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Nicola Montano,1 Giulio Conforti,1 Rina Di Bonaventura,1 Mario Meglio,2 Eduardo Fernandez,1 Fabio Papacci1 1Institute of Neurosurgery, Catholic University, Rome, 2Institute of Neurosurgery, Azienda Ospedaliera Universitaria Integrata, Verona, Italy Abstract: Various drugs and surgical procedures have been utilized for the treatment of trigeminal neuralgia (TN). Despite numerous available approaches, the results are not completely satisfying. The need for more contemporaneous drugs to control the pain attacks is a common experience. Moreover, a number of patients become drug resistant, needing a surgical procedure to treat the neuralgia. Nonetheless, pain recurrence after one or more surgical operations is also frequently seen. These facts reflect the lack of the precise understanding of the TN pathogenesis. Classically, it has been related to a neurovascular compression at the trigeminal nerve root entry-zone in the prepontine cistern. However, it has been evidenced that in the pain onset and recurrence, various neurophysiological mechanisms other than the neurovascular conflict are involved. Recently, the introduction of new magnetic resonance techniques, such as voxel-based morphometry, diffusion tensor imaging, three-dimensional time-of-flight magnetic resonance angiography, and fluid attenuated inversion recovery sequences, has provided new insight about the TN pathogenesis. Some of these new sequences have also been used to better preoperatively evidence the neurovascular conflict in the surgical planning of microvascular decompression. Moreover, the endoscopy (during microvascular decompression) and the intraoperative computed tomography with integrated neuronavigation (during percutaneous procedures) have been recently introduced in the challenging cases. In the last few years, efforts have been made in order to better define the optimal target when performing the gamma knife radiosurgery. Moreover, some authors have also evidenced that neurostimulation might represent an opportunity in TN refractory to other surgical treatments. The aim of this work was to review the recent literature about the pathogenesis, diagnosis, and medical and surgical treatments, and discuss the significant advances in all these fields. Keywords: microvascular decompression, percutaneous balloon compression, gamma knife radiosurgery, surgical treatment, magnetic resonance imaging, therapy

Background: Spontaneous non-traumatic subarachnoid hemorrhage (sSAH) is a severe brain vascular accident. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) can be theoretically assayed to predict a patient's progression, picturing different aspects of clinical failure after sSAH. The study aims to: a) explore the correlation between sSAH blood volume and biomarkers variation; b) evaluate if these can be predictive of the neurogenic response after sSAH and be prognostic of patient outcome; c) establish eventual threshold levels of biomarkers to define patients' clinical outcome., Methods: Blood volumetry at CT scan upon admission, GFAP and UCH-L1 were collected at 24 h, at 72 h, and after 7 days from hemorrhage. Trends and cut-off serum sampling were determined. Clinical outcome was assessed with mRS scale at 14 days., Results: A strong correlation between GFAP and UCH-L1 and blood diffusion volume in all explored serum intervals related to unfavorable outcome. GFAP and UCH-L1 were very early predictors of unfavorable outcomes at 24 h from sSAH (p = 0.002 and 0.011 respectively). Threshold levels of UCH-L1 apparently revealed a very early, early and late predictor of unfavorable outcomes., Conclusion: GFAP and UCH-L1 represent a potential tool for prompt monitoring and customization of therapies in neurosurgical patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In accordance with technique advancement and minimal invasiveness surgical approaches, the minipterional has progressively replaced the standard pterional approach for treatment of unruptured middle cerebral artery (MCA) aneurysms. Nowadays, multimodal intraoperative resources including microDoppler and microflow probes, indocyanine green videoangiography, and neurophysiologic monitoring constitute a fundamental prerequisite for increasing the safety of the clipping procedure. Our study investigated and compared in a single-center experience the effect of the evolution of a minimally invasive and multimodal approach in unruptured MCA aneurysm surgery by measuring postoperative complication rate, recovery time, and long-term neuropsychological and functional outcomes., Methods: One hundred and thirty-one patients who underwent surgical treatment for unruptured MCA aneurysms at our institution were evaluated retrospectively. Patients' clinical, radiologic, and surgical reports were collected. Cognitive evaluation and quality of life were assessed through validated tests in telephone interviews. Patients who met the inclusion criteria were divided into 2 groups: "PT (pterional)" and "MPT (minipterional).", Results: Ninety-two patients were included in the analysis. A significant reduction of postoperative complication rates and new-onset postoperative seizures was recorded in the MPT group (P value = 0.006). Severe cognitive deficits were lower in the MPT group, although without a clear statistical correlation., Conclusions: Decreased complication rates, faster recovery time, and a trend toward better cognitive and functional performances were documented for the MPT group of patients. In our experience, the minipterional approach with multimodality-assisted microsurgery reduced neurologic complications and recovery time and improved long-term cognitive outcome and quality of life., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Interruption of the fistulous point is the goal of treatment of spinal dural arteriovenous fistulas (dAVFs). Microsurgery remains a highly efficient treatment in terms of complete occlusion with the lowest risk of recurrence rate. It is reported that the hardest step involves finding the fistulous site itself, potentially extending surgical access and time and increasing potential postoperative surgical-related complications. The accurate preoperative detection of the shunt and spinal level together is crucial for guiding optimal, fast, and safe microsurgical treatment., Methods: We describe a preoperative angiographic protocol for achieving a safe and simple resection of spinal dural arteriovenous fistulas based on a 6-year institutional experience of 42 patients who underwent minimally invasive procedures. Two illustrative cases are included to support the technical descriptions., Results: The suspected artery associated with the vascular malformation of interest is studied in our angiographic protocol through nonsubtracted selective acquisitions in lateral projection. The resulting frames are reconstructed with three-dimensional rotational angiography. The implementation of the preoperative angiographic protocol allowed 100% of intraoperative identification of the fistulous point in all cases with the use of a minimally invasive approach., Conclusions: Nowadays, neurosurgeons advocate for minimally invasive procedures and procedures with low morbidity risk for treatment of spinal dural arteriovenous fistulas. Our preoperative approach for accurate angiographic localization of the fistulous point through nonsubtracted and three-dimensional reconstructed angiography allowed us to achieve safe and definitive occlusion of the shunt., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Surgery and endovascular therapy are the primary treatment options for spinal dural arteriovenous fistula (SDAVF). Due to the absence of a consensus regarding which therapy yields a superior outcome, we conducted a comparative analysis of the surgical and endovascular treatment of SDAVF through a multicenter case series and a systematic literature review. Patients with SDAVF, surgically or endovascularly treated at four neurosurgical centers from January 2001 to December 2021, were included in this study. Level of SDAVF, primary treatment modality, baseline and post-procedural neurological status were collected. The primary outcomes were failure, complication rates, and a newly introduced parameter named as therapeutic delay. A systematic review of the literature was performed according to PRISMA-P guidelines. The systematic review identified 511 papers, of which 18 were eligible for analysis, for a total of 814 patients, predominantly male (72%) with a median age of 61 and mainly thoracic SDAVFs (65%). The failure rate was significantly higher for endovascular therapy (20%) compared to surgery (4%) (p < 0.01). Neurological complications were generally rare, with similar rates among the two groups (endovascular 2.9%; surgery 2.6%). Endovascular treatment showed a statistically significantly higher rate of persistent neurological complications than surgical treatment (2.9% versus 0.2%; p < 0.01). Both treatments showed similar rates of clinical improvement based on Aminoff Logue scale score. The multicenter, retrospective study involved 131 patients. The thoracic region was the most frequent location (58%), followed by lumbar (37%). Paraparesis (45%) and back pain (41%) were the most common presenting symptoms, followed by bladder dysfunction (34%) and sensory disturbances (21%). The mean clinical follow-up was 21 months, with all patients followed for at least 12 months. No statistically significant differences were found in demographic and clinical data, lesion characteristics, or outcomes between the two treatment groups. Median pre-treatment Aminoff-Logue score was 2.6, decreasing to 1.4 post-treatment with both treatments. The mean therapeutic delay for surgery and endovascular treatment showed no statistically significant difference. Surgical treatment demonstrated significantly lower failure rates (5% vs. 46%, p < 0.01). In the surgical group, 2 transient neurological (1 epidural hematoma, 1 CSF leak) and 3 non-neurological (3 wound infections) complications were recorded; while 2 permanent neurological (spinal infarcts), and 5 non-neurological (inguinal hematomas) were reported in the endovascular group. According to the literature review and this multicenter clinical series, surgical treatment has a significantly lower failure rate than endovascular treatment. Although the two treatments have similar complication rates, endovascular treatment seems to have a higher rate of persistent neurological complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The concept of aneurysm "complexity" has undergone significant changes in recent years, with advancements in endovascular treatments. However, surgical clipping remains a relevant option for middle cerebral artery (MCA) aneurysms. Hence, the classical criteria used to define surgically complex MCA aneurysms require updating. Our objective is to review our institutional series, considering the impacts of various complexity features, and provide a treatment strategy algorithm. Methods: We conducted a retrospective review of our institutional experience with "complex MCA" aneurysms and analyzed single aneurysmal-related factors influencing treatment decisions. Results: We identified 14 complex cases, each exhibiting at least two complexity criteria, including fusiform shape (57%), large size (35%), giant size (21%), vessel branching from the sac (50%), intrasaccular thrombi (35%), and previous clipping/coiling (14%). In 92% of cases, the aneurysm had a wide neck, and 28% exhibited tortuosity or stenosis of proximal vessels. Conclusions: The optimal management of complex MCA aneurysms depends on a decision-making algorithm that considers various complexity criteria. In a modern medical setting, this process helps clarify the choice of treatment strategy, which should be tailored to factors such as aneurysm morphology and patient characteristics, including a combination of endovascular and surgical techniques.

Glioblastoma, isocitrate dehydrogenase-wildtype (GB), is the most common and aggressive primary brain malignancy with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GB and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumour microenvironment (TME) immunity. This study aimed to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single-cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression-free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) were found to be linked to clinical outcome. Low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios-HR [95%CI]: 0.14 [0.04-0.52] p < 0.001, 0.39 [0.16-0.96] p = 0.04, respectively). The CD8+CD103+ Trm subgroups were also age-related predictors for survival in GB., (© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.)

Background/aim: The Mediterranean diet may be deemed as the best combination of nutrients to play a protective role against cancer. Previous studies have demonstrated how a healthy lifestyle, and the adherence to the Mediterranean diet might affect the onset of most common cancers, focusing less on their relationship with central nervous system (CNS) tumoral pathologies, especially benign ones, such as meningiomas., Patients and Methods: This was a retrospective multicenter study, involving 52 patients who underwent meningioma resection and a group of 100 subjects not affected by brain tumors. This preliminary study aimed to investigate whether the non-adherence to a dietary pattern, such as the Mediterranean diet, and pre-existing cardiovascular risk factors can affect the onset of cranial meningiomas., Results: Patients affected by meningioma had a significantly lower mean Mediterranean Diet Score (MDS), and a similar distribution of the main cardiovascular risk factors., Conclusion: A larger patient cohort is required to corroborate our findings. However, these promising results open up a new avenue for further exploration of the role of the Mediterranean diet in the development of meningiomas., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

(1) Background: Innovation and continuous demand in the field of visual enhancing technologies and video streaming have led to the discovery of new systems capable of improving visualization and illumination of the surgical field. The exoscope was brought into neurosurgical routine, and nearly ten years later, modern 3D systems have been introduced and tested, giving encouraging results. (2) Methods: In order to evaluate the surgeon's confidence with the exoscope and their increasing ability in terms of time spent and quality of the final achievement since their first encounter with the technique, an experimental trial on 18 neurosurgeons from a single Institution was performed to evaluate the learning curve for the use of the VITOM-3D exoscope in neurosurgical practice on a model of brain and dura mater. (3) Results: A significant improvement in the quality of the performance, number of errors made, and reduction in the time was found after the third iteration of the task, by when almost all the participants felt more comfortable and confident. No significant differences between senior neurosurgeons and resident neurosurgeons were reported. (4) Conclusions: Our results show that three iterations are enough to gain confidence with the exoscope from its first use, regardless of previous experience and training with an operating microscope.

Intraoperative neurophysiological monitoring (IONM) represents one of the available technologies able to assess ischemia and aimed to improve surgical outcome reducing the treatment related morbidity in surgery for intracranial aneurysms. Many studies analyzing the impact of IONM are poised by the heterogeneity bias affecting the cohorts. We report our experience with IONM for surgery of unruptured middle cerebral artery (MCA) aneurysm in order to highlight its influence on functional and radiological outcome and surgical strategy. We retrospectively reviewed all MCA unruptured aneurysms treated between January 2013 and June 2021 by our institutional neurovascular team. Patients were divided into 2 groups according to the use of IONM. A total of 153 patients were included in the study, 52 operated on without IONM and 101 with IONM. The groups did not differ preoperatively regarding clinical status and aneurysm characteristics. Patients operated with IONM had better functional outcomes at discharge as well as at follow-up (p= 0.048, p=0.041) due to lower symptomatic ischemia and better radiological outcome due to lower rate of unexpected aneurysmal remnants (p= 0.0173). The introduction of IONM changed the use of temporary clipping (TeC), increasing its average duration (p= 0.01) improving the safety of dissecting and clipping the aneurysm. IONM in surgery for unruptured MCA aneurysm could improve the efficacy and safety of clipping strategy in the way it showed a role in changing the use of TeC and was associated to the reduction of unexpected aneurysmal remnants' rate and improvement in both short- and long-term patient's outcome., (© 2023. The Author(s).)

Background: Acute hydrocephalus is a frequent complication of aneurysmal subarachnoid hemorrhage, and it is generally treated by external ventricular drainage. In the last decades, antibiotic-impregnated ventricular catheters have been introduced in the neurosurgical practice in order to reduce secondary cerebrospinal fluid infections which increase morbidity, mortality, and health care costs., Methods: Data of 100 patients treated at Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2012 and December 2019 were retrospectively reviewed in order to determine the cost-effectiveness and budget impact of antibiotic impregnated versus non-impregnated catheters in the management of patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. A budget impact model was built depending on the use of antibiotic impregnated versus non-impregnated catheters. The model was populated with data extrapolated from existing literature concerning the Italian healthcare setting and national tariffs., Results: A 25% reduction in the number of cerebrospinal fluid infections was achieved by using antibiotic impregnated catheters, resulting in an overall saving equal to €5730.52/patient. Expanding results to a 100-patient sample, the possible savings would amount to €573,052.40 for the National Health Service., Conclusions: Antibiotic impregnated catheters use was associated to a reduction in cerebrospinal fluid infections rate as well as in costs related to hospital care when compared to nonimpregnated catheters. Thus these catheters represent, besides lifesaving, cost-saving devices that reduce the economic burden and ensure a safe clinical outcome in patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. The present study provides concrete evidence of the benefit of Antibiotic impregnated catheters to decision-makers responsible of defining health policies.

Background and Aim: While many components of the ECM have been isolated and characterized, its modifications in the specific setting of GBMs have only been recently explored in the literature. The aim of this paper is to provide a systematic review on the topic and to assess the ECM's role in shaping tumoral development., Methods: An online literature search was launched on PubMed/Medline and Scopus using the research string "((Extracellular matrix OR ECM OR matrix receptor OR matrix proteome) AND (glioblastoma OR GBM) AND (tumor invasion OR tumor infiltration))", and a systematic review was conducted in accordance with the PRISMA-P guidelines., Results: The search of the literature yielded a total of 693 results. The duplicate records were then removed (n = 13), and the records were excluded via a title and abstract screening; 137 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 59 articles were finally included and were summarized as follows based on their focus: (1) proteoglycans; (2) fibrillary proteins, which were further subdivided into the three subcategories of collagen, fibronectin, and laminins; (3) glycoproteins; (4) degradative enzymes; (5) physical forces; (6) and glioma cell and microglia migratory and infiltrative patterns., Conclusions: Our systematic review demonstrates that the ECM should not be regarded anymore as a passive scaffold statically contributing to mechanical support in normal and pathological brain tissue but as an active player in tumor-related activity.

Background: Failure of clinical trials with targeted therapies in glioblastoma (GBM) is probably related to the enrollment of molecularly unselected patients. In this study we report the results of a precision medicine protocol in recurrent GBM., Methods: We prospectively evaluated 34 patients with recurrent GBM. We determined the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor variant III (EGFRvIII), and phosphatase and tensin homolog (PTEN). According to the molecular pattern we administered bevacizumab alone in patients with VEGF overexpression, absence of EGFRvIII, and normal PTEN (group A; N.=16); bevacizumab + erlotinib in patients with VEGF overexpression, expression of EGFRvIII, and normal PTEN (group B; N.=14); and bevacizumab + sirolimus in patients with VEGF overexpression and loss of PTEN, irrespective of the EGFRvIII status (group C; N.=4). We evaluated the response rate, the clinical benefit rate, the 6-month progression-free survival (PFS-6), the 12-month PFS (PFS-12) and the safety profile of the treatment. Moreover, we compared our results with the ones of EORTC 26101 trial., Results: Response rate was 50% in the whole cohort with the highest rate in group C (75%). Clinical benefit rate was 71% with the highest rate in group C (75%). PFS-6 was 56% in the whole cohort with the highest rate in group B (64%). PFS-12 was 21% in the whole cohort with the highest rate in group B (29%). When comparing our results with those from the combination arm of the EORTC 26101 trial we found a significantly higher PFS-6 and PFS-12 in our cohort., Conclusions: The precision medicine protocol for recurrent GBM is feasible and leads to improved results if compared with studies lacking molecular selection.

Grade 3 meningiomas are rare malignant tumors that can originate de novo or from the progression of lower grade meningiomas. The molecular bases of anaplasia and progression are poorly known. We aimed to report an institutional series of grade 3 anaplastic meningiomas and to investigate the evolution of molecular profile in progressive cases. Clinical data and pathologic samples were retrospectively collected. VEGF, EGFR, EGFRvIII, PD-L1; and Sox2 expression; MGMT methylation status; and TERT promoter mutation were assessed in paired meningioma samples collected from the same patient before and after progression using immunohistochemistry and PCR. Young age, de novo cases, origin from grade 2 in progressive cases, good clinical status, and unilateral side, were associated with more favorable outcomes. In ten progressive meningiomas, by comparing molecular profile before and after progression, we identified two subgroups of patients, one defined by Sox2 increase, suggesting a stem-like, mesenchymal phenotype, and another defined by EGFRvIII gain, suggesting a committed progenitor, epithelial phenotype. Interestingly, cases with Sox2 increase had a significantly shortened survival compared to those with EGFRvIII gain. PD-L1 increase at progression was also associated with worse prognosis, portending immune escape. We thus identified the key drivers of meningioma progression, which can be exploited for personalized treatments.

Spinal atypical meningiomas are rare, and those whose main extension is in the epidural space are anecdotal. Here, we report a case of a young woman presenting with sensory disturbances and a radiological diagnosis of a dorsal epidural sleeve-like mass. The surgical resection of the lesion allowed the decompression of the spinal cord and led to the histopathological diagnosis of atypical meningioma. At the 3-month follow-up, her neurological recovery was complete. Because of the gross total removal of the lesion, adjuvant radiotherapy was not performed: At the 2-year follow-up, no recurrence of disease was detected. A comprehensive literature review was performed, and just two more case reports on epidural atypical meningiomas were found in the English literature. Through this case report and literature review, we described a rare manifestation of spinal meningioma that entered into a differential diagnosis for extradural spinal lesions, such as secondary malignancies., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Microvascular Doppler (MicroV) is a new-generation Doppler technique developed by Esaote (Esaote s.p.a., Genova, Italy), which is able to visualize small and low-flow vessels through a suppression of interfering signals. MicroV uses advanced filters that are able to differentiate tissue artifacts from low-speed blood flows; by exploiting the space-time coherence information, these filters can selectively suppress tissue components, preserving the signal coming from the microvascular flow. This technique is clinically applied to the study of the vascularization of parenchymatous lesions, often with better diagnostic accuracy than color/power Doppler techniques. The aim of this paper is to develop a reproducible protocol for the recording and collection of MicroV intraoperative ultrasound images by the use of a capable intraoperative ultrasound machine and post-processing aimed at evaluation of brain-tumor microvascularization through the analysis of radiomic features. The proposed protocol has been internally validated on eight patients and will be firstly applied to patients affected by WHO grade IV astrocytoma (glioblastoma-GBM) candidates for craniotomy and lesion removal. In a further stage, it will be generally applied to patients with primary or metastatic brain tumors. IOUS is performed before durotomy. Tumor microvascularization is evaluated using the MicroV Doppler technique and IOUS images are recorded, stored, and post-processed. IOUS images are remotely stored on the BraTIoUS database, which will promote international cooperation and multicentric analysis. Processed images and texture radiomic features are analyzed post-operatively using ImageJ, a free scientific image-analysis software based on the Sun-Java platform. Post-processing protocol is further described in-depth. The study of tumor microvascularization through advanced IOUS techniques such as MicroV could represent, in the future, a non-invasive and real-time method for intraoperative predictive evaluation of the tumor features. This evaluation could finally result in a deeper knowledge of brain-tumor behavior and in the on-going adaptation of the surgery with the improvement of surgical outcomes.

Meningiomas are mostly benign tumors that, at times, can behave aggressively, displaying recurrence despite gross-total resection (GTR) and progression to overt malignancy. Such cases represent a clinical challenge, particularly because they are difficult to recognize at first diagnosis. SOX2 (Sex-determining region Y-box2) is a transcription factor with a key role in stem cell maintenance and has been associated with tumorigenesis in a variety of cancers. The purpose of the present work was to dissect the role of SOX2 in predicting the aggressiveness of meningioma. We analyzed progressive/recurrent WHO grade 1−2 meningiomas and WHO grade 3 meningiomas; as controls, non-recurring WHO grade 1 and grade 2 meningioma patients were enrolled. SOX2 expression was evaluated using both immunohistochemistry (IHC) and RT-PCR. The final analysis included 87 patients. IHC was able to reliably assess SOX2 expression, as shown by the good correlation with mRNA levels (Spearman R = 0.0398, p = 0.001, AUC 0.87). SOX2 expression was an intrinsic characteristic of any single tumor and did not change following recurrence or progression. Importantly, SOX2 expression at first surgery was strongly related to meningioma clinical behavior, histological grade and risk of recurrence. Finally, survival data suggest a prognostic role of SOX2 expression in the whole series, both for overall and for recurrence-free survival (p < 0.0001 and p = 0.0001, respectively). Thus, SOX2 assessment could be of great help to clinicians in informing adjuvant treatments during follow-up.

Background: Trans-sphenoidal endoscopic surgery has drawn huge benefits from advances in surgical visualization. The Ultra-HD "4K" endoscope has improved 4-fold image resolution compared with HD, but its actual advantages are unclear. Aim of the present study was to assess its usefulness in the early outcome of trans-sphenoidal surgery., Methods: We analyzed a series of 199 trans-sphenoidal pituitary adenoma procedures performed by an experienced team using alternatively HD (N.=102) or 4K (N.=97) endoscopes. We evaluated extent of resection both subjectively, based on intraoperative surgeon's impression, and objectively based on postoperative MR scan., Results: Baseline patients' characteristics were balanced. Objective near-total and total resection rates were comparable between 4K and HD groups (91.5% vs. 86.3% and 64.9% vs. 56.9%, respectively). 4K endoscope slightly improved resection rate in recurrent adenoma. At multivariate analysis, the only independent prognosticator of total resection was cavernous sinus invasion. Importantly, 4K endoscope enhanced the reliability of intraoperative judgement on extent of resection, significantly reducing unexpected residuals (12.8% vs. 33.3% for HD). Operative features and clinical outcomes were similar., Conclusions: The HD endoscope remains the standard-of-care for pituitary surgery. The 4K enhanced, "immersive" visualization significantly improved the reliability of surgeon's judgment on resection and might be useful in surgically difficult cases.

Magnetic resonance imaging is considered the most accurate examination to study the spinal cord. Nevertheless, the use of diffusion tensor imaging (DTI) can demonstrate additional key details about spinal cord lesions. We examined the literature to investigate and discuss the role, limitations, and possible evolution as a prognostic tool of DTI in spinal cord injury (SCI). For this systematic literature review, a detailed search was performed using PubMed (2005-2021), Cochrane Database of Systematic Reviews (2016-2021), and Cochrane Central Register of Controlled Trials (2016-2021). To be included, studies had to report the use of DTI in SCIs, its clinical relevance, and its use as a prognostic tool. We identified 17 studies comprising 299 patients. The mean age of patients was 41.22 ± 10.62 years. There was a prevalence of males (70.9%) compared with females (29.1%). The main spinal cord tract involved and studied in SCIs was the cervical tract (57.5%), followed by conus terminalis (15.4%) and dorsal tract (13.7%). In all studies based on American Spine Injury Association impairment scale score for neurological assessment, a correlation was found between FA values and American Spine Injury Association impairment scale: patients with complete SCI had a statistically significative lower FA value at the injured site compared with patients with incomplete SCI. Published clinical studies showed promising results for the utility of DTI parameters as noninvasive biomarkers in SCI grade evaluation, remaining an evolving area of further investigation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The ischemia/reperfusion mechanism is believed to be responsible for parenchymal damage caused by temporary hypoperfusion and worsened by the subsequent attempt of reperfusion. This represents a true challenge for physicians of several fields, including neurosurgeons. A limited number of papers have shed the light on a rare pathologic condition that affects patients experiencing an unexplained neurologic deficit after spine surgery, the so-called "white cord syndrome." This entity is believed to be caused by an "ischemia/reperfusion" injury on the spinal cord, documented by a postoperative intramedullary hyperintensity on T2-weighted magnetic resonance imaging sequences. To date, the cases of white cord syndrome reported in literature mostly refer to cervical spine surgery. However, the analysis of several reviews focusing on spine surgery outcome suggests postoperative neurologic deficits of new onset could be charged to a mechanism of ischemia/reperfusion, even if the physiopathology of this event is seldom explored or at least discussed. The same neuroradiologic finding can suggest mechanical damage due to inappropriate surgical manipulation. On this purpose, we performed a systematic review of the literature with the aim to identify and analyze all the factors potentially contributing to ischemic/reperfusion damage of the spinal cord that may potentially complicate any spinal surgery, without distinction between cervical or thoracic segments. Finally, we believe that postoperative neurologic deficit after spinal surgery constituting the "white cord syndrome" could be under-reported; both neurosurgeons and patients should be fully aware of this rare but potentially devasting complication burdening cervical and thoracic spine surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background : In recent decades, the application of machine learning technologies to medical imaging has opened up new perspectives in neuro-oncology, in the so-called radiomics field. Radiomics offer new insight into glioma, aiding in clinical decision-making and patients' prognosis evaluation. Although meningiomas represent the most common primary CNS tumor and the majority of them are benign and slow-growing tumors, a minor part of them show a more aggressive behavior with an increased proliferation rate and a tendency to recur. Therefore, their treatment may represent a challenge. Methods: According to PRISMA guidelines, a systematic literature review was performed. We included selected articles (meta-analysis, review, retrospective study, and case-control study) concerning the application of radiomics method in the preoperative diagnostic and prognostic algorithm, and planning for intracranial meningiomas. We also analyzed the contribution of radiomics in differentiating meningiomas from other CNS tumors with similar radiological features. Results: In the first research stage, 273 papers were identified. After a careful screening according to inclusion/exclusion criteria, 39 articles were included in this systematic review. Conclusions: Several preoperative features have been identified to increase preoperative intracranial meningioma assessment for guiding decision-making processes. The development of valid and reliable non-invasive diagnostic and prognostic modalities could have a significant clinical impact on meningioma treatment.

Spine represents the most common site for metastatic disease involvement. Due to the close relationship between the spinal cord and critical structures, therapeutical management of metastatic spinal cord disease remains challenging. Spinal localization can lead to neurological sequelae, which can significantly affect the quality of life in patients with a limited life expectancy. The authors conducted a systematic literature review according to PRISMA guidelines in order to determine the impact of the most updated palliative care on spinal metastases. The initial literature search retrieved 2526 articles, manually screened based on detailed exclusion criteria. Finally, 65 studies met the inclusion criteria and were finally included in the systematic review. In the wide scenario of palliative care, nowadays, recent medical or surgical treatments represent valuable options for ameliorating pain and improving patients QoL in such this condition.

Gliomas, particularly high-grade gliomas, represent the most common and aggressive tumors of the CNS and are still burdened by high mortality and a very poor prognosis, regardless of the type of therapy. Their diagnosis and monitoring rely on imaging techniques and direct biopsy of the pathological tissue; however, both procedures have inherent limitations. To address these limitations, liquid biopsies have been proposed in this field. They could represent an innovative tool that could help clinicians in the early diagnosis, monitoring, and prognosis of these tumors. Furthermore, the rapid development of next-generation sequencing (NGS) technologies has led to a significant reduction in sequencing cost, with improved accuracy, providing a molecular profile of cancer and leading to better survival results and less disease burden. This paper focuses on the current clinical application of liquid biopsy in the early diagnosis and prognosis of cancer, introduces NGS-related methods, reviews recent progress, and summarizes challenges and future perspectives.

Brain biopsy is the gold standard in order to establish the diagnosis of unresectable brain tumors. Few studies have investigated the long-term outcomes of biopsy patients. The aim of this single-institution-based study was to assess the concordance between radiological and histopathological diagnoses, and the long-term patient outcome. Ninety-three patients who underwent brain biopsy in the last 5 years were analyzed. We included patients treated with stereotactically guided needle, open, and neuroendoscopic biopsies. Most patients (86%) received needle biopsy. Gliomas and primary brain lymphomas comprised 88.2% of cases. The diagnostic yield was 95.7%. Serious complication and death rates were 3.2% and 2.1%, respectively. The concordance rate between radiological and histological diagnoses was 93%. Notably, the positive predictive value of radiological diagnosis of lymphoma was 100%. Biopsy allowed specific treatment in 72% of cases. Disease-related neurological worsening was the main reason that precluded adjuvant treatment. Adjuvant treatment, in turn, was the strongest prognostic factor, since the median overall survival was 11 months with vs. 2 months without treatment ( p = 0.0002). Finally, advanced molecular evaluations can be obtained on glioma biopsy specimens to provide integrated diagnoses and individually tailored treatments. We conclude that, despite the huge advances in imaging techniques, biopsy is required when an adjuvant treatment is recommended, particularly in gliomas.

The cranial window (CW) technique provides a simple and low-cost method to assess tumor angiogenesis in the brain. The CW combined with histology using selective markers for tumor and endothelial cells can allow a sensitive monitoring of novel antiangiogenesis therapies in preclinical models. The CW was established in cyclosporine immunosuppressed rats that were stereotactically grafted with fluorescent U87MG glioblastoma cells. One to 3 weeks after grafting, brain vasculature was visualized in vivo and assessed by immunofluorescence microscopy using antibodies against endothelial and smooth-muscle cells and blood brain barrier. At 1-2 weeks after grafting, the CW reliably detected the hypertrophy of venous-venous anastomoses and cortical veins. These structures increased highly significantly their pregrafting diameter. Arterialized veins and hemorrhages were seen by three weeks after grafting. Immunofluorescence microscopy showed significant branching and dilation of microvessels, particularly those surrounded by tumor cells. Mechanistically, these changes lead to loss of vascular resistance, increased venous outflow, and opening of venous-venous anastomoses on the cortical surface. Data from the present study, namely, the hypertrophy of cortical venous-venous anastomoses, microvessel branching, and dilation of the microvessels surrounded by tumor cells, indicate the power of this in vivo model for the sensitive monitoring of early tumor angiogenesis., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Quintino Giorgio D'Alessandris et al.)

Background: Safety and efficacy in surgical treatment of cerebral arteriovenous malformations (AVMs) are dictated by thorough understanding of angioarchitectural features, intraoperative identification of feeding vessels, and appreciation of surrounding eloquent areas. Our aim was to describe the preliminary results of combined application of color Doppler ultrasound (CDUS) and contrast-enhanced ultrasound (CEUS) in a consecutive surgical series of AVM. We pointed out the tool's efficacy in distinguishing feeding from bystander vessels and in identifying pattern of venous drainage. We examined its role as an adjunct for semiquantitative evaluation of the nidus inflow., Methods: We used combined CDUS and CEUS in patients surgically treated for cerebral AVMs. We adopted these techniques following a designed protocol to guide safer AVM resection as an adjunct to indocyanine green videoangiography. Intraoperative assessment by ultrasound was performed before, during, and following nidus resection., Results: Four surgically treated cerebral AVMs availed of the ultrasound protocol. Postoperative conventional angiography showed complete resection of the AVMs. CDUS and CEUS proved to be valuable adjunctive tools to indocyanine green videoangiography and micro-Doppler in properly navigating and discerning vascular structures, especially vessel feeders from bystanders. The protocol allows us to identify flow direction, estimate blood velocity within the nidus, and appreciate flow modifications following temporary clipping. Ultimately, it allows us to evaluate the degree of nidus deafferentation, residual flow, restoration of venous drainage and absence of arteriovenous shunts., Conclusions: The CDUS and CEUS protocol is safe and repeatable and works as real-time imaging, further supporting complete surgical resection of AVMs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In our institution, standard pterional craniotomy (PC) with an extended Sylvian fissure opening (ESFO) represented the standard approach for unruptured middle cerebral artery (MCA) aneurysm clipping until 2014, when we progressively started to prefer minipterional craniotomy (MPC) associated with a focused Sylvian fissure opening (FSFO). In the present study, we compared our results in terms of the efficacy of clipping and the rate of complications with these 2 different techniques., Methods: We included patients with small- and medium-size unruptured MCA aneurysms from January 2008 to December 2018 with follow-up of >12 months. The clinical and radiologic data were reviewed from the medical records. The outcomes were measured in terms of efficacy (aneurysmal exclusion rate) and safety (intracranial complication rate)., Results: Overall, 134 patients who had presented with unruptured MCA aneurysms <1.5 cm were treated at our institution from January 2007 to December 2018: PC and ESFO were used in 73 patients and MPC and FSFO in 61. The demographics and angioarchitectural features were comparable between the 2 groups, except for age, which was older in the FSFO group. The aneurysm exclusion rate was not different between the 2 groups. The intracranial complication rate was, overall, significantly lower in the FSFO group (P < 0.001), especially for the rate of postoperative seizures. Finally, the FSFO group had had shorter postoperative hospitalization and better short- and long-term clinical outcomes., Conclusions: The association between MPC and FSFO should represent the standard of treatment of unruptured MCA aneurysms in all referral cerebrovascular centers, allowing for the achievement of the same efficacy of standard PC with ESFO and minimizing the complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Contrast-enhanced ultrasound (CEUS) is a real-time, feasible technique. Both intraoperatively and bedside, it satisfies the need for serial assessment and easy performability. Initially employed in neuro-oncology, it has recently overcome this first application. We aimed to evaluate the literature and give a comprehensive view of its use in the fields listed below. A systematic review of all pertinent literature was performed via PubMed access according PRISMA P guidelines. Studies not involving human adults and not reporting original data were excluded. Cross-check of references of selected articles was performed to complete bibliographical research. 67 articles were then grouped by field of application: Oncology (26 articles) further subdivided in a) cranial tumors (23 articles) and b) spinal tumors (3 articles); Vascular (31 articles), divided in three sections: a) aneurysms, AVMs and AVFs surgery (6 articles), b) cerebral perfusion assessment and acute stroke patients management (15 articles), c) carotid plaques treatment (10 articles); TBI (2 articles); Pediatrics (4 articles); Peripheral nerve surgery (2 articles) and others (2 articles). CEUS versatility across the aforementioned areas was analyzed, underlining its complementarity to other well-settled imaging techniques. This review is focused on reporting CEUS advantages and disadvantages, suggesting a further broadening of the already numerous applications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The use of adjuvant radiotherapy is controversial in patients with atypical meningiomas treated with gross total resection (GTR). This study aimed to determine whether clinico-pathological features could be helpful to predict the recurrence risk in this group of patients and to identify high-risk ones who could benefit from adjuvant treatment. We collected 200 patients with primary atypical meningiomas treated with GTR but with no adjuvant radiotherapy from 5 different centers. A risk score, formulated by assigning 1 point for the presence and 0 points for the absence of 5 high-risk parameters (male sex, parasagittal site, Simpson grade 3, mitotic index ≥ 6/10 HPF, and sheeting), was the most significant predictor of recurrence. A score ≥2 was associated with 4.7 risk of shorter disease-free survival (p < 0.0001). Our findings indicate that the presence of at least 2 clinico-pathological high-risk factors predicts recurrence of totally resected primary atypical meningiomas and could be helpful for identifying patients who could benefit from adjuvant radiotherapy., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)