Intraarterial Thrombolysis

Compared to IV approaches, intraarterial (IA) administration of thrombolytics via a microcatheter positioned in the cerebral vasculature affords rapid local delivery of greater therapeutic treatment concentrations to the site of vascular occlusion. The selective nature of the delivery system maximizes lysis while limiting systemic conversion and resultant hemorrhage. Intraarterial thrombolysis represents a targeted strategy that lengthens the total therapeutic window for acute stroke intervention. The technique entails performing a catheter-based cerebral angiogram to confirm the point of occlusion. Under fluoroscopic guidance, a microcatheter is advanced though a larger guide catheter to the base of, into, or distal to the clot. Once positioned, a thrombolytic agent is injected over a 1- to 2-hour time period as intermittent control angiograms are performed (Gandhi et al., 2009). Clinical trials have been performed using streptokinase, urokinase, rtPA, recombinant prourokinase, and reteplase. These agents differ in fibrin selectivity, stability, half-life, and mechanism of action (Gandhi et al., 2009; Schellinger et al., 2001). The Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial demonstrated the effectiveness of IA prourokinase when given within 6 hours of acute stroke caused by middle cerebral artery occlusion (Furlan et al., 1999). Patients were randomized to IA recombinant prourokinase and IV heparin or heparin alone. The primary clinical outcome, the proportion of patients with minimal or no disability at 90 days (modified Rankin Scale [mRS] score ≤ 2), was achieved in 40% of the treatment group (patients administered heparin and IA prourokinase) and 25% of the controls (patients administered heparin only).

Although IA thrombolysis is an effective treatment, the time delay required for cerebral angiography and microcatheter positioning is an inherent shortcoming. To address this, bridging strategies have employed a combined IV/IA approach. The first such trial was the Emergency Management of Stroke Bridging Trial (Lewandowski et al., 1999). This was a double-blind randomized placebo-controlled phase-I trial of IV rtPA or placebo followed by immediate IA treatment with rtPA. Although recanalization was significantly greater in the IV/IA rtPA group, there was no difference in 3-month functional outcomes, and an increased incidence of death was observed in that treatment group.

The Interventional Management of Stroke (IMS) study investigators compared acute stroke patients treated with a bridging IV rtPA dose (0.6 mg/kg) followed by IA rtPA, with historical controls given only the traditional IV dosing regimen from the NINDS trial. The IMS I study was an open-label single-arm feasibility study using a standard microcatheter to infuse a total dose of up to 22 mg of IA rtPA over 2 hours (IMS Study Investigators, 2004). The objective of the second IMS study (IMS II) was to continue investigating the feasibility of a combined IV/IA approach, permitting the use of the EKOS MicroLysUS (EKOS Corp., Bothell, Washington) microinfusion catheter, which incorporates sonographic technology to increase permeability and penetration of the intraluminal clot (IMS II Trial Investigators, 2007). The IMS study cohorts demonstrated better functional outcomes and a decreased mortality rate compared to historic controls. The rate of symptomatic intracranial hemorrhage was similar to that of the IV rtPA group in the NINDS trial (IMS Study Investigators, 2004; IMS II Trial Investigators, 2007; National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group, 1995). These data suggest that bridging protocols combining IV therapy and subsequent endovascular procedures may improve recanalization rates and functional outcome following acute stroke (Mazighi et al., 2009). Definitive evidence to support this combination may not be available, however, until the prospective randomized IMS III trial is completed.

Mechanical Recanalization

Although outcomes following acute stroke have improved with the administration of IV/IA thrombolytics, there are many patients who are not candidates for these treatment schemes (Furlan et al., 1999; Williams et al., 2009). Narrow time windows and the risk of hemorrhage associated with thrombolytic agents have prompted the design and application of mechanical thrombectomy devices. Endovascular clot retrieval provides potential for rapid restoration of flow, with a decreased incidence of clot fragmentation and distal embolism (Nogueira et al., 2009). Catheter-based retrieval/aspiration systems are used in acute stroke patients who are either ineligible for or have failed IV rtPA administration; they may be used in conjunction with thrombolytic infusion. Clot-retrieval devices have effectively lengthened the treatment window for acute stroke.

The first device to have received U.S. Food and Drug Administration (FDA) approval for IA stroke treatment is the MERCI clot retriever (Concentric Medical Inc., Mountain View, California). This retrieval system includes the MERCI retrieval device, a compatible microcatheter, and a balloon guide catheter. The retriever is a flexible tapered nitinol wire with radiopaque helical loops at the distal tip (Fig. 47.1). Newer-generation retrievers (L series and V series) have cylindrical rather than tapered loops (X series) and a bound suture material that enhances clot capture. An 8F or 9F balloon guide catheter is advanced into a proximal vessel and inflated to cease anterograde blood flow and thus prevent distal emboli during clot extraction. The microcatheter is advanced coaxially over a microguidewire into the target vessel and through the clot. Once situated in the distal vessel, the microguidewire is exchanged for the clot retriever. The device is unsheathed to position several loops distal to the clot, and the retriever/microcatheter unit is then withdrawn into the balloon guide catheter under constant manual suction (Fig. 47.2).

Fig. 47.1 MERCI clot retrieval device (left) and diagram demonstrating mechanism of action (right). Spiral loops and suture material are designed to engage the clot and mechanically remove it from the vessel.

(Picture courtesy Concentric Medical Inc.)

Fig. 47.2 Anteroposterior (AP) (top left) and lateral oblique (top middle) angiogram demonstrating a left carotid terminus thrombus with no filling of the middle cerebral artery. X-ray image showing the MERCI clot retrieval device deployed in left middle cerebral artery (top right). AP (bottom left) and lateral oblique (bottom middle) angiograms demonstrating recanalization after mechanical thrombectomy with the MERCI device. Photograph demonstrating an extracted thrombus on the MERCI retrieval device (bottom right).

Results from the nonrandomized Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial demonstrated safety and efficacy of the X-series clot retrieval system in restoring the patency of occluded intracranial vessels within the first 8 hours of acute stroke (Smith et al., 2005). Some 48% of occluded vessels were recanalized, a rate significantly higher than that of the control arm in the PROACT II trial (18%) (Furlan et al., 1999; Nogueira et al., 2009b). After adjuvant therapy (IA rtPA, angioplasty, snare), the rate of recanalization was 60.3%. The overall rates of good outcome (mRS score ≤2) and mortality were 27.7% and 43.5%, respectively, with a clinically significant procedural complication rate of 7.1%. Revascularization was found to be an independent predictor of decreased mortality and favorable neurological outcome at 90 days.

More recently, the Multi-MERCI Stroke Trial was conducted. This was an international multicenter, prospective, single-arm trial similar to the previous MERCI trial (Smith et al., 2008). However, this study included patients receiving IV rtPA with persistent arterial occlusion and allowed utilization of a newer-generation retrieval device (L5). Treatment with the retriever alone resulted in successful recanalization of 55% of treatable vessels. Recanalization rate was 68% after adjuvant therapy. The overall rates of good outcome (36%) and mortality (34%) were substantially improved when compared to those of the original MERCI trial. Once again, good outcomes were more frequent and mortality was lower with successful recanalization. The authors concluded that mechanical thrombectomy after IV rtPA seems as safe as mechanical thrombectomy alone, and that thrombectomy is efficacious in opening intracranial vessels during acute stroke in patients who are either ineligible for or have failed to recanalize with IV rtPA.

The Penumbra System (Penumbra Inc., Alameda, California) is an aspiration device through which a thromboembolic clot can be retrieved following acute stroke (Fig. 47.3). The device removes thrombus via aspiration, mechanical disruption, and extraction. Multiple aspiration catheters of varying luminal diameters are available for use in the cervical and intracranial vasculature, depending on vessel caliber. The aspiration device is advanced coaxially to the level of the thrombus through a guide catheter. Once positioned just proximal to the target lesion, an aspiration pump is connected to the reperfusion catheter. The separator is then advanced through the catheter into the distal clot and repeatedly retracted and advanced, aiding in the debulking process. A multicenter prospective, single-arm, phase I trial of the Penumbra reperfusion catheter was designed to assess safety and efficacy (Bose et al., 2008). The primary endpoint was revascularization, defined by a Thrombolysis in Myocardial Infarction (TIMI) score of 2 or 3. Recanalization was achieved in all vessels in which the device was deployed. A secondary endpoint of mRS score of 2 or less or improvement of NIHSS score by 4 or better was achieved in 45% of patients. The Penumbra device has recently received FDA approval (Fig. 47.4).

Fig. 47.3 Penumbra reperfusion catheters and separator wires of different sizes. Wire is used to fragment clot as catheter provides suction/aspiration.

(Picture courtesy Penumbra Inc.)

Fig. 47.4 Anteroposterior (top left) and lateral (top right) angiogram demonstrating right M1 segment middle cerebral artery occlusion. Aspiration with Penumbra catheter resulted in complete recanalization of middle cerebral artery (bottom left and right).

No other mechanical embolectomy device is currently approved by the FDA for use in acute stroke. The Phenox Clot Retriever (Phenox GmbH, Bochum, Germany), Neuronet Endovascular Snare (Guidant Corp., Temecula, California), Catch Mechanical Thrombus Retriever (Balt, Montmorency, France), Alligator retriever (Chestnut Medical Technologies Inc., Menlo Park, California), Amplatz GooseNeck Snare (ev3 Inc., Irvine, California), and TriSpan device (Boston Scientific, Natick, Massachusetts) have all been used successfully in a limited number of acute stroke patients, without large-scale demonstration of safety or efficacy (Gandhi et al., 2009; Katz et al., 2006; Nogueira et al., 2009a).

Angioplasty and Stenting

Despite increased experience with IA thrombolytic administration and technical advancements in the development of embolic retrieval or aspiration devices, many intracranial thrombi remain recalcitrant to thrombolysis or embolectomy. Mature fibrinous clots are often difficult to treat pharmacologically, and thrombi adherent to the vascular intima or associated with underlying atheromatous disease pose inherent structural risks to mechanical embolectomy procedures. Percutaneous transluminal angioplasty (PTA) and stenting procedures have been successful in acute coronary revascularization. Recanalization in the absence of clot dissolution or extraction may be sufficient for successful acute stroke treatment (Levy et al., 2009). Several small studies have reported improvement in clinical outcome following angioplasty and thrombolytic administration in the setting of acute stroke (Nogueira et al., 2008; Ringer et al., 2001; Yoneyama et al., 2002). Recently a single-arm prospective trial of primary intracranial stenting for acute stroke demonstrated promising results. The authors reported 100% TIMI 2-3 recanalization in a cohort of 20 patients treated with intracranial stenting. Self-expanding stents (Wingspan [Boston Scientific, Natick, Massachusetts]; Enterprise [Cordis Neurovascular Inc., Miami Lakes, Florida]) designed exclusively for cerebral indications facilitated access and navigation through tortuous craniocervical anatomy. Although adjuvant IA antiplatelet therapy was used in 50% of patients, the authors reported only a 5% rate of symptomatic intracranial hemorrhage. At 1 month, 60% of patients had mRS scores of 3 or below, and 45% had mRS scores of 1 or below. These results are encouraging. Larger studies are needed, however, to adequately assess the safety and efficacy of this treatment modality.

Alternative Reperfusion Strategies

Alternatives to recanalization strategies focus on collateral perfusion as well as flow reversal following acute stroke. One such mechanical approach to flow augmentation is the NeuroFlo catheter (CoAxia Inc., Maple Grove, Minnesota), a dual-balloon catheter designed for partial occlusion of the descending aorta, above and below the renal arteries (Fig. 47.5). Temporary partial aortic occlusion is thought to augment cerebral blood flow through mechanical flow diversion. Multicenter clinical trials are currently being conducted to assess the safety and efficacy of this treatment modality (Liebeskind, 2010; Nogueira et al., 2009a; Uflacker et al., 2008). If efficacious, such alternate reperfusion strategies may serve to supplement existing recanalization treatments or represent a novel paradigm for patients ineligible for direct revascularization.

Fig. 47.5 X-ray images of the NeuroFlo device. Balloons are inflated in suprarenal and infrarenal segments of aorta to divert blood flow to collateral cerebral circulation.

Carotid Artery Angioplasty and Stenting

Carotid angioplasty and stenting (CAS) has evolved in part because of a need for alternative, less invasive treatment modalities for patients deemed poor operative candidates on the basis of anatomical or clinical parameters. A percutaneous transluminal approach is used to gain endovascular access to the stenotic lesion.

Angioplasty and Stenting Procedure

In anticipation of carotid artery angioplasty and stenting, double antiplatelet therapy is initiated prior to the intervention to decrease the risk of thromboembolic complications. Most procedures are performed awake or under monitored anesthesia care, allowing for continuous neurological assessment. Following a diagnostic cerebral angiogram, a guide catheter or shuttle sheath is advanced into the common carotid artery. These delivery systems effectively maintain position and accommodate most stents. If more stability is necessitated, a “buddy” wire can be placed in the external carotid artery. Based upon the diagnostic angiograms, measurements of the stenotic diameter, the length of the lesion, and the diameter of the native common carotid and internal carotid arteries are obtained.

Next, embolic protection is secured in all attainable cases. Carotid plaques may be extremely friable, and even minor manipulation can result in distal embolization or vessel occlusion. Cerebral protection devices of varying construction are used to prevent embolic complications during CAS procedures. Most commonly, over-the-wire distal filters measured to the diameter of the native cervical internal carotid artery (ICA) are navigated past the stenotic lesion to capture embolic material (Fig. 47.6). Such devices allow continuous cerebral perfusion through pores in the filter baskets. Following angioplasty and stenting, the device is collapsed and withdrawn and embolic material retrieved. Alternatively, balloon occlusion devices may be used to completely prevent anterograde flow within the ICA. Any displaced material can be aspirated prior to balloon deflation. However, temporary carotid occlusion may not be well tolerated in all patients, limiting the applicability and utility of this strategy. Guide catheters with distal occlusion balloons may be inflated in the common carotid artery to achieve proximal control and distal flow reversal. Concomitant balloon inflation in the external carotid artery results in more thorough protection. Temporary proximal occlusion is generally performed when distal deployment of an embolic protective device (EPD) is not feasible owing to vessel size, tortuosity, or other anatomical restrictions.

Fig. 47.6 Over-the-wire distal embolic protection device (EPD). Filter is positioned in distal cervical internal carotid artery (beyond stenotic segment) to prevent embolic debris from reaching intracranial circulation.

Once embolic protection is achieved, balloon predilatation of tight stenoses can help ensure safe advancement of a self-expanding stent past the target lesion. Balloon inflation is done slowly to lessen the incidence of thromboembolism. Deflation must also be undertaken in a controlled, deliberate fashion. An experienced anesthesiologist and open communication are critical during this portion of the procedure. The endovascular surgeon must inform the anesthesia team of possible bradycardia associated with balloon inflation. This way, changes in the heart rate can be managed in a timely and proper fashion during angioplasty. Stent diameter is calibrated to 100% of the common carotid artery diameter, and length is measured to traverse the entire lesion with a margin of several millimeters both proximally and distally. Tapered stents are available to accommodate the larger diameter of the common carotid artery and the smaller lumen of the ICA. Depending on residual stenosis and distal perfusion, post-stent balloon dilatation may be undertaken. It is critical that balloon angioplasty remain within the confines of the stented arterial segment to prevent dissection of unprotected vascular intima (Fig. 47.7).

Fig. 47.7 Lateral angiogram demonstrating critical proximal internal carotid artery stenosis (left). Embolic protection device (EPD) is opened in distal cervical internal carotid artery (top of picture, middle). Following balloon dilatation, stent is positioned across stenotic segment (middle). Lateral angiogram showing stent deployed in distal common and proximal internal carotid artery, with minimal residual stenosis (left).

Intracranial Angioplasty

Balloon angioplasty was the first percutaneous transluminal technique evaluated. In a large retrospective study, Marks et al. (2006) reported on 120 patients with intracranial stenoses treated by primary angioplasty. The authors calculated a combined periprocedural stroke and death rate of 5.8% and a total yearly event rate of 3.2%. This and other investigations have reported posttreatment residual vessel stenoses in the range of 40% (Marks et al., 2006; Terada et al., 1996). High incidences of angiographic vessel dissection have been documented, although they have rarely been noted to manifest as clinical events (Kiyosue et al., 2004; Marks et al., 2006; Mori et al., 1998; Wojak et al., 2006). Durability of primary angioplasty has also been questioned, with documented retreatment rates near 20% (Siddiq et al., 2008). Mori et al. (1998) investigated lesion-specific features that predicted successful angioplasty and low restenosis rates. They determined that short segment, concentric narrowing, and subtotal angiographic occlusion correlated with the lowest incidence of restenosis following percutaneous transluminal angioplasty (PTA). By contrast, features that portended poor outcome or higher rates of restenosis were eccentricity, extreme angularity, length greater than 10 mm, or excessive tortuosity of the proximal vessel segment. Additionally, the success rate was significantly lower for lesions treated greater than 3 months from the time of stroke.

Experience in the coronary literature indicated that the shortcomings of primary angioplasty (plaque dislodgement, acute elastic recoil, vessel dissection, recurrent stenosis) could be overcome by subsequent stent deployment (George et al., 1998; Savage et al., 1998; Serruys et al., 1994). These concepts were translated directly to the intracranial vasculature.

Intracranial Angioplasty and Stenting

Several early case reports described angioplasty and stenting of cerebral vessels using coronary artery techniques (Chow et al., 2005; Feldman et al., 1996; Gomez et al., 2000; Yu et al., 2005). Device rigidity and vascular tortuosity rendered navigation difficult, resulting in periprocedural morbidity and mortality rates greater than that of angioplasty alone (Chow et al., 2005; Gomez et al., 2000; Jiang et al., 2004; Kim et al., 2004; Levy et al., 2001; Yu et al., 2005). The multicenter nonrandomized Stenting in Symptomatic Atherosclerotic Lesions of Vertebral and Intracranial Arteries (SSYLVIA) trial reported the safety and efficacy of a balloon-mounted stent (Neurolink, Guidant Corporation, Indianapolis, Indiana) designed specifically for craniocervical application; 43 patients with symptomatic intracranial disease and 18 with extracranial vertebral artery stenoses were evaluated. Successful stent placement was achieved in 95% of patients. The investigators reported a 6.6% periprocedural stroke rate and an additional 7.3% incidence of stroke at 1-year follow-up. However, angiographic restenosis was documented in 35% of patients and was symptomatic in over one-third of these individuals (SSYLVIA Study Investigators, 2004). Based on these data, the FDA granted the stent a humanitarian device exemption (HDE) for the treatment of high-risk patients with significant intracranial and extracranial atherosclerotic disease who had failed medical therapy. More recent studies have investigated modified balloon-mounted stenting systems designed exclusively for the cerebral vasculature. Jiang et al. (2004) documented a 91.7% rate of technical success with the Apollo intracranial stent (MicroPort Medical, Shanghai, China) in patients harboring stenoses greater than 50%. The primary endpoint, ischemic stroke in the target lesion arterial territory or any stroke/death within 30 days, occurred at a rate of 4.3 per 100 patient-years. A restenosis rate of 28% was reported. The Vitesse Intracranial Stent Study for Ischemic Therapy (VISSIT), designed to evaluate the Pharos Vitesse system (Micrus Endovascular, San Jose, California), is currently underway (Kurre et al., 2008b).

The Wingspan stent is the first self-expanding system designed solely for intracranial application (Fig. 47.8). A nitinol (nickel and titanium metal alloy with shape memory and superelasticity) construct with high radial force allows navigation of small and tortuous intracranial vessels. Recently the FDA granted an HDE approval for the Wingspan Stent System with Gateway PTA balloon catheter (Boston Scientific, Natick, Massachusetts) for symptomatic ICAD referable to an intracranial vessel with greater than 50% stenosis and refractory to medical therapy. Endorsement was predicated on a safety study conducted in Europe and Asia (Bose et al., 2007). In that initial investigation, technical success was achieved in 98% of patients, and the 6-month death or ipsilateral stroke rate was 7%, with an all-cause stoke rate of 9.7%. In the more recent NIH Multicenter Wingspan Intracranial Stent Registry Study, 129 patients with symptomatic 70% to 99% intracranial stenoses were enrolled. The technical success rate was 97%. The frequency of any stroke, intracerebral hemorrhage, and death within 30 days or ipsilateral stroke beyond 30 days was 14% at 6 months (Zaidat et al., 2008). The reported frequency of angiographic restenosis was 25%.

Fig. 47.8 Gateway balloon and Wingspan stent (diagrammatic rendering on left). Stent deployment across an intracranial stenotic lesion with resultant opening of vessel lumen (right).

(Pictures courtesy Boston Scientific.)

In-stent restenosis has decreased following cardiac angioplasty and stenting procedures with the advent of drug-eluting stents (Regar et al., 2002). While this generation of stents may be useful in reducing myointimal hyperplasia, no platforms have been specifically designed and approved for use in the small and tortuous intracranial vessels.

Angioplasty/Stenting Procedure

Intracranial angioplasty and stenting with the Gateway/Wingspan system is most often performed under general endotracheal anesthesia. Dual antiplatelet therapy is initiated in anticipation of the procedure. A diagnostic cerebral angiogram is performed to assess degree of stenosis, length of diseased segment, flow restriction, and the presence of leptomeningeal collaterals. A shuttle sheath or guide catheter is used to maintain proximal position and accommodate the angioplasty/stenting platform. Some operators use a distal support catheter in patients with particularly tortuous anatomy. After a microcatheter/microguidewire system is advanced past the lesion, an exchange-length microwire is used to advance, in series, the balloon angioplasty and stent catheters to the level of stenosis. The lesion is initially dilated with a PTA balloon sized to 80% of the native vessel luminal diameter, using the slow inflation technique advocated by Connors and Wojak (Connors and Wojak, 1999). After initial vessel dilation, the balloon catheter is exchanged for the self-expanding stent system, which is deployed across the stenotic lesion. Post-stenting balloon dilation is discouraged by the manufacturer (Figs. 47.9 and 47.10). At the conclusion of the procedure, the average reported residual stenosis (30%) is less than that observed following PTA alone (40%) but more than noted after balloon-mounted stent deployment (10%) (Fiorella and Woo, 2007; Henkes et al., 2005). Follow-up angiograms have demonstrated restenosis rates exceeding 30%, presumably due to elastic recoil, myointimal hyperplasia, and vascular remodeling (Garas et al., 2001). Coating stents with antiproliferative agents such as sirolimus and paclitaxel has been effective in reducing restenosis rates in the cardiology literature (Ong et al., 2006; Stone et al., 2004). Several recent studies have demonstrated encouraging results for the treatment of ICAD patients with drug-eluting stents (Gupta et al., 2006; Qureshi et al., 2006). Difficult vessel navigation with more rigid stenting systems and prolonged postoperative treatment with dual antiplatelet therapies are among the potential limitations to the successful translation of drug-eluting technology to pathologies of the intracranial vasculature.

Fig. 47.9 Anteroposterior (top left) and lateral (bottom right) angiograms demonstrating critical tandem petrocavernous and supraclinoid left internal carotid artery stenoses with no filling of left anterior cerebral artery and diminished flow through right left middle cerebral artery.

Fig. 47.10 Same patient as in Fig. 47.9. Top x-rays demonstrate balloon positioned across petrocavernous stenosis (black marker is the midpoint of the balloon, left) and stents deployed across petrocavernous and supraclinoid lesions (right). Anteroposterior (left) and lateral (right) post-stenting angiograms on the bottom demonstrate increased flow through stenoses and filling of both anterior and middle cerebral arteries on left.

Decision Matrix

Endovascular Treatment Modalities

Coil Embolization

Diagnostic cerebral angiography is necessary prior to coil embolization of both incidentally discovered and ruptured intracranial aneurysms. Often a focused angiographic examination is sufficient when treating an incidental aneurysm in a patient with thorough noninvasive preoperative cerebrovascular imaging. It is critical, however, to evaluate the entire craniocervical vasculature for potential sources of subarachnoid hemorrhage. While many institutions rely upon high-quality CTA or MRA for this purpose, digital subtraction angiography remains the diagnostic gold standard. In the event no aneurysm or vascular malformation is discovered after a complete intracranial angiogram (bilateral internal carotid/vertebral arteries), it is necessary to assess the ascending cervical and posterior deep cervical branches of the subclavian artery and the bilateral external carotid arteries for the presence of a dural arteriovenous fistula. Delayed repeat angiography is often warranted in cases with a comprehensive negative initial study and a suspicious pattern of subarachnoid blood.

Following diagnostic cerebral angiography, aneurysm morphology and regional vascular anatomy are carefully assessed to determine the safety and feasibility of coil embolization. Certain anatomical configurations render endovascular treatment more difficult. Aneurysms with larger neck-to-dome ratios and those that incorporate the origins of critical vessels are less amenable to primary coil embolization.

Once coil embolization is selected as the treatment modality, a microcatheter is advanced over a microguidewire through a larger diagnostic or guide catheter. Under real-time digital subtraction fluoroscopy, the microsystem is advanced into the aneurysm. From this position, coils may be deployed.

Dr. Guglielmi first introduced electrolytically detachable platinum microcoils in 1990. Initially, only aneurysms judged to be high risk for microsurgical clipping were treated by coil embolization. Since that time, rapid technological advancements have resulted in more efficacious endovascular treatment of complex aneurysms. Improved detachment mechanisms, stretch-resistant coils, three-dimensional complex shapes (Piotin et al., 2003; Wakhloo et al., 2007), varying degrees of softness, and coil lattice incorporating a bioabsorbable polymer (Fiorella et al., 2006; Linfante et al., 2005; Murayama et al., 2003) or hydrogel (Cloft, 2006; Gaba et al., 2006) have been designed to minimize procedural complications and help prevent delayed recanalization.

Coil embolization technique involves the careful placement of a framing coil into the aneurysm dome under real-time digital subtraction fluoroscopy. Once appropriate position is confirmed, the coil is detached. Proper selection and methodical placement of the first coil is of paramount importance, as this often establishes technical ease and safety of the entire procedure. If residual aneurysm filling is noted, additional coils of various shapes and successively diminishing sizes are deployed until complete occlusion is obtained (Fig. 47.11).

Fig. 47.11 Three-dimensional coil (left) and diagrammatic depiction of coil deployment through a microcatheter positioned in an aneurysm (right).

(Pictures courtesy Boston Scientific.)

Balloon Remodeling

Initially described by Moret et al. (1997), the balloon remodeling technique affords an ability to effectively treat broad-necked cerebral aneurysms by mechanically protecting the parent vessel from coil prolapse or protrusion. Positioned within the parent artery, a small balloon occlusion microcatheter is intermittently inflated and deflated across the aneurysm neck (Fig. 47.12). This provides temporary structural support against which coils are then deployed through a second microcatheter located within the aneurysm dome. Anterograde flow is completely reestablished within the parent artery after successive balloon deflations. This adjunctive technique extends the indication for endovascular aneurysm treatment to cases with less favorable anatomy. It is suggested that remodeling leads to higher packing densities and more effective parent vessel reconstruction (Kurre et al., 2008). In a review of their initial experience, the Moret group documented complete angiographic occlusion in 20 of 21 broad-necked cerebral aneurysms treated via balloon-assisted coil embolization. They reported sustained occlusion without recanalization at angiographic follow-up of at least 4 months. The authors noted complication rates that were no greater than those experienced with primary coil embolization techniques (Moret et al., 1997). These results have been corroborated by several more recent clinical series (Cottier et al., 2001; Lefkowitz et al., 1999; Malek et al., 2000). Balloon assistance has greatly facilitated the endovascular treatment of wide-necked ruptured cerebral aneurysms in the acute phase, allowing for mechanical coil support and vessel remodeling in the absence of prolonged antiplatelet therapy.

Fig. 47.12 Diagram demonstrating balloon remodeling technique with HyperForm balloon (ev3 Inc., Irvine, California) prior to coil placement. Balloon is positioned across neck of aneurysm to temporarily prevent coil herniation into parent vessel.

Stent-Assisted Coil Embolization

In more challenging broad-necked cerebral aneurysms, balloon remodeling may not be sufficient to prevent coil protrusion into the parent vessel. In such cases an endoluminal/endovascular approach uses a permanently deployed intracranial stent as supportive scaffolding. Nitinol self-expanding stents with either open or closed-cell configuration have been designed exclusively for use in the intracranial vasculature (Akpek et al., 2005; Higashida et al., 2005) (Fig. 47.13). Many groups deploy a stent across the aneurysm neck and then introduce the coiling microcatheter into the sac through the stent interstices. An alternative method is to first position the coiling microcatheter within the aneurysm dome and then “jail” the distal tip in position through subsequent stent deployment. With either strategy, stent placement precedes positioning and detachment of the coils within the aneurysm (Figs. 47.14 and 47.15). Clinical studies have documented favorable results, with initial occlusion rates over 80% (Lylyk et al., 2005). While prospective studies have documented persistent complete or near-complete angiographic occlusion at 20 months, long-term data are necessary to determine sustained viability of stent-assisted coiling techniques (Fiorella et al., 2004). Studies have reported the use of complex stent-assisted techniques such as telescoping/overlapping multiple stents for the treatment of fusiform aneurysms (Crowley et al., 2009) and Y-stent configurations for bifurcation aneurysms (Chow et al., 2004). To date, stent-assisted coil embolization has been largely reserved for the treatment of unruptured aneurysms. Most physicians are reluctant to deploy stents in the setting of SAH, because they require aggressive long-term antithrombotic regimens to protect against thrombosis and embolic events.

Fig. 47.13 Picture of a Neuroform stent with open-cell design (left) and diagrammatic depiction of stent-assisted coil embolization through a microcatheter positioned in an aneurysm (right). Note that stent provides permanent scaffolding for stabilization of coil mass.

(Pictures courtesy Boston Scientific.)

Fig. 47.14 Three-dimensional reconstruction of a left superior hypophyseal region aneurysm (left). Measurements (right) demonstrate cranial-caudad (1) and transverse (3) dimensions of aneurysm and size of the neck (2).

Fig. 47.15 Same aneurysm seen in Fig. 47.12. Large size of aneurysm neck compared to dome led to stent-assisted coiling technique being employed. Top left, Working projection oblique angiogram demonstrating stent tines positioned across neck of aneurysm. Top right, Arrows point to proximal and distal stent tines. Bottom left, Unsubtracted view demonstrating stent position and coil mass. Bottom right, Postintervention angiogram in working projection showing no residual aneurismal neck and no filling within coil mass.

Alternative Treatments

Substantial incomplete occlusion and subsequent recanalization rates following coil embolization have raised concerns regarding the durability of endovascular treatment for cerebral aneurysms with unfavorable geometry (Debrun et al., 1998; Fernandez Zubillaga et al., 1994; Guglielmi et al., 1992; Piske et al., 2009; Taha et al., 2006). Experimental models have demonstrated that coils occupy less than 40% of aneurysmal volume. Therefore, residual flow may remain even in tightly packed lesions (Piotin et al., 2000, 2003). This has prompted the development and application of novel techniques such as liquid embolic agents and flow-diverting stents.

Liquid embolic agents may permit more efficient aneurysmal dome and neck filling. Onyx LES (liquid embolic system [ev3 Inc., Irvine, California]) is an embolic system initially developed to treat high-flow lesions such as AVMs and fistulae. It is an ethylene vinyl alcohol dissolved in the organic solvent, dimethyl sulfoxide (DMSO), that precipitates to form a polymer cast when contacted by aqueous solution. The Cerebral Aneurysm Multicenter European Onyx (CAMEO) study assessed the safety and efficacy of Onyx HD-500 in treating aneurysms that presented difficulties for surgical or endovascular alternatives (wide necks/unfavorable geometry). Balloon remodeling was required in all cases. At 12-month follow-up, the authors reported higher occlusion rates, better outcome, and similar complication rates when compared to those reported with traditional embolization methods in comparable study cohorts (Molyneux et al., 2004). Similar results were noted in several other large case series (Cekirge et al., 2006; Piske et al., 2009).

The advent of flow-diversion devices represents a potential paradigm shift in the treatment strategy for broad-necked intracranial aneurysms. Circumferential endoluminal parent-vessel reconstruction may allow for complete aneurysmal occlusion in the absence of direct endovascular embolization. The Pipeline Embolization Device (PED [ev3 Inc., Irvine, California]) is specifically engineered to reconstruct a segmentally diseased vessel. Lylyk et al. (2009) detailed a large initial experience with the PED; 53 patients with 63 wide-necked aneurysms were treated. The study reported a mean follow-up time of 5.9 months. Complete angiographic occlusion was achieved in 95% of aneurysms, and no major complications were encountered. The investigation found the device to be safe, durable, and curative for selected wide-necked large or giant aneurysms.

Although initial data appear quite promising, further large-scale investigations are needed to determine the clinical efficacy and long-term durability of liquid embolic agents and flow-diversion devices in the treatment of cerebral aneurysms. The rapid emergence of new device technology has vastly increased the number of aneurysms treatable by endovascular methods. However, fusiform aneurysms and those with broad necks or critical branches emanating from the dome are still optimally treated with craniotomy and clip ligation.

Balloon Angioplasty

A technique first applied by Zubkov et al. in 1984, percutaneous transluminal angioplasty commonly results in permanent mechanical reversal of cerebral vasospasm (Zubkov et al., 1984). The precise mode of action remains poorly understood. Proposed mechanisms for smooth-muscle dysfunction include endothelial denudation, collagen fiber stretching, and rupture of internal elastic lamina (Chan et al., 1995; Honma et al., 1995; Macdonald et al., 1995; Yamamoto et al., 1992).

If severe vasospasm is suspected, percutaneous balloon angioplasty is typically performed under general anesthesia with full muscle paralysis. A noncontrast head CT is obtained immediately prior to angiography to rule out rebleeding, hydrocephalus, or completed infarct. If available, careful examination of a prevasospasm angiogram or vascular study is critical. This allows for assessment of congenitally hypoplastic vascular segments and avoidance of dangerous balloon inflation in unaffected vessels. Vigilant blood pressure control and intracranial pressure monitoring are maintained throughout the treatment. The patient is anticoagulated, and a guide catheter is positioned in the proximal segment of the target vessel. Next, a balloon catheter is advanced over a microguidewire to the level of vessel narrowing. Two differing balloon technologies have been employed. Our preference is the more compliant Hyperglide/Hyperform (ev3 Inc., Irvine, California) or Sentry (Boston Scientific, Natick, Massachusetts) balloon catheters. The catheter lumen distal to the balloon tapers and is effectively occluded by a microguidewire, causing injected contrast to expand the balloon. The guidewire is left in place during balloon inflation and a 50 : 50 mixture of contrast and saline is used to ensure adequate angiographic opacification. Dilatation is performed until vessel conformation is noted in the shape of the balloon. Other groups employ less pliable noncompliant balloon devices such as the Gateway system or Maverick coronary balloon (Boston Scientific, Natick, Massachusetts) (Eddleman et al., 2009). In either case, the balloon is slowly inflated over the length of the accessible spastic segment, attempting to attain dilatation to greater than 50% of the original vessel caliber. Abrupt overdilation is avoided to decrease the risk of rupture and arterial dissection. Balloon angioplasty is generally restricted to larger proximal vessels of the circle of Willis and, less commonly, the smaller immediately more distal branches. Balloon angioplasty can also be effectively used to open proximal vessels and facilitate catheterization of small distal vessels previously inaccessible to microcatheters. This permits potential for subsequent injection of IA vasodilators in the respective distal vascular territories (Fig. 47.16).

Fig. 47.16 Top left, Anteroposterior (AP) angiogram demonstrating severe narrowing of M1 segment of left middle cerebral artery and moderate stenosis of A1 segment of left anterior cerebral artery. Top right, Hyperglide balloon positioned across narrowed middle cerebral artery segment. Note two radiopaque markers that confirm position of balloon. Bottom left, Post-dilatation AP angiogram demonstrating an increase in caliber of proximal left middle cerebral artery.

An analysis of six retrospective series reporting treatment of cerebral vasospasm by balloon angioplasty demonstrated a mean clinical improvement of 65% (Komotar et al., 2008b). Eskridge et al. (1998) conducted the largest study, examining 50 patients and 170 arterial segments; 61% of patients demonstrated sustained clinical improvement within 72 hours of balloon angioplasty treatment. In a 2005 literature review, Hoh and Ogilvy (2005) found an overall clinical improvement in 62% of patients treated for vasospasm with balloon angioplasty. Rosenwasser et al. (1999) sought to ascertain the time period during which balloon angioplasty was maximally effective. The authors determined that 70% of patients treated within 2 hours of symptom onset demonstrated clinical improvement. By contrast, only 40% of those treated beyond the 2-hour window sustained recovery. Rates of angiographic vasospasm resolution were similar between the two cohorts, indicating that earlier treatment of patients with medically resistant cerebral vasospasm results in superior clinical outcome despite similar radiographic results. Preemptive balloon angioplasty has been advocated for vasospasm prophylaxis in high-risk patients (Muizelaar et al., 1999). A multicenter phase II study published in 2008 that evaluated prophylactic balloon angioplasty in patients with Fisher grade III SAH demonstrated no significant difference in Glasgow Outcome Score when compared to patients treated with standard-of-care therapy. While a statistically significant decrease in the need for therapeutic angioplasty was reported, four procedure-related vessel perforations and three resultant deaths were documented in the prophylaxis cohort (Zwienenberg-Lee et al., 2008).

Intraarterial Vasodilators

Intraarterial vasodilator therapy is often used to treat mild to moderate clinical vasospasm or disease affecting the more distal intracranial vasculature. Administration of IA pharmacological therapy is achieved in a technical fashion similar to that of balloon angioplasty, although often performed under conscious sedation. A guide/diagnostic catheter is advanced into the proximal portion of the affected vessel. The vasodilatory agent is then injected either directly through the larger catheter or via a microcatheter advanced to a more selective distal position within the target vessel. A slow infusion rate coupled with meticulous monitoring is critical in order to avoid systemic hypotension or undesired increases in ICP. To date, the most robust data regarding efficacy of IA pharmacological therapy for the treatment of cerebral vasospasm has been accumulated with papaverine. An opium alkaloid and nonspecific smooth muscle–cell relaxant, papaverine causes vasodilation through cyclic adenosine and guanosine monophosphate phosphodiesterase inhibition and has a half-life of nearly 2 hours. Investigations have documented incidences of immediate angiographic vasospasm relief ranging between 57% and 90% (Firlik et al., 1997; Kassell et al., 1992; Milburn et al., 1998). Hoh and Ogilvy reported in their systematic review that although papaverine produced clinical improvement in 43% of treated patients, the effect was temporary, and individuals often needed multiple treatment sessions. High rates of relapse in clinical vasospasm have been documented within 48 hours of treatment (Hoh and Ogilvy, 2005; Komotar et al., 2008b).

Concerns regarding the toxicity profile and short effect of papaverine have prompted the off-label use of IA calcium channel antagonists in the treatment of cerebral vasospasm (Smith et al., 2004). Feng et al. (2002) reported a 45% increase in vessel diameter and 33% clinical improvement following verapamil administration. Similarly, neurological improvement was documented in 42% of patients receiving IA nicardipine (Badjatia et al., 2004). Biondi et al. (2004) demonstrated a 43% rate of vessel dilation and a 76% incidence of clinical improvement in the first 24 hours following IA administration of nimodipine. The most significant shortcoming associated with the use of IA vasodilator therapy is the transitory efficacy. Repeat endovascular instillation is often necessary (Brisman et al., 2006; Hoh and Ogilvy, 2005). Furthermore, studies have demonstrated that longer durations of vasoconstriction are less responsive to treatment (Scroop, 2004). Side effects including systemic hypotension and increased ICP have further limited the effectiveness of these therapies, each directly related to rate of infusion (McAuliffe et al., 1995).

Polyvinyl Alcohol

Polyvinyl alcohol (PVA) particles (Boston Scientific, Natick, Massachusetts) were the first material approved by the FDA for intravascular use. Dependent on flow, they are sized to the caliber of the target vessel. Consequently, the microcatheter lumen must be able to accommodate the particle diameter and prevent occlusion secondary to aggregation. Particle embolization occurs in a slower fashion than liquid embolic occlusion. Often, low-flow shunts are disconnected first, leading to increased pressure in the remaining feeding arteries and nidal vessels and rendering the AVM susceptible to rupture. Transient and permanent morbidity rates of 14.3% and 8.6%, respectively, have been reported following particle treatment (Schumacher and Horton, 1991). Nidal recanalization is the most significant failing associated with particle embolization. Following proximal occlusion, development of collateral supply results in persistent shunting through the malformation. In a large series, Sorimachi et al. (1999) reported a 43% rate of enlargement following particle embolization and an 80% nidal recanalization rate in completely occluded lesions. Mathis et al. (1995) demonstrated a 12% recanalization rate in AVMs embolized prior to stereotactic radiosurgery.

n-Butyl Cyanoacrylate

n-Butyl cyanoacrylate (nBCA) (TRUFILL [Cordis Neurovascular Inc., Miami Lakes, Florida]) is an adhesive liquid monomeric agent that polymerizes and solidifies upon coming into contact with an ionic solution such as blood (Debrun et al., 1997). Administration results in marked chronic inflammation, fibrosis, and vessel occlusion (Kish et al., 1983; Klara et al., 1985; Wikholm et al., 2001). The safety of nBCA in AVM embolization was assessed in a prospective randomized non-inferiority trial demonstrating that nBCA was equivalent to PVA in achieving target embolization volume goal and reduction in feeding vessel number. The rates of permanent occlusion were more favorable in the nBCA group, with very low incidences of recanalization (n-BCA Trial Investigators, 2002). These results led to FDA approval for this indication. More recent investigations confirm that nBCA embolization results in complete, durable vessel occlusion. Yu et al. (2004) reported no recanalization at 17- to 32-month follow-up in a series of AVMs treated with nBCA. Wikholm et al. (2001) demonstrated a lack of recanalization at 5-year follow-up. Achieving nidal penetration requires modification of polymerization and viscosity parameters according to the hemodynamic characteristics of the lesion. Such factors are adjusted by varying the relative concentrations of Thiodol and nBCA in the treatment mixture. Some groups advocate changing the pH of the solution with an organic acid such as glacial acetic acid to lengthen polymerization time (Lieber et al., 2005). Outcomes following nBCA embolization by experienced operators are favorable. In a series of 103 patients, Liu et al. (2000) reported transient and permanent complications of 4.9% and 1.9%, respectively, as well as two deaths. Gobin et al. (1996) documented morbidity and mortality rates of 12.8% and 1.8%, respectively.

Disadvantages of nBCA include short delivery times and the potential for microcatheter retention, which can result in vessel rupture or adverse ischemic sequelae. Additionally, proper administration requires precise understanding of the polymerization kinetics of acrylate. The nBCA in dextrose solution is injected through a microcatheter under constant real-time roadmapping technique until adequate nidal penetration is achieved with minimal reflux. The microsystem is then quickly withdrawn to avoid catheter retention within the glue cast. In lesions with high-flow fistulous components, coils may be deployed prior to nBCA injection to prevent venous egress of liquid adhesive material. The embolization of feeding artery aneurysms is performed by placing the microcatheter tip in or proximal to the aneurysm and allowing glue to infiltrate the AVM nidus while casting the aneurysmal sac.

Ethylene Vinyl Alcohol Copolymer

Ethylene vinyl alcohol copolymer was first proposed for the treatment of AVMs by Taki in 1990 (Taki et al., 1990). Subsequently, many groups have reported on its use as a liquid embolic agent (Jahan et al., 2001; Murayama et al., 1998). As noted earlier, Onyx consists of an ethyl-vinyl copolymer dissolved in DMSO, with tantalum powder added for increased radiopacity. Slow solidification permits prolonged controlled injections, with allowance for continuous assessment and deeper nidal penetration with each catheterization (Katsaridis et al., 2008; Murayama et al., 1998). Onyx was first tested in a phase I investigation conducted by Jahan et al. (2001). The group demonstrated a 63% volume reduction in 23 AVM patients with 129 targeted feeding artery pedicles. They reported a 12% transient and 4% permanent associated morbidity. Van Rooij and colleagues treated 44 patients with Onyx, embolizing 138 pedicles in 52 sessions. They documented an average volume reduction of 75%, with complete occlusion of 7 lesions (van Rooij et al., 2007). A morbidity rate of 8.5% and a mortality rate of 3.2% were reported. More recently, several large single-center case series have assessed potential for complete AVM occlusion with Onyx embolization. Katsaridis et al. (2008) reported a 53.9% rate of complete occlusion, with an associated morbidity and mortality of 3.7% and 1.4%, respectively, per embolization session. Using a combination of Onyx and nBCA therapy (Onyx as the first-line agent), Mounayer et al. (2007) reported a 49% complete occlusion rate, with similar incidences of complications (8.5% morbidity, 3.2% mortality).

Although it has revolutionized the way many groups treat brain AVMs, Onyx LES carries inherent limitations and disadvantages. It can be used only with DMSO-compatible catheters. This prohibits the use of most flow-guided microsystems that facilitate access to small distal intracranial vessels. Additionally, DMSO can be directly angiotoxic if injected too rapidly into the cerebral vasculature (Jahan et al., 2001). Furthermore, limited opacification may prevent adequate visualization of reflux into small vessels supplying viable cortical tissue (van Rooij et al., 2007). Recent studies have also suggested that Onyx AVM embolization requires increased fluoroscopy and procedure times compared to nBCA (Velat et al., 2008).

Embolization Materials

A number of agents have been used to embolize tumors, including particles (Bendszus et al., 2000; Wakhloo et al., 1993), nBCA (Capo et al., 1991), Onyx (Shi et al., 2008), platinum coils (Guglielmi, 1998), ethanol (Jungreis, 1991), fibrin glue (Probst et al., 1999), and gelfoam pledgets (Manelfe et al., 1986; Richter and Schachenmayr, 1983). Particulate agents are generally favored over liquid embolic materials owing to their ease of use and relative safety. The precise penetration capacity of particles is dependent on their size, so appropriate selection precludes infiltration into the small arterioles supplying cranial nerves. Since the vasa nervorum are small, the use of particles larger than 150 microns in diameter has been suggested to lessen the risk of ischemic cranial nerve injury (Bendszus et al., 2005; Carli et al., 2010). PVA particles are believed to remain occlusive in vessels for weeks, after which vascular recanalization may occur (Kuroiwa et al., 1996). This property is suitable for preoperative tumor embolization. Because the tumor mass is excised during definitive surgical resection, a long-term durable embolization is not necessary. These agents have been shown by several groups to be safe and effective in decreasing intraoperative blood loss in paraganglioma surgery (Persky et al., 2002; Tikkakoski et al., 1997). After particle embolization is performed, a platinum coil or gelfoam pledget may be placed more proximally in the treated vessel to help prevent recanalization and aid in surgical transection (Dowd et al., 2003). In contrast to particles, liquid embolic materials such as nBCA and Onyx can more easily enter anastomotic channels that supply cranial nerves or cortical vessels not evident on the initial diagnostic angiogram. The operator must be acutely aware of this possibility when using such agents for tumor embolization. Additionally, microcatheter retention can result in vessel rupture or ischemic sequelae. As more aggressive liquid embolic agents are often used for palliative embolization, care must be taken to avoid proximal reflux of any embolic material into eloquent vascular branches.

Vessel Selection

Determining target vessels for endovascular therapy may be difficult. Embolization can effectively obliterate high-flow arteriovenous shunting through the tumor vasculature. Most agree that large external carotid artery branches that directly supply a tumor mass and are distant from dangerous anastomoses may be treated. However, intracranial tumors supplied by both the external and internal carotid artery are reported to exhibit increased pial supply subsequent to embolization of external branches (Manelfe et al., 1986). Augmented blood flow and hypertrophy of the small, deep intracranial vessels may increase the difficulty of the surgical resection, since this vascular supply is often not encountered until the end of the operation. Unless necessary, preoperative embolization of pial blood supply is generally avoided; the benefit of embolization is usually outweighed by the potential risk of ischemia.

Clinical Evidence

Several large case series document angiographic, histological, and surgical benefit following meningioma embolization (Dean et al., 1994; Gruber et al., 2000; Macpherson, 1991; Manelfe et al., 1986; Wakhloo et al., 1993; Yoon et al., 2008). Endovascular treatment of juvenile nasopharyngeal angiofibromas has been shown to reduce both perioperative blood loss and the duration of surgical resection (Davis, 1987; Economou et al., 1988; Roberson et al., 1979). Other reports question the benefit, citing no differences in operative time, blood loss, or clinical outcome (Bendszus et al., 2000). Some groups reserve preoperative embolization for difficult skull-base lesions, referencing complication rates deemed unacceptable for straightforward surgical resections (Rosen et al., 2002). The optimal timing of resection following tumor embolization has been debated. Some operators contend that timing of surgery does not affect outcome, but others have advocated delayed resection to allow for interval tumor necrosis. A comparative retrospective analysis of 50 patients who underwent preoperative embolization for meningioma resection indicated that delaying resection more than 24 hours after embolization can decrease intraoperative blood loss (Chun et al., 2002). Other groups have suggested that the optimal interval between embolization and resection is between 7 and 9 days, as this permits maximal tumor softening (Kai et al., 2002). A significantly long interval between particulate embolization and surgical resection, however, may allow for recanalization of blood vessels supplying the tumor.

Significant neurological deficits have been reported following preoperative tumor embolization. Causes include distal vessel occlusion, reflux of embolic agents, cranial nerve injury, and tumor swelling or hemorrhage following devascularization (Bendszus et al., 2005; Carli et al., 2010; Marangos and Schumacher, 1999). Therefore, potential benefits of embolization must be carefully weighed against the risk of adverse outcome. Patients harboring large hypervascular tumors supplied primarily by external carotid artery branches that are located in anatomical regions difficult to access surgically likely derive the greatest benefit from preoperative embolization.