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Inflammation has a destructive effect on the homeostasis of the vascular wall, which is involved in the formation, growth, and rupture of human intracranial aneurysms (IAs) disease progression. However, inflammation-related markers have not been well studied in the risk stratification of unruptured IAs. The purpose of this study was to investigate the predictive value of serum inflammatory markers in the unstable progression of small saccular intracranial aneurysms (SIAs). This study retrospectively included 275 patients with small SIAs (aneurysm diameter less than or equal to 7 mm), to compare the level difference of serum inflammatory complex marker systemic immune-inflammatory index (SII), white blood cell to platelet ratio (WPR), and homocysteine (Hcy) in patients with stable (asymptomatic unruptured) and unstable (symptomatic unruptured, ruptured) small SIAs. 187 patients (68%) had aneurysm-related compression symptoms and rupture outcomes. In the multivariate logistic regression after adjusting for baseline differences, SII, WPR, and Hcy were independent risk factors for the instability of small SIAs, the prediction model combined with other risk factors (previous stroke history, aneurysm irregularity) showed good predictive ability for the instability of small SIAs, with an area under the curve of 0.905. In addition, correlation analysis showed that SII, WPR, and Hcy also had significant differences in patients with symptomatic unruptured and ruptured small SIAs, and higher inflammation levels often promoted the disease progression of small SIAs. Higher levels of SII, WPR and Hcy can be used as independent predictors of instability of small SIAs. As an economical and convenient biomarker, it is crucial for clinical treatment strategies of stable small SIAs., (© 2024. The Author(s).)

Plasma homocysteine (Hcy) has been globally recognized as an independent risk factor for various neurovascular diseases. In this study, the authors investigated the relationship between critical Hcy concentration and the risk of rupture in intracranial aneurysms (IAs). This study collected data from 423 patients with both ruptured and unruptured IAs. We compared demographic data, vascular rupture risk factors, and laboratory test results between the two groups. Multivariable logistic regression analysis was employed to determine the correlation between critical plasma Hcy levels and the risk of rupture in small to medium-sized IAs. A total of 330 cases of ruptured intracranial aneurysms (RIA) and 93 cases of unruptured intracranial aneurysms (UIA) were included. Univariate analysis revealed statistically significant differences between the ruptured and unruptured groups in terms of hypertension, hyperlipidemia, plasma Hcy levels, and IA morphology (all P < 0.05). Multivariable logistic regression analysis indicated that hypertension (odds ratio [OR] 0.504; 95% confidence interval [CI] 0.279-0.911; P = 0.023), hyperlipidemia (OR 1.924; 95% CI 1.079-3.429; P = 0.027), and plasma Hcy levels (OR 1.420; 95% CI 1.277-1.578; P < 0.001) were independently associated with the rupture of small to medium-sized IAs, all with statistical significance (P < 0.05). Our study suggests that critical plasma Hcy levels are an independent risk factor for increased rupture risk in small to medium-sized intracranial aneurysms. Therefore, reducing plasma Hcy levels may be considered a valuable strategy to mitigate the risk of intracranial vascular abnormalities rupture and improve patient prognosis., (© 2024. The Author(s).)

The aim of this study was to investigate the plasma proteome in individuals with intracranial aneurysms (IAs) and identify biomarkers associated with the formation and rupture of IAs. Proteomic profiles (N = 1069 proteins) were assayed in plasma (N = 120) collected from patients with ruptured and unruptured intracranial aneurysms (RIA and UIA), traumatic subarachnoid hemorrhage (tSAH), and healthy controls (HC) using tandem mass tag (TMT) labeling quantitative proteomics analysis. Gene ontology (GO) and pathway analysis revealed that these relevant proteins were involved in immune response and extracellular matrix organization pathways. Seven candidate biomarkers were verified by ELISA in a completely separate cohort for validation (N = 90). Among them, FN1, PON1, and SERPINA1 can be utilized as diagnosis biomarkers of IA, with a combined area under the ROC curve of 0.891. The sensitivity was 93.33%, specificity was 75.86%, and accuracy was 87.64%. PFN1, ApoA-1, and SERPINA1 can serve as independent risk factors for predicting aneurysm rupture. The combined prediction of aneurysm rupture yielded an area under the ROC curve of 0.954 with a sensitivity of 96.15%, specificity of 81.48%, and accuracy of 88.68%. This prediction model was more effective than PHASES score. In conclusion, high-throughput proteomics analysis with population validation was performed to assess blood-based protein expression characteristics. This revealed the potential mechanism of IA formation and rupture, facilitating the discovery of biomarkers. SIGNIFICANCE: Although the annual rupture rate of small unruptured aneurysms is believed to be minimal, studies have indicated that ruptured aneurysms typically have an average size of 6.28 mm, with 71.8% of them being <7 mm in diameter. Hence, evaluating the possibility of rupture in UIA and making a choice between aggressive treatment and conservative observation emerges as a significant challenge in the management of UIA. No biomarker or scoring system has been able to satisfactorily address this issue to date. It would be significant to develop biomarkers that could be used for early diagnosis of IA as well as for prediction of IA rupture. After TMT proteomics analysis and ELISA validation in independent populations, we found that FN1, PON1, and SERPINA1 can be utilized as diagnostic biomarkers for IA, and PFN1, ApoA-1, and SERPINA1 can serve as independent risk factors for predicting aneurysm rupture. Especially, when combined with ApoA-1, SERPINA1, and PFN1 for predicting IA rupture, the area under the curve (AUC) was 0.954 with a sensitivity of 96.15%, specificity of 81.48%, and accuracy of 88.68%. This prediction model was more effective than PHASES score., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The aim of this study is to construct a computational model of blood D-dimer, cystatin C, and CRP levels and to predict the risk of intracranial aneurysms and their rupture., Methods: A total of 69 intracranial aneurysms patients were selected as the case group, including 28 cases in the ruptured group and 41 cases in the unruptured group. Another 64 non-intracranial aneurysm patients were selected as the control group. The detection results of serum D-dimer, cystatin C, and CRP were collected. The logistic regression computational model was used to analyze the occurrence and risk factors of intracranial aneurysms. The receiver operating curves (ROC) of serum D-dimer, cystatin C, and C reactive protein (CRP) levels for predicting intracranial aneurysms and their rupture were drawn, and the area under the curve (AUC), sensitivity, and specificity were calculated., Results: The serum levels of D-dimer, cystatin C, and CRP in patients with intracranial aneurysms were significantly higher than those in the control group and the differences were statistically significant ( P < 0.05). The serum levels of D-dimer, cystatin C, and CRP in patients with ruptured intracranial aneurysms were higher than those in patients with unruptured intracranial aneurysms, and the differences were also statistically significant ( P < 0.05). The combined detection of serum D-dimer, cystatin C, and CRP levels has a higher AUC (0.9014) for predicting intracranial aneurysms and higher AUC (0.9412) for predicting ruptured intracranial aneurysms than D-dimer (0.7118 and 0.8750, respectively), cystatin C (0.6489 and 0.6180, respectively), and CRP (0.7764 and 0.6551, respectively) independent detection; the combined detection had a sensitivity of 93.75% and 87.80 for predicting the occurrence and rupture of intracranial aneurysms, and the specificity was 68.12% and 92.86%, respectively., Conclusion: The combined detection of serum D-dimer, cystatin C, and CRP levels is a very valuable indicator for predicting the occurrence and rupture of intracranial aneurysms, and combined detection can provide scientific evidence-based guidance for clinical prediction of the occurrence and rupture of intracranial aneurysms., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Liang Xing et al.)

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening medical condition with a high mortality and disability rate. aSAH has an unclear pathogenesis, and limited treatment options are available. Here, we aimed to identify critical genes involved in aSAH pathogenesis using peripheral blood gene expression data of 43 patients with aSAH due to ruptured intracranial aneurysms and 18 controls with headache, downloaded from Gene Expression Omnibus. These data were used to construct a co-expression network using weighted gene co-expression network analysis (WGCNA). The biological functions of the hub genes were explored, and critical genes were selected by combining with differentially expressed genes analysis. Fourteen modules were identified by WGCNA. Among those modules, red, blue, brown and cyan modules were closely associated with aSAH. Moreover, 364 hub genes in the significant modules were found to play important roles in aSAH. Biological function analysis suggested that protein biosynthesis-related processes and inflammatory responses-related processes were involved in the pathology of aSAH pathology. Combined with differentially expressed genes analysis and validation in 35 clinical samples, seven gene ( CD27, ANXA3, ACSL1, PGLYRP1, ALPL, ARG1, and TPST1 ) were identified as potential biomarkers for aSAH, and three genes ( ANXA3, ALPL, and ARG1 ) were changed with disease development, that may provide new insights into potential molecular mechanisms for aSAH.

The purpose of our research is to explore whether vitamin D levels were associated with the rupture of intracranial aneurysms. In this retrospective study, 105 patients diagnosed with ruptured intracranial aneurysms (RIAs) and 185 patients diagnosed with unruptured intracranial aneurysms (UIAs) at The First Affiliated Hospital of Zhengzhou University were recruited from September 2019 to September 2020. Patients' demographic and clinical information, including vitamin D levels, were recorded and compared. Univariate analysis showed that patients with UIAs had higher vitamin D levels than RIAs (p = 0.019). In addition, there were significant differences in aneurysm location (p < 0.001), aspirin use (p = 0.001), and comorbid diabetes mellitus (p = 0.037) between patients with UIAs and RIAs. Binary logistic regression analysis showed that the level of vitamin D was independently associated with RIAs [odds ratio (OR) 0.960; 95% confidence intervals (CI), 0.926-0.996, p = 0.028].

Inflammation plays an important role in the pathogenesis and growth of intracranial aneurysms (IAs). We investigated the clinical value of the neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic subclinical inflammation in patients with IAs. Consecutive patients with IAs who underwent endovascular treatment (EVT) were enrolled in the study. The evaluation indicators were aneurysm size and rupture, a poor outcome at 3 to 6 months, and delayed cerebral ischemia (DCI) during hospitalization. In total, 532 patients with IAs underwent EVT (mean age, 54.0 years; 62.4% female). Among patients with ruptured IAs, those with a higher NLR had an increased risk of a poor outcome at 3 to 6 months and DCI during hospitalization than those with a lower NLR. A higher NLR was significantly more strongly associated with the size of unruptured aneurysms and aneurysm rupture than a lower NLR. The NLR and C-reactive protein concentration showed similar predictive ability for aneurysm size and treatment prognosis. The NLR was lower at discharge than admission for patients with ruptured IAs and DCI. An elevated NLR was significantly associated with the size of unruptured IAs, an increased risk of a poor outcome, and DCI in patients with ruptured IAs.

Background: The rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. We sought to characterize the systemic response to IA rupture., Methods: We included 19 patients in the acute phase of IA rupture and 20 control subjects. Flow cytometry was used to analyze alterations in the level of mononuclear leukocytes. Cell-related parameters, including the neutrophil-to-lymphocyte ratio (NL-R), lymphocyte-to-monocyte ratio (LM-R), platelet-to-lymphocyte ratio (PL-R), and systemic immune-inflammation index (SII), were calculated, and the relationship between the analyzed hematological parameters and clinical status was investigated., Results: Patients with ruptured IAs presented with significantly higher white blood cells (WBC) and neutrophil counts but lower lymphocyte counts than control subjects. NL-R and SII values were higher and the LM-R was lower in the acute phase after IA rupture. Analyzing the severity of clinical status and the outcome of patients with subarachnoid hemorrhage, we found that patients with poor clinical status, as measured by the Glasgow Coma Scale (GCS) and the Hunt and Hess scale, had significantly lower lymphocyte counts and higher NL-R, PL-R and SII values than those with good clinical status. Additionally, patients with lower GCS scores presented a lower proportion of CD3+CD4-CD8- cells. Worse outcomes assessed at discharge were associated with lower lymphocyte counts but higher PL-R values., Conclusions: The current study pointed to the significance of systemic immune and inflammatory responses after IA rupture and the potential clinical utility of hematological parameters, which can be easily calculated. In particular, the role of DN T cells and the significance of the SII as a marker related to clinical status should be further investigated., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Inflammation-related factors might give further insight into the pathophysiology of vessel wall inflammation and intracranial aneurysm (IA) rupture. One of these factors is the protein complex S100A8/A9, which is released by neutrophils, monocytes, and activated macrophages and is known for its role in cardiovascular disease., Objective: To determine if venous S100A8/A9 levels in patients with a ruptured IA (rIA) or unruptured IA (uIA) are elevated compared with a control group. Second, to assess differences between venous and intra-aneurysmal S100A8/A9 levels of rIA and uIA patients., Methods: A prospective case study was performed between June 2016 and May 2017 in patients harboring a ruptured or unruptured saccular IA. Primary outcome measures were individual S100A8/A9 serum concentrations as measured in venous and intra-aneurysmal blood samples during endovascular treatment. Venous serum S100A8/A9 concentrations from a healthy control group served as a reference., Results: We included 16 patients with either a rIA or uIA and 47 healthy controls. Venous S100A8/A9 concentrations were higher in aneurysm patients (rIA and uIA) than those of healthy controls (P≤0.001). S100A8/A9 concentrations were higher in intra-aneurysmal samples than in venous samples of rIA patients (P=0.011). This difference was not found in uIA patients (P=0.054). Intra-aneurysmal S100A8/A9 levels were higher in rIAs than in uIAs (P=0.04)., Conclusions: Venous S100A8/A9 levels are elevated in patients with both rIAs and uIAs compared with healthy controls and likely represents aneurysm wall inflammation. S100A8/A9 causes macrophage-induced inflammation and degeneration of the vessel wall which might explain higher intra-aneurysmal S100A8/A9 levels found in rIAs than in uIAs., Competing Interests: Competing interests: Joost de Vries and Hieronymus D. Boogaarts are consultants for Stryker Neurovascular., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objectives: Current guidelines paid little attention to a unique severe disease about intracranial hematoma owing to aneurysm rupture. We attempted to explore the predictive factors for prognosis in these poor patient population., Patients and Methods: One hundred twenty-one aneurysmal subarachnoid hemorrhage combined with intracerebral hematoma patients discharged between 2013 and 2016 were reviewed in this retrospective study. Unfavorable outcome was defined as a modified Rankin Scale (mRS) score of 3, 4, 5, or 6 at 6 months. Multivariable logistic regression was performed to evaluate the association of unfavorable outcome with preoperative and postoperative clinical characteristics., Results: Of 121 patients with intact follow-up data, 34 (28.10 %) had an unfavorable prognosis. The preoperative prognostic model included patients' age, respiratory rate, Hunt-Hess scale, red cell distribution width, and serum sodium at admission. The postoperative prognostic model included patients' age, respiratory rate, red cell distribution width, serum sodium, postoperative delayed cerebral ischemia, and pulmonary infection. Both preoperative and postoperative prognostic models had excellent discrimination with Area Under The Curve (AUC) of 0.864 (P < .001) and 0.898 (P < .001), respectively., Conclusion: In clinical practice, we should pay more attention to those old patients with worse admission Hunt-Hess score, presenting deep-slow respiratory and lower serum sodium. Reduction of postoperative delayed cerebral ischemia and pulmonary infection might improve outcomes after aneurysmal SAH with intracerebral hematoma., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Myelin basic protein (MBP) is the second most abundant protein in central nervous system myelin. Since the 1980s, it has been regarded as a marker of brain tissue injury in both trauma and disease. There have been no recent reports regarding MBP in aneurysmal subarachnoid haemorrhage (SAH)., Methods: One hundred four SAH patients with ruptured aneurysms underwent endovascular treatment within 24 h of rupture, and 156 blood samples were collected: 104 on days 0-3, 32 on days 4-6 and 20 on days 9-12 post-SAH. MBP levels were assayed using ELISA and compared with the clinical status on admission, laboratory results, imaging findings and treatment outcome at 3 months., Results: MBP levels on days 0-3 post-SAH were significantly higher among poor outcome patients (p < 0.001), non-survivors (p = 0.005), patients who underwent intracranial intervention (p < 0.001) and patients with intracerebral haemorrhage (ICH; p < 0.001). On days 4-6 post-SAH, significantly higher levels were found following intracranial intervention (p = 0.009) and ICH (p = 0.039). There was clinically relevant correlation between MBP levels on days 0-3 post-SAH and 3-month Glasgow Outcome Scale (cc = - 0.42) and also ICH volume (cc = 0.48). All patients who made a full recovery had MBP levels below detection limit on days 0-3 post-SAH. Following endovascular aneurysm occlusion, there was no increase in MBP in 86 of the 104 patients investigated (83%)., Conclusions: The concentration of MBP in peripheral blood after intracranial aneurysm rupture reflects the severity of the brain tissue injury (due to surgery or ICH) and correlates with the treatment outcome. Endovascular aneurysm occlusion was not followed by a rise in MBP in most cases, suggesting the safety of this technique.

Background: Subarachnoid hemorrhage (SAH) is an uncommon disease. Considering ruptured intracranial aneurysms as the main cause of this disease and only a minority of the intracranial aneurysms will rupture sooner or later, to understand the underlying pathology or a specific gene expression profile of an impending ruptured intracranial aneurysm is of great importance., Methods: The transcriptome in peripheral blood cells of patients with SAH from ruptured aneurysm was compared with that of control patients suffering from headaches. The microarray dataset GSE36791 comprised 43 patients with SAH from ruptured aneurysms and 18 control patients. Differential expression analysis was performed with the R language packages to identify differentially expressed genes (DEGs). Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway database analysis were performed to identify significantly altered biological functions and pathways, respectively. The protein-protein interaction networks were constructed with information from the STRING database., Results: A total of 528 DEGs were identified, of which 311 were upregulated and 217 downregulated. Clustering analysis confirmed that these genes can distinguish ruptured aneurysm SAH patients from the control patients. The DEGs were mainly enriched for immune/inflammation response and related pathways. Among the DEGs, 8 genes (ARG1, MAPK14, RPS2, SPI1, FYN, CEBPB, FLOT1, and CD4) were identified as the key regulators in the Protein-Protein Interaction network. MAPK14, CEBPB, FLOT1, and CD4 might be potential biomarkers of SAH., Conclusion: This study identified a range of DEGs SAH patients with ruptured aneurysms, which may enhance our current knowledge on this disease and may provide potential biomarkers of this disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: We tested the hypothesis that low hemoglobin levels are associated with acute seizures after aneurysmal subarachnoid hemorrhage (aSAH)., Methods: Patients with ruptured intracranial aneurysms were enrolled in the observational cohort study that prospectively collected age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, hematocrit, serum potassium, sodium, calcium, phosphorus, iron, and modified Rankin Scale. Acute seizures were determined as seizures within 1 week after aSAH., Results: We included 554 patients with requisite data for analysis in the prospective study. Incidence of acute seizures following aSAH was 3.61%. In the univariate analysis, significant differences were detected in admission Hunt-Hess grade, Fisher grade, hemoglobin, and serum iron between epilepsy and nonepilepsy groups. Furthermore, acute seizures were associated with higher modified Rankin Scale score and poor outcome (P = 0.004). Serum hemoglobin levels were 114.30 ± 20.08 g/L in the epilepsy group, which were lower than those in the nonepilepsy group (128.64 ± 17.94 mmol/L, P = 0.001). Serum iron levels were 8.89 ± 5.03 g/L in the epilepsy group, which were also lower than those in the nonepilepsy group (13.71 ± 6.70 mmol/L, P = 0.002). The hemoglobin level was positively correlated with serum iron on admission (ρ = 0.321, P = 0.000). In the multivariate logistic regression model, lower hemoglobin was considered as an independent risk factor of acute seizures (odds ratio 4.286, 95% confidence interval 1.492-12.315, P = 0.007). The optimal cutoff value for hemoglobin level as a predictor for acute epilepsy after aSAH was determined as 119 g/L in the receiver operating characteristic curve (sensitivity was 75.00%, and specificity was 69.48%)., Conclusions: These data support the hypothesis that hemoglobin was inversely associated with acute seizures following aSAH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Iron and its derivatives play a significant role in various physiological and biochemical pathways, and are influenced by a wide variety of inflammatory, infectious, and immunological disorders. We hypothesized that iron and its related factors play a role in intracranial aneurysm pathophysiology and investigated if serum iron values are associated with ruptured intracranial aneurysms. 4,701 patients with 6,411 intracranial aneurysms, including 1201 prospective patients, who were diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 were evaluated. A total of 366 patients with available serum iron, ferritin and total iron binding capacity (TIBC) values were ultimately included in the analysis. 89% of included patients had anemia. Patients were categorized into ruptured and non-ruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the association between ruptured aneurysms and iron, ferritin, and TIBC. TIBC values (10 -3 g/L) within 1 year of diagnosis (OR 0.41, 95% CI 0.28-0.59) and between 1 and 3 years from diagnosis (OR 0.52, 95% CI 0.29-0.93) were significantly and inversely associated with intracranial aneurysm rupture. In contrast, serum iron and ferritin were not significant. In this case-control study, low TIBC was significantly associated with ruptured aneurysms, both in the short- and long term. However, this association may not apply to the general population as there may be a selection bias as iron studies were done in a subset of patients only.

Background: Intracranial aneurysms (IAs) are dangerous because of their potential to rupture and cause deadly subarachnoid hemorrhages. Previously, we found significant RNA expression differences in circulating neutrophils between patients with unruptured IAs and aneurysm-free controls. Searching for circulating biomarkers for unruptured IAs, we tested the feasibility of developing classification algorithms that use neutrophil RNA expression levels from blood samples to predict the presence of an IA., Methods: Neutrophil RNA extracted from blood samples from 40 patients (20 with angiography-confirmed unruptured IA, 20 angiography-confirmed IA-free controls) was subjected to next-generation RNA sequencing to obtain neutrophil transcriptomes. In a randomly-selected training cohort of 30 of the 40 samples (15 with IA, 15 controls), we performed differential expression analysis. Significantly differentially expressed transcripts (false discovery rate < 0.05, fold change ≥ 1.5) were used to construct prediction models for IA using four well-known supervised machine-learning approaches (diagonal linear discriminant analysis, cosine nearest neighbors, nearest shrunken centroids, and support vector machines). These models were tested in a testing cohort of the remaining 10 neutrophil samples from the 40 patients (5 with IA, 5 controls), and model performance was assessed by receiver-operating-characteristic (ROC) curves. Real-time quantitative polymerase chain reaction (PCR) was used to corroborate expression differences of a subset of model transcripts in neutrophil samples from a new, separate validation cohort of 10 patients (5 with IA, 5 controls)., Results: The training cohort yielded 26 highly significantly differentially expressed neutrophil transcripts. Models using these transcripts identified IA patients in the testing cohort with accuracy ranging from 0.60 to 0.90. The best performing model was the diagonal linear discriminant analysis classifier (area under the ROC curve = 0.80 and accuracy = 0.90). Six of seven differentially expressed genes we tested were confirmed by quantitative PCR using isolated neutrophils from the separate validation cohort., Conclusions: Our findings demonstrate the potential of machine-learning methods to classify IA cases and create predictive models for unruptured IAs using circulating neutrophil transcriptome data. Future studies are needed to replicate these findings in larger cohorts.

Background: We tested the hypothesis that high-density lipoprotein (HDL) is associated with intracranial aneurysm growth and rupture., Methods: We used an observational cohort study design. Age, sex, admission systolic blood pressure (SBP), diabetes, hypertension, coronary artery disease, aneurysmal rupture, apolipoprotein (APO)-A1, APO-B, HDL, low-density lipoprotein, triglycerides, cholesterol, and aneurysm location and size were recorded. Aneurysms <8 mm were categorized as small., Results: The data from 581 patients with intracranial aneurysms were analyzed. The predictive factors for small size of aneurysms were female sex (odds ratio [OR], 0.630; 95% confidence interval [CI], 0.428-0.927; P = 0.019) and higher HDL (OR, 0.327; 95% CI, 0.159-0.672; P = 0.0002). In the subgroup of male patients, lower HDL was the only risk factor for large size (P = 0.015). The predictors of aneurysmal rupture were small size (OR, 0.875; 95% CI, 0.842-0.910; P = 0.000), higher HDL (OR, 3.716; 95% CI, 1.623-8.509; P = 0.002), no coronary artery disease (OR, 4.736; 95% CI, 1.528-14.681; P = 0.007), lower APO-A1 (OR, 0.202; 95% CI, 0.064-0.641; P = 0.007), and higher admission SBP (OR, 1.024; 95% CI, 1.015-1.032; P = 0.000). An HDL/aneurysm size ratio >0.31 was associated with a 46.2-fold increased likelihood of aneurysmal rupture (OR, 46.214; 95% CI, 13.386-159.548; P = 0.002)., Conclusions: The HDL level was inversely associated with intracranial aneurysm growth, especially in men. Higher HDL levels and small aneurysm size contributed to a greater risk of aneurysmal rupture. An HDL/size ratio >0.31 was a valuable predictor of intracranial rupture., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background Fragmentation of the tunica media is a hallmark of intracranial aneurysm formation, often leading to aneurysmal progression and subsequent rupture. The objective of this study is to determine the plasma level of elastin fragments in the lumen of ruptured versus unruptured human intracranial aneurysms. Methods and Results One hundred consecutive patients with/without ruptured saccular intracranial aneurysms undergoing endovascular coiling or stent-assisted coiling were recruited. Blood samples were collected from the lumen of intracranial aneurysm using a microcatheter. The tip of the microcatheter was placed inside the aneurysm's sac in close proximity to the inner wall of the dome. Plasma levels of elastin fragments were measured using an ELISA -based method. Mean plasma level of soluble human elastin fragments was significantly greater in ruptured aneurysms when compared with nonruptured aneurysms (102.0±15.5 versus 39.3±9.6 ng/mL; P<0.001). Mean plasma level of soluble human elastin fragments did not have significant correlation with age, sex, size, or aneurysm location. Conclusions The present study revealed that a significantly higher concentration of soluble human elastin fragments in the lumen of ruptured intracranial aneurysms when compared with nonruptured ones.

Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.

Background: There seems to be a pathogenetic link between hemodynamics and inflammatory arterial wall alteration leading to the development and rupture of intracranial aneurysms (IAs). Noninvasive assessment of the inflammatory status of the aneurysm wall may guide the management of unruptured IAs by identifying reliable markers for increased rupture risk., Methods: We conducted a qualitative systematic review following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) framework. A search was made in MEDLINE/PubMed, Embase, and CINAHL from database inception to October 2017 using the terms "intracranial aneurysm" and "cerebral aneurysm" linked with the following key words: inflammation, hemodynamic(s), remodeling, macrophages, neutrophils, lymphocytes, complement system, vascular smooth muscle cells, mast cells, cytokines, and inflammatory biomarkers., Results: One hundred and twenty-three articles were included in the review., Conclusions: In this systematic review, we explore the relationship between hemodynamic stress, inflammation, vascular remodeling, and the formation and rupture of IAs to develop novel strategies to predict the individual risk of aneurysmal rupture., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Purpose: Both low serum calcium and magnesium levels have been associated with the extent of bleeding in patients with intracerebral hemorrhage, suggesting hypocalcemia- and hypomagnesemia-induced coagulopathy as a possible underlying mechanism. We hypothesized that serum albumin-corrected total calcium and magnesium levels are associated with ruptured intracranial aneurysms., Methods: The medical records of 4701 patients, including 1201 prospective patients, diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. One thousand two hundred seventy-five patients had available serum calcium, magnesium, and albumin values within 1 day of diagnosis. Individuals were divided into cases with ruptured aneurysms and controls with unruptured aneurysms. Univariable and multivariable logistic regression analyses were performed to determine the association between serum albumin-corrected total calcium and magnesium levels and ruptured aneurysms., Results: In multivariable analysis, both albumin-corrected calcium (odds ratio, 0.33; 95% confidence interval, 0.27-0.40) and magnesium (odds ratio, 0.40; 95% confidence interval, 0.28-0.55) were significantly and inversely associated with ruptured intracranial aneurysms., Conclusions: In this large case-control study, hypocalcemia and hypomagnesemia at diagnosis were significantly associated with ruptured aneurysms. Impaired hemostasis caused by hypocalcemia and hypomagnesemia may explain this association., (© 2018 American Heart Association, Inc.)

Background and Purpose: Growing evidence from experimental animal models and clinical studies suggests the protective effect of statin use against rupture of intracranial aneurysms; however, results from large studies detailing the relationship between intracranial aneurysm rupture and total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), and lipid-lowering agent use are lacking., Methods: The medical records of 4701 patients with 6411 intracranial aneurysms diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the effects of lipids (total cholesterol, LDL, and HDL) and lipid-lowering medications on intracranial aneurysm rupture risk. Propensity score weighting was used to account for differences in baseline characteristics of the cohorts., Results: Lipid-lowering agent use was significantly inversely associated with rupture status (odds ratio, 0.58; 95% confidence interval, 0.47-0.71). In a subgroup analysis of complete cases that includes both lipid-lowering agent use and lipid values, higher HDL levels (odds ratio, 0.95; 95% confidence interval, 0.93-0.98) and lipid-lowering agent use (odds ratio, 0.41; 95% confidence interval, 0.23-0.73) were both significantly and inversely associated with rupture status, whereas total cholesterol and LDL levels were not significant. A monotonic exposure-response curve between HDL levels and risk of aneurysmal rupture was obtained., Conclusions: Higher HDL values and the use of lipid-lowering agents are significantly inversely associated with ruptured intracranial aneurysms., (© 2018 American Heart Association, Inc.)

Background: Intracranial aneurysms are arterial anomalies affecting 2% to 3% of the general population in the world and these ruptures are associated with a high mortality. Some risk factors, such as age, gender, smoking, alcohol, hypertension and familial history are associated with the number of aneurysms and their size. In addition, inflammatory processes within the blood vessels of the brain can activate matrix metalloproteinase-9 (MMP-9), which degrades various components of the extracellular matrix, such as elastin. Thereby, this work has aimed at evaluating the relationship between plasma MMP-9 levels and the risk factors that are associated with intracranial aneurysm, as well as investigating the aneurysm statuses (ruptured and unruptured) and comparing them with the control volunteers., Methods: Between August 2014 to June 2016, blood samples were collected from 282 patients (204 ruptured and 78 unruptured saccular intracranial aneurysms) and 286 control volunteers. The MMP-9 plasma levels were measured by ELISA. Statistical analyzes were performed with SPSS software when using parametric or nonparametric tests, after the normality tests., Results: Higher levels of MMP-9 were found in the aneurysm groups as a whole and when they were stratified by rupture status, then compared with the control group (p < 0.0001). When stratifying them by diameter, those smaller than 7 mm presented high levels of MMP-9 (p < 0.0001), especially in the ruptured ones. As for risk factors, hypertension and smoking were the most important. However, hypertension was mostly associated with the ruptured aneurysms (p < 0.0001)., Conclusions: High levels of MMP-9 were found in smaller ruptured and unruptured intracranial aneurysms (<7 mm) with strongest statistical associations than other sizes, especially when associated with smoking and hypertension., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24 h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p = 0.02, OR = 3.16, 95%CI = [1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.

Background and Purpose: Previous studies have suggested a protective effect of diabetes mellitus on aneurysmal subarachnoid hemorrhage risk. However, reports are inconsistent, and objective measures of hyperglycemia in these studies are lacking. Our aim was to investigate the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agent use and glycated hemoglobin levels., Methods: The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariate and multivariate logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agents and glycated hemoglobin levels. Propensity score weighting was used to account for selection bias., Results: In both unweighted and weighted multivariate analysis, antihyperglycemic agent use was inversely and significantly associated with ruptured aneurysms (unweighted odds ratio, 0.58; 95% confidence interval, 0.39-0.87; weighted odds ratio, 0.57; 95% confidence interval, 0.34-0.96). In contrast, glycated hemoglobin levels were not significantly associated with rupture status., Conclusions: Antihyperglycemic agent use rather than hyperglycemia is associated with decreased risk of aneurysmal subarachnoid hemorrhage, suggesting a possible protective effect of glucose-lowering agents in the pathogenesis of aneurysm rupture., (© 2017 American Heart Association, Inc.)

BACKGROUND This study aimed to identify more potential genes and miRNAs associated with the pathogenesis of intracranial aneurysms (IAs). MATERIAL AND METHODS The dataset of GSE36791 (accession number) was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened for in the blood samples from patients with ruptured IAs and controls, followed by functional and pathway enrichment analyses. In addition, gene co-expression network was constructed and significant modules were extracted from the network by WGCNA R package. Screening for miRNAs that could regulate DEGs in the modules was performed and an analysis of regulatory relationships was conducted. RESULTS A total of 304 DEGs (167 up-regulated and 137 down-regulated genes) were screened for in blood samples from patients with ruptured IAs compared with those from controls. Functional enrichment analysis showed that the up-regulated genes were mainly associated with immune response and the down-regulated DEGs were mainly concerned with the structure of ribosome and translation. Besides, six functional modules were significantly identified, including four modules enriched by up-regulated genes and two modules enriched by down-regulated genes. Thereinto, the blue, yellow, and turquoise modules of up-regulated genes were all linked with immune response. Additionally, 16 miRNAs were predicted to regulate DEGs in the three modules associated with immune response, such as hsa-miR-1304, hsa-miR-33b, hsa-miR-125b, and hsa-miR-125a-5p. CONCLUSIONS Several genes and miRNAs (such as miR-1304, miR-33b, IRS2 and KCNJ2) may take part in the pathogenesis of IAs.

An elevated serum tryptase concentration is considered a specific marker for systemic mast cell activation, a central feature of anaphylaxis. However, in some cases of acute cardiovascular death, high concentrations of serum tryptase are also observed. We compared the postmortem serum tryptase concentrations in 74 cases assigned to the following four groups: anaphylactic deaths (Group A, n = 20), acute cardiac deaths (Group ACD, n = 30), acute dissecting aneurysm ruptures (Group ADA, n = 10), and controls (Group C, n = 14). Additionally, the cutoff between Group A and the other groups was calculated using receiver-operating characteristic (ROC) curve analysis. Tryptase concentrations were markedly elevated in Group A (p < 0.001), Group ACD (p = 0.015), and Group ADA (p = 0.005). The optimal cutoff was 43 ng/mL, the sensitivity was 90%, and the specificity was 98%. While elevated concentrations of tryptase were noted in practical autopsy cases, due attention should be paid to the differential diagnosis between anaphylactic and acute cardiovascular deaths., (© 2017 American Academy of Forensic Sciences.)

Aim: To determine a prognostic role of leukocyte count in the venous blood in the acute stage of cerebral aneurysm (CA) rupture., Material and Methods: Fifty-one patients with CA rupture, aged from 20 to 65 years, hospitalized in the first 72 h over the period from 01.10.12 to 01.02.16 were examined. The severity of disease and anatomical form of hemorrhage was corresponded to III-IV degree on the W. Hunt - R. Hess scale and Fisher scale. All patients underwent surgery. Outcomes after open and endovascular surgeries were similar., Results: Normal leukocyte number in the venous blood at admission was identified in 12 (24%) of patients (on average 7.3±1.4·109/L), leukocytosis in 39 (76%) (14.3±3.1·109/L) (p<0.0001). Leukocyte number in the acute stage of CA rupture was correlated with the frequency and severity of the vessel spasm. In 28 (55%) of patients with ischemic lesions of the brain matter, mean leukocyte number in the first 72 h after hemorrhage was higher by 2-24% (3±4.8·109/L) compared to patients without ischemia (11.9±2.5·109/L) (p=0.06). The level of leukocytes in survivors was lower by 3 - 28% (122±3.4·109/L) compared to patients with fatal outcome and patients with severe neurological deficit after the surgery (14.5±3.9·109/L) (p>0.05)., Conclusion: The increase in leukocyte number in the venous blood in the first 72 h after CA rupture ≥10,1·109/L is a reliable risk factor of marked vessel spasm. The level of leukocytes in patients with cerebral ischemia and poor prognosis in the first 72h after aneurysmal hemorrhage was higher by 2-28% compared to survivors without neurological impairment or mild neurological deficit.

Introduction: Intracranial aneurysms (IAs) remain a devastating clinical challenge, and the pathogenesis of IA formation and progression continues to be unclear. Biomarker analysis can help us understand IA development. The authors performed a systematic review of current literature on genetic and serum biomarkers for IAs in an attempt to identify diagnostic/prognostic factors for ruptured and unruptured aneurysms., Methods: All relevant studies on PubMed that reported blood/cerebrospinal fluid (CSF) biomarkers and genes that regulate biomarker levels for IAs were assessed for whether the biomarkers/genes studied correlated with IA formation and rupture., Results: Thirty-three studies were reviewed. IAs are associated with an increase in levels of immunologic markers, particularly complement C3 and C9, immunoglobulins IgG and IgM, M1/M2 macrophages, monocytes, and B and T lymphocytes; increase in blood and CSF levels of adhesion molecules; selectins found on vascular endothelium, platelets, and leukocytes; doubled ratios of elastase-to-alpha-1-antitrypsin as controls; elevated levels of neurofilament heavy chain SM135 and S-100 post rupture; and locus 19q13 with many candidate genes., Conclusion: Though the pathophysiology of the disease remains unclear, the current literature supports the role of inflammatory and cell adhesion molecules, enzymes and hormones that effect cerebral vasculature, and other cerebral proteins related to brain and vascular damage in both the formation and progression to rupture of IAs. Future investigations are needed to validate results from previous studies and identify new diagnostic/prognostic biomarkers of IAs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The pathogenesis of development and rupture of intracranial aneurysms (IA) is largely unknown. Also, screening for IA to prevent aneurysmal subarachnoid hemorrhage (aSAH) is inefficient, as disease markers are lacking. We investigated gene expression profiles in blood of previous aSAH patients, who are still at risk for future IA, aiming to gain insight into the pathogenesis of IA and aSAH, and to make a first step towards improvement of aSAH risk prediction., Methods and Results: We collected peripheral blood of 119 patients with aSAH at least two years prior, and 118 controls. We determined gene expression profiles using Illumina HumanHT-12v4 BeadChips. After quality control, we divided the dataset in a discovery (2/3) and replication set (1/3), identified differentially expressed genes, and applied (co-)differential co-expression to identify disease-related gene networks. No genes with a significant (false-discovery rate <5%) differential expression were observed. We detected one gene network with significant differential co-expression, but did not find biologically meaningful gene networks related to a history of aSAH. Next, we applied prediction analysis of microarrays to find a gene set that optimally predicts absence or presence of a history of aSAH. We found no gene sets with a correct disease state prediction higher than 40%., Conclusions: No gene expression differences were present in blood of previous aSAH patients compared to controls, besides one differentially co-expressed gene network without a clear relevant biological function. Our findings suggest that gene expression profiles, as detected in blood of previous aSAH patients, do not reveal the pathogenesis of IA and aSAH, and cannot be used for aSAH risk prediction.

Cyclophilin A (CyPA), an oxidative stress-induced factor, was found to play an important role in the aneurysm formation. Our working hypothesis was that the plasma level of CyPA in ruptured intracranial aneurysm could predict the neurological outcome. From 2011 to 2013, a total of 36 patients with ruptured saccular intracranial aneurysm were recruited in our study. Before coil embolization, we draw blood samples at the orifice of a culprit aneurysm and in the remote peripheral vein for measurements of the CyPA levels. We utilized the modified Rankin scale 30 days after aneurysm rupture as the outcome measure. Generalized linear models were used to estimate the adjusted odds ratios of the poor neurological outcome given the presence of high plasma level of CyPA. The aneurysmal and venous CyPA levels were significantly associated with the initial clinical severity (P = 0.004 and 0.03, respectively) and 30-day outcome (P = 0.01 and 0.02, respectively). The aneurysmal CyPA levels modestly correlated with age and high Fisher grade (ρ = 0.39 and 0.41; P = 0.02 and 0.01, respectively). The aneurysmal CyPA levels strongly correlated with the venous counterpart (ρ = 0.89; P < 0.001). Patients with high levels of aneurysmal CyPA were 15.66 times (95% CI, 1.48-166.24; P = 0.02) more likely to have worse neurological outcome than those with the low levels after adjustment of the age, gender, and the documented confounding factors. High plasma level of CyPA is a significant prognostic biomarker for poor neurological outcome in patients with ruptured intracranial aneurysm.

Objectives: Over the last decade, computed tomography scanners have gained resolution and have become the standard of care in the investigation of neurologically intact patients suffering from acute headache. The added value of the combined assessment of red blood cells count, visual and spectrophotometric xanthochromia, to detect ruptured aneurysmal subarachnoid hemorrhage (ASAH) following a negative head computed tomography (NHCT) was studied., Methods: The population consisted of all patients who had cerebrospinal fluid tested for spectrophotometric xanthochromia between 2003 and 2009 identified through the clinical-laboratory database and who met all the inclusion criteria: >14 years old, had an initial Glasgow Coma Score of 15, a non-traumatic acute headache with a suspected subarachnoid hemorrhage recorded in the initial ED differential diagnosis and an initial negative head CT scan., Results: A total of 706 patients were included. LP identified 5 ASAH (prevalence: 0.7%). In these patients, LP parameters were as follows: high red blood cell count (from 1310 to 63,000×10(6)/L), positive visual xanthochromia in 4 out of 5 ASAH, and positive spectrophotometric xanthochromia in 5 out of 5 ASAH. All ASAH patients were neurologically intact after intervention. No deaths or missed ASAH were reported. Angiographies were performed on 127 patients (19.5%) of which 47 (34.1%) had positive xanthochromia (visual or spectrophotometric)., Conclusions: Considering the low prevalence of ASAH following an NHCT, intense resources were utilized to identify all 5 ASAH. Lumbar puncture analyses combining red blood cell count, visual and spectrophotometric xanthochromia identified all ASAH, allowing intervention and a positive clinical outcome. Our data support 1) that LP identifies the presence of a ruptured ASAH after an NHCT and 2)` that a guide to define a subpopulation of patients who would benefit from a lumbar puncture after an NHCT would be desirable., (Copyright © 2015. Published by Elsevier Inc.)

Background and Purpose: Cerebral aneurysm (CA) affects 3% of the population and is associated with hemodynamic stress and inflammation. Myeloperoxidase, a major oxidative enzyme associated with inflammation, is increased in patients with CA, but whether myeloperoxidase contributes to CA is not known. We tested the hypotheses that myeloperoxidase is increased within human CA and is critical for formation and rupture of CA in mice., Methods: Blood was drawn from the lumen of CAs and femoral arteries of 25 patients who underwent endovascular coiling of CA, and plasma myeloperoxidase concentrations were measured with ELISA. Effects of endogenous myeloperoxidase on CA formation and rupture were studied in myeloperoxidase knockout mice and wild-type (WT) mice using an angiotensin II-elastase induction model of CA. In addition, effects of myeloperoxidase on inflammatory gene expression in endothelial cells were analyzed., Results: Plasma concentrations of myeloperoxidase were 2.7-fold higher within CA than in femoral arterial blood in patients with CA. myeloperoxidase-positive cells were increased in aneurysm tissue compared with superficial temporal artery of patients with CA. Incidence of aneurysms and subarachnoid hemorrhage was significantly lower in myeloperoxidase knockout than in WT mice. In cerebral arteries, proinflammatory molecules, including tumor necrosis factor-α, cyclooxygenase-2 (COX2), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C motif) ligand (XCL1), matrix metalloproteinase (MMP) 8, cluster of differentiation 68 (CD68), and matrix metalloproteinase 13, and leukocytes were increased, and α-smooth muscle actin was decreased, in WT but not in myeloperoxidase knockout mice after induction of CA. Myeloperoxidase per se increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in endothelial cells., Conclusions: These findings suggest that myeloperoxidase may contribute importantly to formation and rupture of CA., (© 2015 American Heart Association, Inc.)

A content of C-reactive protein (CRP) in the blood serum was determined in 36 patients in acute period of a ruptured intracranial arterial aneurysm (AA). It was significantly more, than in a control group, and have exceeded 10 mg/I in 1 - 4th day of the disease. The level of CRP have had differ, depending on severity of cerebral vasospasm (CVS), determined in accordance to the ultrasound investigation data. In a pronounced CVS in majority of patients the level of CRP in the blood serum have had exceed 10 mg/l, and have secured elevated in a spinal liquor on the 7 - 10th day of the disease, differing from this index in patients with moderately pronounced CVS or without it. In patients with severe invalidization or those, who have died, the level of CRP was trust-worthy higher.

Background: This study aimed to examine prospectively whether the inflammatory marker C-reactive protein (CRP) increases in patients with aneurysmal subarachnoid haemorrhage (aSAH) treated by endovascular coiling and investigate whether CRP could be used as prognostic factor for long-term neurological outcome., Methods: This single-hospital study comprised 98 consecutive patients with confirmed aSAH treated by endovascular coiling. Admission status was classified according to the World Federation of Neurosurgical Societies (WFNS) Scale and initial cerebral computed tomography according to Fisher scale. CRP was analysed on days 0, 1, 2, 3, 4, 6 and 8 after the initial bleed. A neurological follow up was performed 1 year later according to the Extended Glasgow Outcome Scale (GOSE) for overall outcome and National Institute of Health Stroke Scale (NIHSS) for focal deficit., Results: CRP values increased from normal to peak at 53 mg/l at day 3-4 and then declined, without normalising, at day 8. Patients with a higher increase in CRP had a poorer neurological outcome after 1 year. CRP during the first week had a stronger correlation to outcome (r = 0.417) and NIHSS (r = 0.449) than initial clinical status (WFNS; r = 0.280 and 0.274) and radiology (Fisher scale; r = 0.137 and 0.158). CRP increase indicated a risk of poor outcome (GOSE) (P < 0.001) and permanent loss of neurological function (NIHSS) (P < 0.001). Logistic regression analysis suggested that elevated CRP already on day 2 is an independent prognostic marker for outcome., Conclusion: Early CRP values can perhaps be used as a prognostic factor for long-term neurological outcome prediction after endovascular treatment of aSAH., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Biological markers that can be used to predict the risk of intracranial aneurysms (IAs) are not available., Methods and Results: To clarify whether circulating microRNAs could be used as biomarkers for IA, we carried out microarray assays in a screening cohort of 40 IA patients (20 unruptured and 20 ruptured) and 20 healthy volunteers. We identified 20 microRNAs that were unanimously changed in both ruptured and unruptured patients. We confirmed 60% of these changed microRNAs by a separate microarray test with an independent validation cohort (n=143 including 93 IA patients). To identify potential biomarkers, we combined the 2 cohorts and performed quantitative real-time polymerase chain reactions for selected target microRNAs. Logistic regression analysis demonstrated that miR-16 and miR-25 were independent factors for IA occurrence (P<0.001). After controlling for age, sex, smoking, and history of hypertension, the contributions of miR-16 and miR-25 were still highly significant (P<0.001). The adjusted odds ratio values for miR-16 and miR-25 were 1.52 (95% CI 1.31 to 1.77) and 1.53 (1.30 to 1.79). Combining both miR-16 and miR-25 in a single model did not improve the performance of risk association., Conclusions: Our data suggest that circulating miRNAs may be novel biological markers that are useful in assessing the likelihood of IA occurrence., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background/aims: To explore the surgical way of treating giant hepatic artery aneurysm(HAA)., Methodology: Three hepatic artery aneurysm patients who were performed aneurysm resection without revascularization of the hepatic artery were reviewed. After surgery, the values of liver function and enhanced CT scan of the patients were followed., Results: All the three patients were recovered well postoperatively and only several values of biochemistry marks of liver function as ALT, AST, TBIL and DB in one case with liver cirrhosis were elevated and decreased to normal ranges in a few days postoperatively. The values of biochemistry marks of liver function in other two cases were within normal limits. The enhanced CT scan also showed arteries in the liver after hepatic artery aneurysm resection., Conclusions: Giant HAA may be safely removed without revascularization of the hepatic artery.

Background and Purpose: Insular injuries are known to cause autonomic derangements. Patients with ruptured middle cerebral artery aneurysms frequently develop temporal hematomas (THs) in addition to subarachnoid hemorrhages, and those with TH may sustain autonomic derangements more frequently than those without TH. Hemispheric lateralization in autonomic derangements has been reported in patients with insular ischemic stroke, and this study was conducted to clarify whether such lateralization was also observed in patients with TH resulting from middle cerebral artery aneurysm rupture., Methods: A retrospective analysis on the medical records of 79 patients with ruptured middle cerebral artery aneurysms was performed on the basis of lateralization and presence of TH. They were quadrichotomized as left TH+ (LTH+; n=17), right TH+ (n=25), left TH- (n=15), and right TH- (n=22). Comparisons, mainly between LTH+ and right TH+, were made on demographic variables, autonomic/cardiac parameters, plasma catecholamine and glucose levels, and outcomes., Results: There were no significant differences in demographic or cardiac parameters between the 2 groups. Systolic blood pressures were lower in LTH+ (139±34 versus 174±47 mm Hg; P=0.05). The LTH+ group also tended to be more bradycardiac (80±19 versus 101±22 bpm; P=0.13). The LTH+ group exhibited significantly lower plasma norepinephrine (1008±975 versus 2549±2133 pg/mL; P=0.03) and glucose levels (9.3±1.8 versus 12.2±4.5 mmol/L; P=0.04). However, in-hospital mortality did not differ significantly (41% versus 44%; P=1.00)., Conclusions: Lateralization of autonomic derangements observed might not have had a significant effect on the outcomes. Nevertheless, autonomic derangements associated with insular injury should be considered in the management of subarachnoid hemorrhage patients with TH.

Background and Purpose: Inflammation may play an important role in the formation and rupture of cerebral aneurysms. Chemokines act as chemoattractants for leukocytes directing them toward sites of tissue inflammation. The purpose of this study was to determine whether chemokines and chemoattractant cytokines were increased in the lumen of human cerebral aneurysms., Methods: The concentrations of chemokines and other inflammatory molecules in blood samples drawn from the lumen of human cerebral aneurysms of 16 consecutive patients (harboring 18 aneurysms) were compared with blood samples from the femoral arteries of the same patients. Three aneurysms had ruptured., Results: The mean plasma concentration of regulated on activation, normal T cell expressed and secreted (RANTES), monokine-induced-by-γ-interferon (MIG), interferon-γ-induced protein-10 (IP-10), eotaxin, interleukin (IL) 8, and IL17 was significantly higher in samples taken from cerebral aneurysms compared with femoral arteries. In contrast, plasma concentrations of all remaining inflammatory molecules (except IL6) that were tested did not differ between cerebral aneurysms and femoral arteries. For unruptured aneurysms, there was a significantly higher mean plasma concentration of monocyte chemoattractant protein-1 as well as RANTES, MIG, IP-10, eotaxin, IL8, and IL17 in samples obtained from cerebral aneurysms., Conclusions: High plasma concentrations of chemokines (monocyte chemoattractant protein-1, RANTES, MIG, IP-10, and eotaxin) and chemoattractant cytokines (IL8 and IL17) were found in the lumen of human cerebral aneurysms. These findings suggest that there may be an active recruitment of inflammatory cells into the aneurysm wall that may be exploited therapeutically.

The molecular mechanisms underlying the systemic response to subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms (RAs) are not fully understood. We investigated whether the analysis of gene expression in peripheral blood could provide clinically relevant information regarding the biologic consequences of SAH. Transcriptomics were performed using Illumina HumanHT-12v4 microarrays for 43 RA patients and 18 controls (C). Differentially expressed transcripts were analyzed for overrepresented functional groups and blood cell type-specific gene expression. The set of differentially expressed transcripts was validated using quantitative polymerase chain reaction in an independent group of subjects (15 RA patients and 14 C). There were 135 differentially expressed genes (false discovery rate 1%, absolute fold change 1.7): the abundant levels of 78 mRNAs increased and 57 mRNAs decreased. Among RA patients, transcripts specific to T lymphocyte subpopulations were downregulated, whereas those related to monocytes and neutrophils were upregulated. Expression profiles of a set of 16 genes and lymphocyte-to-monocyte-and-neutrophil gene expression ratios distinguished RA patients from C. These results indicate that SAH from RAs strongly influences the transcription profiles of blood cells. A specific pattern of these changes suggests suppression in lymphocyte response and enhancements in monocyte and neutrophil activities. This is probably related to the immunodepression observed in SAH.

Background: Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine:ADMA ratio, and nitrite/nitrate levels were associated with survival and cerebral vasospasm in SAH patients., Methods: One hundred and eleven patients were observed day 1 to 15 after SAH, with serial measurements of transcranial Doppler flow velocities (VMCA) and plasma biomarkers. Clinical status was assessed by the World Federation of Neurosurgical Societies grading scale., Results: Overall 30-day mortality was 18%, but differed between patients grouped by low, midrange, and high arginine:ADMA ratio in the first week after SAH. Mortality rates were 14/37, 1/37, and 5/37 in the 3 groups, respectively (P-logrank=0.0003). Cox regression showed that low versus midrange or high arginine:ADMA was associated with a hazard ratio of 4.1 independent of World Federation of Neurosurgical Societies grade (95% confidence interval, 1.5-10.9; P=0.006). ADMA or arginine:ADMA had no association to VMCA, but there was an inverse relationship between VMCA and nitrite/nitrate levels (P<0.0001). The NOS3 894G/G genotype was associated with 15% lower VMCA (P=0.01). ATbG-NOS3 haplotype homozygosity was associated with up to 64% higher nitrite/nitrate levels (P=0.003)., Conclusions: This study suggests that plasma arginine:ADMA ratios predict mortality after SAH. Both clinical and physiological measures of changes in cerebral hemodynamics are coupled to the nitric oxide system.

Emerging evidence shows that circulating endothelial progenitor cells (EPCs) promote regeneration of the endothelium at sites of vessel injury. This study was designed to test the hypothesis that EPCs are mobilized in patients who had ruptured cerebral aneurysm (CA) and underwent endovascular therapy. Fourteen patients with ruptured CAs were recruited and blood samples were analyzed after coil embolization surgery. Blood samples were also obtained from 18 healthy control subjects who had no evidence of CAs and did not undergo endovascular surgery. We measured the numbers of circulating EPCs, levels of plasma vascular endothelial growth factor (VEGF) and platelet counts. EPCs significantly increased in patients with ruptured CAs and underwent surgical coil embolization, reaching a peak level on day 14 post operation. The levels of plasma VEGF and platelet counts also significantly increased in parallel with the increase in EPCs, leading to significant positive correlations of circulating EPCs with VEGF in plasma (r=0.636, P<0.01) and platelet counts (r=0.721, P<0.001), respectively. The finding suggests that EPCs are mobilized upon surgery and may play a critical role in repairing injured vascular endothelium. Levels of EPCs in peripheral blood could also serve as a prognostic marker for the outcomes of ruptured cerebral aneurysms after surgical repair., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Subarachnoidal hemorrhage (SAH) occurring after aneurysmal rupture produces an inflammatory response in the cerebral circulation. Tumor necrosis factor (TNF)-alpha is a major cytokine in this process. Adhesion molecules provide information on inflammatory reactions taking place in the walls of blood vessels. Clinical evidence suggests a role of soluble intercellular adhesion molecule (sICAM)-1 in early hemorrhagic events. This study aimed to evaluate the implementation of early TNF-alpha and sICAM-1 serum measurement for the prognosis of patient outcome after intracranial aneurysmal rupture., Materials and Methods: The study consisted of 27 patients with a diagnosis of intracranial aneurysm. SAH was evaluated on admission according to the Fisher scale, patients' consciousness with the Glasgow Coma Scale, clinical grading with the Hunt and Hess scale, and clinical outcome with the Glasgow Outcome Scale (GOS). Blood samples were drawn within 72 h after arrival at the emergency room. Serum concentrations of TNF-alpha and sICAM-1 were assayed with the ELISA method., Results: The initial serum TNF-alpha concentration in the aneurysmal patients was low and did not correlate with radiological and clinical scores. The serum sICAM-1 level positively correlated with the severity of bleeding assessed by the Fisher scale and negatively with the patient's scoring in the GOS., Conclusions: This study demonstrated the absence of a systemic TNF-alpha-mediated inflammatory response at the onset of subarachnoid hemorrhage. Early measurement of serum sICAM-1 levels offers a potential prognostic value in the assessment of patients' outcome after brain aneurysmal rupture.

Background: The purpose of the present study was to investigate the relationship between serum concentrations of the immunoglobulin-like superfamily, selectins, hsCRP, and the development of DIND in patients with aneurysmal SAH., Methods: Serum ICAM-1, VCAM-1, E-selectin, P-selectin, L-selectin, and hsCRP were measured in 33 patients with SAH who underwent aneurysmal clipping within 48 hours of the onset of symptoms. Serum samples were obtained during the early period (day 0) and the late period (day 7)., Results: The serum concentrations of ICAM-1 (P = .009), VCAM-1 (P = .0383) and hsCRP (P = .0014) during the early period were significantly higher in patients with SAH than in control patients. Further, serum hsCRP concentration during the late period was significantly higher in patients with SAH than in control patients (P = 0033). Finally, serum concentrations of ICAM-1, VCAM-1, and hsCRP during the early (P = .0055, P = .0266, and P = .0266) and late (P = .0423, P = .0041, and P = .0004) period were significantly higher in patients with DIND than in patients without DIND., Conclusions: Serum levels of ICAM-1, VCAM-1 and hsCRP during the early and late period following SAH correlate with DIND.

Objectives: Transfusion-related acute lung injury may contribute to the development of acute lung injury in the critically ill, due to plasma from female donors containing antileukocyte antibodies. In July 2003, the U.K. National Blood Service stopped using female donor plasma for the production of fresh frozen plasma. Patients undergoing repair of a ruptured abdominal aortic aneurysm receive large amounts of fresh frozen plasma and often develop acute lung injury. We investigated whether the change to male fresh frozen plasma was associated with a change in the frequency of acute lung injury in these patients., Design: A retrospective, before and after, observational, single-center study., Setting: Tertiary care center and a regional blood center., Patients: The study included 211 patients undergoing open repair of a ruptured abdominal aortic aneurysm between 1998 and 2006., Interventions: None., Measurements and Main Results: Primary outcome was the development of acute lung injury in the first 6 hrs after surgery. Secondary outcomes were significant hypoxia (PaO2/FiO2 ratio <300), time to extubation, and survival at 30 days. Groups were well matched and received similar volumes of intravenous fluids and blood components. There was significantly less acute lung injury following the change to male fresh frozen plasma (36% before vs. 21% after, p = .04). At 6 hrs after surgery, fewer patients were hypoxic (87% before vs. 62% after, p < .01). In multivariate analysis, the change in donor policy was associated with a decreased risk of developing acute lung injury (odds ratio 0.39; 95% confidence interval, 0.16-0.90). Time to extubation and survival at 30 days were not statistically different between groups., Conclusions: The policy to exclude female donors from the production of fresh frozen plasma was associated with a decrease in the frequency of acute lung injury in patients undergoing repair of a ruptured abdominal aortic aneurysm.

Blood and cerebrospinal fluid (CSF) of 30 Fisher grade 3 aneurysmal subarachnoid hemorrhage (ASAH) patients were analyzed for the presence of the phosphorylated axonal form of the major neurofilament subunit NF-H (pNF-H), a promising biomarker of axonal injury. Patient demographic data including development of vasospasm and outcome scores at 6 months after aneurysmal rupture (AR) were evaluated. Higher pNF-H blood levels in the first few days after AR were strongly predictive of a negative outcome. Blood pNF-H levels in most recovering patients showed a steady increase into the second week after AR, presumably reflecting axonal degeneration secondary to the original insult. Almost half of the patients studied showed sudden dramatic peaks of pNF-H protein release into CSF in the 3- to 14-day time period after AR, which must reflect profound, coordinated, and secondary loss of axons. Patients in whom vasospasm was detected had significantly more pNF-H in both blood and CSF compared with those in whom vasospasm was not detected. We conclude that the analysis of pNF-H levels in blood and CSF differentiates between patients with poor and favorable outcomes and also reveals several novel features of ASAH progression and recovery.

Previous studies have indicated that medical therapy provides excellent outcomes for patients with uncomplicated Stanford type B acute aortic dissection. However, affected aortas are often compromised by aneurysmal dilatation and rupture, resulting in poor outcomes. The purpose of this study was to determine predictors of aortic events in patients with Stanford type B acute aortic dissection receiving conservative medical therapy. The study group consisted of 78 consecutive patients with Stanford type B acute aortic dissection who were admitted to the hospital within 48 hours of onset. These patients were treated medically and followed up for 1 year. Aortic events were defined as rupture, recurrent dissection, aortic expansion with diameter>or=60 mm, rapid aortic expansion at a rate of >or=10 mm/yr, and the development of visceral or limb ischemia. Predictors of these events were determined using multivariate analyses. During 1-year follow-up, aortic events were observed in 13 (17%) patients, including aortic rupture in 3 (4%), aortic diameter>or=60 mm in 4 (5%), rapid expansion of the aorta in 3 (4%), and the development of visceral or limb ischemia in 3 (4%). On multivariate analysis, fibrinogen-fibrin degradation product level>or=20 microg/ml (odds ratio 7.802, 95% confidence interval 1.405 to 43.335) on admission was the only independent predictor of aortic events at 1 year. In conclusion, careful monitoring is required for patients with medically treated Stanford type B acute aortic dissection associated with fibrinogen-fibrin degradation product level>or=20 microg/ml on admission.