Rationale: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding 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 that inflammation contributes to delayed cerebral ischemia and poor outcome 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 relevant endpoint in SAH patients. Methods and design: FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. Sample size estimates: In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1–7 and then 8 mg od for days 8–21. Study outcome: The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0–3) versus unfavorable (mRS 4–6). Discussion: The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.
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.
Acute kidney injury (AKI) is a known predictor of unfavorable outcome in patients treated at the ICU, irrespective of the disease. However, data on the potential influence of serum creatinine (sCr) on hospital admission on the outcome in patients suffering from aneurysmal subarachnoid hemorrhage (SAH) is scarce. A total of 369 consecutive patients suffering from SAH were included in this retrospective cohort study. Patients were divided into good-grade (WFNS I–III) versus poor-grade (WFNS IV–V). Outcome was assessed according to the modified Rankin Scale (mRS) after 6 months and stratified into favorable (mRS 0–2) versus unfavorable (mRS 3–6). SAH patients with sCr levels <1.0 mg/dL achieved significantly a favorable outcome more often compared to patients with sCr levels ≥1.0 mg/dL (p = 0.003). In the multivariable analysis, higher levels of sCr (p = 0.014, OR 2.4; 95% CI 1.2–4.7), poor-grade on admission (p < 0.001, OR 9.8; 95% CI 5.6–17.2), age over 65 years (p < 0.001, OR 3.3; 95% CI 1.7–6.1), and delayed cerebral ischemia (p < 0.001, OR 7.9; 95% CI 3.7–17.1) were independently associated with an unfavorable outcome. We identified increased sCr on admission as a predictor for unfavorable functional outcome after SAH. Further studies elucidating the pathophysiology of this association are necessary.
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.
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.
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.