Microsurgery for Unruptured Intracranial Aneurysms

10.1055/b-0034-80444

Microsurgery for Unruptured Intracranial Aneurysms

Ducruet, Andrew F., Meyers, Philip M., Solomon, Robert A.

Pearls

With rare exceptions, all symptomatic unruptured aneurysms should be treated.
Small, incidental aneurysms <5 mm should be managed conservatively in most cases.
Patients <60 years of age with aneurysms ≥5 mm should be offered treatment unless there is a significant contraindication.
Large, incidental aneurysms >10 mm should treated in all healthy patients <70 years of age.
Microsurgical clipping rather than endovascular coiling should be the first choice in low-risk cases (young patients with small, anterior circulation aneurysms).

The management of unruptured intracranial aneurysms (UIAs) remains one of the most controversial topics in neurosurgery. Multiple efforts have been undertaken both to determine the natural history of this condition and to define the risks of UIA surgery as related to patient age, aneurysm size, and location.1 ^– 3 Based on our interpretation of the literature and our experience treating patients with cerebral aneurysms, in this chapter we present a management algorithm for patients presenting with UIA. These recommendations are based on careful patient selection and the integration of the latest microsurgical and endovascular techniques. We employ a working collaboration of an experienced team of microvascular and endovascular neurosurgeons at a tertiary medical center with high case volume, as well as a decision-making paradigm committed to offering only low-risk treatments. In certain cases where both treatment and natural history carry a high risk, such as with complex giant aneurysms in an older patient, conservative management is elected.

♦ Epidemiology and Natural History

Intracranial aneurysms (IAs) are common lesions, occurring in 1 to 6% of the population and affecting equal numbers of women and men younger than 40 years, whereas women are affected more frequently in older age groups.4 IAs are believed to result from intrinsic aberrations of the cerebral vasculature in which the integrity of the internal elastic lamina is compromised, engendering muscular defects in the adjacent layers of the tunica media and adventitia that augment the pathologic effects of chronic hemodynamic stress on the arterial wall. The tendency toward development of IAs is likely partly genetic, as multiple inherited conditions are associated with a diagnosis of IAs, including autosomal-dominant polycystic kidney disease, fibromuscular dysplasia, Marfan syndrome, and Ehlers-Danlos syndrome type IV.5 A familial inheritance pattern, however, has been noted in only approximately 2% of IA.5 Therefore, it is likely that a multifactorial etiology exists, reflecting the interaction of environmental factors, such as cigarette smoking, atherosclerosis, or hypertension, overlying a congenital predisposition.

Unruptured intracranial aneurysms are typically discovered incidentally, as the majority of these lesions are asymptomatic prior to rupture. However, neurologic symptoms, either acute or chronic, may spur diagnosis, particularly in the case of larger aneurysms and those undergoing acute expansion. Acute neurologic symptoms referable to UIA include ischemia, headache, seizures, and cranial neuropathies. Chronic neurologic symptoms such as headache, visual deficits, weakness, and facial pain may also occur. Regardless of symptomatology, the vast majority of UIAs are identified through noninvasive computed tomography (CT), magnetic resonance imaging (MRI), CT angiography, and MR angiography. However, as digital subtraction angiography (DSA) affords better visualization of aneurysm and parent vessel geometry, as well as the subtle anatomic relationships of the perforators, DSA remains the gold standard for definitive diagnosis and is often preferred in planning an elective operation for an UIA.

The annual risk of rupture of a UIA has been estimated to range from 0.1 to 8% or higher and is the subject of significant controversy. The publication of retrospective results from the International Study of Unruptured Intracranial Aneurysms (ISUIA), purporting a dramatically low risk of acute subarachnoid hemorrhage (aSAH) from aneurysms <10 mm, engendered a debate favoring observation for the vast majority of small UIAs.6 However, several key investigations, including the subsequent prospective ISUIA,6 the study by Juvela et al7 with 18-year follow-up, and the comprehensive metaanalysis by Rinkel and colleagues,2 suggest a higher rate of hemorrhage. These studies warrant careful review to help establish the natural history of UIA (Table 20.1).

**Table 20.1** Summary of Natural History Studies of Unruptured Intracranial Aneurysm
Authors (Year)	Number of Patients	Number of Aneurysms	Mean Follow-Up (years)	Rate of Rupture
ISUIA Investigators (1998)	1449	1937	8.3	Group 1: <10 mm: 0.05%/yr ≥10 mm: 1%/yr
				Group 2: <10 mm: 0.5%/yr ≥10 mm: 1%/yr
Rinkel et al (1998)	3907	N/A	N/A	Overall: 1.9%/yr <10 mm: 0.7%/yr >10 mm: 4%/yr
Juvela et al (2001)	142	181	18.1	10.5% at 10 yrs 23% at 20 yrs 30.3% at 30 yrs
Wiebers et al (2003)	1692	2686	4.1	Group 1: <7 mm: 0%/yr 7–12 mm: 2.6%/yr 13–24 mm: 14.5%/yr ≥25 mm: 40%/yr
				Group 2: <7 mm: 2.5%/yr 7–12 mm: 14.5%/yr 13–24 mm: 18.4%/yr ≥25 mm: 50%/yr
Abbreviations: N/A, not available.

The ISUIA is an ongoing collaboration of major neurosurgical centers attempting to delineate the natural history and interventional outcomes for UIA. The first of the two landmark papers arising from this study assessed the natural history of UIA in a retrospective fashion.6 These patients were divided into two groups: 727 who had no history of aSAH (group 1), and 722 who had a history of aSAH from a different lesion (group 2). The rupture rates for UIA in these cohorts were drastically lower than in the previous estimates (Table 20.1). The authors found that increasing size and location (posterior circulation and posterior communicating artery [PCoA]) were significantly associated with rupture for group 1, whereas location (basilar tip) and increasing age were predictive of rupture for group 2. Although this study evaluated a large number of aneurysms across several centers, it has several serious design flaws and has since been discredited by the authors themselves.8 The cohort of patients comprising this retrospective evaluation was subjected to a very significant selection bias, as all patients had already been evaluated for surgery and selected for observation. As a result, it is likely that the majority of the patients harbored extremely low-risk aneurysms due to location (cavernous carotid aneurysms were identified in groups 1 and 2 at rates of 16.9% and 9.5%, respectively) or size (in groups 1 and 2, aneurysms of 2 to 5 mm were identified in 32.7% and 61.2% of patients, respectively). In addition, it is likely that the patients were medically ill, with increased deaths due to causes other than aSAH. Moreover, patients whose lesions were originally selected for conservative management may have crossed over to surgical treatment due to new symptoms. This crossover would remove patients who were imminently at risk for aSAH, lowering the observed rupture rate.

The second ISUIA study8 was a prospective evaluation of the natural history of UIA. In this analysis, there were 1077 patients in group 1 and 615 patients in group 2 as previously defined. The total risk of rupture for patients in both groups 1 and 2 was calculated excluding those with aneurysms in the cavernous internal carotid artery (ICA) (Table 20.1). This prospective ISUIA also contained selection bias; for example, of the 1692 patients, 534 crossed to a therapeutic intervention and were removed from follow-up. In a significant portion of these crossover patients, the management strategy was likely changed because of either an increase in aneurysm size or the development of new symptoms. As well, 193 patients (11%) died of causes other than aSAH; these patients were excluded. It is also troubling that 52 of these patients died of intracranial hemorrhage, and it is not clear whether there was adequate evaluation to ensure that these hemorrhages were not due to aneurysms. In short, some caution is indicated when extrapolating these data to the population at large.

Rinkel et al2 published an invaluable analysis of the natural history of UIA through a thorough review of the literature published between 1955 and 1996. To estimate the prevalence of UIA, data were summed from 23 studies that evaluated 56,304 patients. The overall prevalence of these lesions in adults with no known risk factors was 2.3%. For analysis of the bleeding rate of UIA, the authors identified nine studies including 3907 patients (Table 20.1). The large number of patients analyzed makes this study an important investigation into the natural history of UIA. Additionally, these results are strengthened by the fact that their estimates of the prevalence of and incidence of bleeding in UIA corroborate very closely with the known incidence of aSAH.

Juvela and colleagues7 provide a comprehensive observational study that lacks the inherent bias of surgical selection found in ISUIA, as they examined all patients with UIA seen at their institution over a given time period. This study was possible because it was department policy to manage all UIA conservatively prior to 1979. In addition, Finland’s sociomedical structure facilitated 100% follow-up to record the outcome over a longer period of time than in any other study. The cumulative rupture of aSAH is depicted in Table 20.1 . Aneurysm size and patient age (inversely) were significant predictors of aSAH, as was active cigarette smoking. Major flaws in this study were the small total number and ethnic homogeneity of the patients and the overwhelming proportion (92%) of patients with prior aSAH. Despite these major flaws, the lack of a surgical selection bias and the outstanding long-term follow-up make this a valuable contribution to our understanding of the bleeding rates for UIA.

When interpreting the literature reporting the natural history of UIA, there are several factors to consider. For example, studies tend to break down aneurysms into size categories. It is unlikely that such a cutoff will result in substantially different rupture rates. In actuality, the risk of bleeding most likely reflects a nonlinear continuum of increasing risk with greater aneurysm size. Additionally, it is important to realize that aneurysms are likely not static in size. For instance, Juvela et al1 ^, 7 ^, 9 found that in 31 of 87 (36%) patients, the size of conservatively managed aneurysms increased by >3 mm over a mean follow-up of 18.9 years. The relative effect of aneurysm growth on our ability to estimate hemorrhage risk is unknown, but it would be reasonable to assume that a growing aneurysm has an increased risk of rupture. Also, any estimation of rupture risk must take into account the aneurysm location. For instance, the results of the ISUIA demonstrate that aneurysms of the posterior communicating artery (PCoA) and posterior circulation display a much higher risk of rupture than those of the middle cerebral artery (MCA) and ICA. The literature indicates that posterior circulation, PCoA, and anterior communicating artery (ACoA) aneurysms carry the highest risk of subarachnoid hemorrhage (SAH), whereas aneurysms of the cavernous ICA carry an extremely low risk.6 ^, 8

Despite conflicting data in the literature, we recommend that the natural history of a given UIA should be assessed in each individual case. For instance, family history, smoking, excessive alcohol consumption, female sex, previous aSAH, presence of symptoms attributable to the lesion, aneurysm location, and lesion size have all predicted a worse natural history.9 ^, 10 Any risk/benefit analysis of intervention must take into account the patient’s life expectancy and medical comorbidities. Despite these concerns, it is helpful to have a general algorithm for predicting rupture risk that may then be adjusted depending on risk factors. Our general estimate for the yearly risk of SAH for an UIA is approximately 1% for lesions 7 to 10 mm in diameter. The risk of rupture grows logarithmically as aneurysm size increases.

♦ Indications for Treatment

When determining a management paradigm for an UIA, one must weigh the natural history of the condition against the risks of intervention. Although there are no strict guidelines, certain factors may represent indications for treatment of UIA. Although 7 mm is the average size of ruptured aneurysms, and smaller aneurysms may exhibit a lower risk of rupture, we generally advocate treatment for aneurysms ≥5 mm in diameter. This criterion ensures that 99% of patients with aneurysms that should be treated will be offered treatment. In addition to size, any neurologic symptoms attributable to an aneurysm are generally considered a strong indication for surgery. Depending on the exact symptoms, many surgeons would favor urgent rather than elective treatment.

Additionally, it is our experience that there is a phenomenon of excessive psychological stress in patients with UIA. Even when patients fall into a subgroup of minimal treatment benefit and are appropriately counseled, they often insist on treatment. Although rigorous studies of this issue have yet to be performed, it appears that the psychological stress associated with having a UIA is enough to compel a patient to forgo the recommended conservative management for the peace of mind of treatment. These patients may be borderline candidates, and such strong feelings on the patients’ part indicating quality-of-life issues may tilt the risk/benefit analysis toward intervention.

♦ Techniques of Treatment

Microsurgical Clipping

Microsurgical clipping remains the gold standard for exclusion of UIA from the circulation. It is our opinion that patients younger than 60 years of age with non-giant, anterior circulation aneurysms should be offered microsurgical clipping as the first-line treatment (Fig. 20.1). This contention is supported by several large published series that report high rates of total aneurysm obliteration and low rates of recurrence.11 ^, 12 Furthermore, it is well accepted that successful surgical clipping translates into long-standing aneurysm obliteration and low subsequent rates of aSAH from a treated lesion.

The success of microsurgery is also measured in terms of the surgical outcome, which has been independently associated with patient age, aneurysm size, and location. Surgical outcomes are favorable for small, anterior circulation aneurysms in young patients. For example, in our prior series of 202 consecutive cases, we observed a 50% morbidity and mortality after surgery in unruptured giant basilar aneurysms compared with a 13% rate in giant anterior circulation aneurysms.3 Our morbidity and mortality was 0% for aneurysms less than 10 mm, 6% for aneurysms between 10 and 25 mm, and 20% for aneurysms >25 mm. By comparison, Drake13 reported a 15% morbidity and mortality rate in nongiant posterior circulation aneurysms compared with 39% for giant posterior circulation lesions. He also reported a 14.3% rate of morbidity and mortality after surgical treatment of asymptomatic UIA in the posterior circulation, relative to 0% morbidity in the anterior circulation. By comparison, the more recent ISUIA reports a relative risk of 2.6 for poor outcome for aneurysms larger than 12 mm in diameter, and an increase of 2.4 in relative risk was observed in patients older than 50 years of age.8 Surgical risk factors have thus been identified, which might suggest alternative methods of aneurysm treatment in specific populations.