Occurrence Of Cerebral Aneurysms Research Articles

Cerebral Aneurysms: Are They Associated with Anatomic Variations of Carotid and Main Cerebral Arteries?

Vascular anatomic variations are very common in the population, but their coexistence with life-threating vascular malformations remains unclear. The objective of the study was to assess the correlation between the presence of anatomic variants of both carotid and main cerebral arteries and the occurrence of cerebral aneurysms. We analyzed examinations of 194 patients who underwent computed tomography angiography of the head and neck between September of 2016 and November of 2017. The assessed parameters were: the variation of the common carotid arteries origin, hypoplasia or duplication of any of the main cerebral arteries, carotid artery kinking, and the presence of cerebral aneurysms. We found 5.7% of patients had a cerebral aneurysm. Hypoplasia of at least 1 main cerebral artery occurred in 34.5% of patients, with the most frequent being the vertebral artery (21.6%). Duplication of at least 1 main cerebral artery was detected in 2.6%. Cerebral aneurysms occurred more often together with hypoplasia (P= 0.041; OR= 3.175) or duplication (P < 0.001; OR=18.500) of at least 1 main cerebral artery. In 7.2% of cases, the origin of common carotid arteries created a true bovine arch, and in 4.1% the so-called bovine arch. Patients with alternative variants of aortic arch branching were more likely to have cerebral aneurysms (P= 0.002; OR= 5.903). We found 27.3% of patients had internal carotid arteries affected by kinking. Carotid kinking did not predispose the patient to the formation of a cerebral aneurysm (P=0.378). There is an evident correspondence between the presence of vascular anatomic variants (abnormal origin of the carotid arteries, hypoplasia, or duplication of the main cerebral artery) and the occurrence of cerebral aneurysms.

Abstract TP95: Hypothyroidism is Associated With Cerebral Aneurysms in Women

Background: Endocrine dysfunction, including thyroid function, has been known to affect cerebral vascular dysfunction. Hypothyroidism has been shown to cause mucopolysaccharide deposition which has been associated with the weakening of blood vessel walls and aneurysm formation in some case reports. However, the connection between hypothyroidism and cerebral aneurysm has not been well studied. We hypothesized that hypothyroidism maybe associated with occurrence of cerebral aneurysms. Methods: We performed a retrospective case-control study of consecutive patients receiving cerebral angiography at our tertiary-care academic medical center. Inclusion criteria included undergoing 3-vessel angiography. Exclusion criteria included any ruptured aneurysm or previous intracranial hemorrhage. Medical history of hypothyroidism was noted along with all other risk factors. The control group of patients did not have any intra-cranial abnormality on angiography. Patients with cerebral aneurysm were matched with controls for known risk factors of cerebral aneurysm, including: age, hypertension, and smoking history. Cases were further subdivided base on gender given females are known to have higher incidence of hypothyroidism. Results: From 2008 through 2013, 82 female and 59 male patients with aneurysms were identified for this study and were matched with equal numbers of controls. Among women, hypothyroidism was present in 20.7% (17/82) among patients with cerebral aneurysms vs. in only 6.1% (5/82) among matched controls: odds ratio (OR) 4.03 (95% CI 1.41-11.51, p=0.01). Among men, 8.5% (5/59) cases and 0/59 controls had hypothyroidism, showing no significant association, with an odds ratio of 12.01 (95% CI 0.65-222.3, p=0.095). Conclusion: We found a significant association of history of hypothyroidism with cerebral aneurysm in women in our patient cohort. Given the potential pathophysiologic connection between hypothyroidism and vascular wall dysfunction, this should be explored further.

Polymorphisms of the NADPH Oxidase p22phox Gene in a Caucasian Population with Intracranial Aneurysms

Background: Vascular remodeling generated by reactive oxygen species contributes to aneurysm formation. The NADPH oxidase system is a major source of superoxide anion not only in phagocytes, but also in endothelial and vascular smooth muscle cells. Polymorphisms of p22phox, an essential component of the NADPH oxidase system, are found to be associated with atherosclerosis, while a recent study found a significant association between the 214C>T polymorphism and the occurrence of ischemic cerebrovascular disease. We conducted a case-control study to investigate the relationship of five polymorphisms of the p22phox gene and the occurrence of cerebral aneurysms. Methods: The study population consisted of 113 patients with intracranial aneurysms and 53 control subjects. The 214C>T polymorphism was investigated by restriction fragment length polymorphism analysis, while polymorphisms 381T>C, 480G>A, 521C>T, and *24A>G were analyzed by direct sequencing of exon 6 and adjacent intronic sequences. Results: The analysis of a primary study sample comprising 35 cases and 28 controls failed to show a significant association between any of the five polymorphisms and the occurrence of intracranial aneurysms using both allele frequencies and genotypes (all nominal p > 0.05). Although there was a deviation from Hardy-Weinberg equilibrium in cases at the 521C>T locus (nominal p < 0.05), this could not be confirmed in a second study sample of 78 patients. Haplotypes were constructed regarding three frequent polymorphisms (214C>T, 521C>T, and *24A>G); haplotype frequencies in cases and controls were not significantly different. Conclusion: Although polymorphisms of the p22phox gene located in the coding region and the 3′-untranslated region were reported to be associated with atherosclerosis and cerebrovascular disease, our data provide evidence that there is no association between these polymorphisms and the occurrence of cerebral aneurysms in Caucasians.

Magnetic resonance angiographic evidence of sex-linked variations in the circle of willis and the occurrence of cerebral aneurysms.

In this study the authors investigated the relationship between variations in the circle of Willis observed on magnetic resonance (MR) angiograms and locations of cerebral aneurysms, and evaluated the risk of aneurysm formation. One hundred thirty-one patients with cerebral aneurysms were retrospectively selected from a series of 4518 patients who underwent MR angiography at one neurosurgical institute. Variations in the anatomy of the circle of Willis were simply classified into Type A, in which there was no visualization of a unilateral A1 segment, and Type P, in which there was a fetal type of posterior cerebral artery that was continuously delineated from the internal carotid artery (ICA) through the posterior communicating artery. All other variations in the circle of Willis were defined as Type O (ordinary type of variations). An additional 440 patients who did not harbor cerebral aneurysms were randomly selected for a comparison. Anterior communicating artery aneurysms were significantly related to the Type A anatomy and ICA aneurysms to Type P anatomy. Male patients who did not harbor aneurysms tended to have Type A anatomy, whereas women had a significantly greater incidence of Type P. This sex-linked difference in anatomical variations may be correlated to the well-known sex-linked difference in aneurysm distribution.

Abstracts of literature

Abstracts of literature

Identification of a Serum Gelatinase Associated With the Occurrence of Cerebral Aneurysms as Pro-Matrix Metalloproteinase-2

Subarachnoid hemorrhage from intracranial aneurysm rupture produces a severe form of stroke. Extracellular matrix remodeling is associated with cerebral aneurysms and may play a role in the formation or rupture of these lesions. We previously reported a 3-fold increase in a 72-kDa serum gelatinase in a subgroup of aneurysm patients. The purpose of the present study was to further characterize and identify this gelatinase. Serum samples were collected from surgical patients with intracranial aneurysms. The following series of experiments was designed to further characterize and identify the predominant serum gelatinase found in the subgroup of patients with increased gelatinase activity. Gelatin zymography was performed on native serum samples and compared with serum that had been pretreated with a known metalloproteinase activator (4-aminophenylmercuric acetate [APMA]). Gelatin zymography was repeated in the presence of a matrix metalloproteinase (MMP) inhibitor (EDTA) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride [PMSF]). Final identification was made by Western blotting with the use of monoclonal antibodies to MMP-2 and MMP-9. A consistent gelatinolytic band (72 kDa) was identified in all serum samples (n = 60). Pretreatment of the serum by APMA (n = 60) lowered the molecular weight of the band to 66 kDa. The band was inhibited by EDTA (n = 10) but not PMSF (n = 10), thus characterizing the circulating 72-kDa gelatinase as an inactive pro-MMP. Western blotting (n=20) identified the 72-kDa band as MMP-2. These findings confirm that the increased gelatinolytic activity observed in vitro in a subset of cerebral aneurysm patients is due to pro-MMP-2.

Gelatinase activity and the occurrence of cerebral aneurysms.

Cerebral aneurysms are associated with decreased arterial collagen content; however, whether this deficiency results from impaired collagen synthesis or enhanced collagen degradation is unknown. This study tested the hypothesis that enhanced collagen degradation, not impaired collagen synthesis, is associated with the occurrence of cerebral aneurysms. Cultured skin fibroblasts and serum samples were studied in patients with angiographic evidence of aneurysm (n = 31) and control subjects (n = 14). Transcription of the type III collagen gene was assessed with the use of Northern blots prepared from RNA harvested from confluent cultured fibroblasts. Translation of type III collagen was assessed by Western blot analysis of proteins produced by cultured skin fibroblasts. Collagen metabolism was assessed by radioimmunoassay for type I (PICP) and type III (PIIINP) procollagen peptides in conditioned tissue culture media and serum. We assessed collagen degradation in serum and conditioned tissue culture media by evaluating gelatinase activity using quantitative zymography. Type III collagen synthesis was the same in aneurysm and control patients. Neither the molecular weight nor the relative amount of type III collagen mRNA differed between aneurysm and control patient fibroblasts. Western blot analysis revealed no difference in the relative amount or molecular weight of procollagen III synthesized by aneurysm and control cells. Aneurysm patients had a threefold increase in native serum gelatinase activity compared with control subjects (P = .004). This increase occurred along with serum evidence of increased collagen metabolism. Serum levels of PICP (P = .03) and PIIINP (P = .02) were decreased in aneurysm patients. Elevated serum gelatinase activity and altered collagen metabolism could not be explained by enhanced secretion of gelatinase by cultured fibroblasts or altered net collagen synthesis by fibroblasts. High serum gelatinase activity was more common in men than in women (P = .04). These findings are consistent with the hypothesis that accelerated enzymatic degradation of collagens and other structural proteins compromises the mechanical integrity of the cerebral vessel wall and leads to conditions that favor aneurysm formation.