Surgical and Endovascular Treatments for Intracranial Aneurysms

Bradley A. Gross, BS Ziad A. Hage, MD Marc Daou Christopher C. Getch, MD H. Hunt Batjer, MD Bernard R. Bendok, MD
Corresponding author Bernard R. Bendok, MD Department of Neurological Surgery and Radiology, The Feinberg School of Medicine, Northwestern University, 676 North St. Clair Street, Suite 2210, Chicago, IL 60611, USA. E-mail: bbendok@nmff.org Current Treatment Options in Cardiovascular Medicine 2008, 10:241252 Current Medicine Group LLC ISSN 1092-8464 Copyright 2008 by Current Medicine Group LLC

Opinion statement
The goals of microsurgical and endovascular treatment of intracranial aneurysms are to prevent subarachnoid hemorrhage and/or eliminate mass effect symptoms. Debate has raged regarding which aneurysms to treat and with which technique or combination of techniques. It is our impression that studies that have assessed aneurysm natural history and treatment options are compromised by the inherent limitations of clinical trials, with many natural history studies likely underestimating rupture risk over long-term follow-up. Endovascular therapy and open neurosurgery should both be used strategically, and our current interest is in integrating these techniques in a fashion extending beyond the simplistic clip-versus-coil debate.

Introduction
Intracranial aneurysms are relatively common, with prevalences ranging from 2% to 6% [1,2]. Their etiology is multifactorial, including congenital medial arterial wall defects, degenerative changes, and accruing hemodynamic stress, particularly at sites of turbulent blood flow. Risk factors for aneurysm formation include a family history of aneurysms, smoking, female sex, intracranial arteriovenous malformations, autosomal dominant polycystic kidney disease, type IV Ehlers-Danlos syndrome, hypertension, and hypercholesterolemia [24]. With the increased availability and cultivation of noninvasive imaging, the frequency of their incidental discovery has risen. Given the 45% mortality rate of aneurysmal subarachnoid hemorrhage (SAH) with 30% of survivors suffering moderate to severe disability [5], appropriate management lies among the most important tasks faced by neurosurgeons today.

TO TREAT OR NOT TO TREAT UNRUPTURED, ASYMPTOMATIC ANEURYSMS

Risk of rupture, patient longevity and feasibility, and risk of treatment are the primary determinants when deciding whether intervention is warranted. Quantification of these four parameters remains imprecise. Unfortunately most available data concerning hemorrhage risk consider only size as a risk factor. Undoubtedly numerous other structural, biological, and environmental forces are at work for the individual patient. Although symptomatic aneurysms should be treated, Table 1 delineates potential risk factors for rupture that we use in our decision analysis for treatment of unruptured, asymptomatic aneurysms [24,6]. Young patients are good candidates for treatment because they have greater tolerance of and derive greater benefit from intervention. Patients over age 70 are generally observed unless a facile endovascular treatment

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Table 1. Factors that increase aneurysm rupture rates of unruptured, asymptomatic aneurysms promote treatment, whereas those associated with low rupture rates or poor treatment efcacy promote observation
Factor Age, y Patient condition/characteristics Favors observation > 70 Limited life expectancy Moribund Multiple comorbidities Favors treatment < 50 Family history of aneurysmal SAH Hx of aneurysmal SAH Smoker Hx of HTN +/- Japanese or Finnish heritage Aneurysm location Small asymptomatic intracavernous PComm AComm Posterior circulation Aneurysm morphology Aneurysm size < 3 mm Daugter sac Irregular morphology > 3 mm or enlarging
ACommanterior communicating artery; HTNhypertension; Hxhistory; PCommposterior communicating artery; SAHsubarachnoid hemorrhage.

Table 2. ISUIA annual rupture rates by aneurysm size and location

Location Cavernous ICA Anterior circulation* PComm and posterior circulation < 7 mm < 7 mm (group 1), % (group 2), % 0 0 0.5 0 0.3 0.7 712 mm 1324 mm (both groups), % (both groups), % 0 0.5 2.9 0.6 2.9 3.7 25 mm (both groups), % 1.3 8.0 10.0

*Excluding cavernous ICA and PComm aneurysms. ICAinternal carotid artery; ISUIAInternational Study of Unruptured Intracranial Aneurysms; PCommposterior communicating artery.

is feasible, the lesion is considerably large or has irregular morphology, or the aneurysm is in the posterior circulation. Anterior communicating artery location, in particular, encourages treatment, even at smaller lesion sizes (eg, 6 mm) and particularly in the setting of unilateral internal carotid artery occlusion, given increased rupture rates reported at this location [7]. The International Study of Unruptured Intracranial Aneurysms (ISUIA) was a nonrandomized, observational study [8,9] demonstrating that increasing aneurysm size and posterior circulation or posterior communicating artery location are significant risk factors for aneurysm rupture. In its initial retrospective component, 727 patients with no SAH history (group 1) and 722 patients with a history of SAH from a separate aneurysm (group 2) were followed for a mean of 8.3 years [8]. An annual rupture rate of 0.05% per year was cited for aneurysms less than 10 mm in group 1, increasing to 1% if greater than 10 mm. For group 2, these rates were 0.5% and 1%, respectively. The prospective arm of ISUIA allocated 1077 patients to group 1 and 615 patients to group 2, with a mean followup of 4.1 years [9]. Annual rupture rates for given aneurysm sizes and location are summarized in Table 2. In addition to increasing aneurysm size, following multivariate analysis with internal carotid artery aneu-

rysms as a reference, basilar tip location (relative risk [RR], 2.3; 95% CI, 1.14.8), cavernous carotid location (RR, 0.15; 95% CI, 0.040.64), and posterior communicating artery location (RR, 2.1; 95% CI, 1.14.2) were found to be statistically significant predictors of aneurysm rupture. Although anterior communicating artery location was not associated with increased hemorrhage rates, 65% of aneurysms at this location were treated, explaining their unexpectedly low prevalence in the observed group. Thus, the anterior circulation rupture risk cited in this study may not be applicable to these lesions. In fact, a recent meta-analysis demonstrated an overall 2.2% annual risk of rupture for anterior communicating artery aneurysms [7]. Furthermore, they were shown to rupture at sizes smaller than those of their other intracranial counterparts. ISUIA was not randomized. Patients were selected out for treatment before and during observation; 534 patients crossed over for treatment, likely because of changes in aneurysm size or morphology or the development of mass effect symptoms, representing significant selection bias. Aneurysm enlargement and unusual morphology are two of the strongest predictors of subsequent hemorrhage [10]. Not only were these factors left unaccounted for in ISUIA, they also

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Figure 1. Digital subtraction angiography demonstrating 3-mm anterior communicating artery aneurysms in two patients (A and B). The rst patient (A), with no medical or family history of subarachnoid hemorrhage (SAH), presented to our institution as a Hunt-Hess grade 4 after rupture (C). Three weeks later, another patient (B), also with no medical or family history of SAH, presented to our institution as a Hunt-Hess grade 4 following rupture of his aneurysm (D).

make the linear rupture rates, proposed by ISUIA because of limited follow-up, tenuous at best. Juvela et al. [4] demonstrated that 45% of aneurysms grew 1 mm or more and 36% of aneurysms grew at least 3 mm over a mean follow-up period of 18.9 years. ISUIA also did not account for family history or smoking history, factors known to increase rupture risk, the former at smaller sizes and earlier age [3,11]. In addition to the fact that the average aneurysm size at rupture is 7.5 mm, given that the observed annual incidence of SAH is 30 to 40 per 100,000 people, one can predict an overall aneurysm rupture rate of at least 1% per year, underscoring that the rates proposed by ISUIA are likely underestimates [10]. These unexpectedly low rates, particularly the original 0.05% annual rate for aneurysms less than 10 mm, underscore the fact that neurosurgeons are selecting out higher-risk lesions for

treatment. This was reflected by, for example, the high prevalence of observed cavernous carotid and relative paucity of observed anterior communicating artery aneurysms in ISUIA. In contrast to ISUIA, Juvela et al. [12] observed all patients with unruptured intracranial aneurysms (181) seen at their institution without surgical/interventional selection bias over a mean of 18.1 years. The annual rupture rate was 2.6% in symptomatic patients, 1.3% in patients with prior SAH, and 1% in those with incidental aneurysms. In a review of the literature from 1955 to 1996, Rinkel et al. [1] found an overall annual risk of rupture of 0.7% for unruptured aneurysms less than 10 mm and 4% for those greater than 10 mm. Clearly, however, there is a continuum of rupture risk with varying lesion sizes and no dome diameter below which the risk of rupture disappears (Fig. 1).

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Table 3. A comparison of factors that favor surgical and endovascular management of intracranial aneurysms
Factor Patient age, y Patient condition Favors surgery < 60 Healthy Mass effect from aneurysm Unreliable for follow-up Aneurysm location PComm MCA Distal ACA PICA Basilar apex, young patient Basilar apex, ant. projecting Basilar apex, incorporating PCA Basilar trunk, young patient Tortuosity/severe atherosclerosis of access vessels Aneurysm characteristics Large or giant size Intraluminal thrombus Wide neck Parent/branch artery in neck/wall Other factors IPH, particularly if mass effect Calcication at neck Multiple remote aneurysms Fusiform Dissecting Petrous or cavernous ICA SHA, older patient Carotid cave, older patient AComm, post. projecting Basilar apex, older patient Basilar apex, sup. projecting Favors endovascular treatment > 60 High HH grade*, swollen brain Multiple comorbidities

*Unless high HH grade is the result of a hematoma. ACAanterior cerebral artery; ACommanterior communicating artery; ant.anterior; HHHunt-Hess; ICAinternal carotid artery; IPHintraparenchymal hematoma; MCAmiddle cerebral artery; PCAposterior cerebral artery; PCommposterior communicating artery; PICAposteroinferior cerebellar artery; post.posteriorly; SHAsuperior hypophyseal artery; sup.superiorly.

Treatment
Surgical and endovascular management
The ultimate goal of treatment is complete, immediate, and permanent occlusion of the aneurysm while preserving blood flow in the parent artery and adjacent branching and perforating vessels. When parent artery preservation is not feasible, cerebrovascular reserve testing via balloon test occlusion and possible bypass may be necessary. Table 3 compares features favoring surgical clipping to those encouraging endovascular coiling, the two most common treatment modalities. A crucial issue in the choice of therapy is one of access. For example, proximal internal carotid artery aneurysms are relatively more accessible endovascularly, whereas distal anterior cerebral artery and posteroinferior cerebellar artery (PICA) aneurysms are more easily accessible with open surgery. Surgical clipping of directly superiorly oriented basilar apex aneurysms and posteriorly oriented anterior communicating artery aneurysms may cause significant morbidity from brain retraction and perforator injury, making endovascular coiling an attractive choice for older patients as durability is less of an issue. Although surgery is intuitively more desirable for patients with an intraparenchymal hematoma or with aneurysm mass effect, factors such as calcification at the aneurysm neck may complicate clipping. Endovascular therapy obviates the need for multiple craniotomies in cases of multiple remote aneurysms; however, wide aneurysm necks or incorporation of parent or branching arteries into the neck or wall of the aneurysm, both more commonly seen with middle cerebral artery and/or larger aneurysms, favor surgical management, particularly in younger patients.

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The International Subarachnoid Aneurysm Trial (ISAT) was a multicenter, prospective, randomized trial of neurosurgical clipping compared with endovascular coiling of ruptured aneurysms subjectively deemed amenable to either treatment [13]. This study randomly assigned 2143 of 9559 (22.4%) aneurysmal SAH patients at participating centers to either procedure. The patients were primarily in good clinical grade (88%) with anterior circulation aneurysms (97%) less than 10 mm (93%). Microsurgical clipping was completed in 96.4% of attempts, whereas endovascular coiling was completed in 92.5%. The primary outcome, death or dependence at 1 year, was found in 30.9% of patients allocated to neurosurgery compared with 23.5% who underwent endovascular coil embolization. Notably, 28 patients allocated to neurosurgery died before the intervention, resulting in 19 deaths, whereas 17 patients allocated to coiling had rebleeding before intervention, resulting in seven deaths. Complete aneurysm occlusion rates were 82% and 66% for microsurgery and coiling, respectively. Retreatment was performed in 17.4% of patients (9% early, 9% late) after coiling and in 3.8% patients (2.9% early, 0.9% late) who underwent clipping (hazard ratio, 6.9; 95% CI, 3.414.1) [14]. Early retreatment denoted incomplete or failed primary treatment, whereas late treatment denoted rebleeding, reopening, or regrowth of the aneurysm. Younger age, large lumen size, posterior communicating artery location, and incomplete occlusion were significant risk factors for late retreatment after coiling. Including crossovers, 36 patients who underwent coiling (18 deaths) and 12 who underwent clipping (6 deaths) had rebleeding in the first year, and eight patients who underwent coiling and one who underwent clipping had rebleeding after the first year at most recent follow-up [14]. The retreatment and rebleeding rates seen in ISATlow albeit more common in the coil embolization grouphave been supported by the literature. In the Cerebral Aneurysm Rerupture After Treatment (CARAT) study, significantly more rebleeding episodes in the first year were seen after coil embolization (3%) than after clipping (1.3%; P = 0.04) [15]. The primary outcome measure, bleeding after 1 year of treatment, was seen in one patient treated with coiling (0.6%) and none treated with clipping. In addition, significantly more patients in the embolization group (13.3% vs 2.6%, P < 0.0001) required additional treatment in the first year. No clipped aneurysm was re-treated after the first year, whereas retreatment rates were 7.7% in the first year, 4.5% in the second year, and 1.1% in subsequent years after coiling (P < 0.0001 for each year). Given these results, it remains clear that close imaging follow-up is essential in patients who have undergone coiling. However, the primary outcome measure of ISAT, particularly the outcomes for surgically managed patients, is inconsistent with the published literature. In fact, significant differences in outcome are apparent only for patients with modified Rankin scale (mRS) scores of 0 and 3 to 6; there is no significant difference for any other individual mRS score or for combined scores for the treatment modalities [16]. Operator experience was not controlled for, and the overwhelming bias for endovascularly treating posterior circulation aneurysms underscores the relative skill of the surgeons involved. Raftopoulos et al. [17] reported a mere 1.7% permanent surgical morbidity rate (93% obliteration rate) associated with the treatment of unruptured aneurysms in the anterior circulation and a 7.5% permanent morbidity rate (56% obliteration rate) associated with coiling. Incomplete microsurgical obliteration rates, intraoperative rupture rates (20%), postsurgical rebleeding rates, and morbidity and mortality for good grade patients with small,

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Cerebrovascular Disease and Stroke anterior circulation aneurysms were unrealistically high in the ISAT surgical group, inconsistent with contemporary North American cerebrovascular center results. One single-center prospective randomized control study of coiling versus clipping found no significant difference in 1-year clinical Glasgow Outcome Scale and neuropsychological outcomes in 109 patients [18]. This was generally consistent with the only other prospective trial comparing cognitive outcomes, which in fact demonstrated superior performance on tests of intellectual function following clipping at 6-month follow-up [19]. The incidence of vasospasm also did not significantly differ between the two groups, consistent with a recent review [20]. Again, obliteration rates were superior for the group treated with clipping. Indeed, in a review of the literature of aneurysm recurrence after surgical clipping and endovascular treatment, Lawton et al. [21] found that of 1002 surgically treated aneurysms, the complete obliteration rate was 95.4% and recurrence occurred in 0.6% of cases over a mean period of 12.6 years. Of 1016 endovascularly managed aneurysms, complete obliteration was achieved in 58.3% of cases, with 12.9% subsequent recurrence (time to recurrence could not be averaged).

Microsurgery
The ultimate goal of microsurgery is exclusion of the aneurysm from the circulation, ideally by placing a clip across its neck with preservation of the parent artery and adjacent branching and perforator arteries. The primary advantage of this approach is the proven long-term durability of the procedure and excellent rates of initial complete occlusion. In a detailed review of the literature from 1979 to 1999, complete angiographic obliteration after clipping was seen in 94.8% of aneurysms [22]. In one long-term angiographic follow-up review of microsurgically treated aneurysms, 1.5% recurred after successful clip occlusion [23], and another retrospective review of 105 successfully clipped aneurysms observed for a median of 8.8 years demonstrated SAH in only one case after 11 years [24]. Thus, in equipoise, we prefer surgical clip application, particularly in younger patients, given the aforementioned ultimate goal of aneurysm treatment. Decision making for posterior circulation aneurysms is more complex. Just as posterior circulation location is a risk factor for increased surgical morbidity, it similarly may affect endovascular outcomes [9]. The posterior circulation should also not be viewed as a homogeneous entity stereotyped by challenging surgical access. As mentioned earlier, access to PICA aneurysms may be relatively simple surgically whereas other posterior circulation aneurysms may be more easily accessed endovascularly. In 303 cases of surgically managed basilar tip aneurysms (94% complete obliteration), good outcome was achieved in 81% after 6 months and no rebleeding was reported on follow-up [25]. This study included all comers: ruptured, unruptured, all sizes, and all grades. We recently published our extended lateral transsylvian approach for these lesions that can be used in most cases with the exception of directly posteriorly projecting or very low-lying aneurysms, which require subtemporal exposure if surgery is entertained [26]. In the experience of our senior authors, directly anterior-projecting basilar apex aneurysms are the easiest to manage surgically because they are not encumbered by perforators, whereas posteriorly oriented aneurysms are often inferior to these vessels and rank second in difficulty. Directly superiorly projecting basilar apex aneurysms are encumbered by perforators posteriorly and at the contralateral neck and by the need to

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Figure 2. Endovascular management of intracranial aneurysm. A 69-year-old woman with an incidentally discovered, unruptured 7-mm basilar apex aneurysm (A) underwent successful coil embolization (B), affording complete angiographic occlusion of the lesion (C).

mobilize the aneurysm out of the interpeduncular fossa for safe management. Temporary occlusion is required and trapping with deflation is often needed. Challenges of microsurgery include appropriate visualization and preservation of adjacent perforating arteries and avoidance of brain retraction. Factors shown to adversely affect surgical outcome include increasing aneurysm size, location in the posterior circulation in certain series, and increased age [9]. In a meta-analysis of 28 articles published between 1966 and 1992 with data on 733 patients treated surgically for asymptomatic, unruptured aneurysms, overall surgical morbidity and mortality rates were found to be 4.1% and 1%, respectively [27]. This study did, however, have a relatively small number of giant, complex lesions and basilar aneurysms. Another meta-analysis of surgically treated unruptured aneurysms included 2460 patients and at least 2568 unruptured aneurysms (27% > 25 mm and 30% in the posterior circulation). Permanent morbidity was found in 10.9% of patients; the overall mortality rate was 2.6% [28]. These rates dwindled to 1.9% morbidity and 0.8% mortality for small anterior circulation aneurysms and increased to 37.9% morbidity and 9.6% mortality for large and giant aneurysms of the posterior circulation. Although these reviews amalgamate reports of unruptured aneurysms, the relatively low morbidity and mortality seen across multiple series spanning several decades help explain the critical eye that many experienced cerebrovascular neurosurgeons cast on the outcomes in ISAT [13].

Endovascular therapy
Endovascular management entails aneurysm embolization with platinum coils, excluding it from the circulation (Fig. 2) [29]. Obviating the need for a craniotomy is advantageous in high-grade SAH patients, the elderly, or individuals with multiple comorbidities. This approach may also afford access to locations that would require challenging skull base approaches, and it has essentially become the standard for intracavernous aneurysms

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Cerebrovascular Disease and Stroke and many superior hypophyseal, carotid cave, and superiorly oriented basilar tip aneurysms. Highly dependent on endovascular accessibility and aneurysm neck and dome size, coil embolization has not achieved complete aneurysm obliteration levels comparable to those of surgery. The neck is not always addressed and endothelialization is often incomplete. Incorporation of the parent artery into the neck or dome generally necessitates at least one surgical element for treatment. In addition to potential short-term thromboembolic complications, long-term durability is hindered by the potential for aneurysm recanalization, particularly for aneurysms greater than 10 mm, for neck sizes greater than 4 mm, and following treatment during the acute phase of aneurysm rupture [30]. Partial thrombosis is associated with a high rate of recurrence because the coils may be driven into the thrombus by blood flow. In addition, it is not necessarily clear that coiled unruptured aneurysms have improved natural histories compared with their untreated, unruptured counterparts. Weakening of the aneurysm wall may occur as a result of an inflammatory response to the coils, a theoretical process supported by the oft-cited finding of coil extrusion into the subarachnoid space at surgical exploration [31]. These extruded coils often adhere to adjacent structures such as the parent artery and local perforators, making reoperation after coiling more challenging than an initial clipping, supporting surgical clipping in equipoise. Coil incorporation into the neck tissue can make clipping itself all but impossible without coil removal, which in itself carries significant risks from temporary trapping as well as from the removal itself. Thus young patients, those with partially thrombosed aneurysms, or those with unreliable follow-up may derive better long-term benefit from surgical clipping. Age has not been shown to increase endovascular morbidity, but increasing aneurysm size, wide neck, and posterior circulation location adversely affect outcomes [9]. Murayama et al. [32] reported their institutions 11-year overall endovascular morbidity and mortality rate of 9.4% for 916 unruptured aneurysms. Complete occlusion was achieved in 55%. The overall recanalization rate was 20.9% and the incidence of delayed aneurysm rupture was 1.6%. Large and giant aneurysms had recanalization rates of 35.3% and 59.1%, respectively. Another large study of 1811 endovascularly treated aneurysms noted a 65.8% complete occlusion rate and a 6.8% combined morbidity and mortality rate [33]. A similar study of 501 aneurysms treated over 10 years reported a 33.6% recurrence rate (21.3% for small and 50.6% for large aneurysms) with a 0.8% rebleeding rate [30]. To facilitate coiling of wider-necked aneurysms, balloon remodeling or stent-assisted coiling techniques have been cultivated. In balloon-assisted coil embolization, a balloon spanning the aneurysm neck is inflated during coil placement, tucking the coils into the aneurysm and preventing prolapse. Disadvantages to this approach include an increased risk of thromboembolic complications, potential distal flow compromise, and the fact that coils may prolapse after the balloon is removed or deflated. Stent deployment across the neck of the aneurysm is a permanent approach to prevent coil protrusion into the parent artery. Distal flow is preserved, and the incidence of aneurysm recurrence may decrease owing to redirected flow and facilitated endothelialization at the aneurysm neck. In the senior authors experience, the emergence and use of the Enterprise (Cordis Neurovascular, Miami Lakes, FL) and Neuroform (Smart Therapeutics, San Leandro, CA) stents have particularly increased feasibility, decreased recurrence rates, and improved the initial angiographic results and outcomes for endovascularly managed patients. We recently demonstrated

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in vitro that packing density and effective neck coverage significantly increased whereas the likelihood of dome remnants and coil prolapse significantly decreased when stenting was employed with aneurysm coiling [34]. Limitations to this approach include the possibility of in-stent stenosis, thromboembolism, the possibility of intraprocedural stent movement, and the continued need to use antiplatelet agents post intervention.

Combined surgery and endovascular management

In addition to the feasibility of endovascular coiling for obliteration of remnants after clipping or after intentionally surgically fashioning a wide-necked complex aneurysm into a narrow-necked lesion [35], endovascular and surgical techniques may be used simultaneously. Adjunctive endovascular retrograde suction decompression for surgical treatment of large or giant paraclinoid internal carotid artery aneurysms provides proximal control and facilitates aneurysm neck exposure [3638]. We have recently revised this approach using a 7F concentric balloon-containing guide catheter for retrograde suction following balloon inflation and application of a temporary clip distal to the aneurysm [38]. Besides the greater blood volumes that can be aspirated via the larger guide catheter, this approach also allows endovascular access for proximal hunterian coil occlusion or temporary balloon occlusion across the neck of the aneurysm, if needed. A superior illustration of the combined approach is the emerging paradigm for managing giant, complex, and some blisterlike aneurysms lesions with considerably malignant natural histories. In his extensive experience managing giant aneurysms, Drake [39] noted that 80% of patients left untreated were dead at 5 years. Also, 62% of giant aneurysms in his series were not amenable to clip reconstruction, underscoring their proclivity toward unfavorable neck morphology. Thus, a hunterian strategy of proximal clip occlusion or endovascular coiling of the parent artery is often used after attempts at direct clipping fail, prompting the need for preoperative cerebrovascular reserve testing. At our institution, we typically use revascularization only when evidence of cerebral ischemia due to hypoperfusion is evident, assessed via balloon test occlusion with examination of collateral circulation and added provocative testing (hypotension), electroencephalographic monitoring, and radionuclide single photon emission CT imaging [40]. Looking forward, the major cerebrovascular centers will see a higher volume of highly complex vascular lesions requiring combined techniques. Contemporary operating rooms are poorly equipped for advanced image processing and complex endovascular procedures, and contemporary interventional suites are poorly equipped for general anesthetic techniques and open surgical procedures. The ultimate marriage of endovascular and microvascular surgery will need to be accomplished in hybrid operating suites with biplanar imaging, advanced image post processing, surgical navigation, intraoperative MRI, and sufficient size for two surgical teams and all the aforementioned technology.

Emerging techniques
Endovascular
Advances in coil technology, liquid embolics, flow diverters, and parent artery reconstruction devices may ultimately help overcome the primary endovascular shortcomings of incomplete obliteration and recanalization.

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Cerebrovascular Disease and Stroke Matrix detachable coils (MDCs) are coated with a bioabsorbable polymer thought to accelerate thrombosis and facilitate intra-aneurysmal fibrosis, potentially enhancing occlusion durability. Unfortunately, in a prospective study of 131 primarily small-sized, small-necked aneurysms embolized with MDCs, 36.6% of 82 lesions seen at follow-up had undergone recanalization, stratified into recanalization rates of 26.1% for small lesions and 75% for large aneurysms [41]. Hydrogel-coated coils are covered by a hydrophilic polymer that expands after contact with blood and have the potential advantage of increasing packing density of aneurysms. A significant, added limitation of this approach is the need to remove the coil if it is exposed to blood for more than 5 to 7 minutes before final deployment, requiring withdrawal of both the coil and microcatheter. In addition, a small albeit significant risk of aseptic meningitis and hydrocephalus with hydrogel-coated coil use has been reported [42]. In one study of 33 aneurysms treated with these coils, 31 attempts (94%) resulted in successful coil deployment with 23 (70%) of lesions completely or nearly completely occluded. Ten percent of these 23 lesions demonstrated angiographic recanalization at 6-month follow-up [43]. Most recently, the use of Cerecyte coils (Micrus Endovascular Corp., San Jose, CA) has shown significant promise [44]. Unlike with MDCs, the bioactive substance, polyglycolic acid, is on the inside of the coil; as a result, these coils were reported to have mechanical properties of handling (eg, stiffness) similar to those of bare platinum coils. Compared with bare platinum coils, however, complete occlusion at 6 months follow-up improved from 62% to 78% of aneurysms treated (P = 0.045) and retreatment rates were lower (2% vs 11%, P = 0.056). Ultimately, the results of multiple ongoing trials will elucidate and guide optimal coil technology for endovascular use. Onyx (ev3 Neurovascular, Irvine, CA), an ethylene vinyl alcohol copolymer that forms a cast when in contact with water, can be directed and kept in the aneurysm dome as it solidifies via adjunctive use of balloon inflation at the neck. In the Cerebral Aneurysm Multicenter European Onyx (CAMEO) trial, a prospective observational study of a consecutive series of 123 aneurysms embolized with Onyx, 79% were completely occluded at 12-month follow-up [45]. Procedure-related morbidity was 8.2% and mortality, 2.2%. A limitation of this approach, however, is delayed occlusion of the parent vessel, which occurred in nine patients in the study.

Microsurgical
Intraoperative indocyanine green (ICG) videoangiography entails injection of a fluorescent dye to visualize arterial anatomy in the surgical field. In contrast to intraoperative angiography, it takes less than 2 minutes, has no side effects, and visualizes perforators. It is limited to visualization of arteries exclusively in the microscopes field, allowing for obscuration by blood clots, deep location, and limited exposure. Stenosis or complete vessel occlusion may also be obscured by the clip or retrograde filling by collateral flow and pulsations. In a prospective comparison of 187 cases, ICG videoangiography corresponded to intra- or postoperative angiography in 90%, missing angiographically relevant findings in 2.7% [46]. In 9% of cases, it provided significant information to the surgeon, prompting clip correction. Besides providing a simpler, safer, and more expedient alternative to intraoperative angiography, ICG videoangiography specifically addresses and presents a solution to one poignant weakness of microsurgery for aneurysmspreservation of perforating arteries.

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Obviating the need for occlusion of the recipient artery, excimer laserassisted nonocclusive anastomosis (ELANA) has emerged as an exceptional approach to high-flow extracranialintracranial or intracranial intracranial bypass [47]. An anastomotic ring and donor segment are sewn to a recipient. A laser suction catheter is then passed through the donor graft, affixed to the recipient arterial wall, and activated to create an opening in the recipients wall, rendering the anastomosis functional. Because room on the recipient artery for temporary clipping is not needed, less exposure is required, allowing for less brain retraction and less invasive approaches. This allowed for successful transsylvian external carotid to posterior cerebral artery bypass as one example [48]. In the largest case series to date, a 92% patency at 4 weeks to 4 years post surgery was reported in 35 of 40 patients [49]. Two of five complications were attributed to severe atherosclerotic disease, underscoring its place as a contraindication to ELANA bypass. Advances continue with ELANA: recently sutureless ELANA with an expanded polytetrafluoroethylene graft was demonstrated in rabbits [50]. This approach allowed for more facile, expeditious bypass construction (1525 minutes) while maintaining a patency rate of 89% in this series.

Disclosures
No potential conflicts of interest relevant to this article were reported.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: Of importance Of major importance
1. 2. 3. 4. 5. 6. 7. Rinkel GJ, Dijbuti M, Algra A, et al.: Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke 1998, 29: 251256. Zipfel GJ, Dacey RG: Update on the management of unruptured intracranial aneurysms. Neurosurg Focus 2004, 17: E2. Juvela S, Hillbom M, Numminen H, et al.: Cigarette smoking and alcohol consumption as risk factors for aneurysmal subarachnoid hemorrhage. Stroke 1993, 24:639646. Juvela S, Poussa K, Porras M: Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke 2001, 32:485491. Hop JW, Rinkel GJ, Algra A, et al.: Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 1997, 28: 660664. Feigin VL, Rinkel GJ, Lawes CM, et al.: Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke 2005, 36: 27732780. Mira JM, Costa FA, Horta BL, et al.: Risk of rupture in unruptured anterior communicating artery aneurysms: meta-analysis of natural history studies. Surg Neurol 2006, 66: S12S19. The International Study of Unruptured Intracranial Aneurysms Investigators: Unruptured intracranial aneurysmsrisk of rupture and risks of surgical intervention. N Engl J Med 1998, 339:17251733. Wiebers DO, Whisnant JP, Huston J, et al.: Unruptured intracranial aneurysms: a natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003, 362:103110. Juvela S, Porras M, Heiskanen O: Natural history of unruptured intracranial aneurysms: a long-term follow-up study. J Neurosurg 1993, 79:174182. 11. Lozano AM, Leblanc R: Familial intracranial aneurysms. J Neurosurg 1987, 66:522528. 12. Juvela S, Porras M, Poussa K: Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg 2000, 93: 379387. 13. Molyneux AJ, Kerr RSC, Yu L, et al.: International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 2005, 366:809817. Prospective randomized study of coiling versus clipping for ruptured aneurysms deemed amenable to either therapy. The investigators demonstrated worse short-term outcome, dened as dependency or death, in the group treated with clipping. Retreatment and rerupture rates were low but greater in the group treated with coiling. We have enumerated several of the limitations of this study. 14. Campi A, Ramzi N, Molyneux AJ, et al.: Retreatment of ruptured cerebral aneurysms in patients randomized by coiling or clipping in the International Subarachnoid Aneurysm Trial (ISAT). Stroke 2007, 38:15381544. 10.

8.

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34. Bendok BR, Parkinson RJ, Hage ZA, et al.: The effect of vascular reconstruction device-assisted coiling on packing density, effective neck coverage, and angiographic outcome: an in vitro study. Neurosurgery 2007, 61:835840. Bendok BR, Ali MJ, Malisch TW, et al.: Coiling of cerebral aneurysm remnants after clipping. Neurosurgery 2002, 51: 693697. Fahlbusch R, Nimsky C, Huk W: Open surgery of giant paraclinoid aneurysms improved by intraoperative angiography and endovascular retrograde suction decompression. Acta Neurochir (Wien) 1997, 139:10261032. Ng PY, Huddle D, Gunel M, et al.: Intraoperative endovascular treatment as an adjunct to microsurgical clipping of paraclinoid aneurysms. J Neurosurg 2000, 93:554560. Parkinson RJ, Bendok BR, Getch CC, et al.: Retrograde suction decompression of giant paraclinoid aneurysms using a No. 7 French balloon-containing guide catheter. J Neurosurg 2006, 105:479481. Drake CG: Giant intracranial aneurysms: experience with surgical treatment in 174 patients. Clin Neurosurg 1979, 26:1295. OShaughnessy BA, Salehi SA, Mindea SA, et al.: Selective cerebral revascularization as an adjunct in the treatment of giant anterior circulation aneurysms. Neurosurg Focus 2003, 14: E4. Fiorella D, Albuquerque FC, McDougall CG: Durability of aneurysm embolization with matrix detachable coils. Neurosurgery 2006, 58:5159. Kang HS, Han MH, Lee TH, et al.: Embolization of intracranial aneurysms with hydrogel-coated coils: result of a Korean multicenter trial. Neurosurgery 2007, 61:5158. Arthur AS, Wilson SA, Dixit S, et al.: Hydrogel-coated coils for the treatment of cerebral aneurysms: preliminary results. Neurosurg Focus 2005, 18: E1. Bendszus M, Bartsch AJ, Solymosi L: Endovascular occlusion of aneurysms using a new bioactive coil. A matched pair analysis with bare platinum coils. Stroke 2007, 38: 28552857. Molyneux AJ, Cekirge S, Saatci I, Gl G: Cerebral aneurysm Multicenter European Onyx (CAMEO) Trial: results of a prospective observational study in 20 European centers. AJNR Am J Neuroradiol 2004, 25:3951. Raabe A, Nakaji P, Beck J, et al.: Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg 2005, 103:982989. Tulleken CA, Verdaasdonk RM, Berendsen W, et al.: Use of the excimer laser in high-flow bypass surgery of the brain. J Neurosurg 1993, 78:477480. Tulleken CA, Zwan A, van Rooij WJ, et al.: High-flow bypass using nonocclusive excimer laser-assisted end-to-side anastomosis of the external carotid artery to the P1 segment of the posterior cerebral artery via the sylvian route. Technical note. J Neurosurg 1998, 88:925927. Tulleken CA, Verdaasdonk RM, Mansvelt Beck HJ: Nonocclusive excimer laser-assisted end-to-side anastomosis. Ann Thor Surg 1997, 63:138142. Bremmer JP, Verweij BH, van der Zwan A, et al.: Sutureless nonocclusive bypass surgery in combination with an expanded polytetrafluoroethylene graft. Laboratory investigation. J Neurosurg 2007, 107:1190197.

15. The CARAT Investigators: Rates of delayed rebleeding from intracranial aneurysms are low after surgical and endovascular treatment. Stroke 2006, 37:14371442. Recent multicenter study demonstrating signicantly more rebleeding episodes in the rst year after coil embolization than after clipping. The study also showed that patients who underwent embolization required additional treatment measures signicantly more often in the rst year versus those who underwent clipping. 16. Harbaugh RE: Commentary. Surg Neurol 2003, 59:165167. 17. Raftopoulos C, Goffette P, Vaz G, et al.: Surgical clipping may lead to better results than coil embolisation: results from a series of 101 consecutive unruptured intracranial aneurysms. Neurosurgery 2003, 52:12801290. 18. Koivisto T, Vanninen R, Hurskainen H, et al.: Outcomes of early endovascular versus surgical treatment of ruptured cerebral aneurysms. Stroke 2000, 31: 23692377. 19. Frazer D, Ahuja A, Watkins L, et al.: Coiling versus clipping for the treatment of aneurysmal subarachnoid hemorrhage: a longitudinal investigation into cognitive outcome. Neurosurgery 2007, 60:434442. 20. deOliveira JG, Beck J, Ulrich C, et al.: Comparison between clipping and coiling on the incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Neurosurg Rev 2007, 30: 2230. 21. Lawton MT, Quinones-Hinojosa A, Sanai N, et al.: Combined microsurgical and endovascular management of complex intracranial aneurysms. Neurosurgery 2003, 52: 263274. 22. Thornton J, Bashir Q, Aletich VA, et al.: What percentage of surgically clipped intracranial aneurysms have residual necks? Neurosurgery 2000, 46:12941300. 23. David CA, Vishteh AG, Spetzler RF, et al.: Late angiographic follow-up review of surgically treated aneurysms. J Neurosurg 1999, 91:396401. 24. Tsutsumi K, Ueki K, Usui M, et al.: Risk of subarachnoid hemorrhage after surgical treatment of unruptured cerebral aneurysms. Stroke 1999, 30:11811184. 25. Samson D, Batjer HH, Kopitnik TA: Current results of the surgical management of aneurysms of the basilar apex. Neurosurgery 1999, 44: 697702. 26. Bendok BR, Getch CC, Parkinson R, et al.: Extended lateral transsylvian approach for basilar bifurcation aneurysms. Neurosurgery 2004, 55:174178. 27. King JT, Berlin JA, Flamm ES: Morbidity and mortality from elective surgery for asymptomatic, unruptured, intracranial aneurysms: a meta-analysis. J Neurosurg 1994, 81:837842. 28. Raaymakers TWM, Rinkel GJE, Limburg M, et al.: Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 1998, 29:15311538. 29. Bendok BR, Hanel RA, Hopkins LN: Coil embolization of intracranial aneurysms. Neurosurgery 2003, 52:11251130. 30. Raymond J, Guilbert F, Weill A, et al.: Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke 2003, 34:13981403. 31. Veznedaroglu E, Benitez RP, Rosenwasser RH: Surgically treated aneurysms previously coiled: Lessons learned. Neurosurgery 2004, 54:300305. 32. Murayama Y, Nien YL, Duckwiler G, et al.: Guglielmi detachable coil embolization of cerebral aneurysms: 11 years experience. J Neurosurg 2003, 98:959966. 33. Henkes H, Fischer S, Weber W, et al.: Endovascular coil occlusion of 1811 intracranial aneurysms: early angiographic and clinical results. Neurosurgery 2004, 54: 268285.

35. 36.

37. 38.

39. 40.

41. 42. 43. 44.

45.

46.

47. 48.

49. 50.