**3. Discussion**

Different endovascular techniques have been used in the treatment of vertebral and internal carotid artery aneurysms. These include covered stent placement, flow diverting device (FDD) placement, parent vessel occlusion with detachable balloons or coils, coil embolisation of the aneurysm with or without a stent placement.

#### **3.1. Covered stents**

In the past decade, covered stent placement has been proved to be effective for managing arteriovenous fistulas, aneurysms, and aortic dissections. Covered stents consist of a

synthetic material that either covers or is attached to a metallic stent to create a graft endoprosthesis. There are two different types of stent-deployment system - balloonexpandable or self-expanding. Balloon-expandable system represent Jostent Graftmaster (Abbott Laboratories, Abbott Park, Ill) and iCast (Atrium Medical, Hudson, NH), selfexpanding covered stents are Fluency stent (Bard Peripheral Vascular, Tempe, Ariz), GORE VIABAHN (W.L. Gore & Assoc, Newark, Del), Wallgraft (Boston Scientific, MA) and Willis covered stent (MicroPort, Shanghai, China). Compared with aneurysm coil embolization, a covered stent has the following advantages: (1) a relatively simple and rapid performance; (2) a low risk of procedural-related rupture or rebleeding; (3) no coil herniation, delayed migration, and coil loop protrusion; (4) disappearance or reduction of mass effects in large or giant aneurysms; and (e) no aneurysm recanalization and recurrence.

The Jostent graft is a composite stent with an ultrathin layer of expandable PTFE sandwiched between two stainless steel stents. It is balloon-expandable, covered-tube stent with radial strength. Jostent has been used for aneurysms up to the ophthalmic artery or up to the vertebrobasilar junction [9,10]. The Graftmaster has also been used for carotidocavernous fistulas and dissections [11]. Bergeron et al. recently published a series of six patients with EICA in which stent-grafts were used. They had no adverse event perioperatively and the long follow-up revealed patency of all grafts without sign of in-stent stenosis [12]. Chan et al. also reported two cases of successful endovascular treatment of distal internal carotid aneurysms using Jostent, with both patients remaining symptom-free at 1 year and no signs of graft restenosis [13]. Th disadvantage of Jostent is, that it might cause intimal damage at the stent edges as a result of irritation from vessel motion or anatomic distortion and also requires a relatively straight delivery path and is not well suited for use in very tortuous vessels.

The Willis covered stent is specifically designed for use in the intracranial vasculature and consists of 3 parts: a bare stent, an expandable polytetrafluoroethylene (ePTFE) membrane, and a balloon catheter. The bare stent was constructed from a strand of cobalt chromium super alloy wire, which was 0.06mm in diameter. The ePTFE membrane, which was in a tubular configuration with a thickness of 30 to 50μm is glued along the length of the stent struts with use of organic agglomerate. To facilitate the membrane gluing along the stent, the diameter of tubular membrane is generally 0.05mm, which is wider than that of the inflated stent. To prevent the balloon from scaling the inner wall of the stent on withdrawal, the balloon is made into 5 valvae, instead of the commonly used 3 valvae. The whole body of the stent is radiopaque under fluoroscopy to facilitate precise placement of the stent. The stent can be manufactured in any diameter from 3 to 5mm and in any length from 7 to 15 mm . The stent is mounted on a deflated balloon catheter with an outside diameter of 3.8F. Li at. al. performed successfull endovascular treatment of pseudoaneurysms of cranial internal carotid artery in 8 patients without procedural-related complications, and all of the stents were easily navigated to the targeted lesions. Complete resolution of the pseudoaneurysm was observed in 6 patients immediately after the procedure, and a minimal endoleak into the aneurysm persisted in 2 patients. No morbidity or mortality and no technical adverse event occurred. A follow-up angiogram confirmed complete reconstruction of the internal carotid artery, with no recurrent aneurysmal filling and no occurrence of stenosis in the area of the stent [14]. The efficacy of the Willis covered stent in the treatment of traumatic pseudoaneurysms of the internal carotid artery was evaluated in 13 patients with 14 delayed pseudoaneurysms with succesfull covered stent placement in all 14 pseudoaneurysms. The initial angiographic results showed complete exclusion in 9 patients with 10 aneurysms and incomplete exclusion in 4 patients. The angiographic mean follow-up 15 months findings exhibited a complete exclusion in 12 patients with 13 aneurysms and an incomplete exclusion in 1 patient and maintained patency of the ICA in all patients with no procedure-related complications or deaths occurred during follow-up [15]. In another study, the navigation and deployment of the Willis covered stents were successful in 97.6% (41 of 42) of the patients with most of the aneurysms located at the C5 through C7 segment. Although some complications occurred, the 93.5% (29 of 31 aneurysms) final complete occlusion rate with no recanalization during follow-up addressed the effectiveness of the Willis covered stent for managing DICA aneurysms. In addition, endoleak occurred in 21.9% (7 of 32) of the patients owing to the tortuous segment of C5 through C7, but it could not been eliminated by means of postprocedural dilation and additional stent implantation [16].

258 Aneurysm

synthetic material that either covers or is attached to a metallic stent to create a graft endoprosthesis. There are two different types of stent-deployment system - balloonexpandable or self-expanding. Balloon-expandable system represent Jostent Graftmaster (Abbott Laboratories, Abbott Park, Ill) and iCast (Atrium Medical, Hudson, NH), selfexpanding covered stents are Fluency stent (Bard Peripheral Vascular, Tempe, Ariz), GORE VIABAHN (W.L. Gore & Assoc, Newark, Del), Wallgraft (Boston Scientific, MA) and Willis covered stent (MicroPort, Shanghai, China). Compared with aneurysm coil embolization, a covered stent has the following advantages: (1) a relatively simple and rapid performance; (2) a low risk of procedural-related rupture or rebleeding; (3) no coil herniation, delayed migration, and coil loop protrusion; (4) disappearance or reduction of mass effects in large

The Jostent graft is a composite stent with an ultrathin layer of expandable PTFE sandwiched between two stainless steel stents. It is balloon-expandable, covered-tube stent with radial strength. Jostent has been used for aneurysms up to the ophthalmic artery or up to the vertebrobasilar junction [9,10]. The Graftmaster has also been used for carotidocavernous fistulas and dissections [11]. Bergeron et al. recently published a series of six patients with EICA in which stent-grafts were used. They had no adverse event perioperatively and the long follow-up revealed patency of all grafts without sign of in-stent stenosis [12]. Chan et al. also reported two cases of successful endovascular treatment of distal internal carotid aneurysms using Jostent, with both patients remaining symptom-free at 1 year and no signs of graft restenosis [13]. Th disadvantage of Jostent is, that it might cause intimal damage at the stent edges as a result of irritation from vessel motion or anatomic distortion and also requires a relatively straight delivery path and is not well

The Willis covered stent is specifically designed for use in the intracranial vasculature and consists of 3 parts: a bare stent, an expandable polytetrafluoroethylene (ePTFE) membrane, and a balloon catheter. The bare stent was constructed from a strand of cobalt chromium super alloy wire, which was 0.06mm in diameter. The ePTFE membrane, which was in a tubular configuration with a thickness of 30 to 50μm is glued along the length of the stent struts with use of organic agglomerate. To facilitate the membrane gluing along the stent, the diameter of tubular membrane is generally 0.05mm, which is wider than that of the inflated stent. To prevent the balloon from scaling the inner wall of the stent on withdrawal, the balloon is made into 5 valvae, instead of the commonly used 3 valvae. The whole body of the stent is radiopaque under fluoroscopy to facilitate precise placement of the stent. The stent can be manufactured in any diameter from 3 to 5mm and in any length from 7 to 15 mm . The stent is mounted on a deflated balloon catheter with an outside diameter of 3.8F. Li at. al. performed successfull endovascular treatment of pseudoaneurysms of cranial internal carotid artery in 8 patients without procedural-related complications, and all of the stents were easily navigated to the targeted lesions. Complete resolution of the pseudoaneurysm was observed in 6 patients immediately after the procedure, and a minimal endoleak into the aneurysm persisted in 2 patients. No morbidity or mortality and no technical adverse event occurred. A follow-up angiogram confirmed complete

or giant aneurysms; and (e) no aneurysm recanalization and recurrence.

suited for use in very tortuous vessels.

The Wallgraft consists of a PET (Dacron; E.I. duPont de Nemours and Co., Wilmington, DE) covered self-expanding cobalt super alloy stent. Wallgraft was utilized in 4 cases of inernal carotid artery trauma or disease leading to contained rupture or pseudoaneurysm formation. During a mean 16-month follow-up (range 6–24), duplex ultrasound and CT scanning found no evidence of restenosis, occlusion, or persistent perfusion of the pseudoaneurysm, which was noted to decrease in all cases [17]. Wallgraft was also used in the treatment of tandem aneurysms of the extracranial internal carotid artery near the skull base with successfully exclusion with deployment of a single Wallgraft across both lesions with no complications encountered. At 2-year follow-up, the patient is doing well, without any sign of aneurysm reperfusion [18]. The Wallgraft has several disadvantages. First, PET is immunogenic which animal studies suggest, increases the rate of vessel thrombosis [19]. Second, the Wallgraft delivery system requires a 9-French arterial sheath in the carotid and vertebral arteries, which may increase the risk of pseudoaneurysms or groin hematomas at the femoral puncture site. Finally, the PET covering is initially porous until a clot forms to seal the fabric.

Viabahn endograft is a PTFE covered nitinol stent with extreme flexibility and conformability to vessel configuration. Covered stents have also shown better closure and shorter procedure time in clinical investigations [20]. Current published evidence of the use of covered stent is limited to stents covered with polytetrafluoroethylene (PTFE) [21]. Synthetic materials are used in biological settings with limited success. Studies have shown that polyester covered stent graft with 50% re-stenosis and e-PTFE covered stent with 24% re-stenosis in a sheep iliac model [22]. It has also been shown that PTFE retards endothelization and that Dacron is prone to infection, due to adherence to and survival of bacteria on its rough surface [23]. Baldi et al. in their three cases had no periprocedural complications and all three PTFE Viabahn endografts were patent at 9 month follow-up without evidence of intimal hyperplasia [24].

A novel CE marked coronary stent covered with pericardium (Aneugraft: ITGI Medical limited, Or Akiva, Israel) is available, which so far shows promising clinical results. The pericardium covered stent (PCS) is a percutaneous implantable device consisting of a 316L stainless steel stent covered by a 100μ thick equine pericardium cylinder which makes this device flexible and trackable. It is available in diameters of 2.5mm, 3.0mm, 3.5mm, and 4.0mm, and lengths of 13, 18, 23 and 27mm. The stent is mounted on a balloon catheter. Gluteraldehyde treated pericardium has been widely used for many years due to its desirable features such as low immunogenicity and durability [25-27]. It has been shown that there is significantly less inflammatory cytokine, significantly less antibody response and inflammatory response compared to un-crosslinked decellularized pericardium [28]. It is now recognized that mammalian extracellular matrix represents an excellent scaffold material suitable for many therapeutic applications [29]. In Neurosurgery, serous sheets are used as dural substitute. An investigation involving 200 patients undergoing a surgical procedure with the application of horse pericardium as a dural prosthesis found that they are free from antigenic effects and do not produce any toxic catabolites [30]. The pericardium proved to be resistant to surgical suture, impermeable to cerebrospinal fluid, transparent and does not cause any clinical evidence or radiological artifacts. Pericardium has also shown decreased intraoperative suture line bleeding compared to Dacron [31]. The PCS has shown to be safe and effective in 2 registries [32], and there is also published evidence attesting to this in other indications [33-36].

There are several disadvantages regarding the use of covered stents in the cranial and extracranial vasculature. First, more clinical trials are required to determine the long-term outcomes. Second, the covered stents may not be flexible and conformable enough to navigate entirely through the extremely tortuous ICA and to fully conform to the configuration of the tortuous targeted arteries. Third, the possibility of a closure of the side branches stemming from the covered segment of the artery might occur after the stent placement. Therefore, balloon occlusion tests and angiography examinations from multiple projections should be routinely performed to avoid coverage of the side branches. In addition, in-stent restenosis might occur in patients who are not following the regular anticoagulation medication regimen after stent placement.

#### **3.2. FDD**

Flow diversion is a new approach to the endovascular treatment of intracranial aneurysms which uses a high density mesh stent to induce sac thrombosis. These devices have been designed for the treatment of complex shaped and large size aneurysms. Flow diversion aims to cure aneurysms by endovascular reconstruction of the parent vessel, without even performing endosaccular embolisation. The primary intent of a flow diversion device (as opposed to a stent) is to optimally alter the flow exchange between the parent artery and the aneurysm so as to promote complete thrombosis of the sac as rapidly as possible while eliciting minimal neointimal hyperplasia. The principal goal of the flow divertor is placement in the parent artery in order to reconstruct the vessel wall [37]. The concept of flow diversion appears promising in challenging lesions, including fusiform and/or giant aneurysms. However, this stent presents major limitations: (a) the aneurysm occlusion process is unpredictable; (b) an associated complication rate much higher than those previously reported with conventional treatments (coiling, balloon- or stent-assisted coiling, parent artery occlusion, clipping); and (c) a high rate of significant parent artery stenosis.

260 Aneurysm

**3.2. FDD** 

A novel CE marked coronary stent covered with pericardium (Aneugraft: ITGI Medical limited, Or Akiva, Israel) is available, which so far shows promising clinical results. The pericardium covered stent (PCS) is a percutaneous implantable device consisting of a 316L stainless steel stent covered by a 100μ thick equine pericardium cylinder which makes this device flexible and trackable. It is available in diameters of 2.5mm, 3.0mm, 3.5mm, and 4.0mm, and lengths of 13, 18, 23 and 27mm. The stent is mounted on a balloon catheter. Gluteraldehyde treated pericardium has been widely used for many years due to its desirable features such as low immunogenicity and durability [25-27]. It has been shown that there is significantly less inflammatory cytokine, significantly less antibody response and inflammatory response compared to un-crosslinked decellularized pericardium [28]. It is now recognized that mammalian extracellular matrix represents an excellent scaffold material suitable for many therapeutic applications [29]. In Neurosurgery, serous sheets are used as dural substitute. An investigation involving 200 patients undergoing a surgical procedure with the application of horse pericardium as a dural prosthesis found that they are free from antigenic effects and do not produce any toxic catabolites [30]. The pericardium proved to be resistant to surgical suture, impermeable to cerebrospinal fluid, transparent and does not cause any clinical evidence or radiological artifacts. Pericardium has also shown decreased intraoperative suture line bleeding compared to Dacron [31]. The PCS has shown to be safe and effective in 2 registries [32], and there is also published

There are several disadvantages regarding the use of covered stents in the cranial and extracranial vasculature. First, more clinical trials are required to determine the long-term outcomes. Second, the covered stents may not be flexible and conformable enough to navigate entirely through the extremely tortuous ICA and to fully conform to the configuration of the tortuous targeted arteries. Third, the possibility of a closure of the side branches stemming from the covered segment of the artery might occur after the stent placement. Therefore, balloon occlusion tests and angiography examinations from multiple projections should be routinely performed to avoid coverage of the side branches. In addition, in-stent restenosis might occur in patients who are not following the regular

Flow diversion is a new approach to the endovascular treatment of intracranial aneurysms which uses a high density mesh stent to induce sac thrombosis. These devices have been designed for the treatment of complex shaped and large size aneurysms. Flow diversion aims to cure aneurysms by endovascular reconstruction of the parent vessel, without even performing endosaccular embolisation. The primary intent of a flow diversion device (as opposed to a stent) is to optimally alter the flow exchange between the parent artery and the aneurysm so as to promote complete thrombosis of the sac as rapidly as possible while eliciting minimal neointimal hyperplasia. The principal goal of the flow divertor is placement in the parent artery in order to reconstruct the vessel wall [37]. The concept of flow diversion appears promising in challenging lesions, including fusiform and/or giant

evidence attesting to this in other indications [33-36].

anticoagulation medication regimen after stent placement.

In contrast to an ideal stent, an ideal flow diversion device has low porosity and high pore density values optimized to promote intraaneurysmal thrombosis while maintaining patency of the parent vessel and side branches. Moreover, lower radial forces are required of this device as compared to a stent, which facilitates the optimization of other device characteristics such as longitudinal flexibility, trackability, and conformability. Recognition of the potential for aneurysm treatment by flow diversion is evidenced by the recent development of these devices by various groups.The major complications with flow divertors have been found to be perforator artery stroke, aneurysm re-rupture, and in-stent stenosis and thrombosis [38,39].

The Pipeline stent (EV3, Irvine, Calif) is the first released flow-diverter stent and it has been evaluated in some series [40,41]. These authors showed that the Pipeline stent represents a safe, durable, and curative treatment of selected wide-necked, large, and giant aneurysms. The Pipeline stent has been used for the treatment of two male patients transferred after acute SAH and dissecting aneurysm on the V4 segment of the dominant vertebral artery with 3 Pipeline stents deployed in each vertebral artery. One dissecting aneurysm was excluded immediately after 3 stents and one patient had complete exclusion demonstrated at the 48 hour control. No morbidity directly related to the procedure was observed and no recanalization and no re-bleeding occurred during the 3 months follow-up [42]. In the recent publication, Yeung et al. demonstrated favourable long-term clinical and angiographic outcomes of FDD use and the ability to maintain parent artery and side branch patency for the endovascular treatment of unruptured dissecting intracranial vertebral aneurysms. In their series, total of 4 aneurysms were successfully obliterated by using flowdiverting devices alone, two devices were deployed in a telescoping fashion in each of 2 aneurysms, whereas only 1 device was inserted in each of the other 2 aneurysms with no periprocedural complications. No patient showed any angiographic evidence of recurrence, in-stent thrombosis, or side-branch occlusion in angiographic reassessment at a mean of 22 months after treatment (range 18-24 months) [43].

The other available flow-diverter device is the Silk stent (Balt, Montmorency, France) and little information is available concerning its use [44-46]. By the use of telescopic catheters, the Silk stent may be placed in most patients. Silk opening and wall apposition frequently require pushing back the delivery catheter. This is particularly mandatory within curved vessel such as the ICA siphon. Because of its low radial force, the Silk stent must be placed with great caution if the vessel shows a stenotic portion because vessel occlusion may occur. Moreover, careful size and length selection is mandatory because stent shortening and migration may happen. For all these reasons, Silk stent placement is more difficult than nonflow-diverter self-expandable stent.

#### **3.3. Parent vessel occlusion**

One of the treatment options available for patients with internal carotid or vertebral artery aneurysms is parent vessel occlusion, either surgical or endovascular. The goal of parent vessel occlusion for the treatment of fusiform aneurysms is intra-aneurysmal thrombosis and involution of the aneurysm. Endovascular occlusion can be achieved with detachable balloons or coils or with a combination of the two. Studies reporting patient outcomes after parent vessel occlusion for treatment of fusiform aneurysms of the vertebrobasilar circulation have been limited. A few series have reported the results of parent vessel occlusion in the posterior circulation, although not exclusively for intracranial fusiform aneurysms. In one study the long-term outcomes for 21 patients with unclippable posterior circulation aneurysms treated with either unilateral or bilateral parent vessel occlusion of the vertebral artery, with a mean follow-up of 2 years (range, 6 months to 6 years) were examined [47]. Six of the patients had fusiform aneurysms, and the remaining 5 had aneurysms that were of saccular morphology. All occlusions in this series were performed by using latex balloons. Thirteen (61.9%) of 21 patients achieved good outcomes, including angiographic cure and clinical improvement. Twenty-eight and six-tenths percent of the patients had partial thrombosis of their aneurysm. One death and one treatment failure occurred.

Occlusion of the internal carotid artery may lead to severe cerebrovascular events and therefore a balloon occlusion test should be performed in advance; if a temporary occlusion test is successful, trapping or parent artery occlusion is an option. However, it has been shown that 5–22% of patients passing the balloon occlusion test develop ischemic complications, including cerebral infarct, while some reports have revealed cerebral aneurysm formation after permanent carotid occlusion [48,49]. The placement of detachable balloons in the ICA above and below the false aneurysm can completely eliminate blood flow. Disadvantages with this endovascular approach include the possibility of embolic cerebrovascular accidents. If the patient cannot tolerate the occlusion test, an extracranial-tointracranial bypass should be contemplated.

#### **3.4. Coil embolisation and stent placement**

Another treatment option in the management of aneurysms represents stent placement with or without coil embolisation and coil embolisation without stent placement. Findings of experimental studies have shown that a metallic stent, bridging the aneurysmal neck, may alter the flow pattern within the aneurysm, promoting thrombus formation and aneurysmal occlusion [50,51]. Although immediate aneurysmal occlusion can be seen after single stent placement for treatment of extracranial pseudoaneurysms, in some cases, 3–6 months or longer may pass before occlusion occurs. To achieve faster complete aneurysmal occlusion, the combination of stents and detachable coils has been suggested for extracranial, as well as intracranial aneurysms [2,52,53] and the combination is currently considered an alternative to single stent placement or other techniques such as the remodeling technique or parent vessel occlusion. Lanzino et al [52] reported 10 cases managed with stent-supported coil embolization; they achieved aneurysmal occlusion of more than 90% in eight patients. In four of these patients, treated with stent placement only, no evidence of intraaneurysmal thrombosis was found either immediately or during follow-up studies performed 48 hours (two patients), 4 days (one patient), and 3 months (one patient) after treatment. Phatouros et al [2] reported a series of seven patients with fusiform aneurysms, wide-neck aneurysms, or pseudoaneurysms who underwent stent-supported coil embolization; technical success was achieved in six. In one patient, a coil became entangled with the stent, resulting in partial coil delivery into the parent artery with no neurologic sequelae.

However, certain limitations, may be encountered when stents are used in conjunction with coils. In some cases, a microcatheter can be navigated through the stent interstices only with difficulty. Packing of the aneurysm sac can be inaccurate because of the density of platinum detachable coils. Multiple projections with big amount of used contrast medium may become necessary, particularly with fusiform aneurysms, and in some cases, complete packing of the aneurysm cannot be achieved. Coil loops may become entangled with the stent struts and unravel during attempts to retrieve them, leading to the risk of moving the stent or leaving coils within the parent artery. A report by Phatouros et al [2] shows the successful use of stent-supported coil embolization in the treatment of fusiform and wide neck aneurysms. The stent mesh allows for attenuated packing of the aneurysm with less concern for herniation of coils into the parent artery. Phatouros et al reported technical success in six of the seven patients treated, with 0% 30-day periprocedural morbidity and mortality. After a mean follow-up of 14.5 months, all the patients treated with stentsupported coil embolization were at their neurologic baseline or had improved. The authors acknowledged the current limitations of this therapy, including the concern for occluding small but important perforators with the struts of the stent. Kurata et al. published their findings in a series of 24 ruptured dissecting vertebral artery aneurysms. Endosaccular embolisation was performed within 4 days of onset of symptoms with no experienced complications with coil embolisation. Radiologic investigation showed complete occlusion of the dissection and patency of the unaffected artery at a mean follow-up of 9 months [54].

The use of double stent placement for complete exclusion of wide-neck aneurysms has been reported in only a single case to date [55], however double stent placement may be a relatively simple technique to more effectively change intraaneurysmal flow and achieve subsequent thrombosis. The influence of stent porosity on changing the local hemodynamics between the aneurysm and the parent vessel was shown in the experimental study [56].
