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Abstract 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.

Abstract Since the dawn of antiquity, scientists, philosophers, and artists have pondered the nature of optical stereopsis—the perception of depth that arises from binocular vision. The early 19th century saw the advent of stereoscopes, devices that could replicate stereopsis by producing a 3D illusion from the super-imposition of 2D photographs. This phenomenon opened up a plethora of possibilities through its usefulness as an educational tool—particularly in medicine. Before long, photographers, anatomists, and physicians were collaborating to create some of the first stereoscopic atlases available for the teaching of medical students and residents. In fields like neurosurgery—where a comprehensive visuospatial understanding of neuro-anatomical correlates is crucial—research into stereoscopic modalities are of fundamental importance. Already, medical institutions all over the world are capitalizing on new and immersive technologies—such as 3D intraoperative recording, and 3D endoscopes—to refine their pedagogical efforts as well as improve their clinical capacities. The present paper surveys the history of stereoscopy from antiquity to the modern era—with a focus on its role in neurosurgery and medical education. Through the tracking of this evolution, we can discuss potential benefits, future directions, and highlight areas in which further research is needed. By anticipating these factors, we may strive to take full advantage of an emergent field of technology, for our ultimate goal of improving patient care.

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.

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.

Abstract Arteriovenous malformations (AVMs) of the trigeminal root entry zone are rare and can be associated with neurovascular compression syndromes as well as intracranial hemorrhage.1 They generally have a small nidus located on and around the pial surface of the brainstem; thus, they are feasible for surgery. Nevertheless, they represent a challenge given the vicinity and involvement of cranial nerves and brainstem perforators.2–4 This video demonstrates the case of a 57-yr-old man with new onset of a severe headache without neurological deficit associated with MRI evidence of a vascular malformation around the cisternal right trigeminal nerve. The nerve showed an altered signal on the MRI. Angiography revealed a Spetzler–Martin grade II AVM with a 16-mm nidus supplied by basilar artery perforators, right anterior inferior cerebellar artery, and the superior cerebellar artery (SCA), with drainage into the superior petrosal vein and sigmoid sinus. After an unsuccessful attempted embolization, the patient was referred for and elected microsurgical treatment. With the patient in a lateral position, a right retrosigmoid approach was performed. After cisternal dissection and identification of the nidus, the feeders were occluded by alternating cauterization and clipping to avoid damage to the critical surrounding structures. The AVM in-situ occlusion was carried on without resection, given the involvement of the trigeminal nerve. The intraoperative indocyanine green angiography allowed recognition of the venous drainage and helped to localize and differentiate the feeders from normal perforators. In the immediate postoperative course, the patient suffered from mild numbness with a V2-V3 distribution that progressively improved. Angiography showed no residual AVM.

Abstract Dural arteriovenous fistulas (dAVFs) are acquired dural shunts between an artery and a vein without parenchymal nidus. DAVFs represent 10%-15% of intracranial arteriovenous malformations, and their manifestations vary from asymptomatic to devastating intracranial hemorrhage.1 They are classified according to their drainage and presence/absence of cortical venous reflux (CVR).2,3 The junction between transverse and sigmoid sinus (SS) is the most common location, and their treatment in case of CVR can involve the sacrifice of the sinus. DAVF occlusion may be achieved with both endovascular and surgical technique and frequently with combined techniques. This video demonstrates the management of a left dAVF of the SS in a 54-yr-old male with recent onset of diplopia and imbalance with venous congestion seen in the left cerebellum on T2 sequence MRI. Angiography revealed a Borden grade 2, Cognard grade IIa + b left SS dAVF supplied by the jugular and hypoglossal branches of the neuromeningeal trunk with retrograde filling of the partially thrombosed SS and drainage to the superior petrosal sinus and multiple cerebellar veins. Endovascular repair was not feasible due to high risk of postoperative cranial neuropathy. The patient consented to surgery. A left retrosigmoid craniotomy was performed to achieve intradural ligation of the fistula at the dural edge along the inferior aspect of the tentorium. After drainage occlusion and cauterization of the transmastoid extradural feeders (via mastoidectomy), the SS was entirely exposed and clipped to prevent any further retrograde arteriovenous shunting. The postoperative course was without complication and angiography showed complete occlusion of the dAVF.

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.

Observations in people with cerebral cavernous malformations, and in preclinical models of this disorder, suggest that the β-blocker propranolol might reduce the risk of intracerebral haemorrhage. We aimed to evaluate the safety and efficacy of prolonged treatment with propranolol to reduce the incidence of symptomatic intracerebral haemorrhage or focal neurological deficit in people with familial cerebral cavernous malformations. We conducted a randomised, open-label, blinded-endpoint, phase 2 pilot trial (Treat_CCM) at six national reference centres for rare diseases in Italy. People aged 18 years or older with symptomatic familial cerebral cavernous malformation were eligible for enrolment. Participants were randomly assigned (2:1) to receive either oral propranolol (20–320 mg daily) plus standard care (intervention group), or standard care alone (control group), for 24 months. Participants, caregivers, and investigators were aware of treatment group assignment. Participants had clinical assessments and 3 T brain MRI at baseline and at 12 and 24 months. The primary outcome was new occurrence of symptomatic intracerebral haemorrhage or focal neurological deficit attributable to cerebral cavernous malformation over 24 months. Outcome assessors were masked to treatment group assignment. The primary analysis was done in the intention-to-treat population. Because of the pilot study design, we chose a one-sided 80% CI, which could either exclude a clinically meaningful effect or show a signal of efficacy. This trial is registered with EudraCT, 2017-003595-30, and ClinicalTrials.gov, NCT03589014, and is closed to recruitment. Between April 11, 2018, and Dec 5, 2019, 95 people were assessed for eligibility and 83 were enrolled, of whom 57 were assigned to the propranolol plus standard care group and 26 to the standard care alone group. The mean age of participants was 46 years (SD 15); 48 (58%) were female and 35 (42%) were male. The incidence of symptomatic intracerebral haemorrhage or focal neurological deficit was 1·7 (95% CI 1·4–2·0) cases per 100 person-years (two [4%] of 57 participants) in the propranolol plus standard care group and 3·9 (3·1–4·7) per 100 person-years (two [8%] of 26) in the standard care alone group (univariable hazard ratio [HR] 0·43, 80% CI 0·18–0·98). The univariable HR showed a signal of efficacy, according to predefined criteria. The incidence of hospitalisation did not differ between groups (8·2 cases [95% CI 7·5–8·9] per 100 person-years in the propranolol plus standard care group vs 8·2 [95% CI 7·1–9·3] per 100 person-years in the standard care alone group). One participant in the standard care alone group died of sepsis. Three participants in the propranolol plus standard care group discontinued propranolol due to side-effects (two reported hypotension and one reported weakness). Propranolol was safe and well tolerated in this population. Propranolol might be beneficial for reducing the incidence of clinical events in people with symptomatic familial cerebral cavernous malformations, although this trial was not designed to be adequately powered to investigate efficacy. A definitive phase 3 trial of propranolol in people with symptomatic familial cerebral cavernous malformations is justified. Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro, Swedish Science Council, Knut and Alice Wallenberg Foundation, CARIPLO Foundation, Italian Ministry of Health.

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.