Introduction

Giant aneurysms (fundus diameter ≥25 mm) comprise approximately 5% of the intracranial aneurysms in most published series.^1–5 These lesions are slightly more common in women. Approximately two thirds are in the anterior circulation and one-third in the posterior circulation.¹ The proportion of patients who present with rupture varies between 20% and 70%, with rebleeding rates similar to those seen for smaller aneurysms in patients presenting with subarachnoid hemorrhage (SAH).^3,5,6 Other presenting signs and symptoms are related to mass effect and ischemic syndromes. Ischemic syndromes are seen in fewer than 10% of giant aneurysms.^3,4

Giant aneurysms include saccular-shaped aneurysms with a demonstrable neck and fusiform-shaped aneurysms, which are fusiform dilatations of the entire vessel wall with a segmental defect in the parent artery.⁴ Saccular aneurysms are thought to develop from smaller saccular aneurysms at points of maximal hemodynamic stress, such as flow vector points or intracranial bifurcations. Fusiform aneurysms are thought to arise from atherosclerotic degeneration of the vessel wall that leads to aneurysmal defects in the parent vessel. They often involve entire segments of a first- or second-order intracranial vessel and incorporate branches and perforators.

Natural history

The natural history of a giant intracranial aneurysm, once diagnosed, is poor. Drake⁶ observed a group of 31 patients with untreatable intracranial aneurysms and found a mortality rate of 66% at 2 years and >80% at 5 years. In the first International Study of Unruptured Intracranial Aneurysms (ISUIA), the relative risk of rupture of an unruptured giant aneurysm when compared to an unruptured aneurysm <10 mm in size was 59.0 (p < 0.001).⁷ In the second ISUIA, 55 giant aneurysms were observed without treatment and the 5-year cumulative rupture risk by location was 6.4% in the cavernous carotid artery, 40% in other segments of the internal carotid artery (ICA), anterior cerebral artery, anterior communicating artery (AComA), and middle cerebral artery (MCA), and 50% in the posterior communicating artery (PComA) and posterior circulation.⁸ In the same study, giant aneurysms were treated with open surgery in 80 patients and endovascular methods in 55 patients. In the surgical group, the chances of poor outcomes (defined as a modified Rankin Scale [mRS] score of 3-5, or an impaired cognitive outcome) were 25% to 35% in the anterior circulation and 45% in the posterior circulation. In the endovascular group, the chances of poor outcomes were 12% to 15% in the anterior circulation and 40% in the posterior circulation. In giant aneurysms, a high-risk natural history is associated with a higher treatment risk. Accordingly, a decision to treat or not may in part be based on the decisions of patients and their physicians about whether risk is preferable immediately or over time; decisions might also be strongly influenced by the patient’s age and presence of medical comorbidities and aneurysmal mass effect.

Surgical management

The two goals of surgical treatment of giant aneurysms are permanent exclusion of the aneurysm from the circulation with possible preservation of distal blood flow and release of mass effect. Reconstructive or deconstructive microsurgical techniques are used. Reconstructive techniques include direct clipping of the aneurysm neck and aneurysmorrhaphy (reconstruction of the vessel using redundant aneurysm sac or graft material). Deconstructive techniques include proximal (Hunterian) ligation and trapping of the aneurysmal segment with or without bypass.

Clipping of the aneurysm neck is generally seen as the best treatment strategy if it is feasible. The results of giant aneurysm surgery have been augmented by (1) use of operative instrumentation and technology, including microscopes, endoscopes, and intraoperative indocyanine green angiography; (2) cerebral protection strategies, such as improvements in anesthetic and intensive care management, cranial base approaches, intraoperative monitoring, hypothermia, adenosine-induced circulatory arrest, and cardiac bypass procedure; (3) preoperative imaging, including 3-D CT or MRA to assess aneurysm geometry, intraluminal thrombus, branches, and perforating vessels, and relationship to the skull base; 6-vessel 3-D angiography to assess the vascular anatomy and availability of donor superficial temporal artery vessels; and balloon occlusion testing with adjunctive measures to assess collaterals for use of temporary occlusion or deconstructive techniques; and (4) intraoperative techniques, such as the use of tandem clips to reinforce the wide aneurysm neck and clip reconstruction of the vessel branch points incorporated in the aneurysm fundus or neck, decompression of the aneurysm by needle puncture, or opening the dome of the aneurysm after flow arrest, performing advanced EC-IC bypass procedure (including ELANA or IC-IC bypass techniques) to preserve distal blood flow.

A meta-analysis by Raaymakers et al.³ that examined the outcome of surgical treatment for unruptured aneurysms in studies from 1970 to 1996 showed posterior circulation aneurysms to have a 9.6% mortality and 37.9% morbidity and anterior circulation aneurysms to have a 7.4% mortality and 26.9% morbidity. The early reports of Drake⁶ and the more modern surgical series of Lawton et al.,^9,10 Samson et al.,¹¹ Surdell et al.,¹² Piepgras et al.,¹³ Hanel et al.,¹⁴ and Sekhar et al.^15–17 have shown improvement in the morbidity and mortality associated with surgically treating these lesions. Most surgical series report an operative mortality of at least 6% and a major morbidity of at least 20%. The results of endovascular therapies should always be compared to these surgical series.

Endovascular therapy

Although the advances made in microsurgical management have reached a plateau in recent years, the endovascular management of giant intracranial aneurysms and all intracranial aneurysms in general is still evolving. The relative importance of surgery and endovascular strategies and their relative merits in terms of safety, effectiveness, ease of use, and durability are being studied. These techniques can be combined in certain situations to augment the advantages and nullify the disadvantages of either modality. Training of aneurysm specialists in both endovascular and microsurgical techniques would stimulate strategies involving both these modalities in a complementary fashion with an aim to decrease overall morbidity and mortality.

Preoperative imaging

Catheter-based angiography, 3-D CT imaging, and MR angiography are helpful in confirming the diagnosis and/or consideration of an endovascular, surgical, or combination therapy approach. The performance of a six-vessel 3-D diagnostic cerebral angiogram is crucial before final decisions about treatment options are made. Catheter-based angiography provides critical information regarding not only the anatomic and morphologic features of the lesion but also the potential for collateral circulation should vessel occlusion be entertained as a treatment option. Cross-compression views can aid in determining the patency of PComAs and AComAs, as appropriate. In addition, potential donor arteries for surgical bypass can be assessed. Multiple angiographic projections or 3-D angiography can be extremely useful at delineating the relevant pathological anatomy. Balloon test occlusion is performed concurrently if permanent vessel occlusion (endovascular or surgical) is considered as a treatment option or as a bailout maneuver. Currently, microsurgical and endovascular deconstructive strategies without a bypass are used only for bailout when other treatment options are not available; this is because all the tests for collateral supply after temporary occlusion have false-negative results and a 16% to 20% chance of an ischemic event exists after carotid sacrifice, even if balloon occlusion tests were negative.^18,19 If surgical bypass is planned, endovascular sacrifice should be performed promptly after the surgical procedure to minimize the risk of graft thrombosis owing to low flow.

3-D CT angiography provides valuable information regarding the relative composition of the aneurysm (thrombus or calcifications) and provides delineation of some anatomic aspects of the aneurysm and any additional aneurysms. The technique is quick, noninvasive, and can aid in decision making (surgical versus endovascular versus combination therapy) in acute emergencies, such as when dealing with a concomitant hemorrhage that is producing significant mass effect. However, this technique is dependent on the quality of 3-D image reconstruction; and suboptimal imaging quality can lead to misinterpretation, especially when the aneurysm is intimately associated with bony structures or multiple surgical clips or coils. MR angiography is useful for screening but typically not for treatment decision making. MR imaging can be quite useful to evaluate for intra-aneurysmal thrombus, mass effect, edema, and any potentially associated ischemic lesions.

Anesthesia

At our center, we prefer to perform endovascular procedures under conscious sedation so that we can conduct neurologic examinations intermittently. Avoidance of general anesthesia also reduces the cardiovascular risk of the overall procedure. However, if a complication does occur, the potential exists for further harm until the patient’s airway can be secured and additional maneuvers (e.g., ventriculostomy, further embolization) can be performed. One must be prepared to intubate at a moment’s notice. Not all patients are candidates for conscious sedation because of poor neurologic status, young age, excessive anxiety, or inability to lie still. General anesthesia offers the advantages of control of the airway as well as reduction or elimination of patient movement during the procedure. General anesthesia is routinely used at most centers.

Antiplatelet therapy

Patients scheduled to undergo elective stent or flow-diversion device placement receive aspirin (325 mg by mouth daily) and clopidogrel (75 mg by mouth daily) for a minimum of 4 days before the procedure. Those undergoing stenting on a more urgent basis receive aspirin (650 mg by mouth) and clopidogrel (600 mg by mouth) 4 hours before the procedure. If stenting is performed as an emergency bailout maneuver, we administer an intravenous bolus dose of glycoprotein IIb-IIIa inhibitor (180 mg/kg eptifibatide at our institution) and then clopidogrel (600 mg by mouth) and aspirin (650 mg by mouth) immediately after the procedure. Eptifibatide (2 mg/kg/min) is continued as an intravenous drip for 4 hours after the procedure to allow the clopidogrel to reach therapeutic levels of platelet inhibition. In the rare case of a patient with an acutely ruptured aneurysm undergoing stent placement, the glycoprotein IIb-IIIa inhibitor can be given after the stent is in place and the first or second coil is in proper position. All patients with a stent or flow-diversion device are placed on clopidogrel (75 mg daily) for 3 months and aspirin (325 mg daily) for life. Patients who do not have stent placement are kept on aspirin for life.

Anticoagulation therapy

Proper decision making regarding periprocedural systemic anticoagulation is essential when using complex endovascular techniques for aneurysm treatment. We routinely administer heparin (an intravenous bolus of 50 to 70 units/kg) to obtain an activated coagulation time of 250 to 300 seconds before catheterization of intracranial vessels for elective and emergent patients, except those with SAH. Anticoagulation therapy is used more judiciously in patients with SAH. In these patients, we typically administer a 25- to 35-unit/kg bolus of heparin after the first coil is placed successfully, followed by a similar bolus after intra-aneurysmal flow is reduced. The effect of the heparin is allowed to wear off after the procedure, unless there is evidence of intraprocedural wire perforation or contrast extravasation, in which case the heparin is reversed during or after the procedure with protamine sulfate.

For patients with SAH, CT examination is performed immediately before treatment to assess for latent intracerebral hemorrhage (whether caused by aneurysm rebleeding or ventriculostomy placement), because such hemorrhage will prevent our use of stents or glycoprotein IIb-IIIa antagonists. Because of the degree of systemic anticoagulation, the arterial access site is typically secured by use of a closure device at the conclusion of the procedure.

Before the procedure, preferably the previous day, the patient should be assessed and all the available imaging studies reviewed in preparation for the case. Decisions about overall strategy should be made ahead of time to permit accurate device selection and smooth and efficient performance during the case. Considerations should include choice of access vessel, endovascular technique (i.e., primary coiling versus stent-assisted or balloon-assisted coiling), and device types and sizes.

Endovascular access

The route for endovascular access, including the iliofemoral artery anatomy, arch anatomy, and supra-aortic vessel, needs to be assessed to decide on the access site and the devices that would facilitate safe access and provide a stable platform for intracranial therapies. Brachial or radial artery access may be considered if there is a disease in the iliofemoral arterial segments or descending aorta. Patients with giant aneurysms have a greater likelihood of having an atherosclerotic arch or tortuous and elongated supra-aortic vessel, especially in cases with associated collagenopathies. In such cases, special devices to access difficult arch anatomy, a carotid cutdown in the neck, or a cutdown of the extracranial vertebral artery (VA) as it traverses over the posterior arch of C1 could be used to access the intracranial vasculature.

Guide catheter selection

A stable guide catheter platform is critical for endovascular treatment of giant aneurysms. We are increasingly using the Neuron™ Intracranial Access System (Penumbra, Alameda, CA) as the guide catheter. This device is more stable the farther distally it is placed. The two guide catheters previously used most often were the Envoy® (Codman and Shurtleff, Inc., Raynham, MA) and the Guider Softip™ XF guide catheter (Boston Scientific, Natick, MA). A 6-French (F) 90-cm Cook Shuttle® (Cook, Bloomington, IN) also provides a large, stable platform for intervention. The guide catheter can be placed directly or by use of an exchange method in patients with tortuous anatomy, atherosclerosis, or fibromuscular dysplasia. We often use a “tower of power” where the Neuron is placed through a large guide catheter for added stability and distal access.

Parent vessel sacrifice

The key step in the sacrifice of a large vessel, such as the ICA or the VA, is the temporary arrest of proximal flow to prevent inadvertent embolization into the cerebral vasculature during the procedure. In general, the vessel should be occluded either at or immediately proximal to the lesion. Vessel occlusion can be accomplished with detachable coils or detachable balloons. Although detachable balloons are not commercially available in the United States at the present time, they are available in Europe and Japan.

Parent vessel preservation

Balloon-Assisted Coil Embolization

The use of balloons to occlude the aneurysm neck during coiling of wide-necked aneurysms was first described in 1994 by Moret et al.²⁴ A 6-F or larger guide catheter is required to accommodate both a balloon catheter and a microcatheter. A microcatheter is placed into the aneurysm fundus, and a balloon catheter is centered over the aneurysm neck. The balloon is subsequently inflated during placement of a coil and then deflated intermittently in between coils to allow antegrade flow. Sequential inflations and deflations are performed as additional coils are placed, until the aneurysm is completely coiled, at which point the balloon is removed. The concept is that the balloon prevents distal embolization and conforms the coil mass to the shape of the balloon and that the coil mass shape becomes stable, thereby protecting the parent artery as the individual coils interlock. Care must be taken during the initial insertion of a coil to form a loop directing the distal end of the coil away from the aneurysm fundus to limit the risk of aneurysm perforation during balloon inflation (Figures 29-1 through 29-3).

Figure 29–1 This 69-year-old woman presented with a giant aneurysm masquerading as a pituitary adenoma. Sagittal (A) and coronal (B) MR images showing a mass lesion near the pituitary region. C, Right ICA injection showing a giant ICA aneurysm. She underwent near-complete coiling with the balloon-assisted technique.

Figure 29–2 AP (A) and lateral (B) plain X-rays obtained during the procedure showing a balloon bridging the neck of the aneurysm.

Figure 29–3 Follow-up angiogram obtained 3 years later shows no recurrence of the aneurysm. AP (A) and lateral (B) projections of right ICA injection.

Forty to 50 coils can be required to fill a giant aneurysm, leading to 40 to 50 cycles of balloon inflations, for which the risk may be prohibitive. In addition, the ability to protect the parent artery lumen by means of balloon occlusion during the coiling procedure, especially when there is extensive fusiform dilation, is minimal. Temporary balloon occlusion exposes the patient to an increased risk of cerebral ischemia resulting from thromboembolic complication and vessel rupture. The increase in thromboembolic complications occurs because of stasis of blood or temporary occlusion of local perforating end arteries covered by the balloon. The risk of vessel rupture stems from the compliant design of most balloons used for these purposes and is associated with dramatic changes in volume and pressure in the balloon with minimal inflation volume changes. Soeda et al.²⁵ reported that the occurrence of diffusion-weighted imaging (DWI) lesions was significantly associated with the use of balloon remodeling. In that series, DWI was positive in 73% of all patients receiving a remodeling procedure, as compared to 49% in the control group. Other authors demonstrated lower rates of DWI lesions in 20% of patients treated with remodeling but did not provide a control group.²⁶ Overall procedural balloon-assisted coiling morbidity and mortality range from 0% to 20.4% in all aneurysms. No results for specific series of balloon-assisted coiling for giant aneurysms have been reported.²⁷

At our center, balloon assistance is used for cases of ruptured wide-necked giant aneurysms in which the use of antiplatelet agents is contraindicated and for those patients in whom the deployment of a stent is not feasible. The number of patients in the second category is decreasing as more deliverable self-expanding intracranial microstents (SEIM) become available. We currently use the HyperGlide and HyperForm balloons (Covidien Vascular Therapies, Mansfield, MA) for these patients having limited options.

Stent-assisted coiling

Intracranial stenting for aneurysm therapy has undergone a remarkable evolution over the past decade. The devices themselves, as well as the manner in which they are applied, have changed dramatically. Initially utilized exclusively as adjunctive devices to simplify (or, in some cases, to allow) the treatment of wide-necked aneurysms, stents have become increasingly used to achieve flow redirection and vascular remodeling in an attempt to augment the durability of endovascular treatments. The newest generations of intracranial microstents have surpassed their predecessors, evolving into stand-alone devices designed to cure aneurysms without other embolic materials.

In the early 1990s, we described the application of stents to treat experimental aneurysms.³⁰ The basic principles of stent-supported therapy delineated by early experiments are (1) parent vessel protection by preventing coil prolapse³⁰ and (2) parent vessel remodeling providing a scaffold for neointimal growth and producing flow-diversion that may facilitate and maintain aneurysm thrombosis.^31,32 Balloon-expanding coronary stents were used initially to support coiling of wide-necked intracranial aneurysms.^33–40 These stents were of limited benefit due to their rigid nature and the challenges involved in their delivery and deployment within the tortuous cerebrovasculature. The newer generation of balloon-mounted stents designed specifically for intracranial use (Pharos, Micrus Endovascular, Sunnyvale, CA) are more stable than the predicate devices designed for coronary applications and have indications for the treatment of both cerebral aneurysms and intracranial atherosclerosis.^41–44

Self-expanding intracranial microstents (SEIMS)

Presently, there are two SEIMs designed specifically for stent-assisted coiling of wide-necked intracranial aneurysms available in the United States: the Neuroform3™ stent (Boston Scientific) and the Enterprise™ Vascular Reconstruction Device (Codman and Shurtleff, Inc., Raynham, MA). Each device consists of a self-expanding nitinol stent that is deployed in the parent vessel adjacent to the aneurysm neck; the stent then acts as a scaffold to hold coils in place inside the aneurysm. Both devices are extremely navigable (compared to delivery of balloon-mounted coronary stents [BMC]); and the Enterprise presents several benefits over the Neuroform including reconstrainability, a lower profile delivery system, and a technically less-complicated deployment mechanism. If sized appropriately, SEIMs automatically expand to appose the walls of the parent artery, even within very tortuous vascular segments. In addition, these devices have the ability to differentially expand to accommodate adjacent vascular segments that vary significantly in diameter. The anatomic distortion of the vessel that is created by the insertion of these devices is minimized by their flexibility and conformability. The superelastic properties of the SEIM result in the device exerting a small chronic outward radial force against the vessel wall, which stabilizes the device in vivo.

The introduction of these devices led to a marked increase in the number of stent-assisted aneurysm treatments performed and greatly broadened the scope of lesions that were amenable to endovascular therapy. As practitioners gained experience with SEIMs, novel approaches to more complex lesions were innovated and the sophistication of endovascular reconstruction increased.^45–52 Over the past decade, stenting has become a standard adjunctive technique used to facilitate the treatment of giant and complex aneurysms.

Recently, SEIM have begun to be viewed not only as adjunctive devices to support coiling but also as tools that could potentially support the long-term durability of coil embolization—particularly for difficult cases in which the aneurysm is prone to recurrence. This is because stents have several possible effects on the physiology and biology of the aneurysm–parent vessel complex. These effects include the following: (1) alteration of the parent vessel configuration, thus possibly a change in the intra-aneurysmal flow dynamics; (2) disruption of the inflow jets; (3) reduction in the vorticity and wall shear stress on the aneurysm wall and reduction of the water-hammer effect of the pulsatile blood flow that causes coil compaction by the tines of the stents; and (4) providing a scaffolding and stimulus for the overgrowth of endothelial and neointimal tissue across the neck of the aneurysm, creating a matrix for “biological remodeling” across the aneurysm neck.

Neuroform stent