Rupture Of Intracranial Saccular Aneurysms Research Articles

Finite element model of size, shape and blood pressure on rupture of intracranial saccular aneurysms

Rupture of intracranial saccular aneurysms is a primary concern for neurologists and patients because it leads to stroke and permanent disability. This paper examines the role of blood pressure, in connection with size of and wall thickness, in the rupture of saccular aneurysms. A bulb-shaped geometry of a saccular aneurysm is obtained from angiographic images of a patient and modeled using Finite Elements based on the principle of virtual work under the Fung stress-strain relationship. The numerical model is subjected to varying levels of systolic blood pressure. Rupture is assumed to occur when the wall stress exceeded its mechanical strength. The results show which sizes of this class of aneurysms are at high risk of rupture for varying levels of blood pressure.

RUPTURE MODEL OF INTRACRANIAL SACCULAR ANEURYSMS DUE TO HYPERTENSION

The risk of rupture of intracranial saccular aneurysms is one of the leading dilemmas for patients and neurologists. Although the probability of rupture is small, the consequences of rupture are usually fatal or crippling, and a concern for the patient is whether or not to treat an existing aneurysm. In this paper, an idealized model of saccular aneurysms with assumed Fung material behavior was investigated for rupture potential when the stresses exceeded the maximum wall strength of the aneurysm wall. Numerical simulations used various levels of blood pressure, from normal to hypertensive, in order to determine correlations of aneurysm size and risk of rupture. Results showed that hypertensive individuals harboring cerebral aneurysms with a size of at least 6 mm are at risk.

Factors affecting formation and rupture of intracranial saccular aneurysms

Unruptured intracranial aneurysms represent a decisional challenge. Treatment risks have to be balanced against an unknown probability of rupture. A better understanding of the physiopathology is the basis for a better prediction of the natural history of an individual patient. Knowledge about the possible determining factors arises from a careful comparison between ruptured versus unruptured aneurysms and from the prospective observation and analysis of unbiased series with untreated, unruptured aneurysms. The key point is the correct identification of the determining variables for the fate of a specific aneurysm in a given individual. Thus, the increased knowledge of mechanisms of formation and eventual rupture of aneurysms should provide significant clues to the identification of rupture-prone aneurysms. Factors like structural vessel wall defects, local hemodynamic stress determined also by peculiar geometric configurations, and inflammation as trigger of a wall remodeling are crucial. In this sense the study of genetic modifiers of inflammatory responses together with the computational study of the vessel tree might contribute to identify aneurysms prone to rupture. The aim of this article is to underline the value of a unifying hypothesis that merges the role of geometry, with that of hemodynamics and of genetics as concerns vessel wall structure and inflammatory pathways.

Risk factors for the formation and rupture of intracranial saccular aneurysms in Shimane, Japan

Background Prevention of aneurysmal subarachnoid hemorrhage (SAH) can be achieved by reducing risk factors, which include those for aneurysm formation and aneurysm rupture. However, neither of these 2 factors has been discussed separately so far. A case control study was undertaken in Shimane, Japan, to identify modifiable risk factors for the formation and rupture of aneurysms. Methods This study included 858 patients with ruptured aneurysms, 285 patients with unruptured aneurysms without a history of SAH, and 798 control subjects. Hypertension, diabetes mellitus, heart disease, hypercholesterolemia, cigarette smoking, and alcohol consumption were assessed as risk factors by using conditional logistic regression. Results After adjustment for other risk factors, hypertension was the most powerful risk factor for aneurysm formation, regardless of age and sex, followed by hypercholesterolemia, heart disease, and cigarette smoking, whereas diabetes mellitus and daily drinking were insignificant for aneurysm formation. Hypertension and daily drinking were not related to the risk of aneurysm rupture, regardless of age and sex, whereas cigarette smoking was associated with an increased risk of aneurysm rupture in patients 60 years or older and in men. In contrast, hypercholesterolemia was strongly associated with a decreased risk of rupture, regardless of age and sex, and in patients with small aneurysms (<5 mm). Diabetes mellitus and heart disease were also related to a decreased risk of rupture in patients 60 years or older and in women. Conclusion Identification of risk factors for aneurysm formation and rupture separately seems to be pivotal for reducing the incidence of SAH.

Subarachnoid hemorrhage in systemic lupus erythematosus in Japan: two case reports and a review of the literature

We report 51- and 43-year-old Japanese female patients with systemic lupus erythematosus (SLE) associated with subarachnoid hemorrhage (SAH) due to rupture of intracranial saccular aneurysms. We also review the literature of Japanese SLE patients with SAH. SAH in Japanese SLE patients is more frequent than in patients from Western countries, has different features from the general population, and can occur regardless of SLE disease activity. Clinicians must pay attention to SAH in all SLE patients.

Morphological Characterization of Intracranial Aneurysms Using 3-D Moment Invariants

Rupture of intracranial saccular aneurysms is the most common cause of spontaneous subarachnoid hemorrhage, which has significant morbidity and mortality. Although there is still controversy regarding the decision on which unruptured aneurysms should be treated, this is based primarily on their size. Nonetheless, many large lesions do not rupture whereas some small ones do. It is commonly accepted that hemodynamical factors are important to better understand the natural history of cerebral aneurysms. However, it might not always be practical to carry out a detailed computational analysis of such factors if a prompt assessment is required. Since shape is likely to be dependent on the balance between hemodynamic forces and the aneurysmal surrounding environment, an appropriate morphological 3-D characterization is likely to provide a practical surrogate to quickly evaluate the risk of rupture. In this paper, an efficient and novel methodology for 3-D shape characterization of cerebral aneurysms is described. The aneurysms are isolated by taking into account a portion of their adjacent vessels. Two methods to characterize the morphology of the aneurysms models using moment invariants have been considered: geometrical moment invariants (GMI) and Zernike moment invariants (ZMI). The results have been validated in a database containing 53 patients with a total of 31 ruptured aneurysms and 24 unruptured aneurysms. It has been found that ZMI indices are more robust than GMI, and seem to provide a reliable way to discriminate between ruptured and unruptured aneurysms. Correct rupture prediction rates of approximately equal to 80% were achieved in contrast to 66% that is found when the aspect ratio index is considered.

ANALYSIS OF RUPTURE OF INTRACRANIAL SACCULAR ANEURYSMS

The factors leading to the rupture of intracranial saccular aneurysms are presented in this paper. The mathematical models based on the Legendre functions are presented, moreover minimisation of difference between actual and calculated radius of aneurysm is shown. The impact was put on the new approach towards estimation of rupture, which is more dependent on curvature and shape of an aneurysm than its size.

Competition Between Radial Expansion and Thickening in the Enlargement of an Intracranial Saccular Aneurysm

Rupture of intracranial saccular aneurysms is the leading cause of spontaneous subarachnoid hemorrhage, which results in significant morbidity and mortality. Although many have suggested that saccular aneurysms enlarge and rupture due to mechanical instabilities, our recent nonlinear analyses suggest that at least certain classes of aneurysms do not exhibit a quasi-static limit point instability or dynamic instabilities in response to periodic loading. Based on an increased understanding of the ubiquitous role of growth and remodeling within the vasculature and recent histopathological data on saccular aneurysms, it is hypothesized that a stress-mediated regulation of collagen turnover causes their enlargement. There is a need, however, for a theoretical framework to explore this and competing hypotheses. In this paper, we present a 2-D constrained mixture model for growth and remodeling of an ellipsoidally shaped saccular aneurysm and numerically simulate enlargement and changes in material symmetry in the aneurysmal wall. Results suggest that ellipsoidal aneurysms tend toward spherical shapes, and a competition between radial expansion and wall thickening plays a critical role in determining the stability of an enlarging lesion.

Patients With Small, Asymptomatic, Unruptured Intracranial Aneurysms and No History of Subarachnoid Hemorrhage Should Be Treated Conservatively

It is foolhardy to remove from consideration of treatment any aneurysm solely because its maximal size is <10 mm or 7 mm. Annually, ≥15 000 American patients have subarachnoid hemorrhage (SAH) from aneurysms with a maximum diameter <7 mm and consequently experience irreparable morbidity and severe mortality. The majority of their aneurysms were, of course, unruptured, single, asymptomatic, and even smaller at some point before rupture. If the rupture rates for <10-mm aneurysms in International Study of Unruptured Intracranial Aneurysm (ISUIA) I1 or <7 mm in ISUIA II2 are used with the known number of ruptured aneurysms of these sizes admitted each year to calculate the prevalence of such small aneurysms in American adults, there is an unbelievably high result: in the range of 7% to 14%. Previous best estimates of prevalence on the basis of retrospective and prospective, radiological and pathological data have been ≈2% for all sizes of aneurysms and for those <10 mm, less than 1%. In autopsy studies, unruptured aneurysms have not outnumbered ruptured ones; the reverse is the case.3 Between ISUIA I1 and ISUIA II,2 the rupture rate …

Prevalence of intracranial saccular aneurysms in a Japanese community based on a consecutive autopsy series during a 30-year observation period. The Hisayama study.

Subarachnoid hemorrhage is a life-threatening disease that occurs mostly because of the rupture of intracranial saccular aneurysms. However, little is known about the prevalence of ruptured and unruptured aneurysms in the general population. The aim of the present study was to examine the prevalence of intracranial aneurysms on the basis of a consecutive autopsy series over a 30-year observation period in a general Japanese population in Hisayama. We evaluated 1230 consecutive autopsy cases with craniotomy among the total deaths of Hisayama residents during 1962 through 1991 (overall autopsy rate, 80.1%). A total of 73 intracranial saccular aneurysms were found in 57 cases (4.6%). The prevalence of aneurysms for women was 2.4 times higher than that for men (7.1% versus 2.9%). Among men, the prevalence of aneurysms remained unchanged across the range of age groups. In contrast, there were 2 peaks in the prevalence of aneurysms for women falling in the 40- to 49-year (14.3%) and 60- to 69-year age groups (14.5%). The most common site of the aneurysms was the middle cerebral artery (31.5%), followed by the anterior communicating artery (30.1%), anterior cerebral artery (15.1%), vertebrobasilar artery (12.3%), and internal carotid artery (11.0%). Among these 73 aneurysms, 29 (39.7%) were ruptured. Ruptured aneurysms were common in subjects <80 years of age, whereas unruptured aneurysms were prevalent in those >/=80 years of age. The frequency of ruptured aneurysms was highest in the vertebrobasilar system (66.7%) and lowest in the middle cerebral artery (13.0%). Our data suggest that intracranial aneurysms are more frequent in women in the general Japanese population. Aneurysms are more prevalent in the middle cerebral artery, but the risk of rupture is highest in the vertebrobasilar system.

Prevalence and risk of rupture of intracranial aneurysms: a systematic review.

The estimates on the prevalence and the risk of rupture of intracranial saccular aneurysms vary widely between studies. We conducted a systematic review on prevalence and risk of rupture of intracranial aneurysms and classified the data according to study design, study population, and aneurysm characteristics. We searched for studies published between 1955 and 1996 by means of a MEDLINE search and a cumulative review of the reference lists of all relevant publications. Two authors independently assessed eligibility of all studies and extracted data on study design and on numbers and characteristics of patients and aneurysms. For data on prevalence we found 23 studies, totalling 56,304 patients; 6685 (12%) of these patients were from 15 angiography studies. Prevalence was 0.4% (95% confidence interval, 0.4% to 0.5%) in retrospective autopsy studies, 3.6% (3.1 to 4.1) for prospective autopsy studies, 3.7% (3.0 to 4.4) in retrospective angiography studies, and 6.0% (5.3 to 6.8) in prospective angiography studies. For adults without specific risk factors, the prevalence was 2.3% (1.7 to 3.1); it tended to increase with age. The prevalence was higher in patients with autosomal dominant polycystic kidney disease (relative risk [RR], 4.4 [2.7 to 7.2]), a familial predisposition (RR, 4.0 [2.7 to 6.0]), or atherosclerosis (RR, 2.3 [1.7 to 3.1]). Only 8% (5 to 11) of the aneurysms were >10 mm. For the risk of rupture, we found nine studies, totalling 3907 patient-years. The overall risk per year was 1.9% (1.5 to 2.4); for aneurysms = 10 mm, the annual risk was 0.7% (0.5 to 1.0). The risk was higher in women (RR, 2.1[1.1 to 3.9]) and for aneurysms that were symptomatic (RR, 8.3 [4.0 to 17]), >10 mm (RR, 5.5 [3.3 to 9.4]), or in the posterior circulation (RR, 4.1 [1.5 to 11]). Data on prevalence and risk of rupture vary considerably according to study design, study population, and aneurysm characteristics. If all available evidence with inherent overestimation and underestimation is taken together, for adults without risk factors for subarachnoid hemorrhage, aneurysms are found in approximately 2%. The vast majority of these aneurysms are small (=10 mm) and have an annual risk of rupture of approximately 0.7%.

Further Roles of Geometry and Properties in the Mechanics of Saccular Aneurysms

Rupture of intracranial saccular aneurysms continues to result in significant morbidity and mortality. Although it has long been thought that biomechanical factors play key roles in the genesis, growth, and rupture of these lesions, few analysis have employed realistic descriptions of the geometries and material properties. This paper presents parametric finite element studies for subclasses of elliptical and spherical lesions which complement those recently reported by Kyriacou and Humphrey. In particular, we show again that lesion shape, not size, is a primary determinant of aneurysmal wall stress. Moreover, material anisotropy and geometry can exhibit competing or synergistic effects on the stress fields — this suggests that these interactions may be important in the formulation of theories on lesion growth. Finally, we show that Laplace's equation (for spherical membranes) yields reasonable approximations for wall stress only for a very limited class of lesions. There is a need, therefore, for detailed analysts and thus more precise data on lesion geometry, material properties, and loading conditions.

Expression of angiogenesis factors and selected vascular wall matrix proteins in intracranial saccular aneurysms.

Little is known about the biological mechanisms associated with the genesis, growth, and rupture of intracranial saccular aneurysms. It is postulated that the vascular wall pathological response of aneurysmal disease is associated with abnormal angiogenesis factor expression. We have examined the expression and distribution of immunoreactivity to angiogenesis growth factors (vascular endothelial growth factor and basic fibroblast growth factor) and selected vascular wall matrix proteins (fibronectin, Type IV collagen, and alpha smooth muscle actin) in the walls of human intracranial aneurysms from surgical biopsy or autopsy specimens. Double antibody immunohistochemical stains were performed in contiguous fixed sections from three control circle of Willis arteries, five berry aneurysms, four giant aneurysms, and one mycotic aneurysm (three unruptured and seven ruptured lesions). The aneurysmal wall exhibited diffuse disorganized expression of matrix proteins as compared to their organization in control vessels. There was strong patchy expression of vascular endothelial growth factor within the walls of all aneurysms, including marked staining of capillaries and small vessels within the thickened walls of giant lesions. The expression of basic fibroblast growth factor was more diffuse and occurred around the fibrocytes and myocytes within the disrupted media of 9 of 10 aneurysms. These results confirm the gross architectural molecular disruption in the walls of intracranial aneurysms and illustrate an apparent biological response involving angiogenesis factors. Further research should elucidate the time course and possible causal relationships of these changes to aneurysm growth and rupture with the aim of possible therapeutic manipulation.

Influence of size, shape and properties on the mechanics of axisymmetric saccular aneurysms

Rupture of intracranial saccular aneurysms is the most common cause of spontaneous subarachnoid hemorrhage which, despite advances in neurosurgery, continues to result in significant morbidity and mortality. Currently, the decision to treat a diagnosed, unruptured aneurysm is based primarily on the maximum dimension of the lesion even though there is controversy over the ‘critical size’ (e.g. many ‘large’ lesions do not rupture whereas some ‘small’ ones do). There is a need, therefore, for improved predictors of the rupture-potential of these lesions. In this paper, we show that it is highly unlikely that saccular aneurysms expand or rupture due to a limit point instability, and suggest that a rupture-criterion should be based on local multiaxial states of stress or strain. Moreover, our results from nonlinear finite element analyses reveal important roles of lesion shape, material properties, and loading conditions, not just size, in governing the distributions of stress and strain within a sub-class of axisymmetric saccular aneurysms. For example, we find that maximum biaxial stresses and strains are most often at the fundus, where rupture tends to occur, and that maximum stresses increase markedly with increases in lesion size, the ratio of neck diameter to lesion height, and the distending transmural pressure.

A nonlinear mathematical model for the development and rupture of intracranial saccular aneurysms

Mathematical models of aneurysms are typically based on Laplace's law which defines a linear relation between the circumferential tension and the radius. However, since the aneurysm wall is viscoelastic, a nonlinear model was developed to characterize the development and rupture of intracranial spherical aneurysms within an arterial bifurcation and describes the aneurysm in terms of biophysical and geometric variables at static equilibrium. A comparison is made between mathematical models of a spherical aneurysm based on linear and nonlinear forms of Laplace's law. The first form is the standard Laplace's law which states that a linear relation exists between the circumferential tension, T, and the radius, R, of the aneurysm given by T = PR/2t where P is the systolic pressure. The second is a 'modified' Laplace's law which describes a nonlinear power relation between the tension and the radius defined by T = ARP/2At where A is the elastic modulus for collagen and t is the wall thickness. Differential expressions of these two relations were used to describe the critical radius or the radius prior to aneurysm rupture. Using the standard Laplace's law, the critical radius was derived to be Rc = 2Et/P where E is the elastic modulus of the aneurysm. The critical radius from the modified Laplace's law was R = [2Et/P]2At/P. Substituting typical values of E = 1.0 MPa, t = 40 microns, P = 150 mmHg, and A = 2.8 MPa, the critical radius is 4.0 mm using the standard Laplace's law and 4.8 mm for the modified Laplace's law.(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen type III deficiency in patients with rupture of intracranial saccular aneurysms.

Samples of the middle cerebral artery (MCA) and the brachial artery were obtained post mortem from 14 patients who died following rupture of intracranial saccular aneurysms and from a control group of 14 age- and sex-matched patients who died of causes unrelated to aneurysm rupture. The biomechanical properties of ring-shaped arterial specimens were investigated by loading the specimens at a constant deformation rate until rupture. The relative amounts of collagen type I and type III were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies of cyanogen bromide peptides of collagen prepared from the arterial samples. A deficiency of collagen type III was demonstrated in specimens of the MCA in six of 14 patients with a ruptured intracranial saccular aneurysm. This deficiency was not accompanied by alterations in the mechanical arterial strength but resulted in a significant increase in the extensibility at stress values corresponding to blood pressures between 100 and 200 mm Hg. No difference was found between aneurysm patients and the control group in regard to the biomechanical properties of the brachial artery, despite the presence of a significant deficiency of collagen type III. The increase in vascular extensibility of the MCA may represent alterations in the fibrous structure and functional integrity of the cerebral arteries of aneurysm patients with collagen type III deficiency. Together with aggravating hemodynamic stresses, this deficiency may be an important factor in the pathogenesis of saccular aneurysms.

Immune complexes and complement activation following rupture of intracranial saccular aneurysms.

Circulating immune complexes (CIC) and complement activation (plasma C3d levels) were monitored during a 2-week period in patients with ruptured cerebral aneurysms and also in patients with cerebral hematoma unrelated to saccular aneurysms. Thirteen of 18 aneurysm patients were found to have CIC on admission as compared to three of 21 healthy blood donors (p less than 0.001). The presence of CIC in aneurysm patients was associated with a poor prognosis. Eight of nine patients who developed angiographic vasospasm had CIC on admission compared with one of four without vasospasm. Patients with vasospasm showed a twofold increase in plasma C3d levels at the time when the spasm occurred, whereas no significant changes in the C3d concentration could be demonstrated in aneurysm patients without spasm or in patients with hematoma unrelated to aneurysm rupture. These findings suggest that immunological processes involving complement-activating immune complexes are involved in the pathogenesis of cerebral vasospasm following rupture of saccular aneurysms.

Origin, growth, and rupture of saccular aneurysms: a review.

Pathological and hemodynamic concepts regarding the origin, growth, and rupture of intracranial saccular aneurysms are reviewed. Aneurysms form as a result of an interplay between hemodynamic factors, such as axial stream impingement and the water hammer effect, and structural weaknesses at apices of arterial bifurcations, such as congenital and acquired medial defects, funnel-shaped dilatations, and areas of thinning. Hypertension and time aid the formation of aneurysms. Unknown factors in women and in some families also play a role. Enlargement of aneurysms results from an interplay between mechanical factors, such as self-excitation and resonance, that produce structural fatigue and pathological processes of repair of the aneurysmal wall. Rupture of aneurysms is caused by the same hemodynamic factors that effect growth and is also influenced by extramural pressure. Pathologically, a major rupture may be preceded by fibrinous and leukocytic infiltration of the wall, bleb formation, and a minor hemorrhage. Such minor leaks can be followed by healing and growth. Aneurysms that escape major hemorrhage or heal successfully after a hemorrhage can grow to giant proportions, but remain susceptible to rupture despite their size, unless they become completely thrombosed. Intramural thrombosis may be stimulated by minor leaks and is dependent upon the physical characteristics of aneurysms. Experimental, angiographic, and clinical studies that pertain to the origin, growth, and rupture of aneurysms are also reviewed.

Scanning electron microscopy (s.e.m.) of biopsy specimens of ruptured intracranial saccular aneurysms.

Surgical specimens of 4 intracranial saccular aneurysms were studied by scanning electron microscopy. The internal surface of the aneurysms showed crater-like defects and cytoplasmic bridges. In some areas the endothelium was preserved, but its longitudinal convolutions were higher and thicker than those found in unchanged areas. On the damaged endothelial surface there was an increased number of blood cells. The adventitia resembled that of a normal cerebral artery. In conclusion the alterations observed are similar to those found in atherosclerosis and are most likely due to the high wear and tear provoked by the blood streaming into the aneurysm. The results of this study are in agreement with the findings of a companion transmission electron microscopy study and emphasize the importance of degenerative changes on the development and rupture of intracranial saccular aneurysms.