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Object Preoperative image-based neuronavigation-assisted endoscopy during intracranial procedures is gaining great interest. This study aimed to analyze the precision of navigation-assisted endoscopy according to the navigation setup, the type of optic and its working angulation. Methods A custom-made box with four screws was referenced. The navigation-assisted endoscope was aligned on the screws (targets). The precision on the navigation screen was defined as the virtual distance-to-target between the tip of the endoscope and the center of the screws. Three modifiers were assessed: (1) the distance D between the box and the reference array (CLOSE 13 cm – MIDDLE 30 cm – FAR 53 cm), (2) the distance between the tip of the endoscope and the navigation array on the endoscope (close 5 cm – middle 10 cm – far 20 cm), (3) the working angulation of the endoscope (0°-endoscope and 30°-endoscope angled at 90° and 45° with the box). Results The median precision was 1.3 mm (Q1: 1.1; Q3: 1.7) with the best setting CLOSE/close. The best setting in surgical condition (CLOSE/far) showed a distance-to-target of 2.3 mm (Q1: 1.9; Q3: 2.5). The distance D was correlated to the precision (Spearman rho = 0.82), but not the distance d (Spearman rho = 0.04). The type of optic and its angulation with the box were also correlated to the precision (Spearman rho = − 0.37). The best setting was the use of a 30°-endoscope angled at 45° (1.4 mm (Q1: 1.0; Q3: 1.9)). Conclusion Navigated-assisted endoscopy is feasible and offers a good precision. The navigation setup should be optimized, reducing the risk of inadvertent perifocal damage.

Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the causal involvement of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a Local-Global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e.,between tones within sequences)and at a global (i.e.,between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) to local prediction violation, as well as a diminished and delayed MMN/P3a complex to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate fundamental impairments in detecting violation of auditory regularity at two hierarchical levels of stimuli abstraction.HighlightsOrbitofrontal lesions reduce auditory MMN (i.e., prediction error) to unpredicted stimuli at the local level.Orbitofrontal lesions reduce local and global level auditory deviance (i.e., prediction error) response, as manifested by diminished and delayed MMN and P3a.

BACKGROUND: Non-vestibular schwannomas are relatively rare, with trigeminal and jugular foramen schwannomas being the most common. This is a heterogenous group which requires detailed investigation and careful consideration to management strategy. The optimal management for these tumours remains unclear, and there are several controversies. The aim of this paper is to provide insight into the main principles defining management and surgical strategy, in order to formulate a series of recommendations. METHODS: A task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumours on a European perspective. To achieve this, the task force performed an extensive systematic review in this field and had discussions within the group. This article is the third of a three-part series describing non-vestibular schwannomas (IX, X, XI, XII). RESULTS: A summary of literature evidence was proposed after discussion within the EANS skull base section. The constituted task force dealt with the practice patterns that exist with respect to preoperative radiological investigations, ophthalmological assessments, optimal surgical and radiotherapy strategies and follow-up management. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the treatment of non-vestibular schwannomas. For each of these tumours, the management paradigm is shifting towards the compromise between function preservation and progression free survival.

Background: Malignant melanomas frequently metastasize to the brain, but metastases in the cerebellum are underrepresented compared with metastases in the cerebrum. Methods: We established animal models by injecting intracardially in athymic nude fox1nu mice two human melanoma cell lines, originating from a cerebral metastasis (HM19) and a cerebellar metastasis (HM86). Results: Using magnetic resonance imaging (MRI), metastases were first detected after a mean of 34.5 days. Mean survival time was 59.6 days for the mice in the HM86 group and significantly shorter (43.7 days) for HM19-injected animals (p < 0.001). In the HM86 group, the first detectable metastasis was located in the cerebellum in 15/55 (29%) mice compared with none in the HM19 group (p < 0.001). At sacrifice, cerebellar metastases were found in 34/55 (63%) HM86- injected mice compared with 1/53 (2%) in the HM19-injected (p < 0.001) mice. At that time, all mice in both groups had detectable metastases in the cerebrum. Comparing macroscopic and histologic appearances of the brain metastases with their clinical counterparts, the cell line-based tumors had kept their original morphologic characteristics. Conclusions: The present work demonstrates that human brain-metastatic melanoma cells injected intracardially in mice had retained inherent characteristics also in reproducing interaction with subtle microenvironmental brain tissue compartment-specific features. The models offer new possibilities for investigating tumor- and host-associated factors involved in determining tissue specificity of brain metastasis.

Objective Surgical clipping has become a relatively rare procedure in comparison to endovascular exclusion of cerebral aneurysms. Consequently, there is a declining number of cases where young neurosurgeons can practice clipping. For this reason, we investigated the application of a new 3-dimensional (3D) simulation and rehearsal device, Surgical Theater, in vascular neurosurgery. Methods We analyzed data of 20 patients who underwent surgical aneurysm clipping. In 10 cases, Surgical Theater was used to perform the preoperative 3D planning (CASCADE group), while traditional imaging was used in the other cases (control group). Preoperative 3D simulation was performed by 4 expert and 3 junior neurosurgeons (1 fellow, 2 residents). During postoperative debriefings, expert surgeons explained the different aspects of the operation to their younger colleagues in an interactive way using the simulator. Questionnaires were given to the surgeons to get qualitative feedback about the simulator, and the junior surgeons' performance at simulator was also analyzed. Results There were no differences in surgery outcomes, complications, and surgical duration (P > 0.05) between the 2 groups. Senior neurosurgeons performed similarly when operating at the simulator as compared with in the operating room, while junior neurosurgeons improved their performance at the simulator after the debriefing session (P Conclusions Surgical Theater proved to be realistic in replicating vascular neurosurgery scenarios for rehearsal and simulation purposes. Moreover, it was shown to be useful for didactic purposes, allowing young neurosurgeons to take full advantage and learn from senior colleagues to become familiar with this demanding neurosurgical subspecialty.

Background We describe the minimally invasive, facet-sparing postero-lateral approach to the thoracic spine for a ventral dural repair in a patient with intracranial hypotension secondary to a spontaneous dural breach. Methods We performed a minimally invasive approach using a short paramedian posterior skin incision followed by a 10 × 10 mm targeted trans-laminar approach, to achieve a microsurgical repair of a symptomatic ventral dural defect causing severe disability. Conclusion The facet-sparing postero-lateral approach is safe and effective in the surgical management of thoracic dural tears, even in the most anterior ones, and avoids the traditional costotransversectomy.

Radiation-induced cavernous malformations (RICMs) are delayed complications of brain irradiation during childhood. Its natural history is largely unknown and its incidence may be underestimated as RCIMS tend to develop several years following radiation. No clear consensus exists regarding the long-term follow-up or treatment. A systematic review of Embase, Cochrane Library, PubMed, Google Scholar, and Web of Science databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed. Based on our inclusion/exclusion criteria, 12 articles were included, totaling 113 children with RICMs, 86 were treated conservatively, and 27 with microsurgery. We were unable to precisely define the incidence and natural history from this data. The mean age at radiation treatment was 7.3 years, with a slight male predominance (54%) and an average dose of 50.0 Gy. The mean time to detection of RICM was 9.2 years after radiation. RICM often developed at distance from the primary lesion, more specifically frontal (35%) and temporal lobe (34%). On average, 2.6 RICMs were discovered per child. Sixty-seven percent were asymptomatic. Twenty-one percent presented signs of hemorrhage. Clinical outcome was favorable in all children except in 2. Follow-up data were lacking in most of the studies. RICM is most often asymptomatic but probably an underestimated complication of cerebral irradiation in the pediatric population. Based on the radiological development of RICMs, many authors suggest a follow-up of at least 15 years. Studies suggest observation for asymptomatic lesions, while surgery is reserved for symptomatic growth, hemorrhage, or focal neurological deficits.

Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors.

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two ‘Core Outcome Sets’ (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508

Background: Neurosurgical randomized controlled trials (RCTs) are difficult to carry out due to the low incidence of certain diseases, heterogeneous disease phenotypes, and ethical issues. This results in a weak evidence base in terms of both the number of trials and their robustness. The fragility index (FI) measures the robustness of an RCT and is the minimum number of patients in a trial whose status would have to change from a nonevent to an event to change a statistically significant result to a nonsignificant result. The smaller the FI, the more fragile the trial's outcome. Methods: RCTs that have influenced neurosurgical practice were included in this analysis. Simulations were run to calculate the FI. To determine associations with a high or low FI, multivariable logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals adjusting for baseline confounders. Results: Of 2975 papers screened, 74 were included. The median FI was 4.5 (interquartile range: 1.5–10). RCTs included a median of 165 patients (interquartile range: 75–330), with a maximum of 10,008. A total of 38 trials had lost to follow-up patients that might have impacted the robustness of the results (51%). Conclusion: Results of neurosurgical RCTs on which we base our clinical decision-making and treatment guidelines are often fragile. Improved methodologies, international collaboration, and cooperation between specialties might improve the evidence base in the future.

Neurosurgical 3D visualizers and simulators are innovative devices capable of defining a surgical strategy in advance and possibly making neurosurgery safer by rehearsing the phases of the operation beforehand. The aim of this study is to evaluate Surgical Theater™, a new 3D neurosurgical planning, simulation, and navigation system, and qualitatively assess its use in the operating room.Clinical data were collected from 30 patients harbouring various types of brain tumours; Surgical Theater™ was used for the preoperative planning and intraoperative 3D navigation. Preoperative and postoperative questionnaires were completed by first and second operators to get qualitative feedback on the system's functionality. Furthermore, we measured and compared the impact of this technology on surgery duration.Neurosurgeons were overall satisfied when using this rehearsal and navigation tool and found it efficient and easy to use; interestingly, residents considered this device more useful as compared to their more senior colleagues (with significantly higher scores, p0.05), possibly because of their limited anatomical experience and spatial/surgical rehearsal ability. The length of the surgical procedure was not affected by this technology (p0.05).Surgical Theater™ system was found to be clinically useful in improving anatomical understanding, surgical planning and intraoperative navigation, especially for younger and less experienced neurosurgeons.

The optimal management of petroclival meningiomas (PCMs) continues to be debated along with several controversies that persist. A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the management of these tumors. To achieve this, the task force reviewed in detail the literature in this field and had formal discussions within the group. The constituted task force dealt with the existing definitions and classifications, pre-operative radiological investigations, management of small and asymptomatic PCMs, radiosurgery, optimal surgical strategies, multimodal treatment, decision-making, and patient’s counselling. This article represents the consensually derived opinion of the task force with respect to the management of PCMs.

Brain arteriovenous malformations (bAVMs) are vascular lesions that carry significant morbidity and mortality risk upon rupture. bAVM rupture causes either intracerebral or intraventricular hemorrhage, or both. In 2014, the first results of the ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) were published in The Lancet , causing a paradigm shift in clinical practice and suggesting the superiority of medical treatment in terms of mortality or stroke compared with any intervention designed to obliterate the AVM. In 2020, the final results of the ARUBA trial were published. In this Viewpoint, we critically review the clinical equipoise behind the trial, highlight issues regarding external validity, and place the results of the trial in the context of other results in scientific literature of bAVMs using Bayesian inference. ARUBA is a trial of decision-making, and only proper knowledge of the nuances of its interpretation within the broader context of bAVM research can lead to proper decision-making when confronted with patients with unruptured bAVMs.

Assessment of long-term functional outcomes after meningioma surgery is important. We systematically reviewed the literature on health-related quality of life (HrQoL) and functional disability (FD) of patients after surgery for intracranial meningiomas. Using PRISMA 2015 guidelines, we screened 289 abstracts and 43 titles were retained for full-paper screening. 15 articles did not present enough data to meet the inclusion criteria and 7 articles failed to assess functional assessment and HrQoL. Twenty-two articles were included in our review. HrQol was assessed in N = 18 publications, most frequently using SF-36 (N = 10), followed by EQ5D-5L (N = 4), EORTC-QLQ (N = 4), and the FACT questionnaire (N = 2). The assessment of FD was reported in N = 11 publications, mostly using the KPS (N = 8). The Barthel index was used in N = 2 publications. Follow-up was reported in N = 12 publications, ranging from 6 months to 9 years. Scientific publications assessing long-term postoperative HrQol and FD in patients undergoing meningioma surgery are scarce and the data are heterogeneously reported, using various scales and follow-up protocols. Efforts should be undertaken to uniformly assess long-term post-operative functional outcomes in meningioma patients.

Foramen magnum meningiomas (FMMs) account for 1.8–3.2% of all meningiomas. With this systematic review and meta-analysis, our goal is to detail epidemiology, clinical features, surgical aspects, and outcomes of this rare pathology. Using PRISMA 2015 guidelines, we reviewed case series, mixed series, or retrospective observational cohorts with description of surgical technique, patient and lesion characteristics, and pre- and postoperative clinical status. A meta-analysis was performed to search for correlations between meningioma characteristics and rate of gross total resection (GTR). We considered 33 retrospective studies or case series, including 1053 patients, mostly females (53.8%), with a mean age of 52 years. The mean follow-up was of 51 months (range 0–258 months). 65.6% of meningiomas were anterior, and the mean diameter was of 29 mm, treated with different surgical approaches. Postoperatively, 17.2% suffered complications (both surgery- and non-surgery-related) and 2.5% had a recurrence. The Karnofsky performance score improved in average after surgical treatment (75 vs. 81, p < 0.001). Our meta-analysis shows significant rates of GTR in cohorts with a majority of posterior and laterally located FMM (p = 0.025) and with a mean tumor less than 25 mm (p < 0.05). FMM is a rare and challenging pathology whose treatment should be multidisciplinary, focusing on quality of life. Surgery still remains the gold standard and aim at maximal resection with neurological function preservation. Adjuvant therapies are needed in case of subtotal removal, non-grade I lesions, or recurrence. Specific risk factors for recurrence, other than Simpson grading, need further research.

Brain arteriovenous malformations management remains controversial despite the numerous, available treatment options. Randomized controlled trials (RCTs) theoretically provide the strongest evidence for the assessment of any therapeutic intervention. However, poorly designed RCTs may be associated with biases, inaccuracies, and misleading conclusions. The purpose of our study is to assess reporting transparency and methodological quality of the existing RCTs.A search was performed in the PubMed, Scopus, Embase, clinicaltrials.gov, and Cochrane databases. The search was limited to English literature. We included all published RCTs reporting on the management of unruptured brain arteriovenous malformations. The eligible studies were evaluated by 5 blinded raters with the CONsolidated Standards of Reporting Trials 2010 statement and the risk-of-bias 2 tool. The inter-rater agreement was assessed with the Fleiss' Kappa.A randomized trial of unruptured brain arteriovenous malformations (ARUBA) and treatment of brain arteriovenous malformations (TOBAS) trials were evaluated. ARUBA achieved high CONsolidated standards of reporting trials compliance, while TOBAS showed a moderate one. In ARUBA the introduction, discussion, and other information sections reached the highest compliance rate (80%-86%). The lowest rates were recorded in the results and the methods (62% and 73%, respectively). The inter-rater agreement was moderate to substantial (54.1% to 78.4%). All the examined studies demonstrated a high risk of bias, mainly related to ill-defined intended interventions, missing outcome data, and selection of the reported results.Our study confirmed the high risk of bias mainly attributed to several protocol violations, deviations, minimal external validity and selection, attrition, and allocation biases of the ARUBA trial. Analysis of the TOBAS trial revealed a moderate overall reporting clarity and a high risk of bias.

Risks and survival times of ventriculoperitoneal (VP) shunts implanted due to hydrocephalus after craniotomies for brain tumors are largely unknown. The purpose of this study was to determine the overall timing of VP shunting and its failure after craniotomy for brain tumors in adults. The authors also wished to explore risk factors for early VP shunt failure (within 90 days). A population-based consecutive patient cohort of all craniotomies for intracranial tumors leading to VP shunt dependency in adults (> 18 years) from 2004 to 2013 was studied. Patients with pre-existing VP shunts prior to craniotomy were excluded. The survival time of VP shunts, i.e., the shunt longevity, was calculated from the day of shunt insertion post-craniotomy for a brain tumor until the day of shunt revision requiring replacement or removal of the shunt system. Out of 4774 craniotomies, 85 patients became VP shunt-dependent (1.8% of craniotomies). Median time from craniotomy to VP shunting was 1.9 months. Patients with hydrocephalus prior to tumor resection (N = 39) had significantly shorter time to shunt insertion than those without (N = 46) (p

Introduction: The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between “gross total removal” and “subtotal removal,” while the latter comprises a five-tiered differentiation of the surgeon’s impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging with 68Ga-DOTATOC allows more sensitive and specific imaging than MRI following surgery of meningiomas. Objective: To develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance of 68Ga DOTATOC PET, we propose “Copenhagen Grading” for meningiomas. Results: Copenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen. Conclusion: Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation.

Three-dimensional (3D) printing (3DP) has seen spectacular progress in recent years, making it widely available to consumers and researchers, but it has also been steadily expanding its capabilities while becoming more and more affordable. This progress has allowed 3DP technology to be seriously tested in various fields of Medicine and Biomedical Technology. Neurological Surgery is widely considered to be among the most demanding and intricate medical specialties, as it concerns fine and highly critical neural and vascular elements even during standard interventions or the most common pathological conditions. As such, advances in 3DP were quick to be applied to neurosurgical practice (depicting brain aneurysms), research and development (spine and disc models), and neurosurgical education. In the past years, we have seen progress in four main distinct directions for the use of 3DP technologies within the prism of Neurological Surgery, where we also envision future progress: (a) neurovascular physiological anatomy and its associated disorders, (b) complex central nervous system tumors and neuroanatomy, (c) spine instrumentation, deformities, and biomechanical implications, and (d) educational purposes, prototyping of implants, devices, and equipment. In this chapter, we critically review the progress of 3DP technology within each of these described directions and discuss the impact it can possibly have on specific diseases and on the Neurosurgical Specialty as a whole in the years to come.

Intracranial meningiomas mostly affect patients in their fifth decade and beyond, raising pertinent questions regarding the risk of surgery, particularly in the elderly. Here, we describe the case of a septuagenarian patient with occipital meningioma causing severe visual field cuts that experienced full recovery of the visual function after a Simpson I resection of the lesion. This case illustrates the potential of recovery of the brain, even in the case of severely impaired function in elderly patients. To complete the picture, we review the literature on occipital meningiomas, advocating for systematic reports and increase data collection on post-operative neurological recovery in the elderly.

Background Work-related musculoskeletal disorders (WMSDs) are a growing and probably undervalued concern for neurosurgeons and spine surgeons, as they can impact their quality of life and career length. This systematic review aims to ascertain this association and to search for preventive measures. Methods We conducted a PRISMA-P-based review on ergonomics and WMSDs in neurosurgery over the last 15 years. Twelve original articles were included, of which 6 focused on spine surgery ergonomics, 5 cranio-facial surgery (mainly endoscopic), and one on both domains. Results We found a huge methodological and content diversity among studies with 5 surveys, 3 cross-sectional studies, 2 retrospective cohorts, and 2 technical notes. Spine surgeons have sustained neck flexion and neglect their posture during surgery. In a survey, low back pain was found in 62% of surgeons, 31% of them with a diagnosed lumbar disc herniation, and 23% of surgery rate. Pain in the neck (59%), shoulder (49%), finger (31%), and wrist (25%) are more frequent than in the general population. Carpal tunnel syndrome showed a linear relationship with increasing cumulative hours of spine surgery practice. Among cranial procedures, endoscopy was also significantly related to shoulder pain while pineal region surgery received some attempts to optimize ergonomics. Conclusions Ergonomics in neurosurgery remains underreported and lack attention from surgeons and authorities. Improvements shall target postural ergonomics, equipment design, weekly schedule adaptation, and exercise.

To perform a systematic review of extracranial-to-intracranial (EC-IC) bypass surgery with parent vessel trapping for blood blister–like aneurysms (BBAs) of the internal carotid artery (ICA) according to PRISMA guidelines. Search of PubMed using “bypass” [all fields] and “ICA” [all fields] or “internal carotid artery” [all fields] and (“blood blister–like aneurysm” [MeSH terms]. Thirty-four original articles were identified, of which 21 were excluded (treatment not including bypass or insufficient details on complications or clinical outcomes). Thirteen articles published between 2008 and 2019 were included, totaling 98 patients, with a median of 7.5 patients per article (range 1–17). Mean age was 53.3 years (range 23–80). The main techniques were external carotid artery to middle cerebral artery (ECA-MCA) in 81% and superficial temporal artery to MCA (STA-MCA) in 19%. The most common grafts were radial artery (74%) and STA (19%). The risk of intraoperative rupture varied from 0 to 75%, with a mean of 12%. With respect to clinical outcomes, the modified Rankin Scale (mRS) was not stated in 30% of the cases. When stated, mRS was ≤ 2 in 79%, mRS was 3–5 in 10%, and 4% had mRS 6 (death). We identified only 13 articles, with no prospective studies. Outcomes were better than generally reported for ruptured aneurysms, both with respect to poor outcome (mRS > 2) and in-hospital mortality, perhaps reflecting a selection bias. In general, the data reporting quality was low, precluding any firm conclusions, but EC-IC bypass with ICA trapping may be a valid treatment option for ruptured ICA BBAs.

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in‐house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM., This work combined molecular subtyping of glioblastomas (GBMs) with gene expression measures of tumor infiltration and identified a subset of GBMs with high abundances of most immune and stromal cell populations. Survival analyses suggested that tumor microenvironment infiltration was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype and low infiltration had the poorest survival.