Association between preventive treatment for unruptured intracranial aneurysms and incident dementia: a nationwide population-based cohort study.

Preventive treatments for unruptured intracranial aneurysms (UIAs) are used worldwide. However, the long-term effects to cognition have been underestimated. Using representative sample data from the National Health Insurance Service-Senior Cohort database, we compared cumulative risk of incident dementia between two groups: (1) treatment versus observation group, and (2) within the treatment group (surgical versus endovascular treatment). Cox proportional hazard ratios were estimated after applying one-to-one propensity score matching. Subgroup analyses were conducted to investigate interactions between treatment effects and sex, age and history of stroke, respectively. After matching, 3,763 participants were included in each group. The 10-year incidence rates of dementia were 9.82 and 8.68 per 1,000 person-years in the treatment and observation groups, respectively (HR: 1.11, 95% CI: 0.90-1.38, P = 0.33). Furthermore, the risk of incident dementia was not different between the surgical and endovascular treatment groups (HR: 0.98, 95% CI: 0.70-1.37, P = 0.91). In the subgroup analysis, surgical treatment was associated with an increased risk of developing dementia, particularly among male patient (HR: 2.34, 95% CI: 1.04-5.28). Preventive treatment of UIAs appears acceptable in terms of long-term effects to cognition. However, further researches are strongly required to identify the high risk patients of development of dementia.

Cigarette Smoking and Observed Growth of Unruptured Intracranial Aneurysms: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Smoking and observed growth of intracranial aneurysms are known risk factors for rupture. The mechanism by which smoking increases this risk is not completely elucidated. Furthermore, an association between smoking and aneurysm growth has not been clearly defined in the literature. We hypothesize that smoking is associated with aneurysm growth, which, in turn, may serve as one of the mechanisms by which smoking drives rupture risk. METHODS: We report a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Using the R software, we performed a meta-analysis to investigate the association between smoking and the growth of unruptured intracranial aneurysms. Studies on familial aneurysms and genetic syndromes known to increase the risk of aneurysms were excluded. RESULTS: Eighteen observational studies were included with a total of 3535 patients and 4289 aneurysms with a mean follow-up period ranging from 17 to 226 months. The mean age among the studies ranged from 38.4 to 73.9 years; 74% of patients were female. Ever-smoking status (odds ratio, 1.10 [95% CI, 0.87-1.38]) and current smoking status (odds ratio, 1.43 [95% CI, 0.84-2.43]) did not show a statistically significant association with growth of intracranial aneurysms. Patients currently smoking did not have a statistically significant association with the growth of intracranial aneurysms (odds ratio, 1.18 [95% CI, 0.72-1.93]) compared with patients without a smoking history. No significant association was found in patients who previously smoked compared with patients who never smoked (odds ratio, 1.46 [95% CI, 0.88-2.43]). CONCLUSIONS: Smoking is not clearly associated with the growth of unruptured intracranial aneurysms, despite trends being observed, there is no statistical association. The mechanism by which smoking increases rupture risk might not be growth. In patients for whom observation is recommended, the absence of growth over time in the setting of smoking history does not, therefore, imply protection from rupture.

Higher Risk of Mental Illness in Patients With Diagnosed and Untreated Unruptured Intracranial Aneurysm: Findings From a Nationwide Cohort Study.

BACKGROUND: We aimed to investigate the association between a diagnosis of untreated unruptured intracranial aneurysms (UIAs) and the development of mental illness. METHODS: This retrospective, propensity-score-matched cohort study was based on the nationwide South Korean database. The UIA diagnosis group included participants newly diagnosed with UIA between 2011 and 2019. For a well-matched control group, patients diagnosed with an acute upper respiratory infection but without UIA during the same period were selected through 1:4 matching based on propensity scores, which were calculated using age, sex, economic status, and comorbidities. The study's outcome measure encompassed the incidence of mental illnesses over a 10-year period, using International Classification of Diseases-Tenth Revision codes for anxiety, stress, depressive, bipolar, and eating disorders, insomnia, and alcohol or drug misuse. RESULTS: After propensity score matching, 85 438 participants with untreated UIAs (50.75% male; average age, 56.41 [±13.82] years; follow-up, 4.21 [±2.56] years) and 331 123 controls (49.44% males; average age, 56.69 [±12.92] years; follow-up, 7.48 [±2.12] years) were compared. Incidence rate of mental illness was higher in the UIA group (113.07 versus 90.41 per 1000 person-years; hazard ratio, 1.104 [95% CI, 1.089-1.119]). The risk of mental illness varied slightly by sex (males: hazard ratio, 1.131 [95% CI, 1.108-1.155]; females: hazard ratio, 1.082 [95% CI, 1.063-1.103]). Hazard ratios showed a U-shaped relationship with age, peaking in younger age groups, decreasing in middle-aged groups, and slightly increasing in older age groups, especially in patients with severe mental illness receiving psychotherapy. CONCLUSIONS: Our findings indicate a higher risk of mental illness in patients with UIA diagnosis in specific demographic groups, suggesting a possible psychological burden associated with UIAs. Clinicians treating cerebral aneurysms should be aware that the psychological burden caused by the diagnosis of UIA itself could contribute to mental illness and strive to provide comprehensive care for these patients.

Additional Relevant Intracranial Findings in Persons Screened with MR for Intracranial Aneurysms.

BACKGROUND: Radiological screening for intracranial aneurysms (IAs) may identify other relevant intracranial findings. We investigated their prevalence on MR in persons screened for IAs. METHODS: We included all persons who were screened for the presence of IAs with brain MRI/MRA between 1996 and 2022 because of a family history of aneurysmal subarachnoid haemorrhage (aSAH) or autosomal dominant polycystic kidney disease (ADPKD). We reviewed radiology reports of initial and repeated brain MR to identify additional intracranial findings that needed follow-up or treatment, or carried a risk of becoming symptomatic. RESULTS: We included 766 persons (positive family history of aSAH: n = 681; ADPKD: n = 85) who had 1446 MRI/MRAs. At initial screening, 49 additional relevant intracranial findings were reported in 47 persons (6.1%, 95% CI 4.7-8.1%). Of all included persons, 338 (44%) underwent one (n = 154) or more (n = 184) follow-up screenings (total MRI/MRAs at follow-up: n = 680). In 15/338 persons (4.4%, 95% CI 2.7-7.2%), 16 new additional relevant findings were reported at a median follow-up duration of 10 years (IQR 5-12). CONCLUSIONS: Persons who are counselled for screening for IAs should be informed that there is a six percent chance of identifying an additional finding that requires follow-up or treatment, or may become symptomatic. Additionally, after 10-year follow-up screening there is a four percent chance of identifying a new additional relevant finding. The impact of such findings on quality of life needs further study.

"Pediatric Spontaneous Intracranial Dissecting Aneurysms: Impact of Ischemic and Hemorrhagic Manifestations on Endovascular Treatment Strategies - Insights from a Developing World Setting".

BACKGROUND: Pediatric spontaneous intracranial dissecting aneurysms are rare, but systematic studies comparing hemorrhagic and ischemic presentations are lacking. This study addresses gaps in understanding their epidemiology, clinical presentation, management, and outcome. METHODS: A retrospective analysis of 23 pediatric patients with nontraumatic intracranial dissecting aneurysms treated between July 2018 and December 2023 was conducted. Patients were divided into 2 groups based on presentation: hemorrhagic (n = 16) and ischemic (n = 7). Clinical data were analyzed, including demographics, radiologic findings, treatment modalities, and outcomes. RESULTS: Clinical presentations varied, with limb weakness being more prevalent in hemorrhagic cases (P = 0.014), while headache and seizures were more common in ischemic cases. Angiographic analysis revealed distinct patterns, with hemorrhagic cases showing more distal involvement on vessel segments with stenosis and dilatation (pearl string sign). At the same time, the ischemic group exhibited the double-lumen sign. Various treatments, including microsurgery and endovascular techniques, were utilized, with perioperative complications observed, including one mortality in a hemorrhagic case. Multiple regression analysis identified significant risk factors for perioperative complications, namely, the configuration of the dissecting aneurysm (P = 0.016) and the type of presentation (P = 0.0006). Long-term Glasgow Outcome Scores were comparable, but patients with hemorrhagic manifestations experienced prolonged hospital and ICU stays (P = 0.001). CONCLUSIONS: Pediatric intracranial dissecting aneurysms, particularly hemorrhagic cases, are associated with severe neurologic deficits and higher perioperative complications. Despite similar long-term outcomes, hemorrhagic cases require prolonged hospitalization, increasing treatment costs. Optimizing management strategies for pediatric intracranial dissecting aneurysms, especially those with hemorrhagic features, is essential to improve outcomes and reduce healthcare expenditures.

Rupture risk of intracranial aneurysms: Comparison between small ruptured intracranial aneurysms and large unruptured intracranial aneurysms.

To compare the differences in clinical and morphological features between small ruptured intracranial aneurysms and large unruptured intracranial aneurysms to evaluate the risk factors for the rupture of IAs. The clinical data of 189 consecutive patients with 193 IAs were reviewed. The patients and IAs were divided into ruptured (<5 mm) and unruptured groups (>10 mm). The characteristics of the patients and the intracranial aneurysms (IAs) were compared between the 2 groups, and the risk factors for rupture of IAs were assessed using multiple logistic regression. Patient age (odds ratio [OR], 0.955), IA located at the internal carotid artery (ICA, OR, 0.202), irregular shape (OR, 0.083) and parent vessel diameter (OR, 0.426) were negatively correlated with the risk of IA rupture. IAs located at bifurcations (OR, 6.766) were positively correlated with the risk of IA rupture. In addition to the size of the IAs, regardless of IAs shape, other factors, such as younger age (<63.5 years), location at a bifurcation, IAs located at the ICA and a small parent vessel diameter (<3.25 mm), can influence the risk of IA rupture.

GWAS-based polygenic risk scoring for predicting cerebral artery dissection in the Chinese population.

OBJECTIVE: Cerebral artery dissection (CeAD) is a rare but serious disease. Genetic risk assessment for CeAD is lacking in Chinese population. We performed genome-wide association study (GWAS) and computed polygenic risk score (PRS) to explore genetic susceptibility factors and prediction model of CeAD based on patients in Huashan Hospital. METHODS: A total of 210 CeAD patients and 280 controls were enrolled from June 2017 to September 2022 in Department of Neurology, Huashan Hospital, Fudan University. We performed GWAS to identify genetic variants associated with CeAD in 140 CeAD patients and 210 control individuals according to a case and control 1:1.5 design rule in the training dataset, while the other 70 patients with CeAD and 70 controls were used as validation. Then Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were utilized to identify the significant pathways. We constructed a PRS by capturing all independent GWAS SNPs in the analysis and explored the predictivity of PRS, age, and sex for CeAD. RESULTS: Through GWAS analysis of the 140 cases and 210 controls in the training dataset, we identified 13 leading SNPs associated with CeAD at a genome-wide significance level of P < 5 × 10- 8. Among them, 10 SNPs were annotated in or near (in the upstream and downstream regions of ± 500Kb) 10 functional genes. rs34508376 (OR2L13) played a suggestive role in CeAD pathophysiology which was in line with previous observations in aortic aneurysms. The other nine genes were first-time associations in CeAD cases. GO enrichment analyses showed that these 10 genes have known roles in 20 important GO terms clustered into two groups: (1) cellular biological processes (BP); (2) molecular function (MF). We used genome-wide association data to compute PRS including 32 independent SNPs and constructed predictive model for CeAD by using age, sex and PRS as predictors both in training and validation test. The area under curve (AUC) of PRS predictive model for CeAD reached 99% and 95% in the training test and validation test respectively, which were significantly larger than the age and sex models of 83% and 86%. CONCLUSIONS: Our study showed that ten risk loci were associated with CeAD susceptibility, and annotated functional genes had roles in 20 important GO terms clustered into biological process and molecular function. The PRS derived from risk variants was associated with CeAD incidence after adjusting for age and sex both in training test and validation.

Declining trend in the estimated annual rupture rate of unruptured cerebral aneurysms in Japan: a nationwide study.

The incidence of subarachnoid hemorrhages (SAHs) in Japan has recently decreased. However, trends in the annual rates of unruptured cerebral aneurysms (UCAs) are unclear because calculations based on follow-up periods are limited to patients with ruptured cerebral aneurysms. We aimed to clarify current trends in the estimated annual rupture rates of UCAs in Japan and to identify the most relevant contributing factors. We analyzed data from the Japanese Ministry of Health, Labour and Welfare and records of the Japan Neurosurgical Society. The estimated annual rupture rates of UCAs between 2003 and 2018 were calculated according to age-adjusted mortality rates of SAH and number of treated ruptured cerebral aneurysms (RCAs). We estimated trends in annual rupture rates using sensitivity analysis and assessed associations between estimated annual rupture rates and the prevalences of hypertension and current smoking. The estimated annual rupture rate of UCAs significantly decreased from 1.44 to 0.87% and from 0.92 to 0.76%, respectively, in terms of age-adjusted mortality rates of SAH and number of treated RCAs (p < 0.001). The range of changes in estimated annual rupture rates of UCAs was - 1.13%‒0.83%, representing a declining UCA trend of 88%. The estimated annual rupture rates of UCAs declined by 0.02-0.10% and 0.01-0.05% with every percent decrease in hypertension and current smoking prevalence, respectively. The estimated annual rupture rate of UCAs has recently decreased in Japan, possibly due to a decrease in the prevalence of hypertension rather than smoking.

Sex differences in risk factor relationships with subarachnoid haemorrhage and intracranial aneurysms: A Mendelian Randomisation study.

Background: The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors. Aims: The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA. Methods: We conducted a sex-specific two-sample Mendelian randomisation study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e., aSAH and unruptured IA combined) as outcomes. Results: We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (P-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (P-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (P-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men. Conclusions: Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.

Prescribed Drug Use and Aneurysmal Subarachnoid Hemorrhage Incidence: A Drug-Wide Association Study.

BACKGROUND AND OBJECTIVES: Current benefits of invasive intracranial aneurysm treatment to prevent aneurysmal subarachnoid hemorrhage (aSAH) rarely outweigh treatment risks. Most intracranial aneurysms thus remain untreated. Commonly prescribed drugs reducing aSAH incidence may provide leads for drug repurposing. We performed a drug-wide association study (DWAS) to systematically investigate the association between commonly prescribed drugs and aSAH incidence. METHODS: We defined all aSAH cases between 2000 and 2020 using International Classification of Diseases codes from the Secure Anonymised Information Linkage databank. Each case was matched with 9 controls based on age, sex, and year of database entry. We investigated commonly prescribed drugs (>2% in study population) and defined 3 exposure windows relative to the most recent prescription before index date (i.e., occurrence of aSAH): current (within 3 months), recent (3-12 months), and past (>12 months). A logistic regression model was fitted to compare drug use across these exposure windows vs never use, controlling for age, sex, known aSAH risk factors, and health care utilization. The family-wise error rate was kept at p < 0.05 through Bonferroni correction. RESULTS: We investigated exposure to 205 commonly prescribed drugs between 4,879 aSAH cases (mean age 61.4, 61.2% women) and 43,911 matched controls. We found similar trends for lisinopril and amlodipine, with a decreased aSAH risk for current use (lisinopril odds ratio [OR] 0.63, 95% CI 0.44-0.90, amlodipine OR 0.82, 95% CI 0.65-1.04) and an increased aSAH risk for recent use (lisinopril OR 1.30, 95% CI 0.61-2.78, amlodipine OR 1.61, 95% CI 1.04-2.48). A decreased aSAH risk in current use was also found for simvastatin (OR 0.78, 95% CI 0.64-0.96), metformin (OR 0.58, 95% CI 0.43-0.78), and tamsulosin (OR 0.55, 95% CI 0.32-0.93). By contrast, an increased aSAH risk was found for current use of warfarin (OR 1.35, 95% CI 1.02-1.79), venlafaxine (OR 1.67, 95% CI 1.01-2.75), prochlorperazine (OR 2.15, 95% CI 1.45-3.18), and co-codamol (OR 1.31, 95% CI 1.10-1.56). DISCUSSION: We identified several drugs associated with aSAH, of which 5 drugs (lisinopril and possibly amlodipine, simvastatin, metformin, and tamsulosin) showed a decreased aSAH risk. Future research should build on these signals to further assess the effectiveness of these drugs in reducing aSAH incidence. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that some commonly prescribed drugs are associated with subsequent development of aSAH.

Neuroform atlas stent treatment for 533 intracranial aneurysms in a large Chinese cohort: complication risk factor analysis.

BACKGROUND: The newest generation of Neuroform Atlas stent™ (Stryker, Fremont, California) represents a recent advance of cerebral laser-cut microstents for the treatment of intracranial wide-necked aneurysms, and postoperative complications have been observed among Western patients. We assessed predictors of complications, morbidity, and unfavourable outcomes in a large cohort of patients with aneurysms that were treated with Neuroform Atlas stents in China. METHODS: This retrospective study included subjects who were treated with Atlas stents in China from November 2020 to January 2022. RESULTS: A total of 522 consecutive patients (mean age, 58.9 ± 9.9 years; female, 65.3% [341/522]) with 533 aneurysms were included in the study. In the early postoperative period, the neurological morbidity rate was 7.3% (38/522), the ischaemic stroke rate was 5.0% (26/522), the aneurysm rupture subarachnoid haemorrhage rate was 2.3% (12/522), and the mRS score deterioration rate was 5.4% (28/522). The mortality rate was 0.8% (4/522) in the postoperative period. The rate of neurological morbidity during the follow-up period was 1.2% (6/486). In the multifactor prediction analysis, cerebral infarction, Hunt-Hess grade (3-5), procedure duration, stent length and coil protrusion into the parent artery were found to be independent predictors of neurologic morbidity. The procedure duration, stent length and coil protrusion into the parent artery were found to be independent predictors of mRS score deterioration. CONCLUSIONS: The incidence of SCA (stent-assisted coiling)-related complications with the Atlas stent in this study population was comparable to that in Western populations. We identified the procedure duration and stent length as novel independent predictors of SCA-related ischaemic stroke, neurological morbidity, and mRS score deterioration among the Chinese population.

Medications and "Risk" of Aneurysm Rupture Based on Presentation: Setting the Record Straight.

OBJECTIVE: Studies assessing aneurysm rupture "risk" based on comparative retrospective analyses of medications taken on presentation may be subject to presentation bias. Are patients with ruptured aneurysms simply less likely to be taking medications than those with unruptured aneurysms? METHODS: A retrospective chart review was conducted among patients with treated aneurysms from June 2016 to July 2023. A step-wise comparison of demographics, clinical characteristics (rupture status), and medications taken upon presentation was performed between ruptured and unruptured cases. RESULTS: One thousand three hundred eleven patients with intracranial aneurysms were included. The majority of patients presenting with ruptured aneurysms took no medications (68%), in contrast to 22% with unruptured aneurysms (P < 0.001). The majority of patients with unruptured aneurysms took 2-5 medications (51%), in contrast to 15% of patients with ruptured aneurysms taking 2-5 medications (P < 0.001). Twelve percent of patients with unruptured aneurysms took more than 5 medications, while only 1% with ruptured aneurysms did (P < 0.001). Thirty-five different medications were associated with unruptured presentation, including all evaluated antiplatelet agents, anti-hypertensives, antacids, pulmonary inhalers, and psychiatric medications (P < 0.05); no medications were associated with rupture on presentation. CONCLUSIONS: One cannot derive conclusions about medications and "risk" of rupture based on analyses at the time of presentation. This study identifies 35 different medications that were statistically significant and associated with an unruptured presentation; it is doubtful that each is "protective" against aneurysm rupture.

Incidence and Characteristics of Cerebral Infarction After Microsurgical Clipping of Unruptured Anterior Circulation Cerebral Aneurysms: Diffusion-Weighted Imaging-Based Analysis of 600 Patients.

BACKGROUND AND OBJECTIVES: Postclipping cerebral infarction (PCI) remains a major concern after treatment for unruptured intracranial aneurysms (UIAs). However, studies of microsurgical clipping based on diffusion-weighted imaging are limited. We aimed to present the incidence, risk factors, and types of PCI and its radiological and clinical characteristics. METHODS: This was a retrospective single-center study in which patients were scheduled to undergo microsurgical clipping for anterior circulation UIAs. The overall incidence and risk factors were calculated. Based on the operation and relevant artery, we categorized PCI on diffusion-weighted imaging into 4 types and presented their radiological and clinical characteristics. RESULTS: We reviewed the radiological and clinical data of 605 patients. The overall incidence of PCI was 16.7% (101/605), of which asymptomatic infarction was 14.9% (90/605) and symptomatic infarction was 1.8% (11/605). Hypertension (adjusted odds ratio [aOR], 2.258; 95% confidence interval [CI]: 1.330-3.833), temporary clipping (aOR, 1.690; 95% CI: 1.034-2.760), multiple aneurysm locations (aOR, 1.832; 95% CI: 1.084-3.095), and aneurysm dome size (aOR, 1.094; 95% CI: 1.006-1.190) were independent risk factors for PCI. Type II (perianeurysmal perforator) infarction was the most common type of PCI (48.6%) and the most common cause of symptomatic infarction (72.7%). Types II and III (distal embolic) infarctions correlated with atherosclerotic changes in the aneurysm wall and temporary clipping (62.4% and 70.6%, respectively). The type IV (unrelated) infarction group had a higher incidence of systemic atherosclerosis (55%). CONCLUSION: Microsurgical clipping is a safe and viable option for the treatment of anterior circulation UIAs. However, modification of the surgical technique, preoperative radiological assessment, and patient selection are required to reduce the incidence of PCI.

Family history as the strongest predictor of aortic and peripheral aneurysms in patients with intracranial aneurysms.

OBJECTIVE: Intracranial aneurysms (IA) and aortic aneurysms (AA) are both abnormal dilations of arteries with familial predisposition and have been proposed to share co-prevalence and pathophysiology. Associations of IA and non-aortic peripheral aneurysms are less well-studied. The goal of the study was to understand the patterns of aortic and peripheral (extracranial) aneurysms in patients with IA, and risk factors associated with the development of these aneurysms. METHODS: 4701 patients were included in our retrospective analysis of all patients with intracranial aneurysms at our institution over the past 26 years. Patient demographics, comorbidities, and aneurysmal locations were analyzed. Univariate and multivariate analyses were performed to study associations with and without extracranial aneurysms. RESULTS: A total of 3.4% of patients (161 of 4701) with IA had at least one extracranial aneurysm. 2.8% had thoracic or abdominal aortic aneurysms. Age, male sex, hypertension, coronary artery disease, history of ischemic cerebral infarction, connective tissues disease, and family history of extracranial aneurysms in a 1st degree relative were associated with the presence of extracranial aneurysms and a higher number of extracranial aneurysms. In addition, family history of extracranial aneurysms in a second degree relative is associated with the presence of extracranial aneurysms and atrial fibrillation is associated with a higher number of extracranial aneurysms. CONCLUSION: Significant comorbidities are associated with extracranial aneurysms in patients with IA. Family history of extracranial aneurysms has the strongest association and suggests that IA patients with a family history of extracranial aneurysms may benefit from screening.

Causal association between circulating inflammatory cytokines and intracranial aneurysm and subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The causal association between inflammatory cytokines and the development of intracranial aneurysm (IA), unruptured IA (uIA) and subarachnoid hemorrhage (SAH) lacks clarity. METHODS: The summary-level datasets for inflammatory cytokines were extracted from a genome-wide association study of the Finnish Cardiovascular Risk in Young Adults Study and the FINRISK survey. The summary statistics datasets related to IA, uIA and SAH were obtained from the genome-wide association study meta-analysis of the International Stroke Genetics Consortium and FinnGen Consortium. The primary method employed for analysis was inverse variance weighting (false discovery rate), supplemented by sensitivity analyses to address pleiotropy and enhance robustness. RESULTS: In the International Stroke Genetics Consortium, 10, six and eight inflammatory cytokines exhibited a causal association with IA, uIA and SAH, respectively (false discovery rate, p < 0.05). In FinnGen datasets, macrophage Inflammatory Protein-1 Alpha (MIP_1A), MIP_1A and interferon γ-induced protein 10 (IP_10) were verified for IA, uIA and SAH, respectively. In the reverse Mendelian randomization analysis, the common cytokines altered by uIA and SAH were vascular endothelial growth factor (VEGF), MIP_1A, IL_9, IL_10 and IL_17, respectively. The meta-analysis results show that MIP_1A and IP_10 could be associated with the decreased risk of IA, and MIP_1A and IP_10 were associated with the decreased risk of uIA and SAH, respectively. Notably, the levels of VEGF, MIP_1A, IL_9, IL_10 and TNF_A were increased with uIA. Comprehensive heterogeneity and pleiotropy analyses confirmed the robustness of these results. CONCLUSION: Our study unveils a bidirectional association between inflammatory cytokines and IA, uIA and SAH. Further investigations are essential to validate their relationship and elucidate the underlying mechanisms.

Prediction of aneurysmal subarachnoid hemorrhage in comparison with other stroke types using routine care data.

Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.

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

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.

Intracranial aneurysms in patients with acute ischemic stroke prevalence and influence on mechanical thrombectomy over 14 years in a tertiary-care center.

INTRODUCTION: The prevalence of intracranial aneurysms (IA) in patients with acute ischemic stroke (AIS) requiring mechanical thrombectomy (MT) is unclear. OBJECTIVE: To describe the prevalence of IA in patients with AIS and their influence on MT. MATERIALS & METHODS: This is a retrospective cohort study on all patients admitted with a diagnosis of AIS from January 2008 to March 2022 at a tertiary academic center. The records were reviewed for demographic, clinical, imaging, and outcomes data. Only patients who had CTA at admission were included in this analysis. RESULTS: Among 2265 patients admitted with AIS, this diagnosis was confirmed in 2113 patients (93.3 %). We included 1111 patients (52.6 %) who had head CTA and 321 (28.9 %) who underwent MT. The observed prevalence of aneurysms on CTA was 4.5 % (50/1111 patients), and 8 (16 %) had multiple aneurysms. MT was performed in 7 patients harboring IAs: 6 ipsilateral (5 proximal and 1 distal to the occlusion)and 1 contralateral aneurysm.. The patient with a contralateral aneurysm had a TICI 2B score In patients with ipsilateral aneurysms, TICI 2B or 3 was achieved in 3 cases (50 %), which is significantly lower than historical control of MT (91.6 %) without IA (p = 0.01). No aneurysms ruptured during MT. The aneurysm noted distal to the occlusion was mycotic. CONCLUSION: In this analysis, the observed prevalence of IA in patients with AIS was 4.5%. Ipsilateral aneurysms (proximal or distal to the occlusion site) deserve particular attention, given the potential risk of rupture during MT. Aneurysms located distal to the occlusion were mycotic and the rate of recanization in patients with ipsilateral aneurysms was low compared to historical controls. Further studies are needed to improve the outcomes in patients with IA requiring MT.

Global Disparities in the Presentation and Management of Aneurysmal Subarachnoid Hemorrhage: A Review and Analysis.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality rates. There is a significant gap in the literature describing global disparities in demographics, management, and outcomes among patients with aSAH. We aimed to conduct a systematic review and meta-analysis to assess global disparities in aSAH presentation and management. METHODS: PubMed and Embase databases were queried from earliest records to November 2022 for aSAH literature. Presentation, demographics, comorbidities, treatment methods, and outcomes data were collected. Articles that did not report aSAH-specific patient management and outcomes were excluded. Pooled weighted prevalence rates were calculated. Random effects model rates were reported. RESULTS: After screening, 33 articles representing 10,553 patients were included. The prevalence of Fisher grade 3 or 4 aSAH in high- and lower-income countries (HIC and LIC), respectively, was 79.8% (P < 0.01) and 84.1 (P < 0.01). Prevalence of male aSAH patients in HIC and LIC, respectively, was 35.8% (P < 0.01) and 45.0% (P < 0.01). Prevalence of treatment in aSAH patients was 99.5% (P < 0.01) and 99.4% (P = 0.16) in HIC and LIC, respectively. In HIC, 35% (P < 0.01) of aneurysms in aSAH patients were treated with coiling. No LIC reported coiling for aSAH treatment; LIC only reported rates of surgical clipping, with a total prevalence of 92.4% (P < 0.01) versus 65.6% (P < 0.01) in HIC. CONCLUSION: In this analysis, we found similar rates of high-grade SAH hemorrhages in HIC and LIC but a lack of endovascular coil embolization treatments reported in LIC. Additional research and discussion are needed to identify reasons for treatment disparities and intervenable societal factors to improve aSAH outcomes worldwide.

Shifts in Diagnostic Testing for Headache in the Emergency Department, 2015 to 2021.

Importance: Subarachnoid hemorrhage is typically diagnosed by noncontrast head computed tomography (CT); lumbar puncture is recommended if computed tomography is nondiagnostic, although CT cerebral angiography has been promoted as an alternative to lumbar puncture in this diagnostic pathway. The outcomes of this debate in practice have not been studied. Objective: To determine whether CT cerebral angiography use has increased in lieu of lumbar puncture among emergency department (ED) patients with headache, with an increase in unruptured intracranial aneurysm detection. Design, Setting, and Participants: This retrospective cohort study took place in 21 community EDs of an integrated health care system in Northern California between 2015 and 2021. Participants were adult (aged >17 years) health plan members with a chief concern of headache. Exclusions were prior diagnoses of subarachnoid hemorrhage, unruptured intracranial aneurysm, cerebral arteriovenous malformation, or cerebrospinal fluid shunt. Data were analyzed from October to November 2023. Exposures: CT cerebral angiography and/or lumbar puncture during the ED encounter. Main Outcomes and Measures: Primary and secondary outcomes were 14-day and 90-day unruptured intracranial aneurysm detection, respectively. Safety outcomes were missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. The annual incidence of unruptured intracranial aneurysm detection was normalized to the incidence of subarachnoid hemorrhage (UIA:SAH ratio). Average annualized percentage changes were quantified using joinpoint regression analysis. Results: Among 198 109 included ED encounters, the mean (SD) age was 47.5 (18.4) years; 140 001 patients (70.7%) were female; 29 035 (14.7%) were Black or African American, 59 896 (30.2%) were Hispanic or Latino, and 75 602 (38.2%) were White. Per year, CT cerebral angiography use increased (18.8%; 95% CI, 17.7% to 20.3%) and lumbar punctures decreased (-11.1%; 95% CI, -12.0% to -10.4%), with a corresponding increase in the 14-day UIA:SAH ratio (3.5%; 95% CI, 0.9% to 7.4%). Overall, computed tomography cerebral angiography use increased 6-fold relative to lumbar puncture, with a 33% increase in the detection of UIA. Results were similar at 90 days and robust to sensitivity analyses. Subarachnoid hemorrhage (1004 cases) and bacterial meningitis (118 cases) were misdiagnosed in 5% and 18% of cases, respectively, with no annual trends (P = .34; z1003 = .95 and P = .74; z117 = -.34, respectively). Conclusions and Relevance: In this cohort study of ED patients with headache, increases in CT cerebral angiography use were associated with fewer lumbar punctures and higher detection of unruptured intracranial aneurysms, with no significant change in missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. While this shift in diagnostic strategy appeared safe in the short-term, the long-term consequences remain unclear.