Introduction

   Endovascular treatment with detachable coils is now considered to be very effective in therapy for cerebral aneurysms.^4)14)23)31) However, aneurysms with wide necks or unfavorable neck-to-fundus ratios are not appropriate for this method because of high risk of coil herniation into the parent artery during the treatment⁷⁾²⁸⁾ and high recanalization rate after the treatment.^12)29)30) For this, balloon remodeling technique or use of three-dimensional coil are introduced.^6)18)21) However, these techniques are not satisfactory in the treatment of wide-necked aneurysms.
   Recently there have been several reports in the endovascular treatment of wide-necked aneurysms with a stent and detachable coils.^{2)10)11)22)27)} Stent placement across the neck of the aneurysm provides protection of the parent vessel, which prevents the coils from herniating into the parent vessel and potentially permits tighter packing of the aneurysm. Although many investigators have reported successful treatment of cerebral aneurysms with this technique, the application of stent technology has been restricted by the difficulty associated with the endovascular navigation of stiff, balloon-expanding coronary stents to the tortuous cerebral vasculature.^11)22)27) 
   Since September 2002, however, the Neuroform(Boston Scientific SMART, San Leandro, CA), self-expanding, stent was developed. It is constructed of a nickel-titanium alloy known as nitinol. It is designed specifically for the treatment of patients with wide-necked intracranial aneurysms. This self-expanding stent has an ulrathin, open-cell mesh design and exerts a low radial force than stents used in the treatment of atherosclerotic disease. It is highly flexible stent system enough to navigate the turns of intracranial vessels, even the carotid siphon, and does not straighten or deform curved parent vessels. Once expanded, the interstices of the stent are larger enough to accommodate the coiling microcatheter. The microguidewire is directed into the aneurysm and the microcatheter is then advanced over the wire between the stent interstices and into the aneurysm. Coil embolization of the aneurysm is then performed in the standard manner. This article describes the endovascular technique, efficacy, and limitations of the stent-assisted coil embolization in wide-necked cerebral aneurysms.

1. Endovascular technique
   Patients who presented for elective treatment of unruptured cerebral aneurysms are pretreated with 100 mg aspirin and 75 mg clopidogrel(Plavix；Bristol-Myers Aquibb/Sanofi Pharmaceuticals, New York, NY) for 3 days. No patients with ruptured aneurysms are pretreated with antiplatelet agents. All procedures are performed while the patients are under general anesthesia with neurophysiological monitoring. All patients are fully anticoagulated after the diagnostic portion of the procedure. Therapeutic anticoagulation is verified with an activated clotting time longer than 200 seconds. After diagnostic angiography is performed, the appropriate working angles for stent delivery and aneurysm coiling are recorded. The dimensions of the parent vessel in the region of the targeted landing zone for stent delivery are defined. The appropriately sized Neuroform stent is selected(available sizes include 3.0-, 3.5-, 4.0-, and 4.5-mm nominal diameters with 15- and 20-mm nominal lengths). Stents are sized to a nominal diameter 0.5 to 1.0 mm greater than the parent vessel at the targeted landing zone. The stent length is chosen to provide at least a 5-mm landing zone on either side of the aneurysm neck.
   A 6-French 90-cm guiding catheter is introduced from the right femoral artery to the cervical segment of the target vessel. The Neuroform stent delivery system, consisting of the self-expanding Neuroform stent preloaded into a 3-French stent delivery microcatheter catheter containing a 0.025-inch over-the-wire stabilizer and 0.014-inch microwire(Transend-14；Boston Scientific, Fremont, CA) is flushed and assembled in the sterile field. The delivery system is then advanced over the microwire and manipulated into the parent vessel, distal to the aneurysm neck, under high-magnification fluo-roscopic roadmap control. The stabilizer catheter is then ad-vanced to push the stent toward the radioopaque marker in-dicating the distal tip of the delivery catheter. When the stent is mobilized within the delivery catheter and pushed to within 2 mm of the distal marker, the entire delivery system is retracted to the targeted landing zone. Once appropriately positioned across the aneurysm neck, the delivery catheter is retracted toward the stabilizer catheter to unsheathe the stent. After deployment of the stent, the stent system with the mi-crowire is removed, and a microcatheter with a preshaped soft microguidewire can be used to enter the aneurysm through the interstices of the stent. Finally, detachable coils are in-troduced into the aneurysm and detached as usual until oc-clusion is achieved. After sufficient packing of the aneurysm, the microcatheter is pulled back.
   There are two ways for selection of an aneurysm after stent deployment. One is to deploy the stent, followed by coil placement. After stent deployment, the microcatheter and microguidewire can then be navigated into the proximal stent. The aneurysm can then be selected with the microguidewire and the catheter. The other is to place the coil microcatheter within the aneurysm sac before stent deployment. In this technique the microcatheter is located between the stent and the parent vessel wall. In most cases an aneurysm can be selected with the former technique. However, in some cases, aneurysm selection is very difficult after stent deployment. In these cases, the latter technique, i.e., aneurysm selection followed by stent deployment, is useful. However, this is potentially dangerous in that it may result in aneurysm perforation, especially in small, acutely ruptured aneurysms, although there is no report on the aneurysm rupture with this technique.
   After the procedure, patients with unruptured aneurysms are maintained on aspirin and clopidogrel for 3 weeks, followed by aspirin alone, which is continued indefinitely. In patients who present with ruptured aneurysms, 100 mg aspirin is administered either by mouth or rectally immediately after the procedure, and 75 mg clopidogrel is administered the next morning. These patients then are treated according to the same antiplatelet regimen administered to patients with unruptured aneurysms. 

2. Advantages of stent-assisted coil embolization

1) Mechanical benefits of stent placement
   Wide-necked intracranial aneurysms present significant challenges for endovascular treatment. The wide neck creates a high risk of coil herniation into the parent vessel and increases the risk for delayed coil compaction and recanalization of the aneurysm. For this, balloon remodeling technique is introduced by Moret et al.²¹⁾ However, drawbacks of this technique include the need for the simultaneous use of two microcatheters and a larger guiding catheter and the temporary interruption of blood flow in the parent artery, which increases the risk of local and distal thromboembolism. This technique may produce a temporary increase of pressure within the aneurysm while occluding the aneurysmal neck during coil delivery. The sudden change of intraaneurysmal pressure may potentially be the cause of aneurysm rupture. Another treatment option for wide-necked aneurysms are three-dimensionally shaped coils. These coils have a omegalike memory and thus configure a basket for subsequent coils.⁶⁾¹⁸⁾ In our experience, these coils do not work well in small aneurysms and do not always allow attenuated packing down to the base without risk of coil protrusion into the parent vessel. Stent placement across the neck of the aneurysm enables a mechanical scaffold to prevent the coils from herniating into the parent vessel and potentially permits tighter packing of the aneurysm(Fig. 1). There have been many reports on the stent-assisted coil embolization in wide-necked aneurysms.^{2)10)11)22)27)} Benitez et al²⁾ reported a large series of 48 cases of stent-assisted coiling in wide-necked aneurysms. They reported 100% occlusion in 28 cases, 99% occlusion in 7 cases, greater than 90% occlusion in 4 cases, less than 90% occlusion in 3 cases, and 0% occlusion in 6 cases. The majority(35 of 48 patients) of the patients had an acute occlusion rate of 99 to 100%.

2) Hemodynamic benefits of stent placement
   There have been several reports on intraaneurysmal thrombosis induced by stent placement in a wide-necked aneurysm.^3)8)19)32) The neck orifice, or inflow zone, of the aneurysm is a surface whose area is proportional to the square of the radius of the neck. Because of this exponential relationship, a small change in the diameter of the neck can dramatically change the area of the inflow zone. Changing the hemodynamics of the inflow zone is critical for promoting thrombosis of wide-necked aneurysms. Placement of a porous stent across the inflow zone alters the dynamics of blood flow, often reducing flow into the aneurysm.^{1)13)17)34)35)} The stent acts as a new flow conduit within that vessel, hemodynamically uncoupling the vessel. The result is stagnant and reduced flow vortices within the aneurysm. A new intima may form across the stent over time, reinforcing the durability of the stent and coil construct and reducing the likelihood of a recurrence (Fig. 2).¹¹⁾ 
   The size of the aneurysm neck influences immediate aneurysmal occlusion and recanalization rate. Zubillaga et al³⁶⁾ showed complete aneurysm occlusion in 85% of small neck aneurysms and in 15% of wide neck aneurysms. Vinuela et al³³⁾ reported that complete obliteration could be obtained in only 31.2% of small aneurysms with wide necks. Debrun et al⁷⁾ also showed that absolute neck diameter significantly affected morphologic percentage occlusion. They reported that aneurysms with neck diameters(5 mm had a lower rate of complete occlusion and a higher rate of neck regrowth. The aneurysms with wider necks allowed prolapse of the coil into the parent artery that led to the prevention of complete occlusion. Tamatani et al²⁹⁾ reported that some of the subtotally embolized aneurysms at the end of initial treatment showed total obliteration on the follow-up angiograms. This might be because of further aneurismal thrombosis. However, this phenomenon was mainly observed in the small aneurysms, especially in small aneurysms with small necks. On the other hand, further aneurysmal thrombosis could not be expected for large or giant aneurysms because of their wide neck diameter. Hayakawa et al¹²⁾ reported similar results, that postembolization angiography revealed progressive thrombosis in 50% of small aneurysms with small necks and in 25% of small aneurysms with wide necks. They also showed that further thrombosis was not observed in large and giant aneurysms. In case of stent-assisted coil embolization, however, the stent alters the hemodynamics of the inflow zone, which promotes the thrombosis within the aneurysm. In our series (unpublished data), three of the four patients(for whom angiographic follow-up examination was available) with partial occlusion on initial angiography showed complete or near complete occlusion. Among these, two cases were giant and large aneurysms. Thus, complete or near complete occlusion in case of stent-assisted coil embolization is expected on follow-up angiography, even if the aneurysm is loosely packed with coils(Fig. 3).

3) Biological benefits of stent placement
   A stent provides a physical matrix for endothelial growth, facilitating the remodeling of the aneurysm neck as well as the parent vessel in the region of the aneurysm neck.¹⁵⁾²⁰⁾ Thus, stenting treats not only the aneurysm but also the diseased parent vessel. This is particularly valuable in the setting of dissecting and fusiform aneurysms in which the goal is not only to achieve aneurysm thrombosis but also, and more important, to reconstruct the parent vessel.

3. Current Issues of stent-assisted coil embolization

1) Intimal hyperplasia induced by stent placement
   One might think that stent placement is associated with a higher risk of intimal hyperplasia, possibly leading to luminal stenosis, particularly in double stent cases. However, there were no reports on in-stent restenosis on follow-up angiographic examination in which stent-assisted coil embolization was done, even in double stent cases. Only a mild intimal hyperplasia was reported in the area of the stent margins covered by the proximal stent but not in the area of stent placement.⁸⁾ Moreover, the placement of overlapping stents and use of double stents are common practice in cardiology and seem to be safe.¹⁶⁾ Furthermore, the parent artery in which stent-assisted coil embolization was done is nonartherosclerotic. Possibly the underlying characteristics of the arterial wall involved with an aneurysm differ from those associated with atherosclerosis, thus avoiding this complicating factor.

2) Occlusion of the side branches induced by stent placement
   One might argue that placement of a stent across the bifurcations and the ostia of small perforating branches risks vessel occlusion. However, experimental evidence in dogs suggests that small, lateral carotid branches that approximate intracranial perforating vessels relative to their diameter and angle of origin remain patent if less than 50% of the ostial diameter is covered by the struts of the stent.³⁵⁾ We have not encountered any perforating vessel occlusion in stent-assisted coil embolization cases.

3) Thrombogenicity of the stent
   The thrombogenicity of endovascular stents represents an important limitation with respect to the treatment of aneurysms, particularly those that are treated in the context of acute subarachnoid hemorrhage. Dual antiplatelet regimens have been established to be superior to aspirin therapy alone as well as other anticoagulation regimens for the prevention of stent occlusion.¹⁶⁾²⁶⁾ Clopidogrel are adenosine diphosphate receptor antagonists that are available for use with aspirin to achieve platelet inhibition with a dual mechanism of action. Clopidogrel is generally used because of its lower incidence of significant adverse effects.⁵⁾ When administrated at a dose of 75 mg/d, clopidogrel achieves maximal platelet inhibition at 3 to 7 days. In contrast, a single loading dose of 300 mg achieves an equivalent effect in 2 to 5 hours.²⁴⁾²⁵⁾ In our institution, patients are administered aspirin and Plavix for 3 days before stent-assisted embolization is performed. In the setting of acute subarachnoid hemorrhage, however, such a pretreatment regimen is not applicable. In patients who present with subarachnoid hemorrhage, no pretreatment regimen is administered. Heparin is not administered until the aneurysm dome is protected with coils. Patients are then treated with heparin for 24 hours, followed by 6 weeks of clopidogrel and aspirin indefinitely. Delayed thromboembolic events need to be considered and long-term follow-up is needed.

Conclusions

   The combination of endovascular reconstruction of the parent vessel by using a neurovascular stent followed by coil embolization offers a promising therapeutic alternative in the treatment of wide-necked aneurysms not amenable to coil embolization alone. Furthermore, stent-assisted coil embolization might be effective in incompletely embolized aneurysms with wide necks, particularly large and giant aneurysms, comparing to those treated with detachable coils only, even though large population of the patients and longer period of follow-up angiographic examination are needed.

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