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Postoperative hemorrhage can severely affect the patients' neurological outcome after awake craniotomy. Higher postoperative blood pressure can increase the risk of postoperative hemorrhage. The aim of this study was to investigate the role of postoperative blood pressure and other common radiological and epidemiological features with the incidence of postoperative hemorrhage. In this retrospective analysis, we included patients who underwent awake surgery at our institution. We assessed the blood pressure both intra- and postoperatively as well as the heart rate for the first 12 h. We compared a cohort with postoperative hemorrhage, who required further treatment (surgical revision or intravenous antihypertensive therapy), with a cohort with no postoperative hemorrhage. We included 48 patients with a median age of 39 years. 9 patients (19%) required further treatment due to postoperative hemorrhage, which was surgery in 2 cases and intensive blood pressure measurements in 7 cases. However, with early treatment, no significant difference in Performance scores at follow-up could be found. Patients with postoperative hemorrhage showed significantly higher postoperative systolic blood pressure during the hours 3-12 (p < 0.05) as well as intraoperatively throughout the procedure (p < 0.05). In ROC and Youden Test, a strong impact of systolic blood pressure over 140mmHg during the early postoperative course could be shown. Postoperative hemorrhage is a rare but possible complication in awake surgery glioma patients. To avoid postoperative hemorrhage, treating physicians should aim strictly on systolic blood pressure of under 140mmHg for the postoperative course., (© 2024. The Author(s).)

Background: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 World Health Organization classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults., Methods: We included molecularly confirmed H3 K27M-mutated glioma cases in patients ≥ 18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors., Results: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 ± 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy. Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, P = .007). Preoperative Karnofsky-Performance Score (KPS) ≤ 80 showed a reduced OS (4.2 vs. 18 months, P = .02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, P = .0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, P = .4006)., Conclusions: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Metastases are the most frequent intracranial malignant tumors in adults. While Karnofsky Performance Status (KPS) and Clinical Frailty Scale (CFS) are known to have significant impact on overall survival (OS), temporal muscle thickness (TMT) has been postulated to be a promising new parameter to estimate prognosis. Patients who received a resection of one to three brain metastases in our institution were included. Temporal muscle thickness was measured in preoperative MRI scans according to a standardized protocol. In 199 patients, the mean TMT was 7.5 mm (95CI 7.3-7.7) and the mean OS during follow-up was 31.3 months (95CI 24.2-38.3). There was no significant correlation of TMT and preoperative or follow-up CFS and KPS. While CFS and KPS did significantly correlate with OS ( p < 0.001 for each), no correlation was demonstrated for TMT. CFS showed a superior prognostic value compared to KPS. TMT failed to show a significant impact on OS or patient performance, whereas the clinical scales (KPS and CFS) demonstrate a good correlation with OS. Due to its superiority over KPS, we strongly recommend the use of CFS to estimate OS in patients with brain metastases.

Objective: Patients with idiopathic trigeminal neuralgia (TN) live in constant fear of triggering shock-like pain episodes, which may cause symptoms of depression and a reduction in quality of life. Microvascular decompressive surgery has been demonstrated to achieve satisfactory and stable results. With this study, we wanted to investigate prevalence and risk factors for depression and perceived stress in correlation with symptom relief after surgical treatment. Methods: In this prospective study, patients undergoing microvascular decompression (MVD) for TN were included. The Barrow Neurological Institute Pain Score (BNI), Beck Depression Inventory (BDI), Chronic Pain Acceptance Questionnaire (CPAQ), Perceived Stress Questionnaire (PSQ) and McGill questionnaire were used to evaluate depression, stress and anxiety disorders before and 3 months after MVD. Results: A total of 35 patients (16 male (46%)) with a mean age of 55.4 (SD 15) years were included in this study. The BDI revealed that 24 (68.8%) patients harbored mild-to-extreme depression preoperatively (2.4 ± 1.4), which improved to 1.2 (±0.6, p < 0.0001). Pain acceptance also changed from 64 (±11.3) to 67.7 (±9.3, p = 0.006). Perceived stress decreased from 46.9 (±21.9) to 19.6 (±18.6) ( p < 0.0001) postoperatively, and pain decreased from 31.0 (±11.7) to 9.4 (±12.9, p < 0.0001). Microvascular decompression reduced the mean BNI pain score significantly from 4.6 to 1.8 postoperatively ( p < 0.00001). Conclusions: Depression and perceived stress are prevalent in patients with idiopathic TN. Adequate treatment not only provides a high rate of satisfaction through pain relief, but also leads to immediate and significant improvements in depression and stress. Thus, in patients with TN who do not reach an adequate and timely pain reduction through medical management and develop signs of depression, early treatment with microvascular decompression should be considered.

Introduction: Imposter syndrome (IS), characterized by persistent doubts about one's abilities and fear of exposure as a fraud, is a prevalent psychological condition, particularly impacting physicians. In neurosurgery, known for its competitiveness and demands, the prevalence of IS remains high., Research Question: Recognizing the limited literature on IS within the neurosurgical community, this European survey aimed to determine its prevalence among young neurosurgeons and identify associated factors., Material and Methods: The survey, conducted by the Young Neurosurgeon Committee of the European Association of Neurosurgical Societies, gathered responses from 232 participants. The survey included demographics, the Clance Imposter Phenomenon Survey (CIPS), and an analysis of potential compensatory mechanisms., Results: Nearly 94% of respondents exhibited signs of IS, with the majority experiencing moderate (36.21%) or frequent (40.52%) symptoms. Analyses revealed associations between IS and factors such as level of experience, sex, and board-certification., Discussion and Conclusion: The findings suggest a significant prevalence of IS among young neurosurgeons, with notable associations with sex and level of experience. Compensatory mechanisms, such as working hours, article reading, and participation in events, did not show significant correlations with IS. Notably, male sex emerged as an independent protective factor against frequent/intense IS, while reading more than five articles per week was identified as a risk factor. The identification of protective and risk factors, particularly the influence of gender and reading habits, contributes valuable insights for developing targeted interventions to mitigate IS and improve the well-being of neurosurgeons., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown., Methods: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors., Results: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response., Conclusions: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors., (© 2024. The Author(s).)

The conventional microscope has the disadvantage of a potentially unergonomic posture for the surgeon, which can affect performance. Monitor-based exoscopes could provide a more ergonomic posture, as already shown in pre-clinical studies. The aim of this study was to test the usability and comfort of a novel head-mounted display (HMD)-based exoscope on spinal surgical approaches in a simulated OR setting. A total of 21 neurosurgeons naïve to the device were participated in this prospective trial. After a standardized training session with the device, participants were asked to perform a single-level thoracolumbar decompression surgery on human cadavers using the exoscope. Subsequently, all participants completed a comfort and safety questionnaire. For the objective evaluation of the performance, all interventions were videotaped and analyzed. Twelve men and nine women with a mean age of 34 (range: 24-57) were participating in the study. Average time for decompression was 15 min (IqR 9.6; 24.2); three participants (14%) terminated the procedure prematurely. In these dropouts, a significantly higher incidence of back/neck pain (p = 0.002 for back, p = 0.046 for neck pain) as well as an increased frequency of HMD readjustments (p = 0.045) and decreased depth perception (p = 0.03) were documented. Overall, the surgeons' satisfaction with the exoscope was 84% (IqR 75; 100). Using a standardized, pre-interventional training, it is possible for exoscope-naïve surgeons to perform sufficient spinal decompression using the HMD-based exoscope with a high satisfaction. However, inaccurate HMD setup prior to the start of the procedure may lead to discomfort and unsatisfactory results., (© 2024. The Author(s).)

Background: The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification., Methods: In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines., Results: The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients., Conclusions: The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer., Competing Interests: M.P. has received honoraria for lectures, consultation, or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, but declares no nonfinancial competing interests. G.L. holds shares in the company contextflow and has received honoraria for lectures from the following for-profit companies: Boehringer Ingelheim, Novartis, and declares no nonfinancial competing interests. All other authors declare no financial or nonfinancial conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Radiation necrosis (RN) is a possible late complication of stereotactic radiosurgery (SRS), but only a few risk factors are known. The aim of this study was to assess tumor location in correlation to the development of radiation necrosis for skull base (SB) and non-skull base tumors., Methods: All patients treated with radiosurgery for benign neoplasms (2004-2020) were retrospectively evaluated. The clinical, imaging and medication data were obtained and the largest axial tumor diameter was determined using MRI scans in T1-weighted imaging with gadolinium. The diagnosis of RN was established using imaging parameters. Patients with tumors located at the skull base were compared to patients with tumors in non-skull base locations., Results: 205 patients could be included. Overall, 157 tumors (76.6%) were located at the SB and compared to 48 (23.4%) non-SB tumors. Among SB tumors, the most common were vestibular schwannomas (125 cases) and meningiomas (21 cases). In total, 32 (15.6%) patients developed RN after a median of 10 (IqR 5-12) months. Moreover, 62 patients (30.2%) had already undergone at least one surgical resection. In multivariate Cox regression, SB tumors showed a significantly lower risk of radiation necrosis with a Hazard Ratio (HR) of 0.252, p < 0.001, independently of the applied radiation dose. Furthermore, higher radiation doses had a significant impact on the occurrence of RN (HR 1.372, p = 0.002)., Conclusions: The risk for the development of RN for SB tumors appears to be low but should not be underestimated. No difference was found between recurrent tumors and newly diagnosed tumors, which may support the value of radiosurgical treatment for patients with recurrent SB tumors.

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Post-hemorrhagic vasospasm with neurological deterioration is a major concern in this context. NicaPlant®, a modified release formulation of the calcium channel blocker nicardipine, has shown vasodilator efficacy preclinically and a similar formulation known as NPRI has shown anti-vasospasm activity in aSAH patients under compassionate use., Research Question: The study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH., Material and Methods: In this multicenter, controlled, randomized, dose escalation trial we assessed the safety and tolerability of NicaPlant®. aSAH patients treated by clipping were randomized to receive up to 13 NicaPlant® implants, similarly to the dose of NPRIs previous used, or standard of care treatment., Results: Ten patients across four dose groups were treated with NicaPlant® (3-13 implants) while four patients received standard of care. 45 non-serious and 13 serious adverse events were reported, 4 non-serious adverse events and 5 serious adverse events assessed a probable or possible causal relationship to the investigational medical product. Across the NicaPlant® groups there was 1 case of moderate vasospasm, while in the standard of care group there were 2 cases of severe vasospasm., Discussion and Conclusion: The placement of NicaPlant® during clip ligation of a ruptured cerebral aneurysm raised no safety concern. The dose of 10 NicaPlant® implants was selected for further clinical studies., Competing Interests: TA is Chief Scientific Officer at BIT Pharma; BJ is Chief Executive Officer, co-founder and shareholder at BIT Pharma; VP is consultant and shareholder at BIT Pharma. The other authors declare no conflict of interests., (© 2023 The Authors.)

Background: GBM research is constantly assessing potential valuable prognostic biomarkers to better understand the disease and prognosticate future outcomes. Measuring temporal muscle thickness (TMT) has appeared to be a promising new surrogate marker for skeletal muscle mass and sarcopenia, which further indicates frailty and predicts overall survival (OS). The aim of this study was to determine its usefulness as a prognostic marker in patients with high-grade glioma compared to functional status scales., Methods: TMT was measured in preoperative axial T1-weighted contrast-enhanced magnetic resonance images in 277 patients who received surgical treatment of newly diagnosed WHO III and IV gliomas in our institution between 2015 and 2020. Clinical Frailty Scale (CFS) and Karnofsky Performance Scale (KPS) were assessed preoperatively and during a follow-up visit., Results: Female gender has shown significant correlation with TMT, while TMT did not correlate with preoperative and follow-up functional scores, age, WHO classification, IDH mutation, MGMT promoter methylation, EGFR and ATRX expression, or 1p/19q co-deletion. No significant prognostic value of TMT could be shown in 6, 12, and 24 months OS, while changes in CFS and KPS proved to have a significant impact., Conclusion: Only female gender, but no other clinical, histological, or molecular marker showed any interrelation with TMT. Functional scores outclass measuring TMT as a reliable prognostic factor for predicting OS in patients with high-grade glioma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Klingenschmid, Krigers, Schön, Pinggera, Kerschbaumer, Grams, Thomé and Freyschlag.)

Introduction: Technological advancements provided several preoperative tools allowing for precise preoperative planning in cranial neurosurgery, aiming to increase the efficacy and safety of surgery. However, little data are available regarding if and how young neurosurgeons are trained in using such technologies, how often they use them in clinical practice, and how valuable they consider these technologies., Research Question: How frequently these technologies are used during training and clinical practice as well as to how their perceived value can be qualitatively assessed., Materials and Methods: The Young Neurosurgeons' Committee (YNC) of the European Association of Neurosurgical Societies (EANS) distributed a 14-items survey among young neurosurgeons between June 1st and August 31st , 2022., Results: A total of 441 responses were collected. Most responders (42.34%) received "formal" training during their residency. Planning techniques were used mainly in neuro-oncology (90.86%), and 3D visualization of patients' DICOM dataset using open-source software was the most frequently used (>20 times/month, 20.34% of responders). Software for 3D visualization of patients' DICOM dataset was the most valuable technology, especially for planning surgical approach (42.03%). Conversely, simulation based on augmented/mixed/virtual reality was considered the less valuable tool, being rated below sufficiency by 39.7% of responders., Discussion and Conclusion: Training for using preoperative planning technologies in cranial neurosurgery is provided by neurosurgical residency programs. Software for 3D visualization of DICOM datasets is the most valuable and used tool, especially in neuro-oncology. Interestingly, simulation tools based on augmented/virtual/mixed reality are considered less valuable and, therefore, less used than other technologies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiri Bartek Jr reports a relationship with Medtronic Inc that includes: consulting or advisory., (© 2023 The Authors.)

Introduction: Preoperative corticosteroid therapy (CST) is common in primary central nervous system lymphoma (PCNSL) and may complicate histopathological diagnosis. There is an ongoing debate on the best management after preoperative CST., Research Question: We aimed to survey how different European neurosurgical units treat PCNSL patients after preoperative CST., Methods: An English-language survey consisting of 21 questions addressing the management of patients with suspected PCNSL and preoperative CST was sent to European hospitals. The survey also included three clinical cases to assess the decision-making process in a clinical setting., Results: The survey was completed by 74 European hospitals. There was no clear consensus on how to treat a patient with PCNSL after CST. Accordingly, 24.3% responded that they would generally defer surgery regardless of a possible radiological response, 47.3% would defer surgery only if there is regression in preoperative MRI and the remaining 28.4% would defer surgery only if the tumor had completely vanished. Furthermore, there were distinct discrepancies in responses of neurosurgical units regarding their general management approach and their case-based decision in the three example cases. The results of our survey also showed regional differences and differences in treatment decisions between high-, intermediate- and low-volume centers., Discussion and Conclusion: There was no clear consensus on how to treat patients with suspected PCNSL and preoperative CST. Furthermore, most centers also showed inconsistencies in their responses regarding their general approach as well as individual patient treatment. More high-quality evidence-based recommendations are needed to improve consensus and thus patient care., Competing Interests: The authors do not have any conflicts of interest, financial or otherwise., (© 2023 The Authors.)

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic., Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients' location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality., Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37-5.74) compared to HIC., Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Purpose: Data on differences in overall survival and molecular characteristics between incidental (iLGG) and symptomatic lower grade Glioma (sLGG) are limited. The aim of this study was to investigate differences between patients with iLGG and sLGG., Methods: All adult patients with a histologically proven diffuse (WHO°II) or anaplastic (WHO°III) glioma who underwent their first surgery at the authors' institution between 2010 and 2019 were retrospectively included. Tumor volume on pre- and postoperative MRI scans was determined. Clinical and routine neuropathological data were gained from patients' charts. If IDH1, ATRX and EGFR were not routinely assessed, they were re-determined., Results: Out of 161 patients included, 23 (14%) were diagnosed as incidental findings. Main reasons for obtaining MRI were: headache(n = 12), trauma(n = 2), MRI indicated by other departments(n = 7), staging examination for cancer(n = 1), volunteering for MRI sequence testing(n = 1). The asymptomatic patients were significantly younger with a median age of 38 years (IqR28-48) vs. 50 years (IqR38-61), p = 0.011. Incidental LGG showed significantly lower preoperative tumor volumes in T1 CE (p = 0.008), FLAIR (p = 0.038) and DWI (p = 0.028). Incidental LGG demonstrated significantly lower incidence of anaplasia (p = 0.004) and lower expression of MIB-1 (p = 0.008) compared to sLGG. IDH1-mutation was significantly more common in iLGG (p = 0.024). Incidental LGG showed a significantly longer OS (mean 212 vs. 70 months, p = 0.005) and PFS (mean 201 vs. 61 months, p = 0.001) compared to sLGG., Conclusion: Our study is the first to depict a significant difference in molecular characteristics between iLGG and sLGG. The findings of this study confirmed and extended the results of previous studies showing a better outcome and more favorable radiological, volumetric and neuropathological features of iLGG., (© 2023. The Author(s).)

Glioblastoma is the most common malignant brain tumor in adults. Standard treatment includes tumor resection, radio-chemotherapy and adjuvant chemotherapy with temozolomide (TMZ). TMZ methylates DNA, whereas O6-methylguanine DNA methyltransferase (MGMT) counteracts TMZ effects by removing the intended proteasomal degradation signal. Non-functional MGMT mediates the mismatch repair (MMR) system, leading to apoptosis after futile repair attempts. This study investigated the associations between MGMT promoter methylation, MGMT and MMR protein expression, and their effect on overall survival (OS) and progression-free survival (PFS) in patients with glioblastoma. MGMT promoter methylation was assessed in 42 treatment-naïve patients with glioblastoma WHO grade IV by pyrosequencing. MGMT and MMR protein expression was analyzed using immunohistochemistry. MGMT promoter methylation was present in 52%, whereas patients <70 years of age revealed a significantly longer OS using a log-rank test and a significance threshold of p ≤ 0.05. MGMT protein expression and methylation status showed no correlation. MMR protein expression was present in all patients independent of MGMT status and did not influence OS and PFS. Overall, MGMT promoter methylation implicates an improved OS in patients with glioblastoma aged <70 years. In the elderly, the extent of surgery has an impact on OS rather than the MGMT promoter methylation or protein expression.

Background: Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors., Methods: The expression of Cx43 and Ki67 were assessed in formalin-fixed paraffin embedded samples of human brain metastases, meningiomas, and neurinomas using immunohistochemistry. Neurinomas and meningiomas were jointly evaluated due to similar non-malignant behavior., Results: A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 ( P  = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 ( P  < 0.001), but did not show statistically significant correlation with Cx43 expression in these tumors., Conclusions: The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.