We identified activating KRAS mutations in the majority of tissue samples of arteriovenous malformations of the brain that we analyzed. We propose that these malformations develop as a result of KRAS-induced activation of the MAPK-ERK signaling pathway in brain endothelial cells. (Funded by the Swiss Cancer League and others.).

Background There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9%) patients had a stroke—123(79%) ischaemic stroke, 27(17%) intracerebral/subarachnoid hemorrhage, and 6(4%) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5% among all centres in all countries, and 0.7% among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95% CI:1.1–3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95% CI:1.4–4.7, p = 0.006) were predictive of stroke. Interpretation The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5%(pooled risk: 0.9%). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding None.

Background and Purpose Saccular intracranial aneurysm (sIA) is a common disease that may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and wall inflammation have been associated with sIA rupture. We investigated how sIA hemodynamics associates with wall remodeling and inflammation of the sIA wall. Methods Tissue samples resected during sIA surgery (11 unruptured, 9 ruptured sIAs) were studied with histology and immunohistochemistry. Patient-specific computational models of hemodynamics were created from preoperative CT-angiographies. Results More stable and less complex flows were associated with thick, hyperplastic sIA walls while slower flows with more diffuse inflow were associated with degenerated and decellularized sIA walls. Wall degeneration (p=0.041) and rupture was associated with increased inflammation (CD45+, p=0.031). High wall shear stress (WSS, p=0.018), higher vorticity (VO, p=0.046), higher viscous dissipation (VD, p=0.046), and high shear rate (SR, p=0.046) associated with increased inflammation. Inflammation was also associated with lack of intact endothelium (p=0.034), and presence of organized luminal thrombosis (p=0.018), although overall organized thrombosis was associated with low minimum WSS (p=0.034) and not with the flow conditions that associated with inflammation. Conclusions Flow conditions in the sIA associate with wall remodeling. Inflammation, which is associated with degenerative wall remodeling and rupture, is associated with high flow activity including elevated WSS. Endothelial injury may be a mechanism by which flow induces inflammation in the sIA wall. Hemodynamic simulations might prove to be useful in identifying sIAs at risk of developing inflammation, a potential biomarker for rupture.

Aneurysmal subarachnoid hemorrhage (aSAH) represents only a small portion of all strokes, but accounts for almost half of the deaths caused by stroke worldwide. Neurosurgical clipping and endovascular coiling can successfully obliterate the bleeding aneurysms, but ensuing complications such as cerebral vasospasm, acute and chronic hydrocephalus, seizures, cortical spreading depression, delayed ischemic neurological deficits, and delayed cerebral ischemia lead to poor clinical outcomes. The mechanisms leading to these complications are complex and poorly understood. Early brain injury resulting from transient global ischemia can release molecules that may be critical to initiate and sustain inflammatory response. Hence, the events during early brain injury can influence the occurrence of delayed brain injury. Since the damage associated molecular pattern molecules (DAMPs) might be the initiators of inflammation in the pathophysiology of aSAH, so the aim of this review is to highlight their role in the context of aSAH from diagnostic, prognostic, therapeutic, and drug therapy monitoring perspectives. DAMPs represent a diverse and a heterogenous group of molecules derived from different compartments of cells upon injury. Here, we have reviewed the most important DAMPs molecules including high mobility group box-1 (HMGB1), S100B, hemoglobin and its derivatives, extracellular matrix components, IL-1α, IL-33, and mitochondrial DNA in the context of aSAH and their role in post-aSAH complications and clinical outcome after aSAH.