The New England Journal of Medicine

Review Articles

Medical Progress

I NTRACRANIAL A NEURYSMS
WOUTER I. SCHIEVINK, M.D.

NTRACRANIAL aneurysms are acquired lesions that are most commonly located at the branching points of the major arteries coursing through the subarachnoid space at the base of the brain (Fig. 1). A subarachnoid hemorrhage due to the rupture of an intracranial aneurysm is a devastating event associated with high rates of morbidity and mortality. Approximately 12 percent of patients die before receiving medical attention,1 40 percent of hospitalized patients die within one month after the event,2-6 and more than one third of those who survive have major neurologic deficits.2-6 Furthermore, persistent cognitive deficits are present in many patients otherwise considered to have a good outcome.7,8 In spite of diagnostic, medical, and surgical advances over the past several decades, the case fatality rate for aneurysmal subarachnoid hemorrhage has not changed.5,6,9,10 In this review I discuss recent developments in our understanding of the epidemiology and pathogenesis of intracranial aneurysms, methods of diagnosis, and approaches to treatment.
EPIDEMIOLOGY
Prevalence of Intracranial Aneurysms

The majority of intracranial aneurysms (80 to 85 percent) are located in the anterior circulation, most commonly at the junction of the internal carotid artery and the posterior communicating artery, the anterior communicating-artery complex, or the trifurcation of the middle cerebral artery.15,16 Aneurysms of the posterior circulation are most frequently located at the bifurcation of the basilar artery or the junction of a vertebral artery and the ipsilateral posterior inferior cerebellar artery.15,16 Multiple intracranial aneurysms, usually two or three in number, are found in 20 to 30 percent of patients.15-17 In rare cases, as many as 13 intracranial aneurysms have been detected in a patient.15,18
Incidence of Subarachnoid Hemorrhage

An intracranial aneurysm is a fairly common incidental finding at postmortem examination, with a prevalence ranging from 1 to 6 percent among adults in large autopsy series.11,12 Many of these aneurysms, however, are very small, and the prevalence of incidental intracranial aneurysms among adults undergoing cerebral angiography is between 0.5 and 1 percent.13,14 These rates suggest that between 1 million and 12 million Americans have intracranial aneurysms.

Aneurysmal subarachnoid hemorrhage is a major clinical problem in the United States, with an annual incidence of approximately 1 per 10,000 people.2,9 This rate suggests that each year approximately 27,000 Americans have ruptured intracranial aneurysms, which are fatal in 14,000. The incidence of aneurysmal subarachnoid hemorrhage is higher than that of many other major neurologic disorders, including primary brain tumors and multiple sclerosis (Table 1). Although the incidence of other types of stroke (i.e., cerebral infarction and intracerebral hemorrhage) decreased substantially between the 1950s and 1980s,19 the incidence of aneurysmal subarachnoid hemorrhage has not changed.2,9 Patients who have had an aneurysmal subarachnoid hemorrhage are at increased risk for the development of a new aneurysm some time after the initial aneurysm has been discovered. Each year, new aneurysms develop in at least 2 percent of patients with previously ruptured aneurysms,25 and in this group of patients, the incidence of aneurysmal rupture is approximately 6 per 10,000 per year,26,27 which is substantially higher than the incidence of aneurysmal subarachnoid hemorrhage in the general population.
PATHOLOGICAL FEATURES

From the Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, where reprint requests should be addressed to Dr. Schievink. 1997, Massachusetts Medical Society.

Aneurysms arising from the intracranial arteries are much more common than those arising from extracranial arteries of similar size. One possible reason for this discrepancy is that as compared with their extracranial counterparts, intracranial arteries have an attenuated tunica media and lack an external elastic lamina. On microscopical examination, the typical saccular, or berry, aneurysm has a very thin tunica media or none, and the internal elastic lamina is either absent or severely fragmented.28,29 Thus, the

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Anterior communicating artery

Anterior cerebral artery Internal carotid artery Middle cerebral artery

Posterior communicating artery Basilar artery Vertebral artery

Posterior cerebral artery Posterior inferior cerebellar artery

Figure 1. Common Sites of Intracranial Aneurysms on the Circle of Willis at the Base of the Brain.

wall of the aneurysm is generally composed of only intima and adventitia, with variable amounts of fibrohyaline tissue interposed between these two layers.28,29 Macroscopically, many intracranial aneurysms, especially those that rupture, have an irregular appearance, with one or more daughter sacs and variable wall thickness. The point of rupture is generally in the dome of the aneurysm.
PATHOGENESIS
Genetic Factors

TABLE 1. INCIDENCE OF SELECTED MAJOR NEUROLOGIC DISORDERS IN THE UNITED STATES.*

ANNUAL INCIDENCE (PER 10,000 PERSONS)

DISORDER

Considerable evidence supports the role of genetic factors in the pathogenesis of intracranial aneurysms. The two main lines of evidence are the association of intracranial aneurysms with heritable connective-tissue disorders30 and their familial occurrence.31 Of the numerous heritable connectivetissue disorders that have been associated with intracranial aneurysms, the most important are autosomal dominant polycystic kidney disease, Ehlers Danlos syndrome type IV, neurofibromatosis type 1, and Marfans syndrome.30,31 It is not known to what extent these specific heritable disorders are present in the population of patients with intracranial aneurysms, but in one series of 100 consecutive patients

Cerebral infarction Aneurysmal subarachnoid hemorrhage Bacterial meningitis Multiple sclerosis Intracranial glioma GuillainBarr syndrome Amyotrophic lateral sclerosis

12.0 1.0 0.9 0.6 0.5 0.2 0.2

*Data are from population studies in Rochester (Olmsted County), Minnesota.2,19-24

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with intracranial aneurysms, 5 had known heritable connective-tissue disorders.32 The true frequency of heritable connective-tissue disorders among patients with aneurysms is probably higher, for two reasons. First, these disorders often remain undiagnosed because of substantial variability in their phenotypic expression, and second, although many of the disorders are inherited in an autosomal dominant fashion, the family history is frequently negative because the disease is caused by a new mutation. With the exception of autosomal dominant polycystic kidney disease, heritable connective-tissue disorders are rarely identified in families with intracranial aneurysms.31 The familial aggregation of intracranial aneurysms was first described in 1954 by Chambers et al.,33 and hundreds of familial cases have since been reported.31 Familial intracranial aneurysms are much more common than has generally been appreciated. According to several epidemiologic studies, 7 to 20 percent of patients with aneurysmal subarachnoid hemorrhage have a first- or second-degree relative with a confirmed intracranial aneurysm.34-37 Recent studies have also indicated that the familial aggregation of intracranial aneurysms is not a matter of chance. Among first-degree relatives of patients with aneurysmal subarachnoid hemorrhage, the risk of a ruptured intracranial aneurysm is approximately four times higher than the risk in the general population.36-38 The risk may be highest among siblings of index patients.36 In most families with intracranial aneurysms, only two or three members are known to be affected, and the inheritance pattern is unclear.31 In a segregation analysis of published pedigrees, no single mendelian model but several possible patterns of inheritance were identified, with autosomal transmission being the most likely.31 This suggests that genetic heterogeneity is an important feature of intracranial aneurysms. As compared with sporadic intracranial aneurysms, familial aneurysms rupture at an earlier age, may be smaller when they rupture, and are more often followed by the formation of a new aneurysm.31,39,40 Affected siblings are often in the same decade of life at the time of the rupture.39,40
Environmental Factors

Several lines of evidence suggest that acquired factors have an important role in the pathogenesis of intracranial aneurysms. For example, intracranial aneurysms are very rare in children, and although the mean age of patients with aneurysmal subarachnoid hemorrhage is only around 50 years, the incidence of hemorrhage increases with age until at least the eighth decade of life.2 Numerous casecontrol and longitudinal studies have attempted to identify risk factors for subarachnoid hemorrhage. Of the various environmental factors that may confer a predisposition to aneurysmal subarachnoid
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hemorrhage, cigarette smoking is the only factor that has consistently been identified in all the populations studied,3,41-46 and it is also the most easily preventable. The estimated risk of an aneurysmal subarachnoid hemorrhage is approximately 3 to 10 times higher among smokers than among nonsmokers.41-46 In addition, the risk increases with the number of cigarettes smoked,42,44,45 and patients who continue to smoke after an initial subarachnoid hemorrhage may be at especially high risk for the development of a new aneurysm.47,48 It is unclear how cigarette smoking affects the development of aneurysms, but several hypotheses have been proposed. Cigarette smoking has been shown to decrease the effectiveness of a1-antitrypsin, the main inhibitor of proteolytic enzymes (proteases) such as elastase, and the imbalance between proteases and antiproteases in smokers may result in the degradation of a variety of connective tissues, including the arterial wall.32,49 In support of this hypothesis is the observation that patients with a genetically determined a1-antitrypsin deficiency may also be at increased risk for the development of intracranial aneurysms.32,49,50 Hypertension is the most frequently studied risk factor for the development and rupture of intracranial aneurysms.2,3,42-46,51-53 Several studies have shown that hypertension is associated with an increased risk of aneurysmal subarachnoid hemorrhage,3,42-44,46 as well as unruptured intracranial aneurysms.52 Some studies, however, have not shown an increased risk.2,45,51 At autopsy, left ventricular hypertrophy is a common finding in patients with intracranial aneurysms.53 Although the data are inconsistent, taken together they suggest that hypertension poses a risk of aneurysmal subarachnoid hemorrhage, but probably not as high a risk as that associated with cigarette smoking. The incidence of aneurysmal subarachnoid hemorrhage, unlike other types of stroke, is higher among women than among men.2-4 Before the fifth decade of life, however, aneurysmal subarachnoid hemorrhage occurs more frequently in men, suggesting the role of hormonal factors. The use of low-dose oral contraceptives by premenopausal women does not increase and may even decrease the risk of subarachnoid hemorrhage,42,54,55 although in studies performed when oral contraceptives had a higher estrogen content than they do now, the risk was significantly increased,41,56 possibly because of the direct effect of estrogen on blood pressure. The risk of aneurysmal subarachnoid hemorrhage is lower among postmenopausal women receiving hormone-replacement therapy than among postmenopausal women not receiving such therapy,54,57 but not as low as the risk among premenopausal women. These data suggest that premenopausal women have a low risk of aneurysmal subarachnoid hemorrhage, postmeno-

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A Figure 2. Hemorrhage from Intracranial Aneurysms. A basal view of the brain of a 59-year-old woman shows extensive subarachnoid blood caused by a ruptured aneurysm of the anterior communicating artery (Panel A). A coronal section through the brain of a 46-year-old man shows right intracerebral and intraventricular hemorrhages caused by a ruptured aneurysm of the middle cerebral artery (Panel B). A view of the brain of a 48-year-old woman shows a large right subdural hematoma caused by a ruptured aneurysm of the internal carotid artery (Panel C). C

pausal women have a relatively high risk, and postmenopausal women receiving hormone-replacement therapy have an intermediate risk. A moderate-to-high level of alcohol consumption is an independent risk factor for aneurysmal subarachnoid hemorrhage.44,45,58,59 Recent, heavy use of alcohol (binge drinking) in particular appears to increase the risk of subarachnoid hemorrhage.44,45 Casecontrol studies have suggested that there may be a J-shaped doseresponse curve, with a low level of alcohol consumption actually lowering the risk of subarachnoid hemorrhage,44,45 but longitudinal studies have not shown such a relation.58,59 The data on hypercholesterolemia as a risk factor for aneurysmal subarachnoid hemorrhage are inconsistent. Of the three studies that have investigated this relation,46,60,61 only one reported an increased risk of hemorrhage among patients with

the highest serum cholesterol and apolipoprotein B concentrations.46

DIAGNOSIS
Clinical Presentation
Subarachnoid Hemorrhage

Most intracranial aneurysms remain asymptomatic until they rupture and cause a subarachnoid hemorrhage (Fig. 2). Although aneurysmal subarachnoid hemorrhage is most common during times of exertion or stress, aneurysms can rupture at any time.62 The typical presentation is that of a uniquely severe headache of acute onset. The headache is often accompanied by nausea or vomiting, and the patient may or may not lose consciousness. One third to one half of patients with subarachnoid hemorrhage have a history of an unusual and acute headache preVo l u m e 3 3 6 Nu m b e r 1

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Figure 3. Funduscopic Photograph of a Subhyaloid Hemorrhage in the Right Eye of a 45-Year-Old Woman with a Ruptured Aneurysm of the Middle Cerebral Artery.

TABLE 2. GRADING SCALE FOR SUBARACHNOID HEMORRHAGE.*

GLASGOW COMA SCORE

GRADE

MOTOR DEFICIT

I II III IV V

15 13 or 14 13 or 14 712 36

Absent Absent Present Absent or present Absent or present

ocular hemorrhages are two signs that are helpful in establishing a clinical diagnosis of subarachnoid hemorrhage. Signs of meningeal irritation are found in most patients with aneurysmal subarachnoid hemorrhage.16 It is caused by the breakdown of blood products within the subarachnoid space, and neck stiffness may not develop until several hours after the hemorrhage. The subsequent circulation of bloody cerebrospinal fluid down the spinal axis may cause severe lower back pain and bilateral radicular leg pain, sometimes overshadowing the head or neck pain. Ophthalmologic examination reveals unilateral or bilateral subhyaloid hemorrhages in approximately one fourth of patients with aneurysmal subarachnoid hemorrhage.66 These hemorrhages are venous in origin and are located between the retina and vitreous membrane. Because subhyaloid hemorrhages are gravity-dependent, they are convex at the bottom and flat at the top (Fig. 3). The most important predictor of the outcome of subarachnoid hemorrhage is the patients clinical condition on arrival at the hospital.2 Numerous grading systems for subarachnoid hemorrhage have been proposed over the years, but the scale developed by the World Federation of Neurological Surgeons67 (based in part on the Glasgow Coma Scale68) has gained universal acceptance and is used most widely (Table 2).
Mass Effect

*The scale was developed by the World Federation of Neurological Surgeons. Data are adapted from Drake.67 The score is derived from the Glasgow Coma Scale, as described by Teasdale and Jennett.68

ceding the hemorrhage by several days or weeks.63,64 Such a prodromal headache is most likely due to minor leaking of blood into the wall of the aneurysm or into the subarachnoid space and is therefore commonly referred to as a warning leak.63,64 These prodromal headaches are often not recognized as such by physicians, and many cases of frank aneurysmal subarachnoid hemorrhage are initially misdiagnosed as migraine headache, sinusitis, influenza, or malingering.65 Aneurysmal rupture may cause not only subarachnoid hemorrhage but also intraventricular, intracerebral, or subdural hemorrhage (Fig. 2). It is rare for aneurysmal rupture to result in these other types of intracranial hemorrhage without any evidence of subarachnoid hemorrhage. In addition to the global or focal neurologic abnormalities that may be found on physical examination, depending on the location and severity of the subarachnoid hemorrhage, meningismus and intra32
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Some intracranial aneurysms become symptomatic because of a mass effect (Fig. 4). Such aneurysms are often, but not invariably, large or giant.69 The most common symptom of an aneurysmal mass effect is headache, and the most common sign is a palsy of the third nerve caused by an aneurysm at the junction of the carotid artery and the posterior communicating artery or an aneurysm of the upper end of the basilar artery. Characteristically, the third-nerve palsy involves the pupillary fibers. Depending on the location of the aneurysm, other manifestations of a mass effect include brain-stem dysfunction, visualfield defects, trigeminal neuralgia, a cavernous sinus syndrome, seizures, and hypothalamicpituitary dysfunction. Unruptured intracranial aneurysms causing a mass effect carry a high risk of subsequent rupture, with an estimated frequency of 6 percent per year.70
Cerebral Ischemia

Cerebral ischemic symptoms referrable to the vascular territory distal to an aneurysm may in rare cases be the presenting clinical manifestation of an unruptured intracranial aneurysm.69,71 Such ischemia is believed to be caused by the embolization of an intraaneurysmal thrombus, and it should be distinguished from intracranial arterial dissection with the secondary formation of an aneurysm, which typically presents with cerebral symptoms.72

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Asymptomatic Intracranial Aneurysms

The discrepancy between the prevalence of incidental intracranial aneurysms at autopsy and the incidence of aneurysmal subarachnoid hemorrhage indicates that most aneurysms never rupture. Similarly, in large autopsy series the majority of intracranial aneurysms are unruptured and apparently have never caused any symptoms.11 With the widespread use of computed tomographic (CT) scanning and magnetic resonance imaging (MRI), many unruptured asymptomatic intracranial aneurysms can now be detected. The natural history of such aneurysms is incompletely understood, but all the large studies have reported annual rupture rates of 0.5 to 2 percent.25,70,73,74 The rate of rupture increases with the size of the aneurysm but appears to be unrelated to the age or sex of the patient or to the presence or absence of hypertension.70 Data presented by Wiebers and colleagues suggest that only intracranial aneurysms that are 10 mm or larger in diameter carry a significant risk of subsequent rupture,70 but there is still considerable controversy about the size below which the risk of rupture is negligible.25,75,76
Diagnostic Studies
Subarachnoid Hemorrhage

CT scanning should be the first diagnostic study performed to evaluate the possibility of a subarachnoid hemorrhage (Fig. 5). CT scans are very sensitive in detecting acute hemorrhage, and they can demonstrate the presence of a subarachnoid hemorrhage in 90 to 95 percent of patients who undergo scanning within 24 hours after the hemorrhage.16,77 Blood is cleared rapidly from the subarachnoid space, however, and the sensitivity of CT scanning decreases to 80 percent at three days, 70 percent at five days, 50 percent at one week, and 30 percent at two weeks.16,77 CT scans are also very useful in detecting any associated intracerebral hemorrhage or hydrocephalus, and the distribution of blood may offer important clues to the location of the ruptured aneurysm (Fig. 5). If there is a strong clinical suspicion of a subarachnoid hemorrhage but the CT scan is normal, then a lumbar puncture should be performed. Bloody cerebrospinal fluid may be caused by a traumatic lumbar tap, and a decrease in the red-cell count from the first to the last tube is an unreliable basis for ruling out a subarachnoid hemorrhage.78 Xanthochromia (yellow discoloration) of the supernatant after centrifugation of the cerebrospinal fluid, however, is diagnostic of a subarachnoid hemorrhage. Xanthochromia is caused by the breakdown of blood products in the cerebrospinal fluid, and it takes several hours for those blood products to break down and circulate to the lumbar theca. A lumbar puncture performed very soon after the subarachnoid

B Figure 4. Mass Effect from Intracranial Aneurysms. A midsagittal section through the brain of a 54-year-old man shows a giant (4.5 cm) aneurysm of the basilar artery that is compressing the medulla and pons (Panel A). A coronal section through the brain of a 55-year-old man shows an unruptured, 9-mm aneurysm of the right internal carotid artery that is compressing the right optic nerve and chiasm (Panel B).

hemorrhage may therefore fail to show xanthochromia.78 With the use of spectrophotometry, xanthochromia is detected in all patients with subarachnoid hemorrhage between 12 hours and 2 weeks after the hemorrhage and is still detectable in more than 70 percent of patients after 3 weeks and in 40 percent after 4 weeks.78 In most hospital laboratories, however, xanthochromia is determined by visual inspection alone and not by spectrophotometry, making the detection of the abnormality less reliable. MRI is not sensitive in detecting acute hemorrhage, and its role in the early evaluation of subarachnoid hemorrhage is limited. However, MRI
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may be very useful in demonstrating subacute or chronic subarachnoid hemorrhage long after the findings on the CT scan have become normal.79
Intracranial Aneurysms

B Figure 5. CT Images of Aneurysmal Subarachnoid Hemorrhage. A CT scan in a 55-year-old woman shows subarachnoid blood within the interpeduncular and ambient cisterns and the right sylvian fissure, caused by a ruptured aneurysm at the junction of the right carotid artery and the posterior communicating artery (Panel A). A CT scan in an 82-year-old woman shows extensive subarachnoid blood within the cortical sulci, intraventricular hemorrhage, and an intracerebral hematoma adjacent to a large, ruptured aneurysm of the anterior communicating artery (Panel B).

The three most commonly used techniques to diagnose an intracranial aneurysm are conventional angiography, MRI angiography, and helical (spiral) CT angiography (Fig. 6). Because of its unsurpassed resolution, conventional angiography remains the method of choice for detecting an intracranial aneurysm and determining its anatomical characteristics. Although the risks associated with conventional angiography are very low, they are not negligible. Such risks include cerebral infarction, the formation of a hematoma or pseudoaneurysm at the puncture site, and renal failure. In most large series, the mortality rate is less than 0.1 percent, and the rate of permanent neurologic injury is approximately 0.5 percent.80 The majority of complications in these series occur in elderly persons with severe atherosclerotic disease, not in patients with intracranial aneurysms. However, the risk associated with angiography is exceedingly high in some groups of patients with intracranial aneurysms (e.g., those with generalized connective-tissue disorders such as the EhlersDanlos syndrome).30 Because it does not require the intravascular administration of contrast material, MRI angiography is the most convenient diagnostic study and carries essentially no risk. Nowadays, MRI angiography can detect intracranial aneurysms as small as 2 or 3 mm in diameter, but in prospective studies the critical size for detection is about 5 mm.81,82 Thus, some small aneurysms will be missed with MRI angiography. Although it is the most commonly used diagnostic study in screening for intracranial aneurysms, MRI angiography is only rarely sufficient for surgical planning. Standard MRI is the best method for demonstrating the presence of a thrombus within the aneurysmal sac. Although uncommon, there have been several instances of thrombosed intracranial aneurysms that were not visualized on angiography but were clearly demonstrated with MRI.83,84 Recently, helical CT angiography has been used to detect intracranial aneurysms, and preliminary reports indicate that the detection rate with this technique is similar to that with MRI angiography.85,86 An advantage of helical CT angiography in surgical planning is its ability to demonstrate the relation of the aneurysm to the bony structures of the skull base. Helical CT angiography is also useful in screening for new aneurysms in patients with initial aneurysms that were treated with ferromagnetic clips; these older clips are an absolute contraindication to MRI angiography. However, MRI can be performed safely in patients who have the more common, non-

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Figure 6. Arteriogram (Panel A), MRI Angiogram (Panel B), and Helical CT Angiogram (Panel C) Showing an Unruptured Aneurysm at the Vertebrobasilar Junction in a 41-Year-Old Woman.

ferromagnetic metallic clips. Conventional CT scanning is the preferred method for detecting calcifications within the wall of the aneurysm.
Screening

Screening for asymptomatic intracranial aneurysms appears to be warranted, because aneurysmal subarachnoid hemorrhage has a dismal prognosis, whereas the treatment of most asymptomatic intracranial aneurysms is associated with a fairly low rate of morbidity (less than 5 percent) and mortality (less than 2 percent).76,87 However, the natural history of asymptomatic intracranial aneurysms is not well defined, and the benefits of screening have never been quantified. A possible caveat for screening programs is based on evidence that intracranial aneurysms may develop over a short period (months, weeks, or even days) and either rupture immediately or remain fairly stable without rupturing.69,88,89 Screening has been suggested for patients at high risk for the development of an aneurysm. The two groups of patients most commonly screened are those with a family history of intracranial aneurysms31,89,90 and those with autosomal dominant polycystic kidney disease.91-95 In the absence of any clinical feature or biologic marker that can identify persons in

whom intracranial aneurysms are most likely to develop, screening is generally recommended for asymptomatic members of families with two or more affected members.31,90 Although the extent of screening depends on the apparent inheritance pattern in a particular family, usually only first-degree relatives are screened. Using such a screening program, Ronkainen and colleagues detected asymptomatic intracranial aneurysms in 37 of 396 persons (9 percent) with affected family members.90 Some investigators have suggested screening of persons with only a single affected family member.38 However, the absolute lifetime risk of subarachnoid hemorrhage for persons with one affected first-degree relative is small (1 percent at the age of 50 and 2 percent at the age of 70), even though they have a risk of aneurysmal rupture that is four times higher than that in the general population.36 Screening is therefore not recommended for such persons. Approximately 5 to 10 percent of asymptomatic adults with autosomal dominant polycystic kidney disease who undergo screening are found to have saccular intracranial aneurysms.91-93 Clustering of intracranial aneurysms has been reported in several families with autosomal dominant polycystic kidney disease, and screening reveals asymptomatic aneuVo l u m e 3 3 6 Nu m b e r 1

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Figure 7. Treatment of Intracranial Aneurysms by Surgical Clipping or Endovascular Coiling. Lateral carotid subtraction angiograms in a 35-year-old woman show a 17-mm supraclinoid aneurysm of the carotid artery before treatment (Panel A) and after the placement of a single, straight SundtKees clip (Panel B). Anteroposterior vertebral subtraction angiograms in a 53-year-old woman show a 13-mm basilar aneurysm before treatment (Panel C) and after the placement of four Guglielmi detachable coils with a total length of 90 cm (Panel D). The densely compacted coils are more easily seen on a plain skull radiograph (Panel E).

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rysms in 20 or 25 percent of the members of such families.92,93 Therefore, although screening for asymptomatic intracranial aneurysms in patients with autosomal dominant polycystic kidney disease remains controversial, most investigators agree that screening is indicated for those patients who also have family histories of intracranial aneurysms.91-95
TREATMENT

The ultimate goal of treatment is to exclude the aneurysmal sac from the intracranial circulation while preserving the parent artery. Treatment of intracranial aneurysms has long been the domain of neurosurgeons, but since 1990, neuroradiologists have been using endovascular techniques to treat increasing numbers of patients with intracranial aneurysms.
Surgery

The placement of a clip across the neck of an intracranial aneurysm is the most definitive treatment and, because of its proven long-term efficacy, remains the treatment of choice (Fig. 7A and 7B). In 1936, Walter Dandy performed the first planned surgical repair of an intracranial aneurysm by placing a silver clip, designed by Harvey Cushing, across the neck of an aneurysm at the junction of the carotid artery and the posterior communicating artery in a patient with a painful third-nerve palsy.96 Surgical techniques for repairing intracranial aneurysms have improved tremendously since then, particularly over the past two decades, with the introduction of microsurgical techniques, the operating microscope, bipolar coagulation, and a variety of self-closing aneurysm clips.97,98 Nowadays, clipping of most intracranial aneurysms carries a fairly low risk directly attributable to the surgery. Some aneurysms are not amenable to safe direct clipping because of their size, location, or configuration, and sophisticated adjunctive techniques, such as vascular bypass grafting or hypothermic cardiac arrest, must be used.97-99 In spite of the availability of these techniques, some intracranial aneurysms are best treated by surgical or endovascular occlusion of the proximal vessel.100 An area of continuing controversy in the management of ruptured intracranial aneurysms is the timing of surgery. Early surgery (i.e., within 48 to 72 hours after the hemorrhage) is beneficial because patients with subarachnoid hemorrhage are at very high risk for a recurrent hemorrhage shortly after the initial one. The rate of recurrent hemorrhage is at least 4 percent within the first 24 hours101 (and may be as high as 10 or 20 percent102,103) and between 1 and 2 percent per day for the first 2 weeks.101 Early surgery also allows aggressive treatment of the secondary intracranial arterial narrowing, or vasospasm, which is an important cause of delayed cerebral ischemia after subarachnoid hemorrhage.104 The

cause of vasospasm is not known, but its incidence is clearly related to the amount of subarachnoid blood seen on the CT scan.104 Vasospasm occurs between 3 and 15 days after the subarachnoid hemorrhage, and the optimal treatment hypervolemia, hypertension, intraarterial papaverine infusion, or endovascular balloon angioplasty is dangerous in the presence of an untreated ruptured aneurysm.104 Because of brain edema and the presence of a tenacious clot around the aneurysm, however, early surgery may be technically more challenging than surgery performed 10 to 14 days after the hemorrhage. Although the approach to patients with subarachnoid hemorrhage who are in poor clinical condition (grade IV or V in Table 2) varies widely from one institution to another, most neurosurgeons recommend early aneurysmal repair in patients with subarachnoid hemorrhage who are in good clinical condition (grade I or II). Moreover, several groups have reported good results with early surgery in patients who are in poor clinical condition.105,106 Emergency surgery is indicated in patients who have a major mass effect from an intracerebral or subdural hematoma.
Endovascular Therapy

Endovascular treatment is emerging as a promising alternative to surgical clipping in selected cases of intracranial aneurysm.107-109 The initial experience with endovascular therapy, in which a detachable balloon was used to occlude an intracranial aneurysm, was disappointing because of arterial rupture and deflation of the balloon. Current endovascular therapy involves the insertion of soft metallic coils within the lumen of the aneurysm, which are detached once they have been satisfactorily placed (Fig. 7C, 7D, and 7E).107-109 Then, through the process of electrothrombosis, a local thrombus forms around the coils within the aneurysm.107 The goal of endovascular coiling is complete obliteration (i.e., thrombosis) of the aneurysmal sac. Many factors affect the obliteration rate, but the most important factor is the ratio of the neck of the aneurysm to the fundus.108,109 Aneurysms with wide necks are less amenable to endovascular treatment than those with narrow necks, because with a wide-necked aneurysm, the coils tend to compact into the body and dome of the aneurysm, resulting in an aneurysm remnant and incomplete treatment. The early experience with coil embolization for the treatment of intracranial aneurysms suggests that the procedural risks are fairly low, but the long-term effectiveness has not yet been proved.108,109 The disadvantages of early surgery in patients with ruptured intracranial aneurysms are of minor importance in endovascular treatment. Some patients may therefore best be treated with emergency endovascular coiling of the dome of the aneurysm, which
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provides at least temporary protection against recurrent hemorrhage and allows aggressive treatment of vasospasm, followed by definitive surgical clipping, if the aneurysm cannot be completely obliterated. Endovascular treatment of intracranial aneurysms is evolving rapidly, and the proportion of patients with intracranial aneurysms who are best treated with endovascular coiling, alone or in combination with surgery, remains to be determined.

I am indebted to Drs. Michael J. Link, Douglas A. Nichols, and David G. Piepgras for their critical reading of the manuscript and to Mr. David A. Factor for the drawing in Figure 1.

REFERENCES
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