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Purpose: Patients with brain metastasis (BM) from solid tumors are in an advanced stage of cancer. BM may occur during a known oncological disease (metachronous BM) or be the primary manifestation of previously unknown cancer (synchronous BM). The time of diagnosis might decisively impact patient prognosis and further treatment stratification. In the present study, we analyzed the prognostic impact of synchronous versus (vs.) metachronous BM occurrence following resection of BM., Methods: Between 2013 and 2018, 353 patients had undergone surgical therapy for BM at the authors' neuro-oncological center. Survival stratification calculated from the day of neurosurgical resection was performed for synchronous vs. metachronous BM diagnosis., Results: Non-small-cell lung carcinoma (NSCLC) was the most common tumor entity of primary site (43%) followed by gastrointestinal cancer (14%) and breast cancer (13%). Synchronous BM occurrence was present in 116 of 353 patients (33%), metachronous BM occurrence was present in 237 of 353 patients (67%). NSCLC was significantly more often diagnosed via resection of the BM (56% synchronous vs. 44% metachronous situation, p = 0.0001). The median overall survival for patients with synchronous BM diagnosis was 12 months (95% confidence interval (CI) 7.5-16.5) compared to 13 months (95% CI 9.6-16.4) for patients with metachronous BM diagnosis (p = 0.97)., Conclusions: The present study indicates that time of BM diagnosis (synchronous vs. metachronous) does not significantly impact patient survival following surgical therapy of BM. These results suggest that the indication for neurosurgical BM resection should be made regardless of a synchronous or a metachronous time of BM occurrence., (© 2023. The Author(s).)

We hypothesized that the enzyme arginase-1 is released into the cerebrospinal fluid (CSF) during red blood cell lysis and contributes to dysregulated metabolism of the nitric oxide (NO) precursor L-arginine during aneurysmal subarachnoid hemorrhage (SAH). This prospective case-control study included 43 patients with aneurysmal SAH and ventricular drainage for clinical reasons. Longitudinal CSF samples (99) were obtained in the course of SAH. Patients were dichotomized regarding the occurrence of cerebral vasospasm syndrome (CVS) (N = 19). Arginase-1 and the amino acids L-arginine and L-ornithine were quantified in CSF. Outcome assessments included delayed cerebral ischemia (DCI) and functional status after 3 months using the modified Rankin Scale (mRS). Arginase-1 was released into the CSF of SAH patients whereas this enzyme was undetectable in controls. Compared to patients without CVS, arginase-1 levels were higher in CVS patients until day 14 after clinical event. The well-known surrogate parameter for arginase acitivity, the L-arginine to L-ornithine ratio (Arg/Orn), correlated with CSF arginase-1 levels. Arg/Orn was reduced in patients with CVS from disease onset (days 1-3, p = 0.0009) until day 14. Logistic regression analysis of early Arg/Orn was predictive for CVS (p = 0.008) and DCI (p = 0.035), independent of age, Hunt and Hess grade, and intraventricular blood. Arg/Orn < 2.71 at disease onset predicted CVS with a sensitivity of 86.7% and specificity of 72.2%. Arg/Orn ≥ 2.71 predicted excellent functional outcome. We propose a novel mechanism contributing to NO deprivation during SAH: arginase-1 is released from erythrocytes into the CSF, leading to L-arginine consumption and reduced NO bioavailability. Furthermore, Arg/Orn is a robust predictor for occurrence of CVS, DCI, and functional outcome 3 months after aneurysmal SAH. Our data provide a novel prognostic biomarker and may contribute to the development of novel therapeutic strategies in SAH. Clinical Trial Registration-URL: http://www.drks.de . Unique identifier: DRKS00015293, date of registration: 13.09.2018., (© 2021. The Author(s).)

Background: Recent investigations showed emerging evidence of the role of inflammation in the growth of sporadic vestibular schwannoma (VS). The present retrospective study investigated the impact of systemic inflammation on tumor progression using serum C-reactive protein (CRP) levels in a series of 87 surgically treated sporadic VS patients., Methods: The optimal cut-off value for CRP was defined as 3.14 mg/dl according to the receiver operating characteristic curve (AUC: 0.70, 95% CI 0.47-0.92). Patient cohort was dichotomized into normal (n = 66; < 3.14 mg/dl) and high baseline (n = 21; ≥ 3.14 mg/dl) CRP groups., Results: No significant differences in age, sex, comorbidities influencing the systemic inflammatory state, Karnofsky performance status (KPS), tumor size, extent of resection, or MIB-1 index were identified between the two groups defined by the baseline CRP levels. Univariable analysis demonstrated that a high CRP level (≥ 3.14 mg/dl) is significantly associated with a shortened progression-free survival (PFS) (hazard ratio (HR): 6.05, 95% CI 1.15-31.95, p = 0.03). Multivariable Cox regression analysis considering age, extent of resection, KPS, tumor size, and baseline CRP confirmed that an elevated CRP level (≥ 3.14 mg/dl) is an independent predictor of shortened PFS (HR: 7.20, 95% CI 1.08-48.14, p = 0.04)., Conclusions: The baseline CRP level thus serves as an independent predictor of PFS. Further investigations of the role of inflammation and tumor inflammatory microenvironment in the prediction of prognosis in sporadic VS are needed., (© 2021. The Author(s).)

Object: The conception of individual patient-adjusted treatment strategies is constantly emerging in the field of neuro-oncology. Systemic laboratory markers may allow insights into individual needs and estimated treatment benefit at an earliest possible stage. Therefore, the present study was aimed at analyzing the prognostic significance of preoperative routine laboratory values in patients with newly-diagnosed glioblastoma., Methods: Between 2014 and 2019, 257 patients were surgically treated for newly-diagnosed glioblastoma at the Neuro-Oncology Center of the University Hospital Bonn. Preoperative routine laboratory values including red blood cell distribution width (RDW) and platelet count were reviewed. RDW to platelet count ratio (RPR) was calculated and correlated to overall survival (OS) rates., Results: Median preoperative RPR was 0.053 (IQR 0.044-0.062). The receiver operating characteristic (ROC) curve indicated an optimal cut-off value for RPR to be 0.05 (AUC 0.62; p = 0.002, 95% CI 0.544-0.685). 101 patients (39%) presented with a preoperative RPR < 0.05, whereas 156 patients (61%) had a RPR ≥ 0.05. Patients with preoperative RPR < 0.05 exhibited a median OS of 20 months (95% CI 17.9-22.1), which was significantly higher compared to a median OS of 13 months (95% CI 10.9-15.1) in patients with preoperative RPR ≥ 0.05 (p < 0.001)., Conclusions: The present study suggests the RPR to constitute a novel prognostic inflammatory marker for glioblastoma patients in the course of preoperative routine laboratory examinations and might contribute to a personalized medicine approach., (© 2021. The Author(s).)

Purpose: Neuro-oncology tumor boards (NTBs) hold an established function in cancer care as multidisciplinary tumor boards. However, NTBs predominantly exist at academic and/or specialized centers. In addition to increasing centralization throughout the healthcare system, changes due to the COVID-19 pandemic have arguably resulted in advantages by conducting clinical meetings virtually. We therefore asked about the experience and acceptance of (virtualized) NTBs and their potential benefits., Methods: A survey questionnaire was developed and distributed via a web-based platform. Specialized neuro-oncological centers in Germany were identified based on the number of brain tumor cases treated in the respective institution per year. Only one representative per center was invited to participate in the survey. Questions targeted the structure/organization of NTBs as well as changes due to the COVID-19 pandemic., Results: A total of 65/97 institutions participated in the survey (response rate 67%). In the context of the COVID-19 pandemic, regular conventions of NTBs were maintained by the respective centers and multi-specialty participation remained high. NTBs were considered valuable by respondents in achieving the most optimal therapy for the affected patient and in maintaining/encouraging interdisciplinary debate/exchange. The settings of NTBs have been adapted during the pandemic with the increased use of virtual technology. Virtual NTBs were found to be beneficial, yet administrative support is lacking in some places., Conclusions: Virtual implementation of NTBs was feasible and accepted in the centers surveyed. Therefore, successful implementation offers new avenues and may be pursued for networking between centers, thereby increasing coverage of neuro-oncology care., (© 2021. The Author(s).)

Introduction: The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures., Methods: Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors' institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2-6)., Results: Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4-515.9)., Conclusions: ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.

Object: Increasing age is a known negative prognostic factor for glioblastoma. However, a multifactorial approach is necessary to achieve optimal neuro-oncological treatment. It remains unclear to what extent frailty, comorbidity burden, and obesity might exert influence on survival in geriatric glioblastoma patients. We have therefore reviewed our institutional database to assess the prognostic value of these factors in elderly glioblastoma patients., Methods: Between 2012 and 2018, patients aged ≥ 65 years with newly diagnosed glioblastoma were included in this retrospective analysis. Patients frailty was analyzed using the modified frailty index (mFI), while patients comorbidity burden was assessed according to the Charlson comorbidity index (CCI). Body mass index (BMI) was used as categorized variable., Results: A total of 110 geriatric patients with newly diagnosed glioblastoma were identified. Geriatric patients categorized as least-frail achieved a median overall survival (mOS) of 17 months, whereas most frail patients achieved a mOS of 8 months (p = 0.003). Patients with a CCI > 2 had a lower mOS of 6 months compared to patients with a lower comorbidity burden (12 months; p = 0.03). Multivariate analysis identified "subtotal resection" (p = 0.02), "unmethylated MGMT promoter status" (p = 0.03), "BMI < 30" (p = 0.04), and "frail patient (mFI ≥ 0.27)" (p = 0.03) as significant and independent predictors of 1-year mortality in geriatric patients with surgical treatment of glioblastoma (Nagelkerke's R 2 0.31)., Conclusions: The present study concludes that both increased frailty and comorbidity burden are significantly associated with poor OS in geriatric patients with glioblastoma. Further, the present series suggests an obesity paradox in geriatric glioblastoma patients.

Introduction: Supra-total resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma. However, aggressive onco-surgical approaches-geared beyond conventional gross total resections (GTR)-may be associated with peri- and postoperative unfavorable events which significantly worsen initial favorable postoperative outcome. In the current study we analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSC) as high standard quality metric profiles in patients that had undergone surgery for temporal glioblastoma., Methods: Between 2012 and 2018, 61 patients with temporal glioblastoma underwent GTR or temporal lobectomy at the authors' institution. Both groups of differing resection modalities were analyzed with regard to the incidence of PSIs, HACs and CSCs., Results: Overall, we found 6 PSI and 2 HAC events. Postoperative hemorrhage (3 out of 61 patients; 5%) and catheter-associated urinary tract infection (2 out 61 patients; 3%) were identified as the most frequent PSIs and HACs. PSIs were present in 1 out of 41 patients (5%) for the temporal GTR and 2 out of 20 patients for the lobectomy group (p = 1.0). Respective rates for PSIs were 5 of 41 (12%) and 1 of 20 (5%) (p = 0.7). Further, CSCs did not yield significant differences between these two resection modalities (p = 1.0)., Conclusion: With regard to ATL and GTR as differing onco-surgical approaches these data suggest ATL in terms of an aggressive supra-total resection strategy to preserve perioperative standard safety metric profiles.

Background: Patients suffering from aneurysmal subarachnoid hemorrhage (SAH) with shunt-dependent hydrocephalus require subsequent placement of a ventriculoperitoneal shunt (VPS) after ventriculostomy. However, in patients with previous ventriculostomy, the site for proximal VPS catheter placement is still controversial. We investigated the effect of catheter placement on postoperative complications by analyzing patients with ventriculostomy and subsequent VPS placement after SAH., Methods: From January 2004 to December 2018, 164 of 1128 patients suffering from SAH underwent subsequent VPS placement after ventriculostomy in the authors' institution. Patients were divided into two groups according to the position of the ventriculostomy and the site of the proximal VPS catheter ("same site" group versus "contralateral site" group). VPS-related infectious and bleeding complications following VPS placement were assessed and analyzed., Results: Overall, VPS-related infections occurred in 11 of the 164 patients (7%). Furthermore, five of the 164 patients (3%) suffered from VPS-related hemorrhage. However, VPS infection rate was lower 5% (6/115) in the same site compared to 10% (5/49) in the contralateral site group, although without reaching statistical significance (OR = 0.48 (0.14, 1.67) 95% confidence interval, p = 0.3). VPS-related hemorrhage rate did not differ significantly between patients in the same site group (3.5%, 4/115) and the contralateral site group (2.0%, 1/49; OR = 1.73 (0.18, 15.9), p = 1.0)., Conclusions: Our study suggests that the use of the ventriculostomy site for VPS placement does not significantly increase the risk of either VPS-related infections or VPS-related hemorrhages.

Background: Facial nerve palsy is a severe morbid condition that occurs after vestibular schwannoma (VS) surgery. The objective of this study was to evaluate facial nerve outcomes based on surgical techniques, tumour size, and immunohistochemical factors., Methods: One hundred eighteen patients with VS were retrospectively analysed. Gross total resection (GTR) was achieved in 83 patients, and subtotal resection (STR) was achieved in 35 patients. Follow-up was 60 months (median). Facial nerve outcomes were assessed for 24 months after surgery. Analysis of the MIB-1 index was performed in 114 patients (97%) to evaluate recurrence and facial nerve outcomes., Results: Immediately after surgery, 16 of 35 patients (45.7%) with STR and 21 of 83 patients (25.3%) with GTR had a good (House-Brackmann (HB) score ≤ 2) facial nerve outcome (p = 0.029). Semi-sitting positioning (p = 0.002) and tumour size class of 3 (> 4 cm) were also associated with worse HB outcomes after 2 years (p = 0.004) in univariate analyses. The MIB-1 index was significantly correlated with diffuse infiltration of tumour-associated CD45 + lymphocytes (r = 0.63, p = 0.015) and CD68 + macrophages (r = 0.43, p = 0.021). ROC analysis found an AUC of 0.73 (95% CI = 0.60-0.86, p = 0.003) for the MIB-1 index in predicting poor facial nerve outcomes. Binary logistic regression analysis revealed an MIB-1 index ≥ 5% (16/28 (57.1%) vs. 5/40 (12.5%); p < 0.001, OR = 14.0, 95% CI = 3.2-61.1) and a tumour size class of 3 (6/8 (75.0%) vs. 2/8 (25.0%); p = 0.01, OR = 14.56, 95% CI = 1.9-113.4) were predictors of poor HB scores (≥ 3) after 1 year., Conclusions: An MIB-1 index ≥ 5% seems to predict worse long-term facial nerve outcomes in VS surgery.

Objective: Supra-total glioblastoma resection has gained growing attention with regard to superior long-term disease control. However, aggressive onco-surgical approaches-geared beyond conventional gross total resections (GTR)-are limited by the impairment of adjacent eloquent areas at risk that may entail severe postoperative functional morbidity. Against this backdrop we analyzed our institutional database with regard to potential survival benefits of anterior temporal lobectomy as a paradigm for supra-total resection in patients with precisely temporal-located, non-eloquent glioblastoma., Methods: Between 2012 and 2017, 38 patients with isolated temporal glioblastoma underwent GTR or temporal lobectomy at the authors' institution. Both groups of differing resection modalities were compared with regard to postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS)., Results: Patients with temporal lobectomy exhibited significantly superior median KPS at the 12 months follow-up compared to the GTR group (median KPS of 80 vs. 60, p = 0.04). Temporal lobectomy was associated with significantly prolonged PFS (p = 0.005) and OS (p = 0.002) coming up to 15 months (95% CI 9.7-22.1) and 23 months (95% CI 14.8-34.5) compared to 7 months (95% CI 3.3-8.3) and 11 months (95% CI 9.2-17.9) for the GTR group. Multivariate analysis revealed temporal lobectomy as the only predictor for both superior PFS (p = 0.037, OR 7.3, 95% CI 1.1-47.4) and OS (p = 0.04, OR 7.8, 95% CI 1.1-55.2)., Conclusions: These results strongly suggest temporal lobectomy as an aggressive supra-total resection policy to constitute the surgical modality of choice for isolated temporal-located glioblastoma.

Background: Under physiological cerebral conditions, levosimendan, a calcium-channel sensitizer, has a dose-dependent antagonistic effect on prostaglandin F2alpha (PGF)-induced vasoconstriction. This circumstance could be used in antagonizing delayed cerebral vasospasm (dCVS), one of the main complications after subarachnoid hemorrhage (SAH), leading to delayed cerebral ischemia and ischemic neurological deficits. Data already exist that identified neuroprotective effects of levosimendan in a traumatic brain injury model and additionally, it has been proven that this compound prevents narrowing of the basilar artery (BA) luminal area after SAH in an in vitro rabbit model. Takotsubo cardiomyopathy, a severe ventricular dysfunction, is also a well-known complication after SAH, associated with pulmonary edema and prolonged intubation., Methods: The polypeptide endothelin-1 (ET-1) plays a key role in the development of dCVS after SAH. Therefore, the aim of the present investigation was to detect functional interactions between the calcium-sensitizing and the ET-1-dependent vasoconstriction after experimental-induced SAH; interactions between levosimendan and a substrate-specific vasorelaxation in the BA were also examined. It was reviewed whether levosimendan has a beneficial influence on endothelin(A) and/or endothelin(B 1 ) receptors (ET-(A) and ET-(B 1 ) receptors) in cerebral vessels after SAH. We also examined whether this drug could have antagonistic effects on a PGF-induced vasoconstriction., Results: Under treatment with levosimendan after SAH, the endothelin system seems to be affected. The ET-1-induced contraction is decreased, not significantly. In addition, we detected changes in the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. Preincubation with levosimendan causes a modulatory effect on the ET-(B 1 ) receptor-dependent vasorelaxation. It induces an upregulation of the NO-cGMP pathway with a significantly increased relaxation. Even after PGF-induced precontraction a dose-dependent relaxation was registered, which was significantly higher (E max ) and earlier (pD 2 ) compared to the concentration-effect curve without levosimendan., Conclusions: After experimental-induced dCVS, levosimendan seems to restore the well-known impaired function of the vasorelaxant ET-(B 1 ) receptor. Levosimendan also reversed the PGF-induced contraction dose-dependently. Both of these mechanisms could be used for antagonizing dCVS in patients suffering SAH. Levosimendan could even be used additionally in treating patients developing takotsubo cardiomyopathy.

Aneurysmal subarachnoid hemorrhage comprises of an early phase after the bleeding and a late phase of delayed consequences of the bleeding. The development of delayed injury mechanisms, like the reduction of cerebral blood flow (CBF) due to cerebral vasospasm (CVS), seems mainly to depend on the amount and the duration of the subarachnoid blood clot. The reduction of CBF may lead to cerebral ischemia and delayed neurological deterioration. The rat double cisterna magna injection model reproduces the time course of the delayed consequences of CVS and imitates the clinical setting more precise than other rodent subarachnoid hemorrhage models. Therefore, the rat double cisterna magna injection model seems to be predisposed to be used to mimick the delayed consequences of subarachnoid hemorrhage. We reviewed the existing literature on this animal model and propose a standard protocol including technical considerations, as well as advantages and limitations of this model.

Gliosarcoma is a relatively rare and highly malignant brain tumor consisting of both a glioblastoma and a mesenchymal component. Because of the natural barrier of the dura mater, that prevents intra or extradural neoplasm dissemination, cases of penetration of the dura and cranium by gliosarcomas without previous surgery or radiation are very rarely reported. We report an unusual case of gliosarcoma that involved the temporal skull base and the dura without antecedent radiation or surgery, although the lesion traversed the dura without radiologic or gross interruption of the dura. Remarkable in our case is the initial integrity of cerebral parenchyma. Follow-up revealed a tumorous infiltration of the temporal lobe almost one year after initial diagnosis. Thus the origin of the gliosarcoma in our case seemed to be extradural in the temporal skull base. Furthermore, this report demonstrates that extensive multi-modality treatment might be effective in patients with gliosarcomas and poor prognostic factors, for example unmethylated MGMT status.

Background: The objective was to assess the surgical results in complex middle cerebral artery (MCA) aneurysms., Methods: From 1999 to 2009 the data of 330 patients with ruptured and unruptured MCA aneurysms were included into a prospective database. Degree of aneurysm occlusion and clinical outcomes were analysed after 271 surgical and 59 endovascular treatments assigned in an interdisciplinary approach. Aneurysms of large size and/or broad base, calcifications, and incorporation of M1 or M2 segments into the aneurysm base were defined as complex., Findings: At least one of the criteria for complexity mentioned above was met in 97.8% of the MCA aneurysms that were treated surgically and in 76.3% that were treated endovascularly. In MCA aneurysms treated surgically, complete occlusion was achieved in 264 of the 271 (97.4%) aneurysms. Aneurysms with remnants after surgical treatment were significantly larger in size (17 ± 3 mm vs 7 ± 5 mm), and exhibited significantly more often parent vessel involvement (M1: 86% vs 27%; M2: 100% vs 67%) compared with the group of aneurysms that could be treated without remnant. Compared with our institutional data (52.5% complete occlusion rate) and data of the literature (up to 46.1% complete occlusion rate), the occlusion rates of endovascularly treated MCA aneurysms were significantly lower compared with MCA aneurysms treated surgically., Conclusions: Surgical treatment of ruptured and unruptured MCA aneurysms results in a significantly higher rate of complete aneurysm occlusion compared with endovascular treatment, despite a high rate of complex aneuryms in the surgically treated group.