple intraoperative tools in recurrent HGG surgery, analyzing their pros and cons as well as their effectiveness in increasing the extent of tumor resection. In addition, they present a review of the relevant literature on this topic.METHODSThe authors reviewed all cases in which recurrent HGG had been histologically diagnosed after a first surgery and the patient had undergone a second surgery involving neuronavigation with MRI, intraoperative CT (iCT), 11C-methionine–positron emission tomography (11C-MET-PET), 5-aminolevulinic acid (5-ALA) fluorescence, intraoperative neurophysiological monitoring (IONM), and intraoperative navigated ultrasound (iUS). All cases were classified according to tumor functional grade (1, noneloquent area; 2, near an eloquent area; 3, eloquent area).RESULTSTwenty patients with recurrent HGG were operated on using a multimodal protocol. The recurrent tumor functional grade was 1 in 4 patients, 2 in 8 patients, and 3 in the remaining 8 patients. In all patients but 2, 100% EOTR was obtained. Intraoperative 5-ALA fluorescence and navigated iUS showed low specificity and sensitivity. iCT detected tumor remnants in 3 cases. Postoperatively, 6 patients (30%) had worsening neurological conditions: 4 recovered within 90 days, 1 partially recovered, and 1 experienced a permanent deficit. The median Karnofsky Performance Status remained substantially unchanged over the follow-up period. The mean progression-free survival after the second surgery was 7.7 months (range 2–11 months). The mean overall survival was 25.4 months (range 10–52 months), excluding 2 long survivors. Two patients died within 60 days after surgery, and 3 patients were still under follow-up at the end of this study.CONCLUSIONSThis is the first study reporting the integration of neuronavigation, 5-ALA fluorescence, iUS, iCT, 11C-MET-PET, and IOM during microsurgical resection of recurrent glioma. The authors believe that the proposed multimodal protocol is useful to increase the safety, effectiveness, and EOTR in patients with recurrent HGG and brain alterations secondary to radio- and chemotherapy.

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.

To evaluate clinical response after external lumbar drainage (ELD) and ventriculoperitoneal shunting (VPS) in a cohort of patients with idiopathic normal pressure hydrocephalus associated with parkinsonism (iNPH-P), considering parkinsonism as clinical primary outcome. Patients underwent long-term 72-h intracranial pressure-controlled CSF ELD. Clinical motor response before and after ELD was evaluated using changes in UPDRS-ME as outcome measure. A standardized cognitive assessment was also performed. iNPH-P patients who underwent VPS were clinically followed-up after surgery. Fourteen iNPH-P patients (age: 69.3 ± 11.6 years) were studied. The time of evaluation after ELD removal was 3.5 ± 1.8 days. We observed a significant motor improvement after the drainage in eight (57.1%) patients. Percent clinical motor response was 18.4 ± 6.7%. Twelve (85.7%) patients underwent VPS. Nine patients were examined after surgery at 31.6 ± 7 months. Four (44.4%) patients presented a clinically detectable improvement in motor response after VPS. No significant changes in cognitive performances were detected. A clinically detectable motor response on parkinsonian signs was observed in a consistent part of iNPH-P patients few days after ELD as well as over two and half years after VPS. Parkinsonism should be considered as outcome measure for the clinical management of patients with iNPH-P.

Introduction Glioblastoma treatment requires a multidisciplinary approach involving oncologists, radiotherapists and surgeons. Surgery constitutes the initial step of the therapeutic strategy and its efficacy is dependent on the extent of resection (EOR). Over the last decade, the goal of surgical treatment was the resection of the contrast enhancement on T1 MRI, defined as gross-total resection (GTR). More recently, an increasing number of studies reports a positive impact on survival parameters of a more aggressive surgical strategy aiming to resect all peri-tumoral infiltrated areas. These areas are histologically characterized by the presence of pathological cells infiltrating normal white matter and surround the neoplastic core of glioblastoma identified by gadolinium enhancement in T1-weighted MR. Intuitively, the major risk of the so called supramarginal resection is related to the possibility of resecting functionally eloquent brain tissue. Several strategies have been proposed to maximize the safety of resection and minimize the occurrence of postoperative functional deficits. The aim of this review was to focus on the clinical impact of supramarginal resection of glioblastomas, highlighting the role of image-guided surgery combined with neuromonitoring to increase surgical safety and efficacy. Evidence acquisition The MEDLINE database has been queried for the literature research. Evidence synthesis Ten studies matched the inclusion criteria, reporting a global number of 3221 patients. Conclusions The current evidence suggests a positive correlation between a more extensive resection based on FLAIR abnormal areas and overall survival.

Objective Analyzing occlusion, complications rate, and clinical results in unruptured saccular middle cerebral artery aneurysms (MCAAs) comparing clipping with the most advance and newer endovascular techniques. Methods We conducted a literature research from January 2009 to December 2018 to evaluate the efficacy and safety of microsurgical clipping or endovascular treatment with new devices (such as Flow-diverter or Woven EndoBridge) in patients with unruptured MCAAs. We extracted data involved: study and intervention features, occlusion rate; time of occlusion assessment; and clinical outcome. Results A total of 29 studies and 1552 patients with unruptured saccular MCAAs were included in our analysis (464 patients included in the endovascular group, 1088 patients in the surgical group). Overall, the rate of long-term complete/near-complete occlusion was 78.1% (311/405, 95% confidence interval [CI], 69%–87.1%) and 95.7% (113/118, 95% CI, 92%–99.3%) after endovascular and surgical treatments, respectively (P = 0.001). The long-term complete occlusion rate was 60% (153/405, 95% CI, 45%–74%) and 95% (112/118, 95% CI, 90%–98%) after endovascular and surgical treatments, respectively (P = 0.001). The overall rate of treatment-related complications was 5.6% (33/464, 95% CI, 3.6%–7.7%) and 2.9% (37/1088, 95% CI, 0.8%–5%) among the endovascular and surgical groups, respectively (P = 0.001). Endovascular treatments were associated with higher rates of good neurologic outcome (283/293 [97%], 95% CI, 95%–98% vs. 570/716 [84%], 95% CI, 67%–98%; P = 0.001). No difference was found for the mortality (3/464 [1.5%], 95% CI, 0.4%–2.6% vs. 1/1088, 95% CI, 0.1%–0.6%; P = 0.5). Conclusions Treatment-related complication and mortality are comparable among these techniques and the risk of aneurysm rupture seems very low for both strategies. The endovascular approach seems to increase the probability of good functional outcome after treatment, compared with surgery.

OBJECTIVEApproximately 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.METHODSClinical, 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.RESULTSSurvival 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).CONCLUSIONSThe 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 GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

Background In the modern era evidence-based medicine, guidelines and recommendations represent a key-point of daily activity. The Spinal Section of the Italian Society of Neurosurgery introduced some recommendations regarding Degenerative Lumbar Spine Stenosis based on those of the Spine Committee of World Federation of Neurosurgical Societies, revising them on the basis of Italian common practice. Methods In June 2019, a Committee of 21 spine surgeons met in Rome to validate the recommendations of the WFNS. Furthermore, they decided to review the ones that did not reach a consensus to create Italian Recommendations on Degenerative Lumbar Spine Stenosis. A literature review of the last ten years was performed and the statements were voted using the Delphi method. Results 41 statements were discussed and 7 statements were voted again to reach a consensus with respect to those of the WFNS. A total of 40 statements reached a consensus, of which 36 reached a positive consensus and 4 a negative consensus, while no consensus was reached in 1 case. Conclusions Conservative multimodal therapy, tailored on the patient, is a reasonable and effective first option choice for the treatment of LSS patients with tolerable moderate symptoms. Surgical treatment is reserved for symptomatic patients non-responding to conservative treatment or with neurological deficits. The best surgical technique to use depends on personal experience; modern MISS techniques are equivalent to open decompressive surgery with some advantages and higher cost-effectiveness. Fusion surgery and mobility preserving surgery only have a marginal role in the treatment of DLSS without instability.

This case report describes a fatal case of a young woman with superior sagittal, transverse and sigmoid sinus thrombosis after administration of the ChAdOx1 nCov-19 vaccination. Eleven days post-vaccination she was found unconscious and transferred to the Emergency Department. Blood parameters showed low platelets, and a CT scan showed an extensive left intracranial hemorrhage and the presence of an occlusive thrombus of the superior sagittal sinus. She under-went a craniectomy, but after the intervention, she remained in a comatose state. After a few days, her clinical conditions worsened, and she died. A complete autopsy was performed which showed a thrombosis of the cerebral venous district, of the upper and lower limbs. A blood sample was also performed to carry out a gene study about the predisposition to thrombosis. The organ samples were studied through light microscope both in hematoxylin-eosin and immunohistochemical examination, and showed a strong inflammatory response in all samples and at the site of thrombosis. Our study aims to provide a proper autopsy technique to study the entire cerebral venous system through a multidisciplinary approach (anatomical dissection and neurosurgery) in post-vaccine venous thrombosis.

Spinal infection (SI) is defined as an infectious disease affecting the vertebral body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2–7% of all musculoskeletal infections. There are numerous factors, which may facilitate the development of SI including not only advanced patient age and comorbidities but also spinal surgery. Due to the low specificity of signs, the delay in diagnosis of SI remains an important issue and poor outcome is frequently seen. Diagnosis should always be supported by clinical, laboratory, and imaging findings, magnetic resonance imaging (MRI) remaining the most reliable method. Management of SI depends on the location of the infection (i.e., intraspinal, intervertebral, paraspinal), on the disease progression, and of course on the patient’s general condition, considering age and comorbidities. Conservative treatment mostly is reasonable in early stages with no or minor neurologic deficits and in case of severe comorbidities, which limit surgical options. Nevertheless, solely medical treatment often fails. Therefore, in case of doubt, surgical treatment should be considered. The final result in conservative as well as in surgical treatment always is bony fusion. Furthermore, both options require a concomitant antimicrobial therapy, initially applied intravenously and administered orally thereafter. The optimal duration of antibiotic therapy remains controversial, but should never undercut 6 weeks. Due to a heterogeneous and often comorbid patient population and the wide variety of treatment options, no generally applicable guidelines for SI exist and management remains a challenge. Thus, future prospective randomized trials are necessary to substantiate treatment strategies.

Radiomics holds great promise in the field of cancer management. However, the clinical application of radiomics has been hampered by uncertainty about the robustness of the features extracted from the images. Previous studies have reported that radiomics features are sensitive to changes in voxel size resampling and interpolation, image perturbation, or slice thickness. This study aims to observe the variability of positron emission tomography (PET) radiomics features under the impact of co-registration with magnetic resonance imaging (MRI) using the difference percentage coefficient, and the Spearman’s correlation coefficient for three groups of images: (i) original PET, (ii) PET after co-registration with T1-weighted MRI and (iii) PET after co-registration with FLAIR MRI. Specifically, seventeen patients with brain cancers undergoing [11C]-Methionine PET were considered. Successively, PET images were co-registered with MRI sequences and 107 features were extracted for each mentioned group of images. The variability analysis revealed that shape features, first-order features and two subgroups of higher-order features possessed a good robustness, unlike the remaining groups of features, which showed large differences in the difference percentage coefficient. Furthermore, using the Spearman’s correlation coefficient, approximately 40% of the selected features differed from the three mentioned groups of images. This is an important consideration for users conducting radiomics studies with image co-registration constraints to avoid errors in cancer diagnosis, prognosis, and clinical outcome prediction.

Retro-odontoid pseudotumor or pannus usually develops secondary to inflammatory disease like rheumatoid arthritis and psoriatic arthritis. However, less frequently it can be associated with noninflammatory conditions like cervical trauma, anatomic variants of C2 odontoid process or craniocervical junction, surgery-related instability, long-term hemodialysis, and degenerative atlantoaxial instability. Different surgical techniques to treat retro-odontoid pseudotumor have been proposed. Some procedures are aimed at direct removal of the retro-odontoid mass, whereas others are performed to induce spontaneous regression of the pseudotumor.

Surgical decision-making in cases of post-traumatic CVJ injuries is challenging because the spinal insult may involve bony structures, ligaments, or both.

Background Angioleiomyoma (ALM) is a soft tissue neoplasm rarely described in the intracranial site. Because of their uncommon presentation, atypical neuroradiologic and pathologic features, ALMs are often misdiagnosed. Case Description We describe the neuroradiologic, clinical, and pathologic data of a 37-year-old male patient suffering from a tentorial ALM. He was admitted at our hospital because of a posterior cranial fossa mass. Magnetic resonance imaging (MRI) showed a left tentorial tumor, hypointense on T1-weighted sequences, with heterogeneous contrast enhancement after gadolinium injection (“salt-and-pepper” fashion) and slightly hyperintense signal on T2-weighted sequence. After surgery, pathological examination showed a tumor composed of several thick-walled blood vessels mixed with a population of deeply eosinophilic spindle-shaped smooth muscle cells arranged in bundles. Necrosis was absent. Neither cellular pleomorphism nor mitoses were detected. Immuno-histochemical analysis confirmed the smooth muscle phenotype of the spindle cell component: diffuse and strong positivity for alpha-smooth muscle actin, desmin, and h-caldesmon. Based on both morphologic and immunohistochemical findings, a diagnosis of primary intracranial ALM was rendered. Conclusions We add to the literature the tenth case of this exceedingly rare tumor and submit that ALM should be suspected when a tentorial mass with a “flame-like” time-dependent pattern of contrast enhancement on MRI, a “salt-and-pepper” post-contrast appearance on MRI T1-weighted sequences, and a relation with large intracranial feeding vessels are present.

We present a case of a 62-year-old man with acute onset of diplopia, headache, and vomiting for a bleeding thalamomesencephalic cavernoma. The lesion was removed via the anterior transcallosal transchoroidal approach. His head was slightly flexed and a right paramedian craniotomy for an interhemispheric approach was performed. The interhemispheric fissure was split and, after callosotomy, the choroidal fissure was opened along the tenia fornicis to enter the velum interpositum and enlarge the foramen of Monro. The cavernoma was then identified and resected. There were no long-term postoperative neurological deficits. This approach is a valid alternative for thalamomesencephalic lesions.The video can be found here: https://youtu.be/DJdorbzDnH0.

Circular RNAs are a large group of RNAs whose cellular functions are still being investigated. We recently proposed that circSMARCA5 acts as sponge for the splicing factor Serine and Arginine Rich Splicing Factor 1 (SRSF1) in glioblastoma multiforme (GBM). After demonstrating by RNA immunoprecipitation a physical interaction between SRFS1 and circSMARCA5, we assayed by real-time PCR in a cohort of 31 GBM biopsies and 20 unaffected brain parenchyma controls (UC) the expression of total, pro-angiogenic (Iso8a) and anti-angiogenic (Iso8b) mRNA isoforms of Vascular Endothelial Growth Factor A (VEGFA), a known splicing target of SRSF1. The Iso8a to Iso8b ratio: (i) increased in GBM biopsies with respect to UC (p-value &lt, 0.00001), (ii) negatively correlated with the expression of circSMARCA5 (r-value = &minus, 0.46, p-value = 0.006), (iii) decreased in U87-MG overexpressing circSMARCA5 with respect to negative control (p-value = 0.0055). Blood vascular microvessel density, estimated within the same biopsies, negatively correlated with the expression of circSMARCA5 (r-value = &minus, 0.59, p-value = 0.00001), while positively correlated with that of SRSF1 (r-value = 0.38, p-value = 0.00663) and the Iso8a to Iso8b ratio (r-value = 0.41, p-value = 0.0259). Kaplan-Meier survival analysis showed that GBM patients with low circSMARCA5 expression had lower overall and progression free survival rates than those with higher circSMARCA5 expression (p-values = 0.033, 0.012, respectively). Our data convincingly suggest that circSMARCA5 is an upstream regulator of pro- to anti-angiogenic VEGFA isoforms ratio within GBM cells and a highly promising GBM prognostic and prospective anti-angiogenic molecule.

A retro-odontoid pseudotumour compressing the spinal cord and causing myelopathy is often associated with an inflammatory condition such as rheumatoid arthritis. A degenerative non-inflammatory retro-odontoid pseudotumour responsible for clinically relevant spinal cord compression is a rare condition described in small clinical series and is likely associated with craniovertebral junction hypermobility or instability-like conditions. For several years, direct removal of the lesion through an anterior or lateral approach has been advocated as the best surgical option. However, in the last decade the posterior approach to the craniovertebral junction, to perform C1-C2 fixation and C1 laminectomy without removal of the retro-odontoid tissue, has demonstrated its efficacy in reducing retro-odontoid pannus as well as in obtaining improvement of myelopathy.In this paper we analyse the clinical and radiological outcomes of seven patients (five males and two females) treated with posterior C1-C2 fixation and C1 laminectomy for a degenerative non-inflammatory retro-odontoid pseudotumour responsible for spinal cord compression. C1 laminectomy provided immediate spinal cord decompression. We also review the relevant literature focusing on associated cervical degenerative conditions that may contribute to triggering or acceleration of atlantoaxial hypermobility or 'instability', causing formation of the retro-odontoid tissue.The mean follow-up period (of six followed-up patients) was 55.8 months (range 10-96 months). In all cases the Nurick score at the latest follow-up visit demonstrated clinical improvement; magnetic resonance imaging during follow-up demonstrated progressive reduction of the retro-odontoid pseudotumour in all but one patient, who died of surgery-unrelated disease in the early postoperative period. No vascular or neural damage secondary to C1-C2 fixation was observed.C1-C2 fixation associated with C1 laminectomy is an effective surgical option to treat myelopathy secondary to a degenerative retro-odontoid pseudotumour. In these cases, direct removal of intracanalar tissue compressing the spinal cord is not required, as C1-C2 fixation is sufficient to cause its disappearance.