Risk Of Intracranial Aneurysms Research Articles

Should Patients with Autosomal Dominant Polycystic Kidney Disease Be Screened for Cerebral Aneurysms?

Autosomal dominant polycystic kidney disease is a genetic disorder affecting 1 in 1000 people worldwide and is associated with an increased risk of intracranial aneurysms. It remains unclear whether there is sufficient net benefit to screening this patient population for IA, considering recent developments in imaging and treatment and our evolving understanding of the natural history of unruptured aneurysms. There is currently no standardized screening protocol for IA in patients with ADPCKD. Our review of the literature focused on the above issues and presents our appraisal of the estimated value of screening for IA in the setting of ADPCKD.

The angiotensin converting enzyme insertion/deletion polymorphism and intracranial aneurysm: A meta-analysis of case-control studies

Previous studies investigating the association between angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and intracranial aneurysm (IA) have provided inconsistent results and no large systematic review or meta-analyses have been conducted regarding this issue. To confirm whether the ACE I/D polymorphism correlates with risk of IA. We conducted a meta-analysis to increase the statistical power by using all the available published data. Two investigators independently searched the PubMed, Medline, Embase, China National Knowledge Infrastructure and Chinese Biomedicine Databases for studies published before December 2012. For included studies, we performed meta-analyses using the Cochrane RevMan software. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for ACE I/D polymorphisms and IA were calculated in a fixed-effects model or a random-effects model when appropriate. We used Cochran's Q statistic and the I 2 statistic to assess heterogeneity and funnel plot to assess potential publication bias. We also carried out stratified analyses and sensitivity analyses by ethnicity, country and source of control group, sample size and Hardy-Weinberg equilibrium (HWE) in controls. Six eligible studies were reviewed and analyzed, involving 854 cases and 1280 controls. Overall, compared with D allele, there was a close relationship between I allele and IA risk (OR: 1.21, 95% CI: 1.07-1.37, P = 0.003; P(heterogeneity) = 0.56; I² = 0%). ACE I+ (I/I and I/D) genotype had significantly increased risk for IA (OR: 1.27, 95% CI: 1.03-1.57, P = 0.03; P(heterogeneity) = 0.14; I² = 40%). This association remained consistently strong when analyses were limited to studies, in which genotype frequencies were in HWE. No publication bias was found in the present study. Our meta-analysis suggests, there is a close relationship between ACE I/D polymorphism and IA risk. Since limited studies and subjects were included, it is critical that larger and especially well-designed multicentric studies, which based on interactions of ACE and different confounding factors should be performed to re-evaluate the association.

Improved depiction of hemodynamics in intracranial aneurysms by 4D flow MRI at 7T compared to 3T

Background Intracranial aneurysms are life threatening conditions and occur in 3-6% of the population. The annual rupture rate is approximately 2% associated with significant morbidity and mortality. Hemodynamic information obtained by 4D flow MRI may contribute to the assessment of rupture risk of intracranial aneurysms. However, the small sizes of intracranial aneurysms require high spatial resolution to accurately capture complex intra-aneurysmal flow. Increasing spatial resolution, however, decreases signal-to-noise ratio (SNR) and thus velocity-to-noise ratio in flow images. Performing 4D flow at 7T has high potential to overcome low SNR limits and enable higher spatial resolution in 4D flow acquisitions. In this study 4D flow in intracranial aneurysms at 7T was compared with 4D flow at 3T.

Arterial distensibility in patients with ruptured and unruptured intracranial aneurysms: Is it a predisposing factor for rupture risk?

BackgroundA risk factor assessment that reliably predicts whether patients are predisposed to intracranial aneurysm (IA) rupture has yet to be formulated. As such, the clinical management of unruptured IA remains unclear. Our aim was to determine whether impaired arterial distensibility and hypertrophic remodeling might be indicators of risk for IA rupture.Material/MethodsThe study population (n=49) was selected from consecutive admissions for either unruptured IA (n=23) or ruptured IA (n=26) from January to December 2010. Hemodynamic measures were taken from every patient, including systolic and diastolic blood pressure using a sphygmomanometer. Unruptured IA and ruptured IA characteristics, including aneurysmal shape, size, angle, aspect ratio, and bottleneck factor, were measured and calculated from transverse brain CT angiography images. With ultrasound, the right common carotid artery intima-media thickness was measured, as well as the lumen diameter during systole and diastole. Arterial wall strain, distensibility, stiffness index, and elastic modulus were calculated and compared between patients with unruptured IAs and ruptured IAs. A p-value less than 0.05 was considered statistically significant.ResultsGeneral demographic data did not differ between patients with unruptured IAs and ruptured IAs. Greater mean intima-media thickness (p=0.013), mean stiffness index (p=0.044), and mean elastic modulus (p=0.026) were observed for patients with ruptured IAs. Moreover, mean strain (p=0.013) and mean distensibility (p=0.024) were decreased in patients with ruptured IAs.ConclusionsPatients with ruptured IAs demonstrated decreased arterial distensibility and increased intima-media thickness at the level of the carotid arteries. By measuring these parameters via ultrasound, it may be possible to predict whether patients with existing IAs might rupture and hemorrhage into the subarachnoid space.

Interactions of interleukin-12A and interleukin-12B polymorphisms on the risk of intracranial aneurysm

Several lines of evidence indicate that inflammatory processes play pivotal role in the development of intracranial aneurysm (IA). Recently, polymorphisms in the interleukin-12 (IL-12) gene were shown to be associated with immune-mediated inflammatory disease. The aim of this study was to investigate the interactions of IL-12A and IL-12B polymorphisms on the risk of IA in a Chinese population. A total of 422 individuals (including 164 patients with IA and 258 controls) were involved in the study. The polymorphisms (i.e., rs2243115 and rs568408 in IL-12A and rs3212227 in IL-12B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing. We found an association of the AC/CC genotypes and C allele of IL-12B rs3212227 with an increased risk of IA, compared with the AA genotype and A allele (AC/CC vs. AA: OR = 2.09, 95 % CI: 1.29-3.38; C vs. A: OR = 1.45, 95 % CI: 1.10-1.91). Moreover, a significant gene interaction of IL-12A and IL-12B was evident on the risk of IA, and subjects carrying variant genotypes of IL-12B rs3212227 had an increased risk of IA. In the stratified analysis by gender, the IL-12B rs3212227 AC/CC genotypes had an increased risk of IA compared with the AA genotype in male patients (AC/CC vs. AA: OR = 4.63, 95 % CI: 1.92-11.16). These findings suggest that the IL-12A and IL-12B independently and jointly be involved in the susceptibility to IA.

Risk factors for multiple intracranial aneurysms rupture: A retrospective study

Background and purposeThe presence of predicting the rupture risk of intracranial aneurysms has recently generated considerable controversy. We retrospectively investigated the risk factors for multiple intracranial aneurysms related to rupture. MethodsBetween July 2007 and July 2011, 134 patients with 294 aneurysms were identified after review. Every patient had two or more aneurysms. Univariate and multivariate logistic regression models were used to analyze the risk factors for multiple intracranial aneurysms with age, gender, site and size. Results134 patients were divided into three groups according to patient age category (<45, 45–65, >65 years of age). The incidence of aneurysms ruptured in the second group was significantly higher. Three groups showed significant difference (P=0.001 versus >65 years of age). Thirteen of 35 AComA aneurysms were ruptured, accounting for 26% of all ruptured aneurysms, and the rate of rupture at AComA aneurysms in patients was 37.1%. The rate of aneurysm rupture in the AComA was significantly higher than that in other sites (P=0.001). In all 294 aneurysms, 88.1% of the aneurysms were 5mm or less, of which 58.2% were less than 3mm. In the ruptured aneurysms, 68% were 5mm or less. ConclusionsOur study reveals the pattern of ruptured multiple intracranial aneurysms, in terms of age, size and location of aneurysms. Age, size, and site of aneurysm should be considered in the decision whether to treat an unruptured aneurysm or not. Especially, in cases of multiple aneurysm, the AComA aneurysm is most prone to hemorrhage.

The Interleukin-6-572G/C Gene Polymorphism and the Risk of Intracranial Aneurysms in a Chinese Population

Interleukin-6 (IL-6) is an important proinflammatory cytokine that plays an important role in the pathogenesis of intracranial aneurysms (IAs). The aim of this study was to investigate the association between the IL-6-572G/C polymorphism and the risk of IAs in a Chinese population. The IL-6-572G/C gene polymorphisms in 220 IA cases and 220 controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. The IL-6-572GG (odds ratio [OR]=3.35, 95% confidence intervals [CIs]=1.65, 6.82; p=0.001) and G allele frequencies (OR=1.48, 95% CIs=1.09, 2.00; p=0.01) in the IA group were higher than those in the control group. The C allele frequencies (OR=0.68, 95% CIs=0.50, 0.92; p=0.01) were significantly lower in patients than in controls. When stratified by the site, shape, size, and the Fisher Grade of IAs, no statistically significant result was observed. This study suggested that the IL-6-572GG genotype was associated with a higher risk of IA in a Chinese population.

Additional risk of hypertension and smoking for aneurysms in people with a family history of subarachnoid haemorrhage

BackgroundSmoking and hypertension increase the risk of aneurismal subarachnoid haemorrhage (SAH) two to threefold whereas a familial predisposition increases the risk sixfold. We assessed the additional risk of smoking and...

Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure

Although genome-wide association studies (GWAS) have identified hundreds of complex trait loci, the pathomechanisms of most remain elusive. Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. Intracranial aneurysms (IA) are rupture-prone pouches at cerebral artery branching sites. IA is a complex disease for which GWAS have identified five loci with strong association and a further 14 loci with suggestive association. To decipher potential underlying disease mechanisms, we tested whether there are IA loci that convey their effect through elevating blood pressure (BP), a strong risk factor of IA. We performed a meta-analysis of four population-based Finnish cohorts (nFIN = 11 266) not selected for IA, to assess the association of previously identified IA candidate loci (n = 19) with BP. We defined systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure as quantitative outcome variables. The most significant result was further tested for association in the ICBP-GWAS cohort of 200 000 individuals. We found that the suggestive IA locus at 5q23.2 in PRDM6 was significantly associated with SBP in individuals of European descent (pFIN = 3.01E-05, pICBP-GWAS = 0.0007, pALL = 8.13E-07). The risk allele of IA was associated with higher SBP. PRDM6 encodes a protein predominantly expressed in vascular smooth muscle cells. Our study connects a complex disease (IA) locus with a common risk factor for the disease (SBP). We hypothesize that common variants in PRDM6 can contribute to altered vascular wall structure, hence increasing SBP and predisposing to IA. True positive associations often fail to reach genome-wide significance in GWAS. Our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. Further, we demonstrate that common disease loci identified in a population isolate may bear wider significance.

Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA

Aneurysmal subarachnoid hemorrhage (aSAH) is the most serious subtype of stroke. Genetic factors have been known to play an important role in the development of intracranial aneurysm (IA), some of which further progress to subarachnoid hemorrhage (SAH). In this study, we conducted a genome-wide association study (GWAS) to identify common genetic variants that are associated with the risk of IA, using 1383 aSAH subjects and 5484 control individuals in the Japanese population. We selected 36 single-nucleotide polymorphisms (SNPs) that showed suggestive association (P <1 × 10(-4)) in the GWAS as well as additional 7 SNPs that were previously reported to be associated with IA, and further genotyped an additional set of 1048 IA cases and 7212 controls. We identified an SNP, rs6842241, near EDNRA at chromosome 4q31.22 (combined P-value = 9.58 × 10(-9); odds ratio = 1.25), which was found to be significantly associated with IA. Additionally, we successfully replicated and validated rs10757272 on CDKN2BAS at chromosome 9p21.3 (combined P-value = 1.55 × 10(-7); odds ratio = 1.21) to be significantly associated with IA as previously reported. Furthermore, we performed functional analysis with the associated genetic variants on EDNRA, and identified two alleles of rs6841581 that have different binding affinities to a nuclear protein(s). The transcriptional activity of the susceptible allele of this variant was significantly lower than the other, suggesting that this functional variant might affect the expression of EDNRA and subsequently result in the IA susceptibility. Identification of genetic variants on EDNRA is of clinical significance probably due to its role in vessel hemodynamic stress. Our findings should contribute to a better understanding of physiopathology of IA.

A functional variant of the collagen type III alpha1 gene modify risk of sporadic intracranial aneurysms

Abnormalities in type III collagen in the arterial walls cause certain familial intracranial aneurysms (IAs); however, it remains unknown whether COL3A1 variants contribute to the risk of sporadic IAs. To study whether COL3A1 variants are associated with sporadic IAs, the association of COL3A1 variants with sporadic IAs was tested in 298 cases and 488 controls, replicated in an independent population of 192 cases and 1,690 controls, and further verified in 633 patients with intra-cerebral hemorrhage, 1,074 hypertensives, and 1,883 controls. We found that allele A of SNP rs1800255 conferred a 1.71-fold increased risk for IAs (adjusted odds ratio: OR = 1.71, 95% confidence interval: CI 1.19-2.45, P = 0.004) and results in an amino acid change of Ala698Thr, which led to a lower thermal stability of the peptide. These results were confirmed in the independent study. The associations were independent of the presence of hemorrhagic stroke and hypertension. These results support the view that the functional variant of COL3A1 is genetic risk factors for IAs in the Chinese population.

Interactions ofmiR-34b/candTP53Polymorphisms on the Risk of Intracranial Aneurysm

Several lines of evidence indicate that inflammatory processes play a key role in the happening and development of intracranial aneurysm (IA). Recently, polymorphisms in the TP53 gene were shown to be associated with inflammation and inflammatory disease. The aim of this study was to investigate the interactions of miR-34b/c and TP53 Arg72-Pro polymorphisms on the risk of IA in a Chinese population. A total of 590 individuals (including 164 patients with IA and 426 controls) were involved in this study. The polymorphisms (i.e., miR-34b/c rs4938723 and TP53 Arg72-Pro) were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing. We found that the CC genotype of miR-34b/c rs4938723 was significantly associated with a decreased risk of IA compared with the TT genotype. Moreover, a significant gene interaction of the carriers with the combined genotypes of miR-34b/c rs4938723CC and TP53 Arg72Pro CG/CC/GG had a decreased risk of IA, compared with those carrying miR-34b/c rs4938723CT/TT+TP53 Arg72Pro GG/CG/CC combined genotypes. These findings suggest that the miR-34b/c rs4938723CC and TP53 Arg72-Pro polymorphisms may be involved in the susceptibility to IA.

Trigger factors for rupture of intracranial aneurysms in relation to patient and aneurysm characteristics

Female gender, age above 60 years, and an aneurysm larger than 5 mm or location on the posterior circulation are associated with a higher rupture risk of intracranial aneurysms. We hypothesized that this association is explained by a higher susceptibility to (one of) the eight trigger factors that were recently identified. We included 250 patients with aneurysmal subarachnoid hemorrhage. We calculated relative risks (RR) with 95% confidence intervals (95% CI) of aneurysmal rupture for trigger factors according to sex, age, site, and size of the aneurysms by means of the case-crossover design. None of the triggers except for physical exercise differed according to patient and aneurysm characteristics. In the hour after exposure to physical exercise: (1) patients over the age of 60 have a six-times-higher risk of rupture (RR 13; 95% CI 6.3−26) than those of 60 years of age and under (RR 2.3; 1.3−4.1); (2) aneurysms at the internal carotid artery have a higher risk than those at other locations (RR 17; 7.8−37), but this was only statistically significant when compared to anterior communicating artery aneurysms (RR 3.2; 1.6−6.1); (3) aneurysms 5 mm or smaller had a higher risk of rupture (RR 9.5; 4.6−19) than larger aneurysms (RR 2.4; 1.3−4.3); and (4) women and men had similar risks. A higher susceptibility to exercise might explain part of the higher risk of rupture in older patients. Why women and patients with aneurysms larger than 5 mm or posterior circulation aneurysms have a higher risk of rupture remains to be settled.

Common variant near the endothelin receptor type A ( EDNRA ) gene is associated with intracranial aneurysm risk

The pathogenesis of intracranial aneurysm (IA) formation and rupture is complex, with significant contribution from genetic factors. We previously reported genome-wide association studies based on European discovery and Japanese replication cohorts of 5,891 cases and 14,181 controls that identified five disease-related loci. These studies were based on testing replication of genomic regions that contained SNPs with posterior probability of association (PPA) greater than 0.5 in the discovery cohort. To identify additional IA risk loci, we pursued 14 loci with PPAs in the discovery cohort between 0.1 and 0.5. Twenty-five SNPs from these loci were genotyped using two independent Japanese cohorts, and the results from discovery and replication cohorts were combined by meta-analysis. The results demonstrated significant association of IA with rs6841581 on chromosome 4q31.23, immediately 5' of the endothelin receptor type A with P = 2.2 × 10(-8) [odds ratio (OR) = 1.22, PPA = 0.986]. We also observed substantially increased evidence of association for two other regions on chromosomes 12q22 (OR = 1.16, P = 1.1 × 10(-7), PPA = 0.934) and 20p12.1 (OR = 1.20, P = 6.9 × 10(-7), PPA = 0.728). Although endothelin signaling has been hypothesized to play a role in various cardiovascular disorders for over two decades, our results are unique in providing genetic evidence for a significant association with IA and suggest that manipulation of the endothelin pathway may have important implications for the prevention and treatment of IA.

Intracerebral malignant peripheral nerve sheath tumor in a child with neurofibromatosis Type 1 and middle cerebral artery aneurysm treated with endovascular coil embolization

Among the neoplastic conditions that affect patients with neurofibromatosis Type 1 (NF1) are malignant peripheral nerve sheath tumors (MPNSTs), which typically arise from peripheral nerves of the limbs, trunk, and lumbar and brachial plexuses. Ionizing radiation is an established risk factor for MPNST development, especially in susceptible patients such as those with NF1. Patients with NF1 are also at risk for intracranial aneurysms, which are increasingly being successfully managed with endovascular therapies. The authors describe the case of a 9-year-old, previously healthy girl who presented in extremis with a right frontal intracerebral hemorrhage resulting from a ruptured right middle cerebral artery (MCA) trifurcation aneurysm. Following urgent decompressive craniectomy, the patient underwent endovascular coil embolization of the MCA aneurysm without complication. Given her mother's history of NF1, the child underwent genetic testing, which disclosed signs positive for NF1. The patient recovered well, but follow-up MR imaging and MR angiography performed at 14 months demonstrated a large frontotemporal mass encasing the right MCA trifurcation. The patient underwent frontotemporal craniotomy and subtotal resection of the mass, which was histologically found to be an intracranial MPNST. The patient received chemotherapy and focal radiation therapy and remains alive at 6 months postresection. To the authors' knowledge, this represents the only known case of intracranial neoplasm arising in the region of an intracranial aneurysm repaired by endovascular coil embolization. While patients with NF1 represent a population with genetic susceptibility to radiation-induced tumors, the pathogenesis of intracerebral MPNSTs remains poorly understood.

Extended Follow-Up of Unruptured Intracranial Aneurysms Detected by Presymptomatic Screening in Patients with Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) patients have an increased risk for intracranial aneurysms (IAs). The importance of screening for unruptured IAs (UIAs) depends on their risks for growth and rupture. ADPKD patients with UIAs found by presymptomatic screening with magnetic resonance angiography (MRA) during 1989 to 2009 were followed initially at 6 months and annually, and less frequently after demonstration of stability. Forty-five saccular aneurysms were detected in 38 patients from 36 families. Most were small (median diameter 3.5 mm) and in the anterior circulation (84%). Median age at diagnosis was 49 years. During cumulative imaging follow-up of 243 years, one de novo UIA was detected and increased in size from 2 to 4.4 mm over 144 months and two UIAs grew from 4.5 to 5.9 mm and 4.7 to 6.2 mm after 69 and 184 months, respectively. Seven patients did not have imaging follow-up. No change was detected in the remaining 28 patients. During cumulative clinical follow-up of 316 years, no aneurysm ruptured. Five patients died from unrelated causes and two were lost to follow-up after 8 and 120 months. Three patients underwent surgical clipping. Most UIAs detected by presymptomatic screening in ADPKD patients are small and in the anterior circulation. Growth and rupture risks are not higher than those of UIAs in the general population. These data support very selective screening for UIAs in ADPKD patients, and widespread screening is not indicated.

Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population

Genetic factors are known to have an important role in intracranial aneurysm (IA) pathogenesis. The purpose of this study is to identify single-nucleotide polymorphisms (SNPs) that are associated with IA in Japanese population. A total of 2050 IA patients and 1835 controls recruited in Biobank Japan, The University of Tokyo were used in this study. In all, 45 SNPs in 24 genes encoding proteins, which have been considered to be possible risk factors to IA pathogenesis, were genotyped using multiplex PCR-invader assay. Association analysis was evaluated by logistic regression analysis before and after adjustment of age, smoking and hypertension status. This case-control association study revealed a SNP, rs6460071 located on LIMK1 gene (P = 0.00069) to be significantly associated with increased risk of IA. In addition, two SNPs, rs243847 (P = 0.00086) and rs243865 (P = 0.00090), on matrix metallopeptidase 2 (MMP2) gene and one SNP rs1799724 (P = 0.0026) on tumor necrosis factor-α (TNF-α) gene, are marginally associated with IA in male- and female-specific manner, respectively. In conclusion, a large-scale case-control association study was conducted to verify genetic variations associated with IA in Japanese population. This study gave insights on the importance of stratified analysis between genders, and suggested that the underlying mechanism of IA pathogenesis might differ between females and males.

Differential Effects of Chromosome 9p21 Variation on Subphenotypes of Intracranial Aneurysm

Recently, a genome-wide association study identified associations between single nucleotide polymorphisms on chromosome 9p21 and risk of harboring intracranial aneurysm (IA). Aneurysm characteristics or subphenotypes of IAs, such as history of subarachnoid hemorrhage, presence of multiple IAs and location of IAs, are clinically important. We investigated whether the association between 9p21 variation and risk of IA varied among these subphenotypes. We conducted a case-control study of 981 cases and 699 controls in Japanese. Four single nucleotide polymorphisms tagging the 9p21 risk locus were genotyped. The OR and 95% CI were estimated using logistic regression analyses. Among the 4 single nucleotide polymorphisms, rs1333040 showed the strongest evidence of association with IA (P=1.5x10(-6); per allele OR, 1.43; 95% CI, 1.24-1.66). None of the patient characteristics (gender, age, smoking, and hypertension) was a significant confounder or effect modifier of the association. Subgroup analyses of IA subphenotypes showed that among the most common sites of IAs, the association was strongest for IAs of the posterior communicating artery (OR, 1.69; 95% CI, 1.26-2.26) and not significant for IAs in the anterior communicating artery (OR, 1.22; 95% CI, 0.96-1.57). When dichotomizing IA sites, the association was stronger for IAs of the posterior circulation-posterior communicating artery group (OR, 1.73; 95% CI, 1.32-2.26) vs the anterior circulation group (OR, 1.28; 95% CI, 1.07-1.53). Heterogeneity in these ORs was significant (P=0.032). The associations did not vary when stratifying by history of subarachnoid hemorrhage (OR, 1.42; 95% CI, 1.18-1.71 for ruptured IA; OR, 1.27; 95% CI, 1.00-1.62 for unruptured IA) or by multiplicity of IA (OR, 1.57; 95% CI, 1.21-2.03 for multiple IAs; OR, 1.36; 95% CI, 1.15-1.61 for single IA). Our results suggest that genetic influence on formation may vary between IA subphenotypes.

Size ratio for clinical assessment of intracranial aneurysm rupture risk

Objectives: We previously used three-dimensional (3D) volumetric analysis to identify a novel intracranial aneurysm (IA) morphological metric, aneurysm-to-parent vessel size ratio (SR), which strongly correlated with aneurysm rupture. However, complex 3D analysis is not easily obtained, and ubiquitous IA risk assessment is traditionally performed with two-dimensional (2D) imaging, typically with size being the sole considered morphometric. Because only easily applicable 2D measurements will be of clinical value, we sought to investigate the correlation of SR determined from 2D angiography with IA rupture status.Methods: SR and traditional aspect ratio (AR) and aneurysm size parameters were measured in a retrospective cohort of 38 IA cases (16 ruptured) with 2D rotational angiographic images. These parameters were analysed for correlation with IA rupture status. Student's t-test or Wilcoxon rank-sum test was used for normally or non-normally distributed data respectively. Logistic regression was performed for independently statistically significant parameters to generate an effect size estimate (odds ratio). Area-under-the-curve (AUC) calculated from the receiver-operating-characteristic curve was additionally obtained for each index to describe differentiating capabilities.Results: Only SR achieved statistical significance (p=0·05) in Wilcoxon rank-sum test. Logistic regression generated an SR odds ratio of 3·52 (p=0·04; 95% confidence interval: 1·035–11·938) for every doubling of SR value. The AUC value of SR (0·688) was higher than that of AR (0·642) and size (0·585).Conclusions: SR had the strongest correlation with IA rupture and was demonstrated to be a valuable parameter in 2D, where it can be easily obtained from angiographic images. When eventually evaluated in a prospective data set, SR may prove to be an important tool for aneurysm rupture-risk assessment.

Confirmation of an Association of Single-Nucleotide Polymorphism rs1333040 on 9p21 With Familial and Sporadic Intracranial Aneurysms in Japanese Patients

Genetic factors are important determinants of intracranial aneurysm (IA). Recently, a multinational, genome-wide association study identified 3 loci associated with IA, located on 2q (rs700651), 8q (rs10958409), and 9p (rs1333040 and rs10757278). The aim of this study was to evaluate these associations. Familial and sporadic cases were investigated. Familial cases, consisting of 96 subjects with IA, and 46 subjects of unknown status from 31 pedigrees were analyzed with the transmission disequilibrium test and linkage analysis. Associations of single-nucleotide polymorphisms (SNPs) with IA were tested in 419 sporadic IA cases and in 408 control subjects. Sequencing of CDKN2A, CDKN2B, and CDKN2BAS revealed additional SNPs, and their associations with IA were also tested. The transmission disequilibrium test revealed associations of 2 SNPs, rs700651 (P=0.036) and rs1333040 (P=0.002), with familial IA. Analysis of SNPs in sporadic cases revealed an allelic association of rs1333040 with IA (odds ratio=1.28; 95% CI, 1.04-1.57; P=0.02) but failed to show associations of rs10757278 and rs496892 with IA. We sequenced 3 candidate genes; CDKN2A, CDKN2B, and CDKN2BAS. All 6 index cases from IA families had the rs1333040-T allele and SNPs (rs10965215, rs10120688, and rs7341791) in CDKN2BAS. None of these SNPs had linkage disequilibrium with rs1333040 and was associated with IA. A region between introns 7 and 15 of CDKN2BAS carrying the rs1333040-T allele may confer risk for IA.