EPIDEMIOLOGY

The prevalence of arterial aneurysms is reported to be 3% to 5% in Western populations, which is approximately 10 times higher than the frequency of arteriovenous malformations (AVMs) in the same group. At autopsy, the overall frequency of aneurysms in the general population ranges from 0.4% to 10%. The recent meta-analysis by Rinkel and colleagues found a prevalence of 2.3% in adults. More than 50% of aneurysms identified at postmortem examination are asymptomatic. In Western countries, the average annual incidence of subarachnoid hemorrhage (SAH) is approximately 10 cases per 100,000 people per year. In both autopsy and clinical series, the incidence of arterial aneurysms and of arterial aneurysm–associated SAH increases with age from the third decade, peaking at the sixth decade. The incidence of arterial aneurysms in children is very low, even in familial arterial aneurysms or associated diseases. Intracranial aneurysms are more common in adult women than adult men but more frequent in boys than girls. The relative frequency of females increases systematically with age, so that the male-to-female ratio changes from 3 : 1 in children up to 8 years of age to 1.2 : 1 in the 10- to 20-year-old age group, reverses in the 5th decade (male to female: 0.9 : 1), and reaches 1 : 3 in the seventh decade of life.

Multiplicity

The incidence of multiple intracranial aneurysms appears to be extremely variable, depending in part on the patient population; whether the series included surgical, radiologic, or autopsy findings; and whether the aneurysms were ruptured or unruptured. The prevalence of multiple intracranial aneurysms varies between 25% and 31% in autopsy series and 12% to 26% in larger clinical series. Female patients account for 60% to 81% of patients with multiple aneurysms. The internal carotid artery (ICA) and middle cerebral artery (MCA) are most prone to form multiple aneurysms.

Mirror-Image or Twin Aneurysms

A special subgroup of multiple aneurysms is the “mirror-like” or “twin” aneurysms at symmetric sites on each side. Twin aneurysms occur in 5% to 10% of all aneurysm patients but in as many as 36% of all multiple aneurysm patients. They are found on all intracranial vessels but are most common in the MCA. Twin aneurysms may be discovered in the same clinical context as “classic” saccular aneurysms (e.g., during SAH), but their origin is likely to be different. The occurrence of mirror-like aneurysms, their association with familial disease, and their tendency to rupture earlier in life than “classic” aneurysms suggests that congenital weakness of the vessel wall may be an underlying cause (Fig. 23-2).

FIGURE 23-2 A to D, Multiple mirror aneurysms in a single patient who harbored bilateral symmetric MCA aneurysms, bilateral symmetric PICA aneurysms, and an anterior communicating artery aneurysm. The multiplicity and the mirror or twin occurrence suggest a congenital predisposition to be more likely than degenerative causes alone for the appearance of these aneurysms.

The intracranial vascular system is composed of multiple different vascular segments. Each segment may have a unique “segmental identity” that carries with it selective vulnerability to specific triggers. During cephalic vasculogenesis, a defect in migrating cells might be transmitted to the next generation of cells, resulting in a clonal distribution of the defect. The synchronous occurrence of mirror-like aneurysms suggests that these aneurysms develop in segments that share the same defective characteristics. For those reasons, “twin” aneurysms might be a better term than “mirror-like” aneurysms.

Familial Forms and Screening

Intracranial aneurysms are found approximately twice as often in first-degree relatives of patients with aneurysmal SAH than in the general population. Within families, the greater the number of members affected, the greater the risk that any one member will have an aneurysm, up to four times the incidence in the general population. Females predominate (54% to 70%) in familial SAH. In males, the SAH occurs 7 to 10 years earlier in familial forms of aneurysms than in nonfamilial forms. Sibling pairs with arterial aneurysms tend to bleed within the same decade. Most familial arterial aneurysms arise in the MCA territory (50%), especially on the right side, and tend to bleed at relatively small arterial aneurysm size (<6 mm at rupture). The rate of multiplicity is not higher in familial arterial aneurysms, but collected data suggest that fewer arterial aneurysms remain asymptomatic in SAH families.

It is not recommended to screen the general population or to screen families with only one affected family member (relative risk, 1.8), because the resulting slight increase in life expectancy does not offset the risk of postoperative sequelae. However, screening programs should be implemented for first-degree relatives of patients with familial forms of SAH because these individuals are four times more likely to experience a SAH than the general population.

PATHOPHYSIOLOGY

Aneurysms that present with similar features, such as SAH, may result from entirely different disease processes, including bacterial or viral infections and inflammations, connective tissue diseases, traumatic or spontaneous dissections, neoplasms, radiation therapy, and high-flow cerebral AVMs. Therefore, in this chapter we will differentiate among “classic saccular,” dissecting, infectious, and traumatic aneurysms and will discuss their individual pathophysiologies in specific subdivisions.

SACCULAR ANEURYSMS

Saccular aneurysms are the most frequently encountered form of aneurysms (70%-80%). They typically arise at arterial bifurcations and resemble berry-like outpouchings of the vessel wall. Their etiology and pathophysiology are complex and poorly understood. Genetic factors contribute to their development as underlined by (1) the familial form of aneurysms described previously and (2) the many genetic diseases that manifest with aneurysmal dilatation. Endogenous factors such as aging, elevated blood pressure, vessel wall shear stresses, and anatomic variations of the circle of Willis as well as exogenous risk factors such as cigarette smoking are thought to contribute to the formation and/or rupture of an aneurysm. In addition to these “offensive” factors, there may also be “defective defense mechanisms,” such as improper spontaneous self-repair of a vessel wall. The roles of these different factors in a given individual are unknown. Therefore, the concept of individual host response must be considered when assessing the etiology of an aneurysm in a given patient. This individual host response is dependent on the individual life span and the regeneration capacity of arteries in normal or in pathologic circumstances, at their branching or nonbranching portions.

Aging, hypertension, and/or smoking are thought to lead to general thickening of the intima of arteries, which is most pronounced distal and proximal to branching sites. These thickened intimal “pads” are inelastic and lead to an increased strain on more elastic parts of the vessel wall adjacent to these pads. Increased strain on the vessel leads to an increased activity of metalloproteinases and other extracellular matrix-degrading proteins, culminating in aneurysmal outpouching of the vessel wall. A vicious circle may then ensue as turbulent flow against the outpouching increases the strain on the vessel wall. Such hemodynamic stress may be especially significant at sites of congenital weakness of the vessel wall. For example, aneurysms often form in the vicinity of anatomic variations such as incomplete fusion of the basilar artery or unilateral absence of the horizontal segment of an anterior cerebral artery (A1) (Fig. 23-3). However, these theories are not able to explain why certain patients develop aneurysms and others with similar “offensive exposures” do not. Therefore, individual defects in host response (e.g., a missing defensive line) may be present that finally lead to the formation of an aneurysm.

FIGURE 23-3 A and B, In the absence of a contralateral A1 segment, aneurysms tend to form more often on the ipsilateral anterior communicating ramus. Whether this is due to increased hemodynamic shear stress forces or to a relative immaturity (and therefore increased fragility) of the vascular system is unclear.

The construction and maintenance of blood vessels are the result of complex biologic factors and events that involve repetitive steps and feedback to the vascular tree. The structural integrity of arteries is maintained and modified according to hemodynamic or metabolic demands (e.g., shear stress forces), which are genetically programmed and controlled. Vascular remodeling is an active and adaptive process of structural alteration and includes changes in cellular processes such as cell growth, cell death, cell migration, and production or degradation of the extracellular matrix. Shear stress forces activate specific (genetically programmed) steps that alter the balance of the mediators of remodeling (e.g., metalloproteinases, nitric oxide synthase, platelet-derived growth factor [PDGF], and transforming growth factor β1). Aging decreases the capacity of the vessel wall to adapt to variations in the hemodynamic parameters or to compensate for stressful events. This progressive aging process is an acquired vulnerability of the vessel wall, which will differ in males and females and with patient age. Congenital alterations in these programs could well result in a variant, defective, or absent reconstruction of the vessel wall. Similarly, we believe that the association of arterial variants with arterial aneurysms points to an incomplete maturation process of the arterial wall. The lack of cell selection that such a pattern implies may preserve “weaker,” that is, less mature endothelial cells that will later develop arterial aneurysms when subject to secondary triggers such as hemodynamic stress.

In the individual patient there is a complex interplay between the aggressive “offensive” factors and the host response. Formation of an aneurysm, therefore, indicates failure of the repair system at a given period in time and/or the persistence of the abnormal triggering factors responsible for the failure of the remodeling processes. Therapy can then be targeted either toward augmenting the host’s defensive system (not yet possible) or toward ameliorating local, aggressive “offensive” factors leading to the aneurysm. The ultimate goal is to stimulate the vascular remodeling system to repair the local injury to the vessel wall triggered by the offensive insult. Spontaneous resolution of berry-like aneurysms, seen after correction of abnormal flow dynamics, holds the promise of such therapy in the future (Fig. 23-4).

FIGURE 23-4 A and B, Spontaneous resolution of an ophthalmic artery aneurysm that was associated with a high-flow shunting lesion of the ophthalmic artery that spontaneously regressed after occlusion of the shunt. This example testifies for the repair system of the vascular system after removing locally aggressive factors.

Clinical Presentation

Most saccular aneurysms of the intracranial circulation remain undetected until they rupture and present as SAH. Arterial aneurysms are the most important cause of primary nontraumatic SAH and account for 65% to 85% of all SAH (Fig. 23-5). After acute SAH, recurrent hemorrhage from the aneurysm poses continued serious threat to the patient, with an estimated risk of re-rupture of more than 20% at 2 weeks and 40% at 6 months. Therefore, treatment of ruptured aneurysms is mandatory.

FIGURE 23-5 Subarachnoid hemorrhage. A, On cranial CT, a subarachnoid hemorrhage is typically hyperdense and fills the subarachnoid spaces. B, On FLAIR-weighted images, blood in the subarachnoid space fails to suppress like usual CSF and is therefore bright as well. The distribution of blood may shed light on the location of the aneurysm, which may be of special importance in the presence of multiple aneurysms. C, Intraoperative photos following opening of the dura, with extensive blood in the subarachnoid space and brain swelling (“angry brain”).

Patients typically complain about a history of abrupt onset of the “worst headache of their life.” Loss of consciousness, meningismus, focal neurologic deficits, and nausea may be present. Many patients report earlier, milder headaches over the days preceding the acute event, most likely representing small “sentinel bleeds” from an unstable aneurysm. In a large series of ruptured intracranial saccular aneurysm, a significantly higher rate of rebleeding was found in patients with poor overall clinical status compared with those with good clinical status.

The clinical consequences of SAH are so severe that emphasis should be placed on the prevention of rupture once the aneurysms are detected incidentally. Therefore, it is useful to identify factors that stabilize or destabilize the aneurysm. Factors known to predict increased risk of future hemorrhage include prior SAH from a different aneurysm, large aneurysm size, and location in the posterior circulation, as shown by the International Study of Unruptured Intracranial Aneurysms (ISUIA) study (Table 23-1). Additional factors suggesting increased risk of rupture include familial SAH, smoking, specific aneurysm morphology (e.g., multilobulated berry aneurysms with “daughter” aneurysms or aneurysmal “blebs”), multiplicity of aneurysms, and the presence of arterial variations in the vicinity of an aneurysm (pointing toward an incomplete maturation that may preserve “weaker” cells that may be more prone to rupture).

TABLE 23-1 Five-Year Cumulative Percentage Risk of Rupture of Previously Unruptured Aneurysms According to the ISUIA Study

Despite the known risk of complications from an intracranial aneurysm, the decision not to intervene should certainly be considered in the appropriate clinical circumstances. Once treatment is considered, the choice of treatment should consider first the patient’s needs and, second, the quality of the treatment available at a given center. One should therefore avoid quoting results reported in the literature that may not reflect the individual physician’s experience. Treatment options include surgical clipping and endovascular therapies (e.g., coiling). Depending on the configuration of the aneurysm, additional endovascular techniques such as the balloon remodeling technique or stenting have been proposed. Over the course of the last years, especially since the results of the International Subarachnoid Aneurysm Trial (ISAT) have been published, the endovascular treatment of cerebral aneurysms has gained more and more importance, not only in those aneurysms that are difficult to access surgically (i.e., those in the posterior circulation) but also in uncomplicated aneurysms of the anterior circulation. It was found that patients harboring ruptured aneurysms that were rated by both the neurosurgeon and the interventional neuroradiologist as possible candidates for their respective therapies had better outcomes concerning morbidity, dependency, and mortality when being treated endovascularly at the 2- and 12-month follow-up evaluations. However, the risk of aneurysm recurrence and even rebleeding is higher in coiled aneurysms than in clipped ones, requiring follow-up imaging in specific intervals. Whether this increased risk is counterbalanced by the better immediate outcome after endovascular treatment remains a matter of debate.

Imaging

Differential Diagnosis

Aneurysm Distribution

Aneurysms typically arise at branch points on the parent artery. The branch point may be formed by the origin of a side branch from the parent artery (e.g., posterior communicating artery) or by subdivision of a main arterial trunk into two trunks (e.g., MCA or terminal ICA bifurcation, tip of the basilar trunk). Sidewall aneurysms are rare and if present usually arise at a turn or curve in the artery and point in the direction that the blood would have gone if the curve was not present. At both the branch points and the curves, local alterations in intravascular hemodynamics are present that exert high shear stress forces on those regions that receive the greatest force of the pulse wave. Therefore, the aneurysm dome typically points in the direction of the maximal hemodynamic thrust in the pre-aneurysmal segment of the parent artery. Aneurysms that are encountered on a straight, nonbranching segment of an intracranial artery should raise the suspicion of a dissecting process, because saccular aneurysms are infrequently encountered at these sites. More than 90% of all saccular intracranial aneurysms are located at one of the following five sites:

In the anterior circulation, other common sites of aneurysms are the origins of the ophthalmic, superior hypophysial, and anterior choroidal arteries. In the posterior circulation the origin of the posterior inferior cerebellar artery (PICA), anterior inferior cerebellar artery (AICA), and the superior cerebellar artery (SCA) and the junction of the basilar and vertebral arteries are likely sites of aneurysm formation.

The size, configuration, and neck morphology of the aneurysm and the location of adjacent perforating arteries are important determinants in the decision whether to treat by neurosurgical approaches (e.g., clipping of the aneurysm) or by endovascular techniques (e.g., coiling) and, if endovascular, what kinds of devices and techniques to employ for the procedure. Therefore, the size, configuration, and neck morphology of the aneurysm and the location of adjacent perforating arteries should be described meticulously in the report.

Supraclinoid Segment of the Internal Carotid Artery

Aneurysms most commonly form along the supraclinoid segment of the ICA immediately distal to the origins of each large branch. Overall, 35% of all intracranial aneurysms arise at five sites along the supraclinoid segment of the ICA:

Supraophthalmic Artery and Superior Hypophysial Artery Aneurysms

Aneurysms arising from the ICA close to the ophthalmic artery constitute about 5% of all intracranial aneurysms and are more frequent in women than men. They typically arise from the superior wall of the carotid artery at the distal edge of the origin of the ophthalmic artery close to the roof of the cavernous sinus (Figs. 23-7 to 23-9). At this point, the ICA changes direction from superior toward posterior, so the maximal hemodynamic force is directed toward the superior wall of the carotid artery just distal to the ophthalmic artery. Therefore, these aneurysms project upward toward the optic nerve. Supraophthalmic aneurysms are easily approached endovascularly but may be complicated to expose surgically, because the ophthalmic artery has a variable origin and course and because multiple folds of the dura enclose the region of the optic foramen and clinoid process. Supraophthalmic aneurysms are often large with complex, multilobulated shape. Many are wide-necked aneurysms that may require remodeling techniques. Unruptured aneurysms may become symptomatic due to headaches or compression of cranial nerves.

FIGURE 23-7 Internal carotid artery aneurysm at the origin of the supraophthalmic artery (“ophthalmic aneurysm”) that was incidentally found in a patient who was evaluated for headaches. A, T2W MR sequences demonstrate a flow void that is directed into the subarachnoid space. B, TOF MRA is able to demonstrate the origin of the aneurysm that was verified by DSA (C).

FIGURE 23-8 A, Supraophthalmic ICA aneurysms are often broad based and typically large. The origin of the ophthalmic artery has to be specially considered to avoid erratic emboli entering the artery during endovascular therapies. B, Most often, 3D rotational angiography is necessary to determine the exact localization of the artery in relation to the neck of the aneurysm.

FIGURE 23-9 A to D, Small-necked large aneurysm of the ICA at the origin of the ophthalmic artery. Typically these aneurysms point superiorly owing to the hemodynamic thrust in this vessel segment.

Superior hypophysial artery aneurysms arise just distal to the origin of the superior hypophysial artery from the medial or posterior wall of the ICA where the curvature of the ICA is convex medially (Fig. 23-10). In this location they lie lateral to the pituitary stalk and point medially under the optic chiasm. Medial expansion of the aneurysm may compromise the perforating arteries to the floor of the third ventricle, the optic nerves, the chiasm, the pituitary stalk, and the hypophysial vascular supply.

FIGURE 23-10 Aneurysm of the internal carotid artery that is directed medially into the superior part of the sella and most closely resembles a superior hypophysial artery aneurysm that in this patient led to a circumscribed subarachnoid hemorrhage, because the superior aspect of the aneurysm is not completely extradural but points toward the dural fold surrounding the cavernous sinus. CTA is especially helpful to detect the close spatial relationship between the aneurysm and the bone, whereas 3D rotational angiography can plan the subsequent endovascular treatment that was carried out with a complete and dense coil packing in this patient.

Posterior Communicating and Anterior Choroidal Artery Aneurysms

The posterior communicating and anterior choroidal arteries arise from the posterior wall of the ICA, where the ICA forms a posteriorly convex curve as it ascends to its terminal bifurcation under the anterior perforated substance. The most frequent ICA aneurysm is the posterior communicating artery aneurysm, which constitutes about 25% of all intracranial aneurysms (Figs. 23-11 to 23-14). These aneurysms arise near the apex of the posteriorly convex turn, immediately superior to the distal edge of the origin of the posterior communicating artery. They point downward and posteriorly toward the oculomotor nerve, so the posterior communicating artery is usually found inferomedial to the neck of the aneurysm and the anterior choroidal artery is found superior or superolateral to the neck of the aneurysm. The oculomotor nerve enters the dural roof of the cavernous sinus lateral to the posterior clinoid process and medial to a dural band that runs between the tentorium cerebelli and the anterior clinoid process. Posterior communicating artery aneurysms larger than 4 to 5 mm may compress the oculomotor nerve at its entrance into the dural roof, causing ophthalmoplegia.