To use or not to use antithrombotics in unruptured cerebrovascular malformations? A systematic review focusing on this clinical and surgical dilemma.

OBJECTIVE: Antithrombotic medications (ATMs), including antiplatelet therapy (APT) and oral anticoagulants (OACs), are widely used in current clinical practice for the prevention and treatment of a variety of cardiovascular diseases, deep vein thrombosis, and pulmonary thromboembolisms. The long-term usage of these drugs, associated with an inherent risk of bleeding, raises concerns for unruptured cerebrovascular malformations (UCVMs), such as arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms (IAs), in which the bleeding risk also poses a major threat. The aim of this study was to assess the safety and risk-benefit ratio of ATMs in these various neurosurgical diseases and to give neurosurgeons a safe and reasonable choice regarding whether to administer ATMs to these patients during the course of the disease. METHODS: The authors conducted a systematic review of the literature (PubMed/MEDLINE and Embase) according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines, which yielded 4 papers about CCMs, 2 about AVMs, and 9 about IAs. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: For AVMs, only 2 studies with a total of only 14 patients were included. Data on AVMs and ATMs are limited and weak, relying on small case series. Nevertheless, there is no evidence for either an increased risk of intracranial hemorrhage in patients with AVMs who are receiving ATMS or the need to interrupt ATMs in those patients who have been diagnosed with sporadic, unruptured brain AVMs. With respect to CCMs, the literature search resulted in 4 cohort studies and 1 meta-analysis. These studies affirmed the absence of a correlation between ATMs and an increased risk of CCM bleeding while simultaneously suggesting a protective role of ATMs against bleeding. Concerning IAs, the topic is more complex and debated, despite larger case series on IAs than on AVMs or CCMs. The benefits of ATMs for IAs may vary according to the type of intervention and specific drug administered. Evidence supports the continuation of long-term APT for all patients newly diagnosed with an IA, whereas starting APT in patients with incidentally discovered IA as a means of prophylaxis against rupture is unclear. CONCLUSIONS: The findings of this review should be taken as a wide overview of UCVM and ATM. Future research should consider the relationship of AVM, CCM, and IA with APT and OAC independently.

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

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

Useful outcome measures in INPH patients evaluation.

Introduction: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder that is potentially reversible and clinically characterized by a specific triad of symptoms, including gait disturbance, cognitive disorders, and urinary incontinence. In INPH assessment, the most commonly used test is the Timed Up and Go test (TUG), but a more comprehensive assessment would be necessary. The first aim of the present study is to verify the sensitivity of a protocol with both clinical and instrumental outcome measures for gait and balance in recognizing INPH patients. The second aim is to verify the most important spatio-temporal parameters in INPH assessment and their possible correlations with clinical outcome measures. Methods: Between January 2019 and June 2022, we evaluated 70 INPH subjects. We assessed balance performances with the Berg Balance Scale (BBS), Short Physical Performance Battery (SPPB), and TUG, both single (ST) and dual task (DT). We also performed an instrumental gait assessment with the GAITRite electronic walkway system, asking the patients to walk on the carpet for one minute at normal speed, fast speed, and while performing a dual task. We compared the results with those of 20 age-matched healthy subjects (HS). Results: INPH patients obtained statistically significant lower scores at the BBS, SPPB, and TUG DT but not at the TUG ST, likely because the DT involves cognitive factors altered in these subjects. Concerning instrumental gait evaluation, we found significant differences between HS and INPH patients in almost all spatio-temporal parameters except cadence, which is considered a relevant factor in INPH guidelines. We also found significant correlations between balance outcome measures and gait parameters. Discussion: Our results confirm the usefulness of BBS and suggest improving the assessment with SPPB. Although the TUG ST is the most commonly used test in the literature to evaluate INPH performances, it does not identify INPH; the TUG DT, instead, might be more useful. The GAITRite system is recognized as a quick and reliable tool to assess walking abilities and spatio-temporal parameters in INPH patients, and the most useful parameters are stride length, stride width, speed, and the percentage of double support. Both clinical and instrumental evaluation may be useful in recognizing subjects at risk for falls.

Stem-like signatures in human meningioma cells are under the control of CXCL11/CXCL12 chemokine activity.

BACKGROUND: Meningiomas are mainly benign brain tumors, although about 20% of histologically benign cases are clinically aggressive and recur after resection. We hypothesize that meningioma brain invasiveness and recurrence may be related to the presence of cancer stem cells and their high responsiveness to the CXCL12-CXCR4/CXCR7 chemokine axis. The aim of this study was to isolate meningioma stem cells from human samples, characterize them for biological features related to malignant behavior, and to identify the role of CXCR4/CXCR7 in these processes. METHODS: Meningioma stem cells were isolated from patient-derived primary cultures in stem cell-permissive conditions, and characterized for phenotype, self-renewal, proliferation and migration rates, vasculogenic mimicry (VM), and in vivo tumorigenesis, in comparison with differentiated meningioma cells and stem-like cells isolated from normal meninges. These cell populations were challenged with CXCL12 and CXCL11 and receptor antagonists to define the chemokine role in stem cell-related functions. RESULTS: Stem-like cells isolated from meningioma cultures display higher proliferation and migration rates, and VM, as compared to meningioma non-stem cells or cells isolated from normal meninges and were the only tumorigenic population in vivo. In meningioma cells, these stem-like functions were under the control of the CXCR4/CXCR7 chemokine axis. CONCLUSIONS: We report a role for CXCL11 and CXCL12 in the control of malignant features in stem-like cells isolated from human meningioma, providing a possible basis for the aggressive clinical behavior observed in subsets of these tumors. CXCR4/CXCR7 antagonists might represent a useful approach for meningioma at high risk of recurrence and malignant progression.

A Novel Patient-Personalized Nanovector Based on Homotypic Recognition and Magnetic Hyperthermia for an Efficient Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the deadliest brain tumor, characterized by an extreme genotypic and phenotypic variability, besides a high infiltrative nature in healthy tissues. Apart from very invasive surgical procedures, to date, there are no effective treatments, and life expectancy is very limited. In this work, an innovative therapeutic approach based on lipid-based magnetic nanovectors is proposed, owning a dual therapeutic function: chemotherapy, thanks to an antineoplastic drug (regorafenib) loaded in the core, and localized magnetic hyperthermia, thanks to the presence of iron oxide nanoparticles, remotely activated by an alternating magnetic field. The drug is selected based on ad hoc patient-specific screenings; moreover, the nanovector is decorated with cell membranes derived from patients' cells, aiming at increasing homotypic and personalized targeting. It is demonstrated that this functionalization not only enhances the selectivity of the nanovectors toward patient-derived GBM cells, but also their blood-brain barrier in vitro crossing ability. The localized magnetic hyperthermia induces both thermal and oxidative intracellular stress that lead to lysosomal membrane permeabilization and to the release of proteolytic enzymes into the cytosol. Collected results show that hyperthermia and chemotherapy work in synergy to reduce GBM cell invasion properties, to induce intracellular damage and, eventually, to prompt cellular death.

Radiofrequency Ablation in Vertebral Body Metastasis with and without Percutaneous Cement Augmentation: A Systematic Review Addressing the Need for SPINE Stability Evaluation.

Vertebral body metastases (VBM) are one of the most frequent sites of bone metastasis, and their adequate therapeutic management still represents an insidious challenge for both oncologists and surgeons. A possible alternative treatment for VBM is radiofrequency ablation (RFA), a percutaneous technique in which an alternating current is delivered to the tumor lesion producing local heating and consequent necrosis. However, RFA alone could alter the biomechanics and microanatomy of the vertebral body, thus increasing the risk of post-procedure vertebral fractures and spine instability, and indeed the aim of the present study is to investigate the effects of RFA on spine stability. A systematic review according to PRISMA-P guidelines was performed, and 17 papers were selected for the systematic review. The results show how RFA is an effective, safe, and feasible alternative to conventional radiotherapy for the treatment of VBM without indication for surgery, but spine stability is a major issue in this context. Although exerting undeniable benefits on pain control and local tumor recurrence, RFA alone increases the risk of spine instability and consequent vertebral body fractures and collapses. Concomitant safe and feasible therapeutic strategies such as percutaneous vertebroplasty and kyphoplasty have shown synergic positive effects on back pain and improvement in spine stability.

Practical Algorithm for the Management of Multisutural Craniosynostosis with Associated Chiari Malformation and/or Hydrocephalus.

INTRODUCTION: The association between multisutural craniosynostosis with Chiari malformation (CM), venous hypertension, and hydrocephalus is widely described in the literature, especially in children with paediatric craniofacial syndromes. Some efforts have been done in the last years to understand the complex pathogenetic mechanisms underlying this association, and several theories have been proposed. In particular, it is now accepted that the hypothesis of the overcrowding of the posterior fossa due to precocious suture fusion is the cause of the cerebellar herniation in syndromic and non-syndromic patients, against the theory of intrinsic cerebellar anomalies, ventriculomegaly, and venous hypertension. However, whatever the pathophysiological mechanism, it is still unclear what the best management and treatment of CM and hydrocephalus are in multisutural craniosynostosis patients. The aim of this study was to report our 25 years' experience in treating paediatric patients affected by these rare pathologies in order to propose a simple and effective therapeutic flow chart for their management. MATERIALS AND METHODS: We retrospectively collected data of each patient who underwent a cranial vault remodelling (CVR) for complex multisutural craniosynostosis in our institution in the last 25 years, while monosutural craniosynostosis was excluded. We recorded data concerning type of craniosynostosis and craniofacial syndromes, presence of ventriculomegaly, and CM at presentation and clinical and radiological follow-up. Therefore, we evaluated the final outcomes (improved, stable, deteriorated) of these patients and created a practical flow chart that could help physicians choose the best surgical treatment when different pathological conditions, as Chiari malformation I (CMI) or hydrocephalus, affect complex craniosynostosis children. RESULTS: Thirty-nine patients (39 out of 55; 70.9%), with an isolated multisutural craniosynostosis at presentation, underwent a two-step CVR as first surgery; 36 patients (92.3%) had an improved outcome, 2 patients (5.1%) had a stable outcome, and 1 patient (2.56%) had a deteriorated outcome. Other eight children (8 out of 55; 14.5%) had a radiological evidence of asymptomatic CMI at presentation. In this group, we performed CVR as first surgery. As for the final outcome, 7 patients had an improved outcome (87.5%) with good aesthetic result and stability or resolution of CMI. Finally, 7 patients (7 out of 55; 12.7%) presented a various combination of CMI and ventriculomegaly or hydrocephalus at presentation. Among them, 3 patients had an improved outcome (42.8%), and 4 patients had a deteriorated outcome (57.1%). DISCUSSION: The prevalence of one pathological condition with associated symptoms over the others was the key factor leading our therapeutic strategy. When craniosynostosis is associated with a radiological CM, the assessment of clinical symptoms is of capital importance. When asymptomatic or pauci-symptomatic, we suggest a CVR as first step, for its efficacy in reducing tonsillar herniation and solving CM symptoms. When craniosynostosis is associated with ventricular enlargement, the presence of intracranial hypertension signs and symptoms forces physicians to first treat hydrocephalus with a ventriculo-peritoneal shunt or endoscopic third ventriculostomy. For patients with various degrees and severity of ventriculomegaly and associated CM, the outcomes were very heterogeneous, even when the same therapeutic strategy was applied to patients with similar starting conditions and symptoms. This is maybe the most unexpected and least clear part of our results. Despite the proposed algorithm comes from a clinical experience on 85% successfully treated patients with multiple craniosynostosis, more extensive and deep studies are needed to better understand CM and hydrocephalus development in such conditions.

Anticoagulant therapy in high grade gliomas: a systematic review on state of the art and future perspectives.

INTRODUCTION: Anticoagulation management in high-grade gliomas is a widely studied but still debated topic, since the increased thrombotic risk is accompanied by the high background rate of intralesional bleeding. Currently, the main challenge when prescribing anticoagulants to HGG patients is to balance the risk between ICH and VTE both in the perioperative period and in the postoperative follow-up during adjuvant chemo- and radiotherapic treatment. EVIDENCE ACQUISITION: A systematic review according to PRISMA-P Guidelines was performed: 12 observational studies were selected, eight retrospective and four prospective. Regarding the reviews 3 were selected, two of which analyzed bleeding complications of anticoagulation therapy and one on thrombotic events. EVIDENCE SYNTHESIS: In the selected studies, the risk of VTEs was between 4 and 33%, while in patients with VTEs subsequently subjected to anticoagulant therapy the cases of ICH ranged from 0% to 15.4%. Regarding the reviews, two meta-analyses have evaluated the incidence of ICH in patients undergoing anticoagulation therapy following thromboembolic events, they agree in quantifying the increased risk of bleeding. CONCLUSIONS: The results of our review are generally consistent in stating that the thrombotic risk is increased in patients with HGG, suggesting that more extensive antithrombotic prophylaxis could positively impact the outcome of these patients, even if currently there are no conclusive elements in indicating or contraindicating prolonged antithrombotic prophylaxis - considering that anticoagulant administration in these patients involves an increased risk of ICH. All the studies examined have considered a prolonged heparin treatment without considering the new oral anticoagulants, so further studies about this topic are needed.

Long-term functional recovery in C5-C6 avulsions treated with distal nerve transfers.

BACKGROUND: In patients suffering from traction lesions of the brachial plexus, complete C5 and/or C6 root avulsion patients with C7 root preservation are relatively uncommon occurrences, but represent excellent candidates for surgical treatment, with satisfactory results. Shoulder abduction and extra-rotation, elbow flexion and forearm supination are lost functions restorable with surgical treatment. METHODS: This single-center, prospective observational study involved a series of 27 young adults with C5 and/or C6 root complete avulsion and C7 preservation, which underwent surgical repair with double or triple nerve transfer. RESULTS: Patients recovered a useful elbow flexion. Electromyographic and clinical signs of biceps reinnervation were observed in each UN-MC nerve transfer. The abduction strength recovery was M5 in 10 patients, M4 in 14 patients and M3 in 3 patients. The external rotation strength recovery was M5 in 4 patients, M4 in 18 patients, M3 in 3 patients and M2 in 2 patients. The elbow flection strength was M5 in 5 patients, M4 in 15 patients and M3 in 7 patients. Elbow extension was preserved in all cases. CONCLUSIONS: The concept of 'peripheral rewiring procedures' represents an advance in the repair of the peripheral nerve injuries. Triple nerve transfer can be nowadays considered a standard treatment for isolated C5-C6 avulsions. We report our experience with the second-biggest casuistry in the literature on patients treated with this technique. We consider our outcome concerning functional recovery to be satisfying and comparable to data reported in the literature.

De novo intracranial aneurysm formation in SARS-CoV-2 infection: first report of a yet unknown complication.

BACKGROUND AND IMPORTANCE: COVID-19 is a viral infection that mainly affects the respiratory tract, but can also cause multiple inflammatory reactions, including neurological and cerebrovascular manifestations. We report the case of a COVID-19 patient who developed 'de novo' multiple cerebral aneurysms with no risk factors for aneurysm formation. CLINICAL PRESENTATION: A 55-year-old man with SARS-CoV-2 infection came to our attention for left eye blindness accompanied by ptosis, palpebral chemosis and retro-orbital pain. Brain CT and CT-angiography were negative for hemorrhages and for vascular malformations. Repeated intracerebral hemorrhages and neurological deterioration then occurred, and a new CT-angiography showed multiple intracranial aneurysms that were not present before. CONCLUSION: Intracranial aneurysm formation as a complication of COVID-19 has not been previously reported. As other viral infections do, COVID-19 may be able to determine a vascular damage that can ultimately lead to development of an aneurysm. It is reasonable to hypothesize an involvement of the renin-angiotensin system as a pathogenic mechanism. A conservative therapy aiming at inflammatory modulation and vascular damage prevention may be warranted in these patients.

Turning tables: a war-like approach to neurosurgical emergencies in the COVID-19 era.

During the Coronavirus-disease-2019 (COVID-19) pandemic emergency, neurosurgeons may have to decide to prioritize treatments to patients with the best chance of survival, as in a war setting triage. In this paper, we discussed factors that should be considered in the perioperative period and neurocritical care management of neurosurgical patients during a pandemic emergency; in particular, we focused on the decision on whether to operate or not a patient during the COVID-19 pandemic. A multidisciplinary expert panel composed by specialists with direct experience in COVID-19 management discussed and reviewed the criteria that should be taken into account in the decision to operate or not a patient during the COVID-19 pandemic. Disease-related factors should be first considered in order to precisely know the enemy we are facing. Patient-related factors should be then evaluated to understand the battleground on which we are facing the enemy. After these considerations, we must ascertain costs and expected outcomes of our surgical intervention by evaluation of surgery-related factors. Finally, the last factor that need to be evaluated before surgery is the availability of resources, staff, and ward availability for perioperative care. All these considerations will lead to the optimal organization and management of neurosurgical emergencies during pandemic times, considering the community and not only the single patient. We provided schematic preoperative considerations that we hope will help neurosurgeons to guide their decisions in these challenging times.

Lymphoplasmacyte-rich meningioma with hematologic signs and PD-L1 over-expression.

Lymphoplasmacyte-rich meningioma (LPRM) is one of the rarest variants of grade I meningiomas. It can be clinically associated with prominent peripheral blood abnormalities, anemia, and/or various gammopathy, which usually disappear after surgical removal of the tumor. We document a case of right frontal LPRM in a 72-year-old male who presented general cognitive decadence. The patient suffered from mild anemia. The LPRM is a rare variant of meningioma, with only a few cases globally reported in the literature. It has been categorized as a grade I tumor in the 2021 World Health Organization (WHO) classification central nervous system. Due to the rarity, this meningioma variant origin and biological behavior are still not clear. Immunohistochemistry profile showed prominent PD-L1 expression, leading to additional interrogation on LPRM immunomorphological characteristics, the significance of the inflammatory tumoral microenvironment and its correlation with the immune-checkpoints.

Peculiar bony involvement of sinus pericranii in children: Extensive diploic erosion in three "karstic" variants.

OBJECT: Sinus pericranii (SP) is a rare, benign, extradural venous anomaly whose extracranial connection consists in an enlarged subgaleal drainage composed of a network of thin-walled veins that form a varix on the external table of the skull. In the present series of three patients we present three variantesof SP which have never been described, characterized by an extensive diploic erosion causing a "karstic" effect. METHODS: A systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A comprehensive search for relevant articles was performed on PubMed from 1992 to 2022 using the following search words: "sinus pericranii". RESULTS: The search produced 77 articles with 137 patients. In all the cases analysed, there were not reported any patients with extensive diploic erosion, namely "karstic" variants. So, the authors present clinical history, neuroimages, treatment strategies and outcome of 3 patients with a "karstic" SP with the aim to describe this clinicradiological entity. CONCLUSIONS: In this study, our group identified a peculiar variant of SP characterized by bony involvement with extensive diploic "karstic" erosion of diploe, with possible tendency to enlarge during time.

Mind the gap: IgG4-related disease mimicking infectious cerebral mass lesions.

BACKGROUND: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. CASE PRESENTATION: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. CONCLUSION: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.

Chloride intracellular channel 1 activity is not required for glioblastoma development but its inhibition dictates glioma stem cell responsivity to novel biguanide derivatives.

BACKGROUND: Chloride intracellular channel-1 (CLIC1) activity controls glioblastoma proliferation. Metformin exerts antitumor effects in glioblastoma stem cells (GSCs) inhibiting CLIC1 activity, but its low potency hampers its translation in clinical settings. METHODS: We synthesized a small library of novel biguanide-based compounds that were tested as antiproliferative agents for GSCs derived from human glioblastomas, in vitro using 2D and 3D cultures and in vivo in the zebrafish model. Compounds were compared to metformin for both potency and efficacy in the inhibition of GSC proliferation in vitro (MTT, Trypan blue exclusion assays, and EdU labeling) and in vivo (zebrafish model), migration (Boyden chamber assay), invasiveness (Matrigel invasion assay), self-renewal (spherogenesis assay), and CLIC1 activity (electrophysiology recordings), as well as for the absence of off-target toxicity (effects on normal stem cells and toxicity for zebrafish and chick embryos). RESULTS: We identified Q48 and Q54 as two novel CLIC1 blockers, characterized by higher antiproliferative potency than metformin in vitro, in both GSC 2D cultures and 3D spheroids. Q48 and Q54 also impaired GSC self-renewal, migration and invasion, and displayed low systemic in vivo toxicity. Q54 reduced in vivo proliferation of GSCs xenotransplanted in zebrafish hindbrain. Target specificity was confirmed by recombinant CLIC1 binding experiments using microscale thermophoresis approach. Finally, we characterized GSCs from GBMs spontaneously expressing low CLIC1 protein, demonstrating their ability to grow in vivo and to retain stem-like phenotype and functional features in vitro. In these GSCs, Q48 and Q54 displayed reduced potency and efficacy as antiproliferative agents as compared to high CLIC1-expressing tumors. However, in 3D cultures, metformin and Q48 (but not Q54) inhibited proliferation, which was dependent on the inhibition dihydrofolate reductase activity. CONCLUSIONS: These data highlight that, while CLIC1 is dispensable for the development of a subset of glioblastomas, it acts as a booster of proliferation in the majority of these tumors and its functional expression is required for biguanide antitumor class-effects. In particular, the biguanide-based derivatives Q48 and Q54, represent the leads to develop novel compounds endowed with better pharmacological profiles than metformin, to act as CLIC1-blockers for the treatment of CLIC1-expressing glioblastomas, in a precision medicine approach.

Effects of positive end-expiratory pressure on lung ultrasound patterns and their correlation with intracranial pressure in mechanically ventilated brain injured patients.

BACKGROUND: The effects of positive end-expiratory pressure (PEEP) on lung ultrasound (LUS) patterns, and their relationship with intracranial pressure (ICP) in brain injured patients have not been completely clarified. The primary aim of this study was to assess the effect of two levels of PEEP (5 and 15 cmH2O) on global (LUStot) and regional (anterior, lateral, and posterior areas) LUS scores and their correlation with changes of invasive ICP. Secondary aims included: the evaluation of the effect of PEEP on respiratory mechanics, arterial partial pressure of carbon dioxide (PaCO2) and hemodynamics; the correlation between changes in ICP and LUS as well as respiratory parameters; the identification of factors at baseline as potential predictors of ICP response to higher PEEP. METHODS: Prospective, observational study including adult mechanically ventilated patients with acute brain injury requiring invasive ICP. Total and regional LUS scores, ICP, respiratory mechanics, and arterial blood gases values were analyzed at PEEP 5 and 15 cmH2O. RESULTS: Thirty patients were included; 19 of them (63.3%) were male, with median age of 65 years [interquartile range (IQR) = 66.7-76.0]. PEEP from 5 to 15 cmH2O reduced LUS score in the posterior regions (LUSp, median value from 7 [5-8] to 4.5 [3.7-6], p = 0.002). Changes in ICP were significantly correlated with changes in LUStot (rho = 0.631, p = 0.0002), LUSp (rho = 0.663, p < 0.0001), respiratory system compliance (rho = - 0.599, p < 0.0001), mean arterial pressure (rho = - 0.833, p < 0.0001) and PaCO2 (rho = 0.819, p < 0.0001). Baseline LUStot score predicted the increase of ICP with PEEP. CONCLUSIONS: LUS-together with the evaluation of respiratory and clinical variables-can assist the clinicians in the bedside assessment and prediction of the effect of PEEP on ICP in patients with acute brain injury.

Oligodendroglioma with ganglioglioma-like maturation: the histopathological diagnostic challenge of a brain neoplasm with aberrant neuronal component - A case report and review of the literature.

Background: Oligodendroglioma with ganglioglioma-like maturation is a rare entity not included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. To date, only a few cases were described in the literature. We report a case of this tumor, along with a review of the previous case reports/ series. Case Description: A 63-year-old man with a left frontal mass and a 2-month history of seizures underwent surgical resection in our center. Grossly, the specimen appeared as a yellowish mass with prominent hemorrhagic component. Microscopically, the lesion was composed by small round cells often surrounded by a clear halo and, near the hemorrhagic area, by scattered large cuboidal cells with vesicular nuclei and prominent eosinophilic nucleoli. On immunohistochemical stains, both cells components tested positive for ATRX, p53, and GFAP; larger ganglion-like cells showed synaptophysin and chromogranin-A expression. IDH1 codon 132 mutation, 1p-19q-codeletion, and MGMT methylation were observed. Eventually, a diagnosis of oligodendroglioma (the WHO grade II) with ganglioglioma-like maturation was rendered. The patient received adjuvant chemotherapy and is currently alive and asymptomatic. Conclusion: Recognition of ganglioglioma-like maturation in oligodendrogliomas may prevent undertreatment of these neoplasms. To this end, fluorescence in situ hybridization assays are crucial for defining the 1p-19q status.

Cerebellar liponeurocytoma in an elderly patient: DNA methylation profiling as a helpful diagnostic tool.

AIM: Cerebellar liponeurocytoma is a rare primary cerebellar neoplasm that mostly occurs in adults, however, it is rare in the elderly. MATERIALS AND METHODS: We report, in a 79-year-old female, a recurrent vermian cerebellar mass that was previously diagnosed as primary cerebellar tumor with neuroendocrine differentiation. The recurrent lesion showed anaplastic features and lipidization. RESULTS: DNA methylation profiling was performed for the recurrent tumor, which showed a high score match for cerebellar liponeurocytoma. CONCLUSION: This report confirms the usefulness of DNA methylation profiling for the diagnosis of challenging CNS tumors.