Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study

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. © 2020 The Author

Immunoliposomes for detection of rupture-prone intracranial aneurysms

BackgroundIt is estimated that significant (3.2%) of population carries intracranial aneurysm (IA). An increasing number of imaging studies have caused that the chance of finding an incidental aneurysm is becoming more common. Since IA rupture causes subarachnoidal hemorrhage (SAH) and have significant mortality and morbidity prophylactic treatment should be considered when IA is detected. The benefit and risk of treatment of IA is based on epidemiological estimate which takes account patient and aneurysm characteristics. However we know that aneurysm rupture is biological process where inflammation of aneurysm wall is actively leading to degeneration of aneurysm wall and finally weakens it until it bursts. Until now, there have not been imaging method to detect inflammatory process of aneurysm wallMethodsWe created targeting immunoliposome for use in the imaging of aneurysm. Immunoliposome comprises antibodies against at least one vascular inflammatory marker associated with aneurysm inflammation and a label and/or a contrast agent.ResultsHistological analysis of IAs where immunoliposome comprises antibodies against vascular inflammation with a label shows promising results for selectively detecting aneurysms inflammation. In magnetic resonance imaging (MRI) we were able to detect immunoliposomes carrying gadolinium.ConclusionOur work opens a new avenue for using contrast labeled immunoliposomes for detecting rupture-prone aneurysms. Immunoliposomes can cary gadolinium and selectively bind to inflammatory section of aneurysm that can be detected with MRI. Further research is needed to develop immunoliposomes to be used with MRI in humans to target treatment to those patients who benefit from it the most.Peer reviewe

CTA analysis and assessment of morphological factors related to rupture in 413 posterior communicating artery aneurysms

Posterior communicating artery (PcomA) aneurysms are frequently encountered, but there are few publications on their morphology. A growing number of aneurysms are incidental findings, which makes evaluation of rupture risk important. Our goal was to identify morphological features and anatomical variants associated with PComA aneurysms and to assess parameters related to rupture. We studied CT angiographies of 391 consecutive patients treated between 2000 and 2014 at a single institution. We determined clinically important morphological parameters and performed univariate and multivariate analysis. There were a total of 413 PComA aneurysms: 258 (62%) were ruptured and 155 (38%) unruptured. Ruptured PComA aneurysms had the potential to cause severe bleeding with IVH and/or temporal ICH (n = 170, 66% of ruptured). The main types of PComA origin were classified as follows: (1) separate (32%), (2) side by side (21%) and (3) a joint neck with the aneurysm (6%). After the multivariate logistic regression, the morphological parameters related to PComA aneurysm rupture were an irregular aneurysm dome, neck diameter, and aspect ratio > 1.5. The most marked morphological features of the PComA aneurysms were: saccular nature (99%), infero-posterior dome orientation (42%), infrequency of large or giant aneurysms (4%), narrow neck compared to the aneurysm size, PComA originating directly from the aneurysm neck or the dome (28%), and fetal or dominant PComA on the side of the aneurysm (35%). There were location-related parameters that were more strongly associated with PComA aneurysm rupture than aneurysm size: an irregular aneurysm dome, larger diameter of the aneurysm neck and aspect ratio > 1.5.Peer reviewe

Circulating biomarkers in familial cerebral cavernous malformation

Background Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression.Methods Here, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n =17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches.Findings Biomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM.Interpretation Overall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease

SARS-CoV-2 and Stroke Characteristics: A Report from the Multinational COVID-19 Stroke Study Group

cited By 0BACKGROUND AND PURPOSE: Stroke is reported as a consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in several reports. However, data are sparse regarding the details of these patients in a multinational and large scale. METHODS: We conducted a multinational observational study on features of consecutive acute ischemic stroke, intracranial hemorrhage, and cerebral venous or sinus thrombosis among SARS-CoV-2-infected patients. We further investigated the risk of large vessel occlusion, stroke severity as measured by the National Institutes of Health Stroke Scale, and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with acute ischemic stroke. In addition, we explored the neuroimaging findings, features of patients who were asymptomatic for SARS-CoV-2 infection at stroke onset, and the impact of geographic regions and countries' health expenditure on outcomes. RESULTS: Among the 136 tertiary centers of 32 countries who participated in this study, 71 centers from 17 countries had at least 1 eligible stroke patient. Of 432 patients included, 323 (74.8%) had acute ischemic stroke, 91 (21.1%) intracranial hemorrhage, and 18 (4.2%) cerebral venous or sinus thrombosis. A total of 183 (42.4%) patients were women, 104 (24.1%) patients were CONCLUSIONS: We observed a considerably higher rate of large vessel occlusions, a much lower rate of small vessel occlusion and lacunar infarction, and a considerable number of young stroke when compared with the population studies before the pandemic. The rate of mechanical thrombectomy was significantly lower in countries with lower health expenditures.Peer reviewe