The pathophysiology of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is incompletely understood. Intrathecal activation of inflammatory immune cells is suspected to play a major role for the induction of DCI. The aim of this study is to identify immune cell subsets and mediators involved in the pathogenesis of DCI. We prospectively collected blood and CSF from 25 patients with aSAH at early and late time points. We performed multicolor flow cytometry of peripheral blood and CSF, analyzing immune cell activation and pro-inflammatory cyto- and chemokines. In addition to the primary immune analysis, we retrospectively analyzed immune cell dynamics in the CSF of all our SAH patients. Our results show an increased monocyte infiltration secondary to aneurysm rupture in patients with DCI. Infiltrating monocytes are defined by a non-classical (CD14dim CD16+) phenotype at early stages. The infiltration is most likely triggered by the intrathecal immune activation. Here, high levels of pro-inflammatory chemokines, such as CXCL1, CXCL9, CXCL10, and CXCL11, are detected. The intrathecal cellular activation profile of monocytes was defined by upregulation of CD163 and CD86 on monocytes and a presumable later differentiation into antigen-presenting plasmacytoid dendritic cells (pDCs) and hemosiderophages. Peripheral immune activation was reflected by CD69 upregulation on T cells. Analysis of DCI prevalence, Hunt and Hess grade, and clinical outcome correlated with the degree of immune activation. We demonstrate that monocytes and T cells are activated intrathecally after aSAH and mediate a local inflammatory response which is presumably driven by chemokines. Our data shows that the distinct pattern of immune activation correlates with the prevalence of DCI, indicating a pathophysiological connection to the incidence of vasospasm.

Immune Characterization in Aneurysmal Subarachnoid Hemorrhage Reveals Distinct Monocytic Activation and Chemokine Patterns

BACKGROUND Low-profiled visualized intraluminal support (LVIS) is suggested as a promising stent for complex intracranial aneurysms. However, the safety and efficacy of LVIS-assisted coiling of acutely ruptured wide-necked intracranial aneurysms have not been well reported. OBJECTIVE To evaluate the safety and efficacy of LVIS-assisted coiling of acutely ruptured wide-necked intracranial aneurysms compared with contemporary coiling-only strategy via propensity score matching in a high-volume center. METHODS A retrospective review of patients with acutely ruptured intracranial aneurysms who underwent LVIS stent placement or coiling only from November 2013 to October 2017 was performed. Perioperative procedure-related complications and clinical and angiographic follow-up outcomes were compared. RESULTS All baseline characteristics were equivalent between the 2 groups except for neck size. The immediate angiographic results, procedure-related complications, procedure-related mortality, and clinical outcomes between the 2 groups demonstrated no significant differences (P = .087, P = .207, P = .685, and P = .865, respectively). The angiographic follow-up outcomes of the LVIS-assisted coiling group showed a significantly higher complete occlusion rate and lower recurrence rate compared with the coiling-only group (92.3% vs 59.9%, 4.8% vs 26.1%, P < .001). Multivariable analysis showed no significant predictors for the overall perioperative procedure-related complications, hemorrhagic complications, and ischemic complications. CONCLUSION The LVIS stent is a safe and effective device for stent-assisted coiling of acutely ruptured wide-necked intracranial aneurysms, with comparable procedure-related complication rates, higher complete occlusion rates, and lower recurrence rates at follow-up compared with coiling only.

Comparison of Low-Profiled Visualized Intraluminal Support Stent-Assisted Coiling and Coiling Only for Acutely Ruptured Intracranial Aneurysms: Safety and Efficacy Based on a Propensity Score-Matched Cohort Study.

BACKGROUND AND PURPOSE The severity of early brain edema (EBE) after aneurysm rupture was reported to be strongly associated with the risk of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Using the recently developed Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), we analyzed the predictors of EBE and its impact on complications related to intracranial pressure (ICP) increase after SAH and on poor outcome. METHODS All consecutive SAH cases treated between January 2003 and June 2016 with assessable SEBES were included (n = 745). Data on demographic characteristics, medical history, initial severity of SAH, need for conservative ICP treatment and decompressive craniectomy, occurrence of cerebral infarctions and unfavorable outcome at 6 months (modified Rankin scale score > 2) were collected. Univariable and multivariable analyses were performed. RESULTS Younger age (<55 years; adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI] 2.28-4.38), female sex (aOR 1.64, 95% CI 1.16-2.31), poor initial clinical condition (World Federation of Neurosurgical Societies score 4-5; aOR 1.74, 95% CI 1.23-2.46), presence of intracerebral hemorrhage (aOR 1.63, 95% CI 1.12-2.36), hypothyroidism (aOR 0.60, 95% CI 0.37-0.98) and renal comorbidity (aOR 0.29, 95% CI 0.11-0.78) were independently associated with SEBES (scores 3-4). There was an independent association between SEBES 3-4 and the need for conservative ICP treatment (aOR 2.43, 95% CI 1.73-3.42), decompressive craniectomy (aOR 2.68, 95% CI 1.84-3.89), development of cerebral infarcts (aOR 2.24, 95% CI 1.53-3.29) and unfavorable outcome (aOR 1.48, 95% CI 1.0-2.17). CONCLUSIONS SEBES is a reliable predictor of ICP-related complications and poor outcome of SAH. Our findings highlight the need for further research of the impact of patients' demographic characteristics and comorbidities on the severity of EBE after SAH.

Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) as a radiographic marker of clinically relevant intracranial hypertension and unfavorable outcome after subarachnoid hemorrhage

After years of research on treatment of aneurysmal subarachnoid hemorrhage (aSAH), including randomized clinical trials, few treatments have been shown to be efficacious. Nevertheless, reductions in morbidity and mortality have occurred over the last decades. Reasons for the improved outcomes remain unclear. One randomized clinical trial that has been examined in detail with these questions in mind is Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS-1). This was a phase-2 trial testing the effect of clazosentan on angiographic vasospasm (aVSP) in patients with aSAH. Clazosentan decreased moderate to severe aVSP. There was no statistically significant effect on the extended Glasgow outcome score (GOS), although the study was not powered for this endpoint. Data from the approximately 400 patients in the study were detailed, rigorously collected and documented and were generously made available to one investigator. Post-hoc analyses were conducted which have expanded our knowledge of the management of aSAH. We review those analyses here.

https://www.mdpi.com/2077-0383/9/9/2970/pdf

Lessons from the CONSCIOUS-1 Study.

Quality Assurance During Brain Aneurysm Microsurgery-Operative Error Teaching.

Objective Clinical data on secondary hemorrhagic complications (SHCs) in patients with aneurysmal subarachnoid hemorrhage (SAH) are sparse and mostly limited to ventriculostomy-associated SHCs. This study aimed to elucidate the incidence, risk factors, and impact on outcome of SHCs in a large cohort of SAH patients. Methods All consecutive patients with ruptured aneurysms treated between January 2003 and June 2016 were eligible for this study. Patients' charts were reviewed for clinical data, and imaging studies were reviewed for radiographic data. SHCs were divided into those associated with ventriculostomy and those not associated with ventriculostomy, as well as into major and minor bleeding forms, depending on clinical impact. Results Sixty-two (6.6%) of the 939 patients included in the final analysis developed SHCs. Ventriculostomy-associated bleedings (n = 16) were independently predicted by mono- or dual-antiplatelet therapy after aneurysm treatment (p = 0.028, adjusted odds ratio [aOR] = 10.28; and p = 0.026, aOR = 14.25, respectively) but showed no impact on functional outcome after SAH. Periinterventional use of thrombolytic agents for early effective anticoagulation was the only independent predictor (p = 0.010, aOR = 4.27) of major SHCs (n = 38, 61.3%) in endovascularly treated patients. In turn, a major SHC was independently associated with poor outcome at the 6-month follow-up (modified Rankin Scale score > 3). Blood thinning drug therapy prior to SAH was not associated with SHC risk. Conclusions SHCs present a rare sequela of SAH. Antiplatelet therapy during (but not before) SAH increases the risk of ventriculostomy-associated bleedings, but without further impact on the course and outcome of SAH. The use of thrombolytic agents for early effective anticoagulation carries relevant risk for major SHCs and poor outcome.

Kathrin Buffen

Papers

Secondary hemorrhagic complications in aneurysmal subarachnoid hemorrhage: when the impact hits hard.