Using a covered stent for large cerebral aneurysms treated with stent-assisted coiling

Abstract

Purpose

The purpose of this article is to evaluate the efficacy and safety of covered stent implantation for large intracranial aneurysms treated with stent-assisted coiling.

Materials and methods

Seven patients with a cerebral aneurysm were selected for this study. The aneurysms were located at the cavernous segment of the internal carotid artery in three cases, the supraclinoid segment in two and the vertebrobasilar junction in one. Aneurysm diameter was 10–25 mm. Mass effect symptoms occurred in six patients, epistaxis in one and subarachnoid hemorrhage in one. All patients underwent endovascular reconstruction with stent-assisted coiling and a covered stent. Five had undergone conventional endovascular embolization with stent-assisted coiling three to six months previously; the covered stent was then navigated through the existing stent and deployed to cover the aneurysm neck. In two cases, the covered stent was deployed after stent-assisted coiling in a single procedure.

Results

Angiography showed that all aneurysms were excluded from the circulation and parent arteries were preserved. No technical adverse events occurred. At the one- to two-year follow-up, complete resolution of clinical symptom had occurred in six patients and partial resolution in one. No recurrent aneurysm filling and no hemodynamic stenosis was observed.

Conclusion

Endovascular reconstruction combining a covered stent with stent-assisted coiling could be an effective and safe strategy for the treatment of large cerebral aneurysms.

Introduction

Large cerebral aneurysms are difficult and complex to treat using endovascular or microsurgical techniques. Morphologically, large aneurysms are typically divided into saccular and fusiform types. Despite advances in endovascular techniques including stent-assisted coiling, large aneurysms with a wide neck present a therapeutic challenge. The role of stents in the treatment of very large aneurysms is debated because the coil mesh often becomes unstable over time, resulting in reopening of the aneurysm lumen^1–6 and requiring retreatment. Methods for and results of recanalization of large aneurysms vary^7–10 and the best definitive management remains unknown. Covered stents have not yet found widespread use in interventional neuroradiology and described in only a few papers.^10,11 Here we describe the successful application of covered stents in the management of large intracranial aneurysms with a wide neck that had been embolized by stent-assisted coiling, demonstrating the potential usefulness of this device.

Materials and methods

Patients

Seven patients with a large cerebral aneurysm were selected for this study; four were male and three female and their age ranged from 19 to 64 years. The aneurysms (fusiform in one, saccular in four, pseudoaneurysm in two) were located at the cavernous segment of the internal carotid artery (ICA) in four patients, the supraclinoid segment in three and the V4 segment of the vertebral artery (VA) in one. The size of the aneurysm was determined by the angiographic projection that could best display the largest diameter of the body of the aneurysm. Aneurysms were considered giant if their greatest diameter was >25 mm; large if their greatest diameter was between 10 and 25 mm; and small if the greatest diameter was less than 10 mm. The patients had neurologic symptoms such as headache, diplopia, reduced visual acuity and cranial nerve palsy, and epistaxis. Detailed information is provided in Table 1.

Table 1.

Angiographic and clinical results of treatment with a covered stent in seven patients with a large aneurysm.

Case no.	Gender/ age (years)	Aneurysmsize (mm)/ location/type	Residual neurologic symptoms	Covered stent size (mm)	Immediate angiographic result	Angiographic follow-up result	Clinical follow-up result
1	F/39	22/Supraclinoid/saccular	SAHa, oculomotor paralysis	3.5 × 10	Excellent	Disappearance	Improved
2	M/51	18/V4 segment/fusiform	SAH	4 × 13, 4 × 16	Excellent	Disappearance	Recovery
3	F/36	16/Supraclinoid/saccular	Diplopia, reduced visual acuity, oculomotor paralysis	3.5 × 10	Good, small endoleak	Disappearance	Improved
4	M/64	23/Cavernous/saccular	Headache	4 × 10, 4 × 7	Excellent	Disappearance	Recovery
5	F/45	23/Cavernous/saccular	Diplopia, intermittent headache	4 × 10	Excellent	Disappearance	Recovery
6	M/19	25/Cavernous/ pseudoaneurysm	Epistaxis, oculomotor paralysis	3.5 × 10	Excellent	Disappearance	Recovery
7	M/42	20/Cavernous/ pseudoaneurysm	Epistaxis	4.0 × 10	Excellent	Disappearance	Recovery

^aSubarachnoid hemorrhage. F: female; M: male.

Covered stents

The rapid-exchange, balloon-expandable Willis covered stent we used in the study was specially designed for intracranial vasculature applications (MicroPort, Shanghai, China). It consists essentially of three parts: a bare stent, an expandable polytetrafluoroethylene (ePTFE) membrane, and a low-pressure flexible balloon catheter. This new stent system is uniquely suited to facilitating intracranial applications because multiple stent bodies can be connected to the next at the two asymmetric points between the crest wall to enhance the flexibility of the stent, the ePTFE membrane is extremely thin and in a tubular configuration (thickness of 30–50 µm), the balloon has five valves instead of the commonly used three to prevent it from scaling the inner wall of the stent when withdrawing, the whole body of the stent is radiopaque under the fluoroscope to facilitate precise placement of the stent, and it is available in various diameters (from 3 to 5 mm) and lengths (from 7 to 15 mm).

Endovascular procedure

Endovascular technique in two stages

Five patients had previously undergone conventional endovascular embolization with stent-assisted coiling (Figure 1(a), (b), (c)); the initial results were near total occlusion in one, subtotal occlusion in three and partial occlusion in one. Detailed information is provided in Table 2. Three to six months later, a second stage of endovascular therapy was performed.

Figure 1.

A 45-year-old woman with initial symptoms of oculomotor nerve paralysis and headache. (a) Anteroposterior and lateral angiograms show a large aneurysm on the cavernous segment of the internal carotid artery (black arrow). (b), (c) Cerebral angiography immediately after Neuroform stent assisted coiling (double black arrows) reveals subtotal occlusion of the aneurysm (black arrow). (d) After six months, a covered stent (4 mm × 10 mm) is placed. The stent is navigated through the stent along a microwire with a J-shaped tip (arrow), then deployed by balloon inflation. (e) Angiography after covered stent deployment shows complete disappearance of the aneurysm and excellent patency of the parent artery.

Table 2.

Treatment strategy in seven patients with a large aneurysm.

Case no.	Gender/age (years)	Aneurysm location/type	Stent assisted coiling	Immediate angiographic result	Interval (months)
1	F/39	Supraclinoid/saccular	Enterprise stent /GDCa	Subtotal	3
2	M/51	V4 segment/fusiform	Neuroform stent/MicroVention	Subtotal	3
3	F/36	Supraclinoid/saccular	Neuroform stent/GDC + EDCb	Subtotal	6
4	M/64	Cavernous/saccular	Enterprise stent/MicroVention	Partial	3
5	F/45	Cavernous/saccular	Neuroform stent /MicroVention	Subtotal	6
6	M/19	Cavernous/pseudoaneurysm	Enterprise stent/MicroVention	Subtotal	0
7	M/42	Cavernous/pseudoaneurysm	Enterprise stent/MicroVention	Partial	0

^aGuglielmi detachable coil. ^bN-(3-dimethylaminopropyl)-N-ethyl carbodiimide. F: female; M: male.

In this second stage, a 6 F sheath was placed into the right femoral and selective catheterization of the ICA or VA was performed using a 6 F guiding catheter (Envoy; Cordis, Miami Lakes, FL, USA). After getting an acceptable tolerance on the balloon occlusion test (BOT), a 300 cm long and 0.014 inch diameter microguide wire (Transcend Floppy; Boston Scientific, Natick, MA, USA) was navigated into the distal branch of the parent artery (PA), with or without microcatheter, under the guidance of the roadmap. The Willis covered stent system was then advanced over the microguide wire, with the proximal and distal ends of the stent bridging the aneurysm orifice of the PA. Multiple control angiographies were obtained during the procedure to confirm the aneurysm orifice by the stent. Under fluoroscopic control, the stent was then deployed across the aneurysm orifice with 5–6 atm of pressure. If the aneurysm orifice was not completely covered and a fast filling of the aneurysm cavity was observed, then another covered stent was employed to cover the orificium fistulae. However, if immediate angiography demonstrated only slow and slight filling of the aneurysm lumen, no further treatment was needed, because significant rerouting of hemodynamics may prompt spontaneous thrombosis, eventually occluding the aneurysm sac completely. The stent must be at least 6 mm longer than the width of the aneurysm neck because the covered membrane is 1 mm shorter than the stent at each end and the membrane must extend at least 2 mm beyond the neck of the aneurysm on both sides. We used stents with diameters approximately 0.5 mm wider than the diameter of the PA. Considering that covered stents were mainly used in the cavernous or supraclinoid segment of the ICA and VA, the anterior choroidal artery (AChA), posterior communicating artery (PComA), the ophthalmic artery (OA) and posterior inferior cerebellar artery (PICA) were important side branches. The PCoA can be covered with the stent, if necessary, in cases where the PComA is not of the fatal-type posterior cerebral artery. For AchA, OA and PICA, if they are adjacent to the aneurysm neck, multiple control angiographies were performed to avoid any coverage of the orifice of these branches during covered stent deployment. According to our experience, if a side branch is more than a 2 mm distance to the aneurysm neck, it is safe for covered stent usage.

In two cases, the neck was too long to be covered completely by one covered stent, so a second stent was navigated to overlap the proximal end of the first stent along the same exchange microwire; the balloon was then inflated to deploy the second stent, with the overlap between the distal end of the second stent and the proximal end of the first stent was about 2 mm.

After deployment of the stent graft, angiograms were obtained to confirm the exclusion of the aneurysm from the circulation. Brain computed tomography (CT) was performed after the procedure to exclude hemorrhage.

All patients were premedicated with antiplatelet therapy of aspirin 100 mg and clopidogrel 75 mg. Clopidogrel 75 mg was continued for a further 12 months and aspirin 100 mg for life. During the procedure, all patients received heparin to raise their activated clotting time two times above baseline. If there was no evidence of intracranial hemorrhage, low molecular weight heparin 4100 U was injected subcutaneously every 12 hours for three days.

Endovascular technique in one stage

In two patients with a large cavernous pseudoaneurysm, a covered stent was deployed after stent-assisted coiling in a single procedure.

A 90 cm 6 F reinforced introducer sheath was used to support a 6 F Envoy guiding catheter. After placement of the guiding catheter in the C1 segment of the ICA, conventional endovascular embolization with stent-assisted coiling was performed using the “jailed” technique (Figure 2(a), (b)). A 4.5 mm × 28 mm Enterprise stent (Codman Neurovascular Inc, Raynham, MA, USA) was deployed in the PA, covering the neck of the aneurysm and scaffolding the cavernous segment, then a microcatheter (Prowler Plus; Codman Neurovascular Inc) was placed in the M1 segment along a microwire through the stent. A MicroVention coil was placed in the lumen of the aneurysm through another microcatheter (SL10; Boston Scientific) that had been placed in the lumen before the stent was deployed. Control angiography showed partial occlusion of the lumen and a residual neck. A 300 cm 0.014 Transcend Floppy exchange wire was then placed through the Prowler Plus microcatheter. A covered stent was navigated over the exchange wire and placed across the residual neck of the pseudoaneurysm.

Figure 2.

A 19-year-old man with epistaxis. (a) Angiography shows a large pseudoaneurysm at the cavernous segment of the internal carotid artery (black arrow), with a wide neck and damage to the wall of the parent artery. (b), (c) After Enterprise stent (4.5 mm × 28 mm)-assisted coiling using the “jailed” technique, an immediate cerebral angiogram shows partial occlusion of the lumen of the aneurysm. The neck of the pseudoaneurysm is scaffolded and restricted by coiling and the parent artery is reconstructed by the bare stent, but a residual neck remains (black arrow). (d) A covered stent (3.5 mm × 10 mm) is immediately placed over the residual neck along the wire that is still within the Enterprise stent, then deployed by balloon inflation (double arrows). (e) Immediate angiography shows complete disappearance of the pseudoaneurysm. (f), (g) At 16-month follow-up, cerebral anteroposterior and lateral angiograms show excellent patency of the parent artery and total occlusion of the aneurysm.

Angiograms were obtained to confirm full coverage of the neck by the graft. The balloon-expandable stent was then deployed across the neck, with the balloon inflated slowly to a pressure of 6 atm. After deployment of the stent, angiography confirmed the exclusion of the aneurysm from the circulation. Brain CT was performed post-procedure to exclude hemorrhage.

Aspirin 300 mg and clopidogrel 300 mg were injected through a gastric tube during the procedure. Clopidogrel 75 mg was continued for a further six to 12 months and aspirin 100 mg for life. During the procedure, the patients received heparin to raise their activated clotting time two times above baseline. No evidence of intracranial hemorrhage was found, and low molecular weight heparin 4100 U was injected subcutaneously every 12 hours for three days.

Evaluation

Angiographic follow-up data were categorized as: 1) excellent, with no endoleak; 2) good, with a small endoleak that was delayed on imaging of the aneurysmal cavity; or 3) poor, with an endoleak seen on angiography of the aneurysmal cavity immediately after stent deployment. Stenosis of the covered segment of the vessel was evaluated by follow-up angiography.

Clinical follow-up data were collected and analyzed retrospectively by grading as follows: 1) full recovery from the neurologic symptoms that were present before stent implantation; 2) improved neurologic symptoms; 3) symptoms unchanged after stent placement; or 4) neurologic symptoms deteriorated or aggravated.

Results

Immediate post-procedure results

Combined covered stenting and stent-assisted coiling were performed successfully in all patients. Angiography showed that all aneurysms were excluded from the circulation, without endoleak (excellent) in six cases and with a small endoleak (good) in one. No important side branches were covered by stents in our study. PAs were preserved in all patients. No technical adverse event such as vessel perforation, stent migration or thromboembolism occurred. Post-procedure CT confirmed that the procedure had been uneventful, with no evidence of bleeding and no evidence of intracranial ischemic stroke immediately after the procedure or during the hospital stay.

Follow-up angiographic results

Follow-up angiography was performed after two years in four patients and one year in three patients. In six cases, complete reconstruction of the PA, without recurrent aneurysmal filling or endoleak (excellent) (Figure 1(e), 2(e)), was confirmed. In the patient with a small endoleak after covered stent deployment, the aneurysm had completely disappeared at the six-month follow-up (Figure 2(f)) owing to spontaneous thrombosis. In one patient, minimal intimal hyperplasia that did not cause significant stenosis was noted at the edge of the stent graft at the nine-month angiogram follow-up. No hemodynamically significant stenosis was observed.

Follow-up clinical results

At the one- to two-year follow-up, neurologic symptoms showed complete recovery in five patients and conspicuous improvement in two. The remaining unimproved symptoms were primarily reduced visual acuity, which cannot be reversed once the damage has occurred. Symptoms such as nerve paralysis, diplopia, headache and epistaxis recovered significantly or completely. No progressive clinical problems occurred after reconstruction of the PA and no neurologic events related to occlusion of side branches or perforating branches were observed.

Discussion

Endovascular treatment of large cerebral aneurysms with a wide neck remains a technically challenging procedure. Reconstruction strategies that preserve the PA, including balloon-assisted embolization by coiling or liquid embolic materials, carry a risk of recurrence because of the difficulty of achieving tight packing in large or giant aneurysms.^{5,8–10,12,13} A bare stent serves as a mechanical scaffold for the placement of aneurysm coils, preventing coil protrusion into the parent vessel and reconstructing the PA by redirecting the blood flow and facilitating endothelialization at the aneurysm neck.^14–17 However, initial aneurysm occlusion and the stability of the coil mesh over time have been poor. According to the literature, recanalization rates after endovascular treatment are 20%–30% for aneurysms with a wide neck.^8,18–21 In patients with large or giant aneurysms, higher rates of recanalization have been reported. In most cases, reopening of large or giant aneurysms over time is caused by coil compaction or migration of the coil mesh into the thrombus. In addition to gradual increase of aneurysm size, local regrowth may occur at the base near the inflow zone many years after coiling. Endovascular treatment of large aneurysms has been reported by several authors, all of whom found poor long-term outcomes.^5,12,13 Sluzewski et al. reported a good clinical outcome in 79% of cases but the rate of incomplete occlusion was in 69% at follow-up; Murayama et al. reported complete occlusion at the end of the treatment in 40% and 26% of large and giant aneurysms, respectively. Repeat treatment is often required, but more coils in the lumen may worsen mass effect symptoms and further therapy is considered impossible.^12,20,22,23

Covered stent reconstruction is a new technique that can both preserve the PA and isolate the aneurysm. According to some reports, this method is effective and safe for aneurysms with a wide neck.^10,24 First, covered stents allow immediate occlusion of the aneurysm sac while preserving the PA. Aneurysms treated with covered stents have greatly reduced recurrence rates compared with those treated with coils or liquid embolic materials. Furthermore, this technique avoids the need for direct manipulations in the aneurysm cavity and reduces the risk of aneurysm rupture. Finally, in the management of very large and giant aneurysms, mass effects after covered stent placement are fewer than with coil or Onyx embolization. The mid-term follow-up data in our series are favorable, with mass effect symptoms improved in all patients. Saatci et al.¹⁰ reported no recanalization on mid-term follow-up and all symptoms were resolved in patients who had initially presented with mass effects.

In recent years, the limited flexibly of covered stents and endoleak have been the main technical limitations of this technique.^10,25 It is difficult to adapt a rigid, balloon-expandable stent to the curves of the neurovascular anatomy enabling navigation of the cerebral arteries. Stent rigidity may lead to arterial dissection and vasospasm, and the low flexibility of covered stents impairs adhesion to the vascular wall, resulting in endoleak.

In our experience, the friction of the covered stent system in curved arteries is directly related to the length of the stent, a shorter length being more flexible and easier to place. Initial deployment of a bare stent not only scaffolds the neck of an aneurysm, but also reconstructs the PA. With endothelialization, reconstruction of the PA may be more uniform and adhesion of the covered stent to the vascular wall may be improved, completely isolating the aneurysm. In our series, the immediate results showed no signs of endoleak in six of seven patients. Aneurysms treated with coils, even if a small endoleak occurs, gradually disappear with thrombosis.

Use of a covered stent may be a logical choice to increase the remaining lumen of a giant aneurysm without any embolizing material in the aneurysm sac; the graft completely isolates the aneurysm from the circulation and reduces pulsation of the aneurysmal mass. However, covered stents have not been widely used in the treatment of aneurysms that have undergone stent-assisted coiling. Deployment of a covered stent in the PA may be complicated by stent migration, restenosis or the covering of branch arteries. Bare stent reconstruction may be more stable if additional stents are placed;^26–28 in our series, we believe that the stented normal arterial wall where endothelial cell coverage is to be of great help to reduce in-stent acute thrombus formation and stent migration when a covered stent advanced or deployed owing to the scaffolding of the neck provided by the bare stent. However, for the aneurysm neck covered by bare stent mesh, there is seldom a chance to complete the endotheliation process, thus a covered stent should be applied. In all cases, the bare stents were stable, the covered stents were deployed successfully and no migration occurred. In two patients with a giant aneurysm with an ultra-wide neck, a single covered stent could not completely cover the neck, but it was easy to deploy a second stent that partially overlapped the proximal end of the first through the reconstructed PA. We believe that the curvature of the PA, potential endoleak risk by covered stent, the neck width and previous coiling treatment are important factors that need to be considered when performing endovascular reconstruction.

The closure of side branches or perforating arteries originating from the covered segment of the artery has always been a major concern in the use of covered stents for cerebral aneurysm treatment. The PCmoA can be covered with the stent, if necessary, in cases where the PComA is not of the fatal-type posterior cerebral artery, not the functionally patent posterior communicating artery, and no other fatal variations such as the trigeminal artery exist. Some reports suggest that the OA can be sacrificed if necessary, because reconstruction of the ophthalmic artery from the external carotid artery collaterals is possible.¹¹ However, other studies have pointed out that acute OA occlusion may cause ocular ischemia syndrome or gradual visual acuity loss.^29,30 The AChA is another important artery that primarily feeds the area of the optic tract, internal capsule, and cerebral peduncle.³⁰ In our study, before stent deployment, we carefully evaluated the angiogram from multiple angles to prevent covering the ostium of the AChA. The PICA is the largest branch of the VA, and is one of the three main arterial blood supplies for the cerebellum, part of the brain. Occlusion of the PICA or one of its branches leads to Wallenberg syndrome. Thus it is a contraindication for covered stent application if the aneurysm is adjacent to the orisum of PICA.³¹ According to our experience, we recommend covered stent usage if a side branch is more than a 2 mm distance to the aneurysm neck; it is a safe distance for stent deployment under multiple angiographic projection confirmation. Other small branches arising from this part of the carotid siphon include the inferolateral trunk (anterolateral branch, posterior branch, anteromedial branch and superior branch), the posteroinferior hypophyseal artery, the lateral clival artery, the recurrent artery of the foramen lacerum and the lateral artery of the gasserian ganglion; the lateral clival artery is the arterial remnant of the trigeminal artery embryonic vessel. There are many anastomoses between these vessels and their contralateral counterparts or vessels arising from the external carotid artery, which permit their covering without neurologic damage. In our series, no symptoms related to branch artery covering occurred and no hemodynamically significant stenoses were observed.

An original bare stent and subsequent telescoping/overlapping covered stents is likely to cause a heavy metal-load in the PA and run high risks of causing immediate or delayed in-stent thrombus or stenosis. So during our procedure, we always tried to deploy only one covered stent into the previous deployed bare stent. In only two cases, the neck was too long to be covered completely by one covered stent, so a second stent was navigated to overlap the proximal end of the first stent. Acute or subacute in-stent thrombosis is a rare but important complication. The risk can be significantly reduced by combination treatment with either ticlopidine and aspirin or clopidogrel and aspirin. In our series, patients received an antiplatelet protocol comprising 75 mg of clopidogrel and 100 mg of aspirin daily for at least three days before the procedure, followed by the same regimen for six to 12 months after the procedure and 100 mg of aspirin every day thereafter. Acute or subacute in-stent thrombosis and microembolic events were successfully avoided. In-stent stenosis is another potential concern associated with covered stent implantation. However, recent evidence suggests a positive long-term outcome in terms of PA patency. In our series, no cases of in-stent hemodynamic stenosis due to intimal hyperplasia were observed at follow-up.

Although these initial results are encouraging, longer-term follow-up will be necessary to definitively determine the effect of the use of covered stents on the durability of aneurysm treatment. Adequate platelet inhibition is an essential component of the safe application of this technique.

Conclusion

Covered stents are an effective and safe method for the treatment of large intracranial aneurysms, including those with a curving PA. This technique for reconstruction of the PA could be an option for recurrent large aneurysms that have undergone stent-assisted coiling.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

None declared.