Integrative spatial analysis reveals a multi-layered organization of glioblastoma.

Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics, spatial proteomics, and computational approaches to define glioma cellular states and uncover their organization. We find three prominent modes of organization. First, gliomas are composed of small local environments, each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. This pairing of states is consistent across tumors. Third, these pairwise interactions collectively define a global architecture composed of five layers. Hypoxia appears to drive the layers, as it is associated with a long-range organization that includes all cancer cell states. Accordingly, tumor regions distant from any hypoxic/necrotic foci and tumors that lack hypoxia such as low-grade IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of cellular states in glioma, highlighting hypoxia as a long-range tissue organizer.

Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.

Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors1,2. Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumour-infiltrating lymphocytes (TILs) recognize tumour-derived bacterial peptides. Bacterial peptides eluted from HLA class II molecules are recognized by TILs, albeit very weakly. Using an unbiased antigen discovery approach to probe the specificity of a TIL CD4+ T cell clone, we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumour antigens. These peptides were also strongly stimulatory for bulk TILs and peripheral blood memory cells, which then respond to tumour-derived target peptides. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumour antigens. The unbiased identification of microbial target antigens for TILs holds promise for future personalized tumour vaccination approaches.

A T-cell antigen atlas for meningioma: novel options for immunotherapy.

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

Successful weaning versus permanent cerebrospinal fluid diversion after aneurysmal subarachnoid hemorrhage: post hoc analysis of a Swiss multicenter study.

OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.

Herniation World Federation of Neurosurgical Societies Scale Improves Prediction of Outcome in Patients With Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort. METHODS: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6). RESULTS: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P<0.001) whereas the sensitivity decreased from 0.88 to 0.37 (P<0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P<0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P<0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P<0.001). CONCLUSIONS: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

The BSCM score: a guideline for surgical decision-making for brainstem cavernous malformations.

Microsurgical resection of brainstem cavernous malformations (BSCMs) can be performed today with acceptable morbidity and mortality. However, in this highly eloquent location, the indication for surgery remains challenging. We aimed to elaborate a score system that may help clinicians with their choice of treatment in patients with BSCMs in this study. A single-center series of 88 consecutive BSCMs patients with 272 follow-up visits were included in this study. Univariable and multivariable generalized estimating equations (GEE) were constructed to identify the association of variables with treatment decisions. A score scale assigned points for variables that significantly contributed to surgical decision-making. Surgical treatment was recommended in 37 instances, while conservative treatment was proposed in 235 instances. The mean follow-up duration was 50.4 months, and the mean age at decision-making was 45.9 years. The mean BSCMs size was 14.3 ml. In the multivariable GEE model, patient age, lesion size, hemorrhagic event(s), mRS, and axial location were identified as significant factors for determining treatment options. With this proposed score scale (grades 0-XII), non-surgery was the first option at grades 0-III. The crossover point between surgery and non-surgery recommendations lay between grades V and VI while surgical treatment was found in favor at grades VII-X. In conclusion, the proposed BSCM operating score is a clinician-friendly tool, which may help neurosurgeons decide on the treatment for patients with BSCMs.

Collagen-bound fibrin sealant (TachoSil®) for dural closure in cranial surgery: single-centre comparative cohort study and systematic review of the literature.

Cerebrospinal fluid (CSF) leakage is a well-known complication of craniotomies and there are several dural closure techniques. One commonly used commercial product as adjunct for dural closure is the collagen-bound fibrin sealant TachoSil®. We analysed whether the addition of TachoSil has beneficial effects on postoperative complications and outcomes. Our prospective, institutional database was retrospectively queried, and 662 patients undergoing craniotomy were included. Three hundred fifty-two were treated with dural suture alone, and in 310, TachoSil was added after primary suture. Our primary endpoint was the rate of postoperative complications associated with CSF leakage. Secondary endpoints included functional, disability and neurological outcome. Systematic review according to PRISMA guidelines was performed to identify studies comparing primary dural closure with and without additional sealants. Postoperative complications associated with CSF leakage occurred in 24 (7.74%) and 28 (7.95%) procedures with or without TachoSil, respectively (p = 0.960). Multivariate analysis confirmed no significant differences in complication rate between the two groups (aOR 0.97, 95% CI 0.53-1.80, p = 0.930). There were no significant disparities in postoperative functional, disability or neurological scores. The systematic review identified 661 and included 8 studies in the qualitative synthesis. None showed a significant superiority of additional sealants over standard technique regarding complications, rates of revision surgery or outcome. According to our findings, we summarize that routinary use of TachoSil and similar products as adjuncts to primary dural sutures after intracranial surgical procedures is safe but without clear advantage in complication avoidance or outcome. Future studies should investigate whether their use is beneficial in high-risk settings.

Determining the impact of postoperative complications in neurosurgery based on simulated longitudinal smartphone app-based assessment.

BACKGROUND: Complications after neurosurgical operations can have severe impact on patient well-being, which is poorly reflected by current grading systems. The objective of this work was to develop and conduct a feasibility study of a new smartphone application that allows for the longitudinal assessment of postoperative well-being and complications. METHODS: We developed a smartphone application "Post OP Tracker" according to requirements from clinical experience and tested it on simulated patients. Participants received regular notifications through the app, inquiring them about their well-being and complications that had to be answered according to their assigned scenarios. After a 12-week period, subjects answered a questionnaire about the app's functionality, user-friendliness, and acceptability. RESULTS: A total of 13 participants (mean age 34.8, range 24-68 years, 4 (30.8%) female) volunteered in this feasibility study. Most of them had a professional background in either health care or software development. All participants downloaded, installed, and applied the app for an average of 12.9 weeks. On a scale of 1 (worst) to 4 (best), the app was rated on average 3.6 in overall satisfaction and 3.8 in acceptance. The design achieved a somewhat favorable score of 3.1. One participant (7.7%) reported major technical issues. The gathered patient data can be used to graphically display the simulated outcome and assess the impact of postoperative complications. CONCLUSIONS: This study suggests the feasibility to longitudinally gather postoperative data on subjective well-being through a smartphone application. Among potential patients, our application indicated to be functional, user-friendly, and well accepted. Using this app-based approach, further studies will enable us to classify postoperative complications according to their impact on the patient's well-being.

The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy.

Antileukemia immunity plays an important role in disease control and maintenance of tyrosine kinase inhibitor (TKI)-free remission in chronic myeloid leukemia (CML). Thus, antigen-specific immunotherapy holds promise for strengthening immune control in CML but requires the identification of CML-associated targets. In this study, we used a mass spectrometry-based approach to identify naturally presented HLA class I- and class II-restricted peptides in primary CML samples. Comparative HLA ligandome profiling using a comprehensive dataset of different hematological benign specimens and samples from CML patients in deep molecular remission delineated a panel of novel frequently presented CML-exclusive peptides. These nonmutated target antigens are of particular relevance because our extensive data-mining approach suggests the absence of naturally presented BCR-ABL- and ABL-BCR-derived HLA-restricted peptides and the lack of frequent tumor-exclusive presentation of known cancer/testis and leukemia-associated antigens. Functional characterization revealed spontaneous T-cell responses against the newly identified CML-associated peptides in CML patient samples and their ability to induce multifunctional and cytotoxic antigen-specific T cells de novo in samples from healthy volunteers and CML patients. Thus, these antigens are prime candidates for T-cell-based immunotherapeutic approaches that may prolong TKI-free survival and even mediate cure of CML patients.

Predictors of In-Hospital Death After Aneurysmal Subarachnoid Hemorrhage: Analysis of a Nationwide Database (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]).

BACKGROUND AND PURPOSE: To identify predictors of in-hospital mortality in patients with aneurysmal subarachnoid hemorrhage and to estimate their impact. METHODS: Retrospective analysis of prospective data from a nationwide multicenter registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009-2015). Both clinical and radiological independent predictors of in-hospital mortality were identified, and their effect size was determined by calculating adjusted odds ratios (aORs) using multivariate logistic regression. Survival was displayed using Kaplan-Meier curves. RESULTS: Data of n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%), active treatment was discontinued after hospital admission (no aneurysm occlusion attempted), and this cohort was excluded from analysis of the main statistical model. In the remaining n=1669 patients, the rate of in-hospital mortality was 13.9% (n=232). Strong independent predictors of in-hospital mortality were rebleeding (aOR, 7.69; 95% confidence interval, 3.00-19.71; P<0.001), cerebral infarction attributable to delayed cerebral ischemia (aOR, 3.66; 95% confidence interval, 1.94-6.89; P<0.001), intraventricular hemorrhage (aOR, 2.65; 95% confidence interval, 1.38-5.09; P=0.003), and new infarction post-treatment (aOR, 2.57; 95% confidence interval, 1.43-4.62; P=0.002). CONCLUSIONS: Several-and among them modifiable-factors seem to be associated with in-hospital mortality after aneurysmal subarachnoid hemorrhage. Our data suggest that strategies aiming to reduce the risk of rebleeding are most promising in patients where active treatment is initially pursued. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03245866.

International multicentre validation of the arteriovenous malformation-related intracerebral haemorrhage (AVICH) score.

OBJECTIVE: The recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score. METHODS: All participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score. Modified Rankin score (mRS) at last follow-up (mean 25.6 months) was dichotomized into favourable (mRS 0-2, n=210) and unfavourable (mRS 3-6;n=115). Univariate and AUROC analyses were performed to validate the AVICH score. RESULTS: Except nidus structure and AVM size, all single parameters forming the SM, sSM, ICH and AVICH score and the scores itself were significantly different between both outcome groups in the univariate analysis. The AVICH score was confirmed to be the highest predictive outcome score with an AUROC of 0.765 compared with 0.705 for the ICH score and 0.682 for the sSM grade. CONCLUSION: The multicentre-validated AVICH score predicts clinical outcome superior to pre-existing scores. We suggest the routine use of this score for future clinical outcome prediction and in clinical research. TRIAL REGISTRATION NUMBER: NCT02920645.

Decision-making and neurosurgeons' agreement in the management of aneurysmal subarachnoid haemorrhage based on computed tomography angiography.

BACKGROUND: To determine the neurosurgeon's agreement in aneurysmal subarachnoid haemorrhage (aSAH) management with special emphasis on the rater's level of experience. A secondary aim was to analyse potential aneurysm variables associated with the therapeutic recommendation. METHOD: Basic clinical information and admission computed tomography angiography (CTA) images of 30 consecutive aSAH patients were provided. Twelve neurosurgeons independently evaluated aneurysm characteristics and gave recommendations regarding the emergency management and aneurysm occlusion therapy. Inter-rater variability and predictors of treatment recommendation were evaluated. RESULTS: There was an overall moderate agreement in treatment decision [κ = 0.43; 95% confidence interval ((CI), 0.387-0.474] with moderate agreement for surgical (κ = 0.43; 95% CI, 0.386-0.479) and endovascular treatment recommendation (κ = 0.45; 95% CI, 0.398-0.49). Agreement on detailed treatment recommendations including clip, coil, bypass, stent, flow diverter and ventriculostomy was low to moderate. Inter-rater agreement did not significantly differ between residents and consultants. Middle cerebral artery (MCA) aneurysm location was a positive predictor of surgical treatment [odds ratio (OR), 49.57; 95% CI, 10.416-235.865; p < 0.001], while patients aged >65 years (OR, 0.12; 95% CI, 0.03-0.0434; p = 0.001), fusiform aneurysm type (OR, 0.18; 95% CI, 0.044-0.747; p = 0.018) and intracerebral haematoma (ICA) aneurysm location (OR, 0.24; 95% CI, 0.088-0.643; p = 0.005) were associated with a recommendation for endovascular treatment. CONCLUSIONS: Agreement on aSAH management varies considerably across neurosurgeons, while therapeutic decision-making is challenging on an individual patient level. However, patients aged >65 years, fusiform aneurysm shape and ICA location were associated with endovascular treatment recommendation, while MCA aneurysm location remains a surgical domain in the opinion of neurosurgeons without formal endovascular training.

The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma.

The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 ± 11.6 years) operated at our institution between 2009 and 2012. Patients were only included if GTR was achieved as judged by early postoperative high-field MRI. Intraoperative technical resection control modalities comprised intraoperative ultrasound (ioUS, n = 48), intraoperative low-field MRI (ioMRI, n = 22), and a control group without either modality (n = 11). The primary endpoint of our study was OS, and the secondary endpoint was PFS-both analyzed in Kaplan-Meier plots and Cox proportional hazards models. Median OS in all 76 glioblastoma patients after GTR was 20.4 months (95 % confidence interval (CI) 18.5-29.0)-median OS in patients where GTR was achieved using ioUS was prolonged (21.9 months) compared to those without ioUS usage (18.8 months). A multiple Cox model adjusting for age, preop Karnofsky performance status, tumor volume, and the use of 5-aminolevulinic acid showed a beneficial effect of ioUS use, and the estimated hazard ratio was 0.63 (95 % CI 0.31-1.2, p = 0.18) in favor of ioUS, however not reaching statistical significance. A similar effect was found for PFS (hazard ratio 0.59, p = 0.072). GTR of glioblastoma performed with ioUS guidance was associated with prolonged OS and PFS. IoUS should be compared to other resection control devices in larger patient cohorts.

Gender dependence of serum soluble Klotho in acromegaly.

OBJECTIVES: In acromegaly, disease activity is biochemically assessed by growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. However, they are often discrepant, as several factors including gender influence their relationship. We recently found excessively high serum levels of soluble Klotho (sKl) in acromegalic patients, which depended on GH to a comparable extent as IGF-1. To further elucidate the relationship between GH and sKl, we examined the effect of gender on sKl in patients with untreated acromegaly. PATIENTS AND DESIGN: We determined GH, IGF-1 and sKl in sera of 62 consecutive patients with newly diagnosed acromegaly (31 females/31 males, aged 20-85 years). RESULTS: For their given GH excess at presentation with acromegaly, females had lower IGF-1 (490 ± 33 vs 604 ± 33 ng/ml, P = 0·02), but higher sKl [5171 ± 590 vs 3439 ± 431 pg/ml (mean ± SE), P = 0·02] levels than males. In multiple regression analysis, IGF-1 was closely associated with logGH (estimate 139, SE 47, P = 0·005) and BMI (estimate 14·2, SE 4·8, P = 0·005). sKl was closely associated with logGH (estimate 3088, SE 652, P = 0·0001) and gender (estimate 2034, SE 612, P = 0·002), and to a lesser extent with BMI (estimate 174, SE 66, P = 0·01). CONCLUSIONS: For a given GH status, sKl concentrations are higher and IGF-1 concentrations are lower in women than in men. GH is the strongest predictor for both sKl and IGF-1, but gender needs to be considered when using these parameters for monitoring acromegalic patients.

A profile on the WISE cortical strip for intraoperative neurophysiological monitoring.

INTRODUCTION: During intraoperative neurophysiological monitoring in neurosurgery, brain electrodes are placed to record electrocorticography or to inject current for direct cortical stimulation. A low impedance electrode may improve signal quality. AREAS COVERED: We review here a brain electrode (WISE Cortical Strip, WCS®), where a thin polymer strip embeds platinum nanoparticles to create conductive electrode contacts. The low impedance contacts enable a high signal-to-noise ratio, allowing for better detection of small signals such as high-frequency oscillations (HFO). The softness of the WCS may hinder sliding the electrode under the dura or advancing it to deeper structures as the hippocampus but assures conformability with the cortex even in the resection cavity. We provide an extensive review on WCS including a market overview, an introduction to the device (mechanistics, cost aspects, performance standards, safety and contraindications) and an overview of the available pre- and post-approval data. EXPERT OPINION: The WCS improves signal detection by lower impedance and better conformability to the cortex. The higher signal-to-noise ratio improves the detection of challenging signals. The softness of the electrode may be a disadvantage in some applications and an advantage in others.

Laser Interstitial Thermal Therapy in a Large Thalamic Glioma with Long-Term Remission: A Case Report.

INTRODUCTION: Thalamic gliomas pose a particular therapeutic challenge as complete resection is rarely achieved due to the deep and eloquent location. Laser interstitial thermal therapy (LITT) may provide a valuable management option for deep-seated gliomas that are not accessible with open surgery. CASE PRESENTATION: A 57-year-old woman presented with a rapidly progressive large thalamic glioblastoma. Opting for full ablation, we selected a challenging trajectory to maximize the possibility of full ablation. At 2.4 cm in diameter, the tumour was larger than recommended for LITT; nevertheless, three laser ablations along a single trajectory resulted in macroscopic ablation without complications. Adjuvant radio-chemotherapy was started soon after surgery without radiological recurrence 1.5 years after the initial surgery. CONCLUSION: This case demonstrates the potential when thalamic tumours are managed with timely LITT treatment and meticulous trajectory planning. Moreover, it highlights the need for close interdisciplinary management with neurosurgeons, neuropathologists, neuroradiologists, and neurooncologists.

Surgical resection of pediatric skull base meningiomas.

PURPOSE: Meningiomas in children are rare, especially those located at the skull base. In this study, we report our experience of meningioma surgery in the pediatric population and compare our findings of skull base (SB) versus non-skull base (NSB) meningiomas. METHODS: From our database of 724 surgically treated meningioma patients at the University Hospital, Zurich between 1995 and 2010, 12 patients under 18 years of age were identified. Data for those patients was retrospectively collected through chart review. A descriptive comparison between SB and NSB meningiomas was undertaken to determine statistical significance. RESULTS: In all 12 children (seven males, five females; mean age 12.2 ± 4.3 years), surgical removal of the meningioma was performed microsurgically with a mean follow-up of 53 months (range 12-137 months). Of the 12 tumors, six were located in the SB and six in the NSB. Comparing SB to NSB lesions, the mean age was 11 ± 3.8 versus 14 ± 4.6 years, male/female gender distribution was 5:1 compared to 1:5, mean tumor size was 7.5 ± 6.2 versus 26 ± 15.8 cm(2) (p = 0.03), and mean surgery time was 347 versus 214 min. While WHO grade was similar for both groups, the Simpson grade revealed more extensive resection for NSB meningiomas. The Glasgow Outcome Scale at last follow-up was favorable for both groups. CONCLUSIONS: Meningioma surgery was safe with favorable outcomes. SB meningiomas were significantly smaller in size, were less likely to undergo complete resection, and had a predilection for younger, male patients.

Bifocal extra- and intradural melanocytoma of the spine: case report and literature review.

BACKGROUND: Spinal melanocytoma is one of the most infrequent space-occupying lesions of the central nervous system. To the best of our knowledge, this is the first report of primary bifocal intradural melanocytoma of heterogeneous pathological grade to date. CASE DESCRIPTION: We report the case of a 43-year old patient with primary bifocal melanocytoma, clinically and radiologically resembling benign schwannoma. The patient presented with myeloradiculopathy of the left C3 dermatome. Magnetic resonance imaging of the upper spine revealed two space-occupying lesions with paraspinal extension, initially diagnosed as neurofibroma. Definitive histopathological classification of both lesions was melanocytoma. Both tumours were only partially removed due to adherence to surrounding structures. The patient underwent stereotactic external beam irradiation (EBR). Follow-up at 1 year after surgery revealed no recurrence and the patient remained free of symptoms. The clinical, radiological and pathological features of this rare tumour entity are presented and the available literature is reviewed. CONCLUSIONS: Intradural melanocytoma, although exceedingly rare, requires a thorough work-up to exclude malignant melanoma. With only two previous reports of multifocal melanocytoma published in the literature, standard therapy has not yet been established and complete surgical removal remains the modality of choice. Patients should be closely monitored to detect local recurrence or malignant degeneration. EBR may be considered in cases where total excision is not achievable and reduces risk of local recurrences.

Facial nerve motor evoked potentials during skull base surgery to monitor facial nerve function using the threshold-level method.

OBJECT: During surgeries that put the facial nerve at risk for injury, its function can be continuously monitored by transcranial facial nerve motor evoked potentials (FNMEPs) in facial nerve target muscles. Despite their advantages, FNMEPs are not yet widely used. While most authors use a 50% reduction in FNMEP response amplitudes as a warning criterion, in this paper the authors' approach was to keep the response amplitude constant by increasing the stimulation intensity and to establish a warning criterion based on the "threshold-level" method. METHODS: The authors included 34 consecutive procedures involving 33 adult patients (median age 47 years) in whom FNMEPs were monitored. A threshold increase greater than 20 mA for eliciting FNMEPs in the most reliable facial nerve target muscle was considered a prediction of reduced postoperative facial nerve function, and subsequently a warning was issued to the surgeon. Preoperative and early postoperative function was documented using the House-Brackmann grading system. RESULTS: Monitoring of FNMEPs was feasible in all 34 surgeries in at least one facial nerve target muscle. The mentalis muscle yielded the best results. The House-Brackmann grade deteriorated in 17 (50%) of 34 cases. The warning criterion was reached in 18 (53%) of 34 cases, which predicted an 83% risk of House-Brackmann grade deterioration. Sensitivity amounted to 88% (CI 64%-99%) and specificity to 82% (CI 57%-96%). Deterioration of FNMEPs and a worse House-Brackmann grade showed a high degree of association (p < 0.001). The impact of FNMEP monitoring on surgical strategy is exemplified in an illustrative case. CONCLUSIONS: In surgeries that put the facial nerve at risk, the intraoperative increase in FNMEP stimulation threshold was closely correlated to postoperative facial nerve dysfunction. Monitoring of FNMEPs is a valid indicator of facial nerve function in skull base surgery. It should be used as an adjunct to direct electrical facial nerve stimulation and continuous electromyographic monitoring of facial nerve target muscles.