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.

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.

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.

Graphical Abstract

Rationale: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding and cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests inflammation contributes to delayed cerebral ischemia and poor out-come in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. Aim: The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically rele-vant endpoint in SAH patients. Methods and design: FINISHER is a multicentre, prospective, randomized, double-blinded, place-bo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. Sample size estimates: 334 patients will be randomized to either dexamethasone or placebo within 48h after SAH. The dexamethasone dose is 8mg tds days 1-7 and then 8mg od for days 8-21 Study outcome: The primary outcome is the modified Rankin Scale (mRS) at 6 months which is dichotomized to favourable (mRS 0-3) versus unfavourable (mRS 4-6). Discussion: The results of this study will provide the first phase III evidence as to whether dexame-thasone improves outcome in SAH. Trial registration: ClinicalTrials.gov NCT05132920. EudraCT Number 2021-000732-54.

ObjectiveMIB-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.MethodsBetween 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.ResultsAn optimal MIB-1 index cut-off value (≥5/&lt;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%.ConclusionThis 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.

Background Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is associated with poor neurological outcome and high mortality. A major factor influencing morbidity and mortality is brain swelling in the acute phase. Decompressive craniectomy (DC) is currently used as an option in order to reduce intractably elevated intracranial pressure (ICP). However, execution and optimal timing of DC remain unclear. Methods PICASSO resembles a multicentric, prospective, 1:1 randomized standard treatment-controlled trial which analyzes whether primary DC (pDC) performed within 24 h combined with the best medical treatment in patients with poor-grade SAH reduces mortality and severe disability in comparison to best medical treatment alone and secondary craniectomy as ultima ratio therapy for elevated ICP. Consecutive patients presenting with poor-grade SAH, defined as grade 4–5 according to the World Federation of Neurosurgical Societies (WFNS), will be screened for eligibility. Two hundred sixteen patients will be randomized to receive either pDC additional to best medical treatment or best medical treatment alone. The primary outcome is the clinical outcome according to the modified Rankin Scale (mRS) at 12 months, which is dichotomized to favorable (mRS 0–4) and unfavorable (mRS 5–6). Secondary outcomes include morbidity and mortality, time to death, length of intensive care unit (ICU) stay and hospital stay, quality of life, rate of secondary DC due to intractably elevated ICP, effect of size of DC on outcome, use of duraplasty, and complications of DC. Discussion This multicenter trial aims to generate the first confirmatory data in a controlled randomized fashion that pDC improves the outcome in a clinically relevant endpoint in poor-grade SAH patients. Trial registration DRKS DRKS00017650. Registered on 09 June 2019.

Surgical treatment of intracranial aneurysm requires advanced technologies to achieve optimal results. Recently, rapid ventricular pacing (RVP) has been described to be an elegant technique that facilitates clip reconstruction of complex unruptured intracranial aneurysm (uIA). However, there is also a growing need for intraoperative tools to ensure safe clip reconstruction of complex ruptured intracranial aneurysm (rIA). We conducted a retrospective analysis of 17 patients who underwent RVP during surgical reconstruction of complex aneurysms. Nine patients had uIA while eight patients underwent surgery for rIA suffering from consecutive subarachnoid hemorrhage (SAH). Hemodynamic data, critical events, laboratory results, and anesthesia-related complications were evaluated. No complications were reported concerning anesthesia induction and induction times were similar between patients exhibiting uIA or rIA (p = 0.08). RVP induced a significant decline of median arterial pressure (MAP) in both groups (p < 0.0001). However, median MAP before and after RVP was not different in both groups (uIA group: p = 0.27; rIA group: p = 0.18). Furthermore, high-sensitive Troponin T (hsTnT) levels were not increased after RVP in any group. One patient in the rIA group exhibited ventricular fibrillation and required cardiopulmonary resuscitation, but has presented with cardiac arrest due to SAH. Otherwise, no arrhythmias or complications occurred. In summary, our data suggest RVP to be feasible in surgery for ruptured intracranial aneurysms.