Unruptured Intracranial Aneurysms Patients Research Articles

Subarachnoid haemorrhage and intracranial aneurysms in Greenland in the period 2018–2021: incidence, outcome and familial disposition

ABSTRACT Subarachnoid haemorrhages (SAH) caused by rupture of intracranial aneurysms (IA) are a severe condition. Earlier studies found a higher incidence of SAH in Greenlandic patients compared to Danish patients, with familial aggregation also higher in Greenland. However, updated data is lacking. To investigate the contemporary incidence, outcome, and familial disposition of SAH/IA in Greenlandic patients in 2018–2021. Greenlandic patients diagnosed with ruptured or unruptured IA (UIA) during 2018–2021 were included. Data was obtained from patient files, x-ray department, and discharge registry. Incidence rates were estimated as cases/100,000/year. Direct age-standardised incidence rates were calculated using WHO 2000–2025 as standards. Of 30 SAH patients, 20 (66.7%) were females, 10 (33.3%) males. Of 36 UIA patients, 27 (75.0%) were females, 9 (25.0%) males. For SAH, crude incidence was 13.4/100,000/year, age-standardised incidence was 10.8/100,000/year. Familial history was observed in 30.0% of SAH patients. 5 patients (16.7%) died before treatment, 28-day case-fatality rate (CFR) for all patients was 23.3%. Overall and age-standardised incidence rates were similar to previous studies but higher among females and compared to neighbouring countries. A high occurrence of familial history was reported. SAH remains a serious condition in Greenland, as evidenced by five fatalities before treatment was administered.

The preliminary study suggests an association between NF-ĸB pathway activation and increased plasma 20S proteasome activity in intracranial aneurysm patients

The significant role of increased activation of 20S proteasomes in the development of abdominal aortic aneurysms has been well-established in a mouse model. The available literature lacks similar studies concerning brain aneurysms. The aim of the study was to verify the hypothesis that patients with unruptured intracranial aneurysms (UIA) have increased 20S proteasome ChT-L activity compared to the control group of individuals without vascular lesions in the brain. In the next step, the relationship between the activity of 20S proteasomes ChT-L and precursor proteins from the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family, namely NF-κB1 (p105), NF-κB2 (p100), NF-κB p65, and the inflammatory chemokine MCP-1, was examined. Patients with UIA had significantly higher 20S ChT-L proteasome activity compared to the control group. Patients with multiple aneurysms had significantly higher 20S proteasome ChT-L activity compared to those with single aneurysms. In patients with UIA, the activity of the 20S proteasome ChT-L negatively correlated with the concentration of NF-κB1 (p105) and NF-κB p65 precursor proteins and positively correlated with the concentration of the cerebrospinal fluid chemokine MCP-1. Our results may suggest that increased 20S proteasome ChT-L activity in UIA patients modulates inflammation in the cerebral arterial vessel via the MCP-1 chemokine as a result of activation of the canonical NF-κB pathway.

Neutrophil-to-lymphocyte ratio associated with symptomatic saccular unruptured intracranial aneurysm

Background and purposeWhether symptomatic unruptured intracranial aneurysms (UIAs) lead to change in circulating inflammation remains unclear. This study aims to evaluate the role of hematological inflammatory indicators in predicting symptomatic UIA.MethodsAdult patients diagnosed with saccular intracranial aneurysm from March 2019 to September 2023 were recruited retrospectively. Clinical and laboratory data, including the white blood cells (WBC), neutral counts (NEUT), lymphocyte counts (LYM), and monocyte counts (MONO) of each patient, were collected. The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were calculated as NLR = NEUT/LYM, LMR = LYM/MONO, SII = PLT*NEUT/LYM. The hematological inflammatory indicators were compared in symptomatic saccular and asymptomatic UIA patients. Multivariable logistic regression analyses were performed to explore the factors predicting symptomatic UIA.ResultsOne hundred and fifty UIA patients with a mean age of 58.5 ± 12.4 were included, of which 68% were females. The NLR and LMR were significantly associated with symptomatic UIA, and the association remained in small UIAs (< 7 mm). The multiple logistic regression analysis showed that NLR was independently associated with symptomatic UIA. On ROC curve analysis, the optimal cutoff value of NLR to differentiate symptomatic from asymptomatic was 2.38. In addition, LMR was significantly associated with symptomatic UIA smaller than 7 mm.ConclusionThere was a significant correlation between NLR and symptomatic UIA. The NLR was independently associated with symptomatic UIA.

Machine learning based outcome prediction of microsurgically treated unruptured intracranial aneurysms

Machine learning (ML) has revolutionized data processing in recent years. This study presents the results of the first prediction models based on a long-term monocentric data registry of patients with microsurgically treated unruptured intracranial aneurysms (UIAs) using a temporal train-test split. Temporal train-test splits allow to simulate prospective validation, and therefore provide more accurate estimations of a model’s predictive quality when applied to future patients. ML models for the prediction of the Glasgow outcome scale, modified Rankin Scale (mRS), and new transient or permanent neurological deficits (output variables) were created from all UIA patients that underwent microsurgery at the Kepler University Hospital Linz (Austria) between 2002 and 2020 (n = 466), based on 18 patient- and 10 aneurysm-specific preoperative parameters (input variables). Train-test splitting was performed with a temporal split for outcome prediction in microsurgical therapy of UIA. Moreover, an external validation was conducted on an independent external data set (n = 256) of the Department of Neurosurgery, University Medical Centre Hamburg-Eppendorf. In total, 722 aneurysms were included in this study. A postoperative mRS > 2 was best predicted by a quadratic discriminant analysis (QDA) estimator in the internal test set, with an area under the receiver operating characteristic curve (ROC-AUC) of 0.87 ± 0.03 and a sensitivity and specificity of 0.83 ± 0.08 and 0.71 ± 0.07, respectively. A Multilayer Perceptron predicted the post- to preoperative mRS difference > 1 with a ROC-AUC of 0.70 ± 0.02 and a sensitivity and specificity of 0.74 ± 0.07 and 0.50 ± 0.04, respectively. The QDA was the best model for predicting a permanent new neurological deficit with a ROC-AUC of 0.71 ± 0.04 and a sensitivity and specificity of 0.65 ± 0.24 and 0.60 ± 0.12, respectively. Furthermore, these models performed significantly better than the classic logistic regression models (p < 0.0001). The present results showed good performance in predicting functional and clinical outcomes after microsurgical therapy of UIAs in the internal data set, especially for the main outcome parameters, mRS and permanent neurological deficit. The external validation showed poor discrimination with ROC-AUC values of 0.61, 0.53 and 0.58 respectively for predicting a postoperative mRS > 2, a pre- and postoperative difference in mRS > 1 point and a GOS < 5. Therefore, generalizability of the models could not be demonstrated in the external validation. A SHapley Additive exPlanations (SHAP) analysis revealed that this is due to the most important features being distributed quite differently in the internal and external data sets. The implementation of newly available data and the merging of larger databases to form more broad-based predictive models is imperative in the future.

Association of preoperative aneurysmal wall enhancement with relief of chronic headache after surgical clipping of unruptured intracranial aneurysms.

To investigate the association between chronic headache outcome and aneurysmal wall enhancement (AWE) on high-resolution vessel wall imaging (HR-VWI) in patients with unruptured intracranial aneurysms (UIAs) who underwent microsurgical clipping. Two hundred seventy-four UIA patients were retrospectively analyzed. Patients were grouped according to presence of AWE. AWE was subclassified as focal or uniform. Clinical and imaging data were recorded. Headache was evaluated using the 10-point numerical rating scale and Headache Impact Test-6 before and 6months after surgery. The proportions of patients reporting chronic headache in the no AWE, focal wall enhancement (FWE), and uniform wall enhancement (UWE) groups were 5.7%, 24.8%, and 41.8%, respectively. All patients in the UWE group who reported headache before surgery experienced headache improvement after surgery. Decrease in headache severity was greater in the UWE group than in the FWE group. Multivariate binary logistic regression showed that FWE (odds ratio (OR) 0.490; 95% confidence interval (CI), 0.262-0.917; p = 0.026) and small intraluminal thrombus (OR 0.336; 95% CI, 0.142-0.795; p = 0.013) were independent factors protective against preoperative headache. FWE (OR 0.377; 95% CI, 0.195-0.728; p = 0.004) and small intraluminal thrombus (OR 0.235; 95% CI, 0.088-0.630; p = 0.004) were independent predictors of no headache relief after surgery. AWE on HR-VWI is associated with relief of chronic headache after surgical clipping in patients with UIAs. Incidence of chronic headache was highest in patients exhibiting UWE. These patients also experienced the greatest improvement in headache after surgical clipping. This study revealed that high-resolution vessel wall imaging can demonstrate aneurysmal wall plaque and intraluminal thrombus, which may be prognostic imaging markers for chronic headache in patients with unruptured intracranial aneurysms. • Aneurysmal wall enhancement may be associated with chronic headache. • Incidence of chronic headache was highest in patients with aneurysms exhibiting uniform wall enhancement. • Patients with aneurysms exhibiting uniform wall enhancement experienced the greatest improvement in headache after clipping.

A deep-learning system to help make the surgical planning of coil embolization for unruptured intracranial aneurysms

BackgroundCoil embolization is a common method for treating unruptured intracranial aneurysms (UIAs). To effectively perform coil embolization for UIAs, clinicians must undergo extensive training with the assistance of senior physicians over an extended period. This study aimed to establish a deep-learning system for measuring the morphological features of UIAs and help the surgical planning of coil embolization for UIAs.MethodsPreoperative computational tomography angiography (CTA) data and surgical data from UIA patients receiving coil embolization in our medical institution were retrospectively reviewed. A convolutional neural network (CNN) model was trained on the preoperative CTA data, and the morphological features of UIAs were measured automatically using this CNN model. The intraclass correlation coefficient (ICC) was utilized to examine the similarity between the morphologies measured by the CNN model and those determined by experienced clinicians. A deep neural network model to determine the diameter of first coil was further established based on the CNN model within the derivation set (75% of all patients) using neural factorization machines (NFM) model and was validated using a validation set (25% of all patients). The general match ratio (the difference was within ± 1 mm) between the predicted diameter of first coil by model and that used in practical scenario was calculated.ResultsOne-hundred fifty-three UIA patients were enrolled in this study. The CNN model could diagnose UIAs with an accuracy of 0.97. The performance of this CNN model in measuring the morphological features of UIAs (i.e., size, height, neck diameter, dome diameter, and volume) was comparable to the accuracy of senior clinicians (all ICC > 0.85). The diameter of first coil predicted by the model established based on CNN model and the diameter of first coil used actually exhibited a high general match ratio (0.90) within the derivation set. Moreover, the model performed well in recommending the diameter of first coil within the validation set (general match ratio as 0.91).ConclusionThis study presents a deep-learning system which can help to improve surgical planning of coil embolization for UIAs.

The markers and risk stratification model of intracranial aneurysm instability in a large Chinese cohort

Intracranial aneurysm is the leading cause of nontraumatic subarachnoid hemorrhage. Evaluating the unstable (rupture and growth) risk of aneurysms is helpful to guild decision-making for unruptured intracranial aneurysms (UIA). This study aimed to develop a model for risk stratification of UIA instability. The UIA patients from two prospective, longitudinal multicenter Chinese cohorts recruited from January 2017 to January 2022 were set as the derivation cohort and validation cohort. The primary endpoint was UIA instability, comprising aneurysm rupture, growth, or morphology change, during a 2-year follow-up. Intracranial aneurysm samples and corresponding serums from 20 patients were also collected. Metabolomics and cytokine profiling analysis were performed on the derivation cohort (758 single-UIA patients harboring 676 stable UIAs and 82 unstable UIAs). Oleic acid (OA), arachidonic acid (AA), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α) were significantly dysregulated between stable and unstable UIAs. OA and AA exhibited the same dysregulated trends in serums and aneurysm tissues. The feature selection process demonstrated size ratio, irregular shape, OA, AA, IL-1β, and TNF-α as features of UIA instability. A machine-learning stratification model (instability classifier) was constructed based on radiological features and biomarkers, with high accuracy to evaluate UIA instability risk (area under curve (AUC), 0.94). Within the validation cohort (492 single-UIA patients harboring 414 stable UIAs and 78 unstable UIAs), the instability classifier performed well to evaluate the risk of UIA instability (AUC, 0.89). Supplementation of OA and pharmacological inhibition of IL-1β and TNF-α could prevent intracranial aneurysms from rupturing in rat models. This study revealed the markers of UIA instability and provided a risk stratification model, which may guide treatment decision-making for UIAs.

Methylprednisolone is related to lower incidence of postoperative bleeding after flow diverter treatment for unruptured intracranial aneurysm.

Regarding the anti-inflammatory effect, methylprednisolone is a candidate to prevent patients with unruptured intracranial aneurysms (UIAs) from postoperative bleeding (PB) after flow diverter (FD) treatment. This study aimed to investigate whether methylprednisolone is related to a lower incidence of PB after FD treatment for UIAs. This study retrospectively reviewed UIA patients receiving FD treatment between October 2015 and July 2021. All patients were observed until 72 h after FD treatment. The patients receiving methylprednisolone (80 mg, bid, for at least 24 h) were considered as standard methylprednisolone treatment (SMT) users, otherwise as non-SMT users. The primary endpoint indicated the occurrence of PB, including subarachnoid hemorrhage, intracerebral hemorrhage, and ventricular bleeding, within 72 h after FD treatment. This study compared the incidence of PB between SMT users and non-SMT users and investigated the protective effect of SMT on PB after FD treatment using the Cox regression model. Finally, after controlling the potential factors related to PB, we performed subgroup analysis to further confirm the protective effect of SMT on PB. This study finally included 262 UIA patients receiving FD treatment. PB occurred in 11 patients (4.2%), and 116 patients (44.3%) received SMT postoperatively. The median time from the end of surgery to PB was 12.3 h (range: 0.5-48.0 h). SMT users had a lower incidence of PB comparing with non-SMT users (1/116, 0.9% vs. 10/146, 6.8%, respectively; p = 0.017). The multivariate Cox analysis demonstrated that SMT users (HR, 0.12 [95%CI, 0.02-0.94], p = 0.044) had a lower risk of PB postoperatively. After controlling the potential factors related to PB (i.e., gender, irregular shape, surgical methods [FD and FD + coil] and UIA sizes), the patients receiving SMT still had a lower cumulative incidence of PB, comparing with patients receiving non-SMT (all p < 0.05). SMT was correlated with the lower incidence of PB for patients receiving FD treatment and may be a potential method to prevent PB after the FD treatment.

172 Health Inequities in Access to Treatment for Unruptured Intracranial Aneurysms in the United States over 20 Years

INTRODUCTION: Literature suggests that minority racial and ethnic groups have lower treatment rates for unruptured intracranial aneurysms (UIA). It is uncertain how these disparities have changed across time. METHODS: The National Inpatient Sample (NIS) database was queried using diagnostic and procedural codes for adult patients who underwent open surgical or endovascular treatment for UIA. Aneurysmal SAH patients were used as a substitute control for patients with intracranial aneurysms that progressed to hemorrhage before intervention. A multivariable logistic regression model was constructed using patient factors and hospital factors to identify predictors of treatment. RESULTS: A total of 213,350 UIA patients and 173,375 aSAH patients from 2000-2019 were included in the final analysis. After adjusting for covariates, Black patients (0.715, 95% CI 0.699-0.730), Hispanic patients (0.734, 95% CI 0.717-0.751) and other racial/ethnic minority patients (0.633, 95% CI 0.617-0.651) had lower odds of intervention for UIA compared to White patients with UIA. Medicare patients had higher odds of treatment than private insurance patients while Medicaid and the uninsured patients had lower odds. Non-White/Hispanic females (0.697, 95% CI 0.646-0.752) and males (0.602, 95%CI 0.556-0.651) had lower treatment odds than their white counterparts, irrespective of insurance status. Multivariable regression analysis revealed that the treatment odds of Black patients improved over time, while other minority group patients had variable treatment odds over time. CONCLUSIONS: This analysis of NIS data from 2000 to 2019 demonstrates disparities in treatment for UIA across race, sex, insurance status, and hospital factors. The persistence of inequalities over time requires attention in order to target improvement.

Serum Interleukin-1 Levels Are Associated with Intracranial Aneurysm Instability.

Serum interleukin-1 (IL-1) are possibly indicative of the inflammation in the intracranial aneurysm (IA) wall. This study aimed to investigate whether IL-1 could discriminate the unstable IAs (ruptured intracranial aneurysms (RIAs) and symptomatic unruptured intracranial aneurysms (UIAs)) from stable, asymptomatic UIAs. IA tissues and blood samples from 35 RIA patients and 35 UIA patients were collected between January 2017 and June 2020 as the derivation cohort. Blood samples from 211 patients with UIAs were collected between January 2021 and June 2022 as the validation cohort (including 63 symptomatic UIAs). Blood samples from 35 non-cerebral-edema meningioma patients (non-inflammatory control) and 19 patients with unknown-cause subarachnoid hemorrhage (hemorrhagic control) were also collected. IL-1β and IL-1.ra (IL-1 receptor antagonist) were measured in serum and IA tissues, and the IL-1 ratio was calculated as log10 (IL-1.ra/IL-1β). Based on the derivation cohort, multivariate logistic analysis showed that IL-1β (odds ratio, 1.48, P = 0.001) and IL-1.ra (odds ratio, 0.74, P = 0.005) were associated with RIAs. The IL-1 ratio showed an excellent diagnostic accuracy for RIAs (c-statistic, 0.91). Histological analysis confirmed the significant correlation of IL-1 between serum and aneurysm tissues. IL-1 ratio could discriminate UIAs from non-inflammatory controls (c-statistic, 0.84), and RIAs from hemorrhagic controls (c-statistic, 0.95). Based on the validation cohort, the combination of IL-1 ratio and PHASES score had better diagnostic accuracy for symptomatic UIAs than PHASES score alone (c-statistic, 0.88 vs 0.80, P < 0.001). Serum IL-1 levels correlate with aneurysm tissue IL-1 levels and unstable aneurysm status, and could serve as a potential biomarker for IA instability.

Antiplatelet therapy adjustment improved the radiomic characteristics of acute silent cerebral infarction after stent-assisted coiling in patients with high on-treatment platelet reactivity: A prospective study.

We aimed to investigate the effects of high on-treatment platelet reactivity (HPR) and antiplatelet therapy adjustment on high-risk radiomic features in patients with antiplatelet therapy adjustment on acute silent cerebral infarction (ASCI) who had unruptured intracranial aneurysms (UIA) after stent placement. This single-institution study prospectively included 230 UIA patients who had ACSI after stent placement in our hospital between January 2015 and July 2020. All patients underwent magnetic resonance imaging with diffusion-weighted imaging (MRI-DWI) after stent placement and 1,485 radiomic features were extracted from each patient. The least absolute shrinkage and selection operator regression methods were used for selection of high-risk radiomic features associated with clinical symptoms. In addition, 199 patients with ASCI were classified into three groups: controls without HPR (n = 113), HPR patients with standard antiplatelet therapy (n = 63) and HPR patients with antiplatelet therapy adjustment (n = 23). We compared high-risk radiomic features between three groups. Of the patients who had acute infarction after MRI-DWI, 31 (13.5%) exhibited clinical symptoms. Eight risk radiomic features associated with clinical symptoms were selected, and the radiomics signature exhibited good performance. In ASCI patients, compared with controls, the radiomic characteristics of ischemic lesion in HPR patients were consistent with the following high-risk radiomic features associated with clinical symptoms: higher gray-level values, greater variance in intensity values, and greater homogeneity. However, the adjustment of antiplatelet therapy in HPR patients modified the high-risk radiomic features, which showed lower gray-level values, less variance in intensity values, and more heterogeneous texture. The radiomic shape feature of elongation showed no notable difference between three groups. Adjustment of antiplatelet therapy might reduce the high-risk radiomic features of UIA patients with HPR after stent placement.

Altered gut microbiomes are associated with the symptomatic status of unruptured intracranial aneurysms.

Gut microbiome has recently been recognized as an important environmental factor affecting the occurrence and development of unruptured intracranial aneurysms (UIA). This study aimed to investigate the relationship between gut microbiome and symptomatic UIA, which is a predictor of instability and a high propensity to rupture. A total of 132 patients including 86 asymptomatic UIA and 46 symptomatic UIA were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA gene sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict the functional composition of the gut microbiome. There is no difference in the fecal microbial alpha diversity between symptomatic and asymptomatic UIA, but gut microbiome composition changed significantly. At the order level, the relative abundance of Clostridiales was significantly enriched in the symptomatic compared with asymptomatic UIA (p = 0.043). In addition, similar alterations were observed at the family levels of Ruminococcaceae. The Linear discriminant analysis (LEfSe) revealed Fournierella, Ruthenibacterium, and Anaerotruncus as discriminative features in the symptomatic group. Notably, functional differences in gut microbiome of patients with symptomatic UIA included decreased propionate metabolism pathway and enrichment of peptidoglycan biosynthesis pathways. The present study comprehensively characterizes gut microbiome in a large cohort of different risk statuses of UIA patients and demonstrates the potential biological function of gut microbiome involved in the development of UIA. It may provide additional benefits in guiding UIA management and improving patient outcomes.

Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement.

Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI. We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA. Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response. Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.

Characteristics and Outcomes of Thrombolysis-Treated Stroke Patients With and Without Saccular Intracranial Aneurysms.

Intravenous thrombolysis seems safe in acute ischemic stroke patients with saccular, unruptured intracranial aneurysms (UIAs), but little is known about the differences in cardiovascular risk factors and outcomes between intravenous thrombolysis-treated stroke patients with and without UIAs. We hypothesized that UIA patients would have a higher burden of cardiovascular risk factors and, therefore, a higher risk of an unfavorable outcome. In this prospective cohort study conducted in Helsinki University Hospital, we identified intravenous thrombolysis-treated patients with concurrent saccular UIAs admitted to a comprehensive stroke center between 2005 and 2019 using 2 overlapping methods. For each UIA patient, a control patient was identified and matched (1:1) for age, sex, admission year, and stroke severity. The primary outcome was an unfavorable outcome at 3 months, defined as a modified Rankin Scale (mRS) score 3 to 6. The secondary outcomes were an excellent outcome (mRS score 0-1) at 3 months and mRS difference in shift analysis. In total, 118 UIA patients and 118 matched control patients were identified. The UIA patients were more often current smokers, and their admission systolic blood pressure was higher. The rate of hemorrhagic complications did not differ between the groups. UIAs were not associated with an unfavorable outcome in the conditional logistic regression analysis (odds ratio, 1.41 [95% CI, 0.79-2.54]; P=0.25). However, the UIA patients were less likely to have excellent outcomes (odds ratio for non-excellent outcome, 2.09 [95% CI, 1.13-3.85]; P=0.02). In shift analysis, UIAs were associated with higher mRS (odds ratio, 1.61 [95% CI, 1.03-2.49]; P=0.04). The intravenous thrombolysis-treated stroke patients with UIAs were more often current smokers and had higher systolic blood pressure than the matched patients without UIAs. They were as likely to have unfavorable outcomes at 3 months but seemed less likely to achieve excellent outcomes and were more likely to have higher mRS in shift analysis.

European Stroke Organisation (ESO) guidelines on management of unruptured intracranial aneurysms.

Unruptured intracranial aneurysms (UIA) occur in around 3% of the population. Important management questions concern if and how to perform preventive UIA occlusion; if, how and when to perform follow up imaging and non-interventional means to reduce the risk of rupture. Using the Standard Operational Procedure of ESO we prepared guidelines according to GRADE methodology. Since no completed randomised trials exist, we used interim analyses of trials, and meta-analyses of observational and case-control studies to provide recommendations to guide UIA management. All recommendations were based on very low evidence. We suggest preventive occlusion if the estimated 5-year rupture risk exceeds the risk of preventive treatment. In general, we cannot recommend endovascular over microsurgical treatment, but suggest flow diverting stents as option only when there are no other low-risk options for UIA repair. To detect UIA recurrence we suggest radiological follow up after occlusion. In patients who are initially observed, we suggest radiological monitoring to detect future UIA growth, smoking cessation, treatment of hypertension, but not treatment with statins or acetylsalicylic acid with the indication to reduce the risk of aneurysm rupture. Additionally, we formulated 15 expert-consensus statements. All experts suggest to assess UIA patients within a multidisciplinary setting (neurosurgery, neuroradiology and neurology) at centres consulting >100 UIA patients per year, to use a shared decision-making process based on the team recommendation and patient preferences, and to repair UIA only in centres performing the proposed treatment in >30 patients with (ruptured or unruptured) aneurysms per year per neurosurgeon or neurointerventionalist. These UIA guidelines provide contemporary recommendations and consensus statement on important aspects of UIA management until more robust data come available.

Serum IL-1, Pyroptosis and Intracranial Aneurysm Wall Enhancement: Analysis Integrating Radiology, Serum Cytokines and Histology.

Background and PurposeAneurysm wall enhancement (AWE) is correlated with the rupture and growth risk of unruptured intracranial aneurysms (UIAs). Pyroptosis is a proinflammation mode of lytic cell death, mediated by pyroptosis-related proteins, i.e., gasdermin D and interleukin 1 β (IL-1β). Integrating serum cytokines and histology, this study aimed to investigate the correlation between AWE and pyroptosis in UIAs.MethodsUIA patients receiving microsurgical clipping were prospectively enrolled from January 2017 and June 2020. UIA samples were collected, as well as the corresponding blood samples. In this study, high-resolution magnetic resonance was employed to identify the AWE. The serum 46-cytokines examination and the histological analysis were conducted to determine pyroptosis, CD68 and MMP2. The IL-1 ra/beta ratio was determined by complying with the serum IL-1β and IL-1.ra. A comparison was drawn in the differences between UIAs with and without AWE. Lastly, the correlation between inflammation in UIA samples and serums was investigated.ResultsThis study included 34 UIA patients. The serum proinflammatory cytokines [IL-1β (P < 0.001) and TNF-α (P < 0.001)] were up-regulated, and serum anti-inflammatory cytokine (IL-1.ra, P = 0.042) were down-regulated in patients with AWE UIAs. The patients with AWE UIAs achieved a higher IL-1.ra/beta ratio (P < 0.001). The multivariate logistic analysis demonstrated IL-1β [odds ratio (OR), 1.15; 95% confidence interval (CI), 1.02–1.30; P = 0.028] and IL-1.ra (OR, 0.998; 95% CI, 0.997–1.000; P = 0.017) as the risk factors correlated with the AWE. IL-1.ra/beta ratio achieved the highest predictive accuracy [area under the curve (AUC), 0.96] for AWE, followed by IL-1.ra (AUC, 0.90), IL-1β (AUC, 0.88) and TNF-α (AUC, 0.85). As compared with the UIAs without AWE, the AWE UIAs were manifested as a severer wall remodeling, with higher relative levels of pyroptosis-related proteins, CD68 and MMP2. The serum IL-1β, IL-1.ra and IL-1.ra/beta ratio had a positive correlation with the relative levels of pyroptosis-related proteins, CD68 and MMP2 in UIA tissues.ConclusionThe serum IL-1β and IL-1.ra were correlated with the AWE. More pyroptosis-related proteins were identified in UIAs with AWE. The serum IL-1β and IL-1.ra were correlated with the pyroptosis-related proteins in aneurysm tissues.

The Impact of Interhospital Competition on Treatment Strategy and Outcomes for Unruptured Intracranial Aneurysms.

Interhospital competition has been shown to affect surgical outcomes and expenditures. However, interhospital competition's impact on neurosurgery is poorly characterized. To assess how interhospital competition is associated with treatment strategy and outcomes for unruptured intracranial aneurysms (UIAs). We identified all elective UIA admissions in the National Inpatient Sample from 2002 to 2011. Competitive intensity of each hospital market was quantified using the validated Herfindahl-Hirschman Index (HHI), with lower values denoting higher competition. We then obtained nationwide HHI values for 2012 to 2016 from the Health Care Cost Project. Outcomes included treatment modality (clipping, coiling, or nonoperative management), inpatient mortality, disposition, complications, length of stay (LOS), and costs. Multivariate regression assessed the association between HHI and outcomes, controlling for patient demographics, severity metrics, hospital characteristics, and treatment. We studied 157 979 elective UIA admissions at 1435 hospitals from 2002 to 2011, with an increase in coiling admissions (13.4% to 33.7%) and decrease in clipping admissions (30.9% to 17.6%). Mean hospital HHI was 0.11 (range=0.001-0.97). Competition decreased for 61.8% of hospitals from 2002 to 2011 and 68.1% of metropolitan localities from 2012 to 2016. Admissions in more competitive hospital markets exhibited increased odds of undergoing surgery (odds ratio [OR] = 1.37, P <.001), with preference toward coiling over clipping (OR=1.27, P <.001). HHI was not associated with mortality, disposition, or LOS. However, increased interhospital competition was associated with more complications (OR=1.09, P=.001) and greater hospital costs (β-coefficient=1.06, P <.001). For UIA patients, admission to hospitals in more competitive geographies was associated with increased rates of surgical intervention, coiling utilization, complications, and hospitalization costs.

Intracranial aneurysm is predicted by abdominal aortic calcification index: A retrospective case-control study

Background and aimsPatients with intracranial aneurysms (IA) have excess mortality for cardiovascular diseases, but little is known on whether atherosclerotic manifestations and IA coexist. We investigated abdominal aortic calcification index (ACI) association with unruptured and ruptured IAs. MethodsThis retrospective case-control study reviews all tertiary centers patients (n = 24,660) who had undergone head computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA) for any reason between January 2003 and May 2018. Patients (n = 2020) with unruptured or ruptured IAs were identified, and patients with available abdominal CT were included. IA patients were matched by sex and age to controls (available abdomen CT, no IAs) in ratio of 1:3. ACI was measured from abdomen CT scans and patient records were reviewed. Results1720 patients (216 ruptured IA (rIA), 246 unruptured IA (UIA) and 1258 control) were included. Mean age was 62.9 ± 11.9 years and 58.2% were female. ACI (OR 1.02 per increment, 95%CI 1.01–1.03) and ACI>3 (OR 5.77, 95%CI 3.29–10.11) increased risk for rIA compared to matched controls. UIA patients' ACI was significantly higher but ACI did not increase odds for UIA compared to matched controls. History of coronary artery disease was less frequent in rIA patients. There was no calcification in aorta in 8.8% rIA and 13.6% UIA patients (matched controls 25.7% and 22.6% respectively, p < 0.01). ConclusionsAortic calcification is greater in rIA and UIA patients than matched controls. ACI increases risk for rIAs.

Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms.

Periodontal infections are associated with the formation and rupture of intracranial aneurysms (IAs). This study investigated the role of two key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Immunoglobulin A (IgA) and IgG antibodies against P.gingivalis and A.actinomycetemcomitans were measured with enzyme immune assay from the serum of 227 IA patients, of whom 64 also underwent clinical oral examination. As a control group, 1096 participants in a cross-sectional health survey, Health 2000, underwent serological studies and oral examination. Logistic regression was used for multivariate analysis. Immunohistochemistry was performed to demonstrate bacteria-derived epitopes in the IA wall. Widespread gingivitis and severe periodontitis were more common in IA patients than in controls (2× and 1.5×, respectively). IgA antibodies against P.gingivalis and A.actinomycetemcomitans were 1.5× and 3-3.4× higher, respectively, in both unruptured and ruptured IA patients compared to controls (p≤0.003). IgG antibodies against P.gingivalis were 1.8× lower in unruptured IA patients (p<0.001). In multivariate analysis, high IgA, but low IgG, antibody levels against P.gingivalis (odds ratio [OR]=1.4, 95% confidence interval [Cl] = 1.1-1.8 and OR=1.5, 95% Cl = 1.1-1.9; OR=0.6, 95% Cl = 0.4-0.7 and OR=0.5, 95% Cl = 0.4-0.7) and against A.actinomycetemcomitans (OR=2.3, 95% Cl = 1.7-3.1 and OR=2.1, 95% Cl = 1.5-2.9; OR=0.6, 95% Cl = 0.4-0.8 and OR=0.6, 95% Cl = 0.5-0.9) were associated with the risk of IA formation and rupture. Immunohistochemistry showed P.gingivalis epitopes in the IA wall. Exposure to the periodontal pathogens P.gingivalis and A.actinomycetemcomitans and dysfunctional acquired immune response against them may increase the risk of IA formation and IA rupture.

Integrated Transcriptional Profiling Analysis and Immune-Related Risk Model Construction for Intracranial Aneurysm Rupture.

Intracranial aneurysms (IAs) may cause lethal subarachnoid hemorrhage upon rupture, but the molecular mechanisms are poorly understood. The aims of this study were to analyze the transcriptional profiles to explore the functions and regulatory networks of differentially expressed genes (DEGs) in IA rupture by bioinformatics methods and to identify the underlying mechanisms. In this study, 1,471 DEGs were obtained, of which 619 were upregulated and 852 were downregulated. Gene enrichment analysis showed that the DEGs were mainly enriched in the inflammatory response, immune response, neutrophil chemotaxis, and macrophage differentiation. Related pathways include the regulation of actin cytoskeleton, leukocyte transendothelial migration, nuclear factor κB signaling pathway, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and chemokine signaling pathway. The enrichment analysis of 20 hub genes, subnetworks, and significant enrichment modules of weighted gene coexpression network analysis showed that the inflammatory response and immune response had a causal relationship with the rupture of unruptured IAs (UIAs). Next, the CIBERSORT method was used to analyze immune cell infiltration into ruptured IAs (RIAs) and UIAs. Macrophage infiltration into RIAs increased significantly compared with that into UIAs. The result of principal component analysis revealed that there was a difference between RIAs and UIAs in immune cell infiltration. A 4-gene immune-related risk model for IA rupture (IRMIR), containing CXCR4, CXCL3, CX3CL1, and CXCL16, was established using the glmnet package in R software. The receiver operating characteristic value revealed that the model represented an excellent clinical situation for potential application. Enzyme-linked immunosorbent assay was performed and showed that the concentrations of CXCR4 and CXCL3 in serum from RIA patients were significantly higher than those in serum from UIA patients. Finally, a competing endogenous RNA network was constructed to provide a potential explanation for the mechanism of immune cell infiltration into IAs. Our findings highlighted the importance of immune cell infiltration into RIAs, providing a direction for further research.