A Long-Term Comparative Analysis of Endovascular Coiling and Clipping for Ruptured Cerebral Aneurysms: An Individual Patient-Level Meta-Analysis Assessing Rerupture Rates.

Background: Although the initial functional outcome findings of the International Subarachnoid Aneurysm Trial (ISAT) study favored coiling at one year after aneurysmal subarachnoid hemorrhage (aSAH), concerns arose regarding limited long-term rerupture data. This meta-analysis is the first to analyze longitudinal individual patient data (IPD) of target aneurysm rerupture in terms of treatment modality. Methods: The present meta-analysis included studies that compared clipping with coiling of ruptured aneurysms regarding long-term rerupture. Rerupture rates' individual patient data (IPD) were extracted from published Kaplan-Meier curves utilizing the R package IPDfromKM in R Version 4.3.1. Results: A total of 3153 patients from two studies were included. The clipping arm included 1755 patients, whereas the coiling arm included 1398 patients. Median reconstructed follow-up was 6.1 years (IQR = 0.5-11.7). The rerupture rates in the clipping arm and the coiling arm were 0.5% and 1.5%, respectively (p = 0.002). Kaplan-Meier chart analysis of the 3153 patients revealed a shortened time to rerupture in the coiling arm (log-rank test: p = 0.01). The hazard ratio (HR) for coiling compared with clipping regarding rerupture was 3.62 (95% CI:1.21-10.86, p = 0.02). Conclusion: Target aneurysm rerupture was rare beyond the initial year. Pooled long-term IPD from the 3153 patients revealed that reruptures of target aneurysms are more common after coiling and might be considered in the pretherapeutic decision-making process for aSAH.

Anti-Inflammatory Drug Therapy in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Prospective Randomized and Placebo-Controlled Trials.

Emerging evidence suggests that neuroinflammation may play a potential role in aneurysmal subarachnoid hemorrhage (aSAH). We aim to analyze the influence of anti-inflammatory therapy on survival and outcome in aSAH. Eligible randomized placebo-controlled prospective trials (RCTs) were searched in PubMed until March 2023. After screening the available studies for inclusion and exclusion criteria, we strictly extracted the main outcome measures. Dichotomous data were determined and extracted by odds ratio (OR) with 95% confidence intervals (CIs). Neurological outcome was graded using the modified Rankin Scale (mRS). We created funnel plots to analyze publication bias. From 967 articles identified during the initial screening, we included 14 RCTs in our meta-analysis. Our results illustrate that anti-inflammatory therapy yields an equivalent probability of survival compared to placebo or conventional management (OR: 0.81, 95% CI: 0.55-1.19, p = 0.28). Generally, anti-inflammatory therapy trended to be associated with a better neurologic outcome (mRS ≤ 2) compared to placebo or conventional treatment (OR: 1.48, 95% CI: 0.95-2.32, p = 0.08). Our meta-analysis showed no increased mortality form anti-inflammatory therapy. Anti-inflammatory therapy in aSAH patients tends to improve the neurological outcome. However, multicenter, rigorous, designed, prospective randomized studies are still needed to investigate the effect of fighting inflammation in improving neurological functioning after aSAH.

Non-Convulsive Status Epilepticus in Aneurysmal Subarachnoid Hemorrhage: A Prognostic Parameter.

A non-convulsive status epilepticus (ncSE) is a potentially fatal complication for patients in neurointensive care. In patients with aneurysmal subarachnoid hemorrhage (SAH), ncSE remains scarcely investigated. In this study, we aim to investigate the frequency and influence of non-convulsive status epilepticus on outcome in patients with SAH. We retrospectively analyzed data of consecutive patients with aneurysmal subarachnoid hemorrhage and evaluated clinical, radiological, demographical and electroencephalogram (EEG) data. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months and stratified into favorable (mRS 0-2) vs. unfavorable (mRS 3-6). We identified 171 patients with SAH, who received EEG between 01/2012 and 12/2020. ncSE was diagnosed in 19 patients (3.7%), only one of whom achieved favorable outcome. The multivariate regression analysis revealed four independent predictors of unfavorable outcome: presence of ncSE (p = 0.003; OR 24.1; 95 CI% 2.9-195.3), poor-grade SAH (p < 0.001; OR 14.0; 95 CI% 8.5-23.1), age (p < 0.001; OR 2.8; 95 CI% 1.6-4.6) and the presence of DIND (p < 0.003; OR 1.9; 95 CI% 1.2-3.1) as independent predictors for unfavorable outcome. According to our study, development of ncSE in patients suffering SAH might correlate with poor prognosis. Even when medical treatment is successful and no EEG abnormalities are detected, the long-term outcome remains poor.

Asymptomatic Postoperative Cerebral Venous Sinus Thrombosis After Posterior Fossa Tumor Surgery: Incidence, Risk Factors, and Therapeutic Options.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a known complication of posterior fossa surgery near the sigmoid and transverse sinus. The incidence and treatment of postoperative asymptomatic CVST are controversial. OBJECTIVE: To analyze incidence, risk factors, and management of asymptomatic postoperative CVST after posterior fossa tumor surgery. METHODS: In this retrospective, single-center study, we included all patients who underwent posterior fossa tumor surgery in the semisitting position between January 2013 and December 2020. All patients underwent preoperative and postoperative imaging using MRI with/without additional computed tomography angiography. We analyzed the effect of demographic and surgical data on the incidence of postoperative CVST. Furthermore, therapeutic anticoagulation or conservative treatment for postoperative CVST and the incidence of intracranial hemorrhage were investigated. RESULTS: In total, 266 patients were included. Thirty-three of 266 (12.4%) patients developed postoperative CVST. All patients were asymptomatic. Thirteen of 33 patients received therapeutic anticoagulation, and 20 patients did not. Univariate analysis showed that age ( P = .56), sex ( P = .20), American Society of Anesthesiology status ( P = .13), body mass index ( P = .60), and length of surgery ( P = .176) were not statistically correlated with postoperative CVST. Multivariate analysis revealed that meningioma ( P < .001, odds ratio 11.3, CI 95% 4.1-31.2) and vestibular schwannoma ( P = .013, odds ratio 4.4, CI 95% 1.3-16.3) are risk factors for the development of new postoperative CVST. The use of therapeutic anticoagulation to treat postoperative CVST was associated with a higher rate of intracranial hemorrhage (n = 4, P = .017). CONCLUSION: Tumor entity influences the incidence of postoperative CVST. In clinically asymptomatic patients, careful decision making is necessary whether to initiate therapeutic anticoagulation or not.

Preoperative Risk Stratification of Increased MIB-1 Labeling Index in Pituitary Adenoma: A Newly Proposed Prognostic Scoring System.

The MIB-1 index is an important risk factor for progression-free survival (PFS) in pituitary adenoma (PA). Preoperatively, the MIB-1 index is not available in the decision-making process. A preoperative method regarding MIB-1 index estimation in PA has not been evaluated so far. Between 2011 and 2021, 109 patients with tumor morphology data, MIB-1 index data, and inflammatory and pituitary hormone laboratory values underwent surgery for PA. An MIB-1 index cutoff point (≥4/<4%) determines the probability of PFS in completely resected PA. An elevated MIB-1 index (≥4%) was present in 32 cases (29.4%) and was significantly associated with increased IGF-1, age ≤ 60, increased ACTH, and increased fibrinogen levels in the multivariable analysis. A scoring system ("FATE") using preoperative IGF-1, age, ACTH, and plasma fibrinogen level enables the estimation of the MIB-1 index (sensitivity 72%, specificity 68%). The FATE score is also significantly associated with the time to PA progression after the complete resection of the PA. We propose the FATE score to preoperatively estimate the risk of an elevated MIB-1 index (≥4%), which might enable tailoring to medical decision-making, and follow-up interval scheduling, as well as inform future studies analyzing proliferative activities.

Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: The Results of Induced Hypertension Only after the IMCVS Trial-A Prospective Cohort Study.

Delayed cerebral ischemia (DCI) is a predictor of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Treatment strategies vary and include induced hypertension and invasive endovascular treatment. After the IMCVS trial (NCT01400360), which failed to demonstrate a benefit of endovascular treatment for cerebral vasospasm (CVS) and resulted in a significantly worse outcome, we changed our treatment policy in patients with diagnosed CVS to induced hypertension only, and we present our prospective results in the subgroup of SAH patients meeting inclusion criteria of the IMCVS trial. All patients underwent screening for DIND when conscious and for CVS using CT-A/-P at day 6-8 after SAH. In the case of CVS, arterial hypertension was induced and continued until re-assessment. In total, 149 of 303 patients developed CVS. DCI developed in 35 patients (23.5%). In multivariate analyses, CVS was a predictor for the development of new infarctions. Poor admission status, re-bleeding before treatment, and DCI predicted poor outcome. The omittance of invasive endovascular rescue therapies in SAH patients with CVS, additional to induced hypertension, does not lead to a higher rate of DCI. Potential benefits of additional endovascular treatment for CVS need to be addressed in further studies searching for a subgroup of patients who may benefit.

Predictive Power of MIB-1 vs. Mitotic Count on Progression-Free Survival in Skull-Base Meningioma.

Although meningiomas are mainly non-aggressive and slow-growing tumors, there is a remarkable recurrence rate in a long-term follow-up. Proliferative activity and progression-free survival (PFS) differs significantly among the anatomic location of meningiomas. The aim of the present study was to investigate the predictive power of MIB-1 labeling index and mitotic count (MC) regarding the probability of PFS in the subgroup of skull-base meningiomas. A total of 145 patients were included in this retrospective study. Histopathological examinations and follow-up data were collected. Ideal cut-off values for MIB-1 and MC were ≥4.75 and ≥6.5, respectively. MIB-1 as well as MC were good predictors for PFS in skull-base meningiomas. Time-dependent analysis of MIB-1 and MC in prediction of recurrence of skull-base meningioma showed that their prognostic values were comparable, but different cut-offs for MC should be considered regarding the meningioma's location. As the achievement of a gross total resection can be more challenging in skull-base meningiomas and second surgery implies a higher risk profile, the recurrence risk could be stratified according to these findings and guide decision-making for follow-ups vs. adjuvant therapies.

Low-Dose Acetylsalicylic Acid Treatment in Non-Skull-Base Meningiomas: Impact on Tumor Proliferation and Seizure Burden.

MIB-1 index is an important predictor of meningioma progression and was found to be correlated with COX-2 expression. However, the impact of low-dose acetylsalicylic acid (ASA) on MIB-1 index and clinical symptoms is unclear. Between 2009 and 2022, 710 patients with clinical data, tumor-imaging data, inflammatory laboratory (plasma fibrinogen, serum C-reactive protein) data, and neuropathological reports underwent surgery for primary cranial WHO grade 1 and 2 meningioma. ASA intake was found to be significantly associated with a low MIB-1 labeling index in female patients ≥ 60 years. Multivariable analysis demonstrated that female patients ≥ 60 years with a non-skull-base meningioma taking ASA had a significantly lower MIB-1 index (OR: 2.6, 95%: 1.0-6.6, p = 0.04). Furthermore, the intake of ASA was independently associated with a reduced burden of symptomatic epilepsy at presentation in non-skull-base meningiomas in both genders (OR: 3.8, 95%CI: 1.3-10.6, p = 0.03). ASA intake might have an anti-proliferative effect in the subgroup of elderly female patients with non-skull-base meningiomas. Furthermore, anti-inflammatory therapy seems to reduce the burden of symptomatic epilepsy in non-skull-base meningiomas. Further research is needed to investigate the role of anti-inflammatory therapy in non-skull-base meningiomas.

MAC-spinal meningioma score: A proposal for a quick-to-use scoring sheet of the MIB-1 index in sporadic spinal meningiomas.

Objective: MIB-1 index is an important predictor of meningioma progression. However, MIB-1 index is not available in the preoperative tailored medical decision-making process. A preoperative scoring sheet independently estimating MIB-1 indices in spinal meningioma (SM) patients has not been investigated so far. Methods: Between 2000 and 2020, 128 patients with clinical data, tumor imaging data, inflammatory laboratory (plasma fibrinogen, serum C-reactive protein) data, and neuropathological reports (MIB-1, mitotic count, CD68 staining) underwent surgery for spinal WHO grade 1 and 2 meningioma. Results: An optimal MIB-1 index cut-off value (≥5/<5) predicting recurrence was calculated by ROC curve analysis (AUC: 0.83; 95%CI: 0.71-0.96). An increased MIB-1 index (≥5%) was observed in 55 patients (43.0%) and multivariable analysis revealed significant associations with baseline Modified McCormick Scale ≥2, age ≥65, and absence of calcification. A four-point scoring sheet (MAC-Spinal Meningioma) based on Modified McCormick, Age, and Calcification facilitates prediction of the MIB-1 index (sensitivity 71.1%, specificity 60.0%). Among those patients with a preoperative MAC-Meningioma Score ≥3, the probability of a MIB-1 index ≥5% was 81.3%. Conclusion: This novel score (MAC-Spinal Meningioma) supports the preoperative estimation of an increased MIB-1 index, which might support preoperative patient-surgeon consultation, surgical decision making and enable a tailored follow-up schedule or an individual watch-and-wait strategy.

Increased MIB-1 Labeling Index Is Associated with Abducens Nerve Morbidity in Primary Sporadic Petroclival Meningioma Surgery: Beyond Location and Approach.

Abducens nerve palsy is a severe dysfunction after petroclival meningioma (PC MNG) surgery. The objective of this investigation was to analyze abducens nerve outcomes in patients who underwent the retrosigmoid approach in relation to the MIB-1 index. Thirty-two patients with primary sporadic PC MNG were retrospectively analyzed. Mean follow-up was 28.0 months. Analysis of the MIB-1 index was performed to evaluate the abducens nerve outcome. An optimal MIB-1 index cut-off value (<4/≥4) in the association with postoperative CN VI palsy was determined by ROC analysis (AUC: 0.74, 95% CI: 0.57−0.92). A new-onset CN VI palsy was present in 7 cases (21.88%) and was significantly associated with an increased MIB-1 index (≥4%, p = 0.025) and a peritumoral edema in the brachium pontis (p = 0.047) which might be caused by the increased growth rate. Tumor volume, cavernous sinus infiltration, auditory canal invasion, and Simpson grading were not associated with new CN VI deficits. Six (85.7%) of the 7 patients with both an increased MIB-1 index (≥4%) and new abducens nerve palsy still had a CN VI deficit at the 12-month follow-up. A peritumoral edema caused by a highly proliferative PC MNG with an elevated MIB-1 index (≥4%) is associated with postoperative abducens nerve deficits.

Red Blood Cell Distribution Width to Platelet Count Ratio Facilitates Preoperative Prediction of Recurrence in Surgically Treated Chronic Subdural Hematoma.

Objective: Recent studies have demonstrated emerging evidence of the role of inflammation in the growth and recurrence of chronic subdural hematoma (cSDH). Red blood cell distribution width to platelet count ratio (RPR) is a novel biomarker for inflammation in cancer, cardiac, and inflammatory diseases. The present retrospective study investigated the impact of RPR on recurrence after burr hole surgery for cSDH in 297 patients. Methods: The optimal cut-off value for RPR was defined as ≥0.0568 according to the receiver operating characteristic curve (AUC:0.64, 95%CI:0.55-0.72, p = 0.007). The study cohort was dichotomized into low (n = 157) and high (n = 140) RPR groups. Results: Significant differences between the groups were identified regarding American Society of Anesthesiologists (ASA) classification and frequency of anticoagulant intake. Demographics, comorbidities, size, morphology, and mass effect of cSDH were homogeneously distributed among the RPR groups. Multivariable binary logistic regression analysis considering location, midline-shift, septation, RPR, anticoagulant intake, sex, and ASA classification revealed that an increased baseline RPR (≥0.0568, OR: 3.1, 95%CI: 1.4-6.8, p = 0.004), and preoperative midline-shift (≥5 mm, OR: 2.7, 95%CI: 1.3-6.0, p = 0.01) are independent predictors of recurrent cSDH. Conclusion: The present findings suggest RPR as a novel inflammatory biomarker enabling risk stratification of recurrence after burr hole surgery for cSDH and might facilitate tailored medical decision making.

Impact of Levetiracetam Treatment on 5-Aminolevulinic Acid Fluorescence Expression in IDH1 Wild-Type Glioblastoma.

The amino acid 5-aminolevulinic acid (5-ALA) is the most established neurosurgical fluorescent dye and facilitates the achievement of gross total resection. In vitro studies raised concerns that antiepileptic drugs (AED) reduce the quality of fluorescence. Between 2013 and 2018, 175 IDH1 wild-type glioblastoma (GB) patients underwent 5-ALA guided surgery. Patients' data were retrospectively reviewed regarding demographics, comorbidities, medications, tumor morphology, neuropathological characteristics, and their association with intraoperative 5-ALA fluorescence. The fluorescence of 5-ALA was graded in a three point scaling system (grade 0 = no; grade 1 = weak; grade 2 = strong). Univariable analysis shows that the intake of dexamethasone or levetiracetam, and larger preoperative tumor area significantly reduce the intraoperative fluorescence activity (fluorescence grade: 0 + 1). Multivariable binary logistic regression analysis demonstrates the preoperative intake of levetiracetam (adjusted odds ratio: 12.05, 95% confidence interval: 3.91-37.16, p = 0.001) as the only independent and significant risk factor for reduced fluorescence quality. Preoperative levetiracetam intake significantly reduced intraoperative fluorescence. The indication for levetiracetam in suspected GB should be carefully reviewed and prophylactic treatment avoided for this tumor entity. Future comparative trials of neurosurgical fluorescent dyes need a special focus on the influence of levetiracetam on fluorescence intensity. Further trials must validate our findings.

Inflammatory Tumor Microenvironment in Cranial Meningiomas: Clinical Implications and Intraindividual Reproducibility.

The MIB-1 index was demonstrated to be significantly correlated to meningioma recurrence. However, to date, the relationship of the intraindividual course of the MIB-1 index and the growth fraction, respectively, to clinical tumor recurrence has not been demonstrated in cranial WHO grade 1 and 2 meningiomas. In the present paper, we compare the MIB-1 indices of 16 solely surgically treated primary meningiomas and their recurrent tumors regarding the course of the MIB-1 indices, time to recurrence, reproducibility and factors influencing the intraindividual MIB-1 indices. Regression analyses revealed (1) a strong intra-lab reproducibility (r = 0.88) of the MIB-1 index at the second versus the first operation, corresponding to a constant intrinsic growth activity of an individual meningioma, (2) a significant inverse correlation of both primary (r = -0.51) and secondary (r = -0.70) MIB-1 indices to time to recurrence, and (3) male sex, low plasma fibrinogen and diffuse CD68+ macrophage infiltrates contribute to an increase in the MIB-1 index. A strong intraindividual reproducibility of the MIB-1 index and a direct relationship of the MIB-1 index to the time to recurrence were observed. Individual MIB-1 indices might be used for tailored follow-up imaging intervals. Further research on the role of macrophages and inflammatory burden in the regrowth potential of meningiomas are needed.

Proliferative Potential, and Inflammatory Tumor Microenvironment in Meningioma Correlate with Neurological Function at Presentation and Anatomical Location-From Convexity to Skull Base and Spine.

Emerging evidence emphasizes the prognostic importance of meningioma location. The present investigation evaluates whether progression-free survival (PFS), proliferative potential, World Health Organization (WHO) grades, and inflammatory burden differ between anatomical locations (skull base, non-skull base, and spinal) meningiomas. Five-hundred-forty-one patients underwent Simpson grade I or II resection for WHO grade 1 or 2 meningiomas. Univariable analysis revealed that spinal meningioma patients are significantly older, had a worse baseline Karnofsky Performance Status (KPS), higher acute-phase protein levels, lower incidence of WHO grade 2, lower mitotic counts, lower MIB-1 index, and less CD68+ macrophage infiltrates. Multivariable analysis identified WHO grade 2 (OR: 2.1, 95% CI: 1.1-3.7, p = 0.02) and cranial location (OR: 3.0, 95% CI: 1.8-4.9, p = 0.001) as independent predictors of diffuse CD68+ macrophage infiltrates. The mean PFS in cranial meningiomas was 115.9 months (95% CI: 107.5-124.3), compared to 162.2 months (95% CI: 150.5-174.0; log-rank test: p = 0.02) in spinal meningiomas. Multivariable Cox regression analysis revealed cranial location as an independent predictor (HR: 4.7, 95% CI: 1.0-21.3, p = 0.04) of shortened PFS. Increased MIB-1 indices ≥5% were significantly associated with location-specific deficits at presentation, such as decreased vision and seizure burden. Spinal meningiomas have a significantly longer PFS time and differ from the cranial meningiomas regarding MIB-1 index and density of tumor-associated macrophages.

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma.

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.

Combining FORGE Score and Histopathological Diagnostic Criteria of Atypical Meningioma Enables Risk Stratification of Tumor Progression.

More than 50% of atypical meningiomas regrow within 5 years after surgery. FORGE score is a newly created tool to estimate the MIB-1 index in cranial meningiomas. In this investigation, we aimed to assess the predictive value of the FORGE score in combination with major diagnostic criteria of atypical meningioma (brain invasion, mitotic count ≥ 4) regarding recurrence in atypical meningiomas. We included patients operated on primary atypical meningiomas in our center from 2011 to 2019. The study included 71 patients (58% women, median age 63 years). ROC curves revealed a superiority of FORGE score combined with histopathological diagnostic criteria of atypical meningioma (AT-FORGE) in the prediction of tumor progression compared to FORGE score only (AUC: 0.72; 95% CI: 0.54-0.91, cut-off: ≥5/<5, sensitivity: 75%, specificity: 78%). Patients with an AT-FORGE score ≥ 5 had a shorter time to tumor progression (32.8 vs. 71.4 months, p < 0.001) in the univariable analysis. Multivariable cox regression analysis revealed significant predictive value of Simpson grade > II, presence of multiple meningiomas and AT-FORGE score ≥ 5 for tumor progression. The combination of histopathological diagnostic criteria for atypical meningioma with FORGE score might facilitate an effective identification of patients with an atypical meningioma who have an increased risk of tumor progression.

FORGE: A Novel Scoring System to Predict the MIB-1 Labeling Index in Intracranial Meningiomas.

The MIB-1 index is an essential predictor of progression-free-survival (PFS) in meningioma. To date, the MIB-1 index is not available in preoperative treatment planning. A preoperative score estimating the MIB-1 index in patients with intracranial meningiomas has not been investigated so far. Between 2013 and 2019, 208 patients with tumor morphology data, MIB-1 index data, and plasma fibrinogen and serum C-reactive protein (CRP) data underwent surgery for intracranial WHO grade I and II meningioma. An optimal MIB-1 index cut-off value (≥6/<6) in the prediction of recurrence was determined by ROC curve analysis (AUC: 0.71; 95% CI: 0.55-0.87). A high MIB-1 index (≥6%) was present in 50 cases (24.0%) and was significantly associated with male sex, peritumoral edema, low baseline CRP, and low fibrinogen level in the multivariate analysis. A scoring system ("FORGE") based on sex, peritumoral edema, preoperative CRP value, and plasma fibrinogen level supports prediction of the MIB-1 index (sensitivity 62%, specificity 79%). The MIB-1 labeling index and the FORGE score are significantly associated with an increased risk of poor PFS time. We suggest a novel score ("FORGE") to preoperatively estimate the risk of an increased MIB-1 index (≥6%), which might help in surgical decision making and follow-up interval determination and inform future trials investigating inflammatory burden and proliferative activity.

MR-Imaging and Histopathological Diagnostic Work-Up of Patients with Spontaneous Lobar Intracerebral Hemorrhage: Results of an Institutional Prospective Registry Study.

Intracerebral hemorrhage (ICH) is a frequently disabling or fatal disease. The localization of ICH often allows an etiological association. However, in atypical/lobar ICH, the cause of bleeding is less obvious. Therefore, we present prospective histopathological and radiological studies which were conducted within the diagnostic workup to identify causes for lobar ICH other than hypertension. From 2016 to 2018, 198 patients with spontaneous, non-traumatic ICH requiring neurosurgical monitoring were enrolled in an institutional prospective patient registry. Patients with deep-seated ICH and/or hemorrhagically transformed cerebral infarcts were excluded from further analysis. Data to evaluate the source of bleeding based on histopathological and/or radiological workup were prospectively evaluated and analyzed. After applying the inclusion criteria and excluding patients with incomplete diagnostic workup, a total of 52 consecutive patients with lobar ICH were further analyzed. Macrovascular disease was detected in 14 patients with lobar ICH (27%). In 11 patients, diagnostic workup identified cerebral amyloid angiopathy-related ICH (21%). In addition, five patients with tumor-related ICH (10%) and six patients with ICH based on infectious pathologies (11%) were identified. In four patients, the cause of bleeding remained unknown despite extensive diagnostic workup (8%). The present prospective registry study demonstrates a higher probability to identify a cause of bleeding other than hypertension in patients with lobar ICH. Therefore, a thorough diagnostic work-up in patients with ICH is essential to accelerate treatment and further improve outcome or prevent rebleeding.

Baseline Serum C-Reactive Protein and Plasma Fibrinogen-Based Score in the Prediction of Survival in Glioblastoma.

Objective: The present study investigates a score based on baseline C-reactive protein (CRP) and fibrinogen values (FC score) in 173 consecutive glioblastoma (GBM) patients. Methods: The optimal cut-off value for fibrinogen and CRP was defined as 3.5 g/dl and 3.0 mg/L, respectively, according to previous reports. Patients with elevated CRP and fibrinogen were classified with a score of 2, those with an elevation of only one of these parameters were allocated a score of 1, and those without any abnormalities were assigned a score of 0. Results: No significant differences in age, gender, tumor area, molecular pathology, physical status, or extent of resection were identified among the three groups defined by this score. Univariate survival analysis demonstrated that a high baseline FC score (≥1) is significantly associated with a shortened overall survival (OS) (HR: 1.52, 95% CI: 1.05-2.20, p = 0.027). A multivariate Cox regression analysis considering age (>65/≤65), extent of resection (GTR/STR), MGMT promoter status (hypermethylated/non-hypermethylated), and FC score (0/≥1) confirmed that an elevated FC score (≥1) is an independent predictor of shortened OS (HR: 1.71, 95% CI: 1.16-2.51, p = 0.006). Conclusions: The baseline fibrinogen and CRP score thus serves as an independent predictor of OS in GBM. Further investigations of the role of inflammation in the prediction of a prognosis are needed.

High Mib-1-score correlates with new cranial nerve deficits after surgery for frontal skull base meningioma.

Postoperative new cranial nerve deficits comprise severe concomitant morbidity in skull base meningioma surgery. Therefore, long-term cranial nerve integrity represents an important outcome measure. In the current study, we analyzed our institutional database in order to identify risk factors for postoperative new cranial nerve morbidity in the course of frontobasal meningioma surgery. Between 2009 and 2017, 195 patients were surgically treated for frontobasal meningioma at the authors' institution. Postoperative cranial nerve function was assessed immediately after surgery as well as 12 months postoperatively. A univariate and multivariate analysis was performed to identify factors influencing favorable postoperative cranial nerve outcome. Tumors with histological Mib-1-labeling indices > 5% were associated with a significantly higher percentage of new cranial nerve deficits immediately after surgery compared with those with Mib-1-labeling indices ≤ 5% (39% versus 20%, p = 0.029). Elevated Mib-1-labeling indices could be correlated with high CD68-positive macrophage staining (54% for Mib-1 index > 5% versus 19% for Mib-1 index ≤ 5%, p = 0.001). Elevated Mib-1-labeling index correlates with initial new cranial nerve dysfunction after resection of frontal skull base meningioma. With regard to elevated CD68-positive macrophage staining in high Mib-1-positive meningiomas, initial postoperative new cranial nerve morbidity might partly reflect macrophage-based inflammatory immune responses.