Treatment of Intracranial Aneurysms by Functional Reconstruction of the Parent Artery: The Budapest Experience with the Pipeline Embolization Device

Discussion

The potential of intravascular stent technology in the treatment of aneurysms has been proposed, and its technical feasibility, assessed in animal experiments in the early 1990s.^1–3 It was hypothesized that stent implantation may impact the results of endovascular treatment by facilitating attenuated coil-packing, modifying local flow dynamics, and providing a framework for the proliferating intima to cover the aneurysm.¹

Further laboratory experiments demonstrated that depending on their mesh attenuation, stents alter and reduce the velocities of vortical flow within the aneurysm, increasing the intra-aneurysmal circulation time and affecting momentum exchange between the sac and the parent vessel.¹⁵ It was also shown that in addition to the porosity, the geometry of the stent has an impact on aneurysm thrombosis, depending on the local flow patterns.^16,17

For clinical practice, following the application of modified balloon-expandable coronary stents,¹⁸ open cell self-expandable intracranial stents became available for the morphologic reconstruction of the parent vessel across the orifice of the aneurysm.^{12,13,18–24} More recently, closed cell-design stents were added to the therapeutic arsenal, presumably providing better coverage of the aneurysm neck.^25–27 Even though most clinical reports published to date have mainly focused on the utility of stents in facilitating coil packing of complex neck aneurysms, several observations suggested that stents not only promote improved packing but may independently contribute to the long-term stability of the aneurysm even with lower packing attenuation.^13,18 This assertion is supported by reports of aneurysms found to thrombose spontaneously after stent placement alone^12,13 or following double-stent coverage of the orifice without coil packing,¹⁸ further highlighting the significance of stent design as proposed by Lieber et al^15,16 and Barath et al¹⁷ in earlier experimental studies.

The above results allowed a conceptual change in the application of stent technology in aneurysm treatment. Instead of using stents as an adjunctive device, one can apply the intraluminar sleeves primarily for functional anatomic reconstruction of the parent artery by altering flow dynamics and inducing intimal proliferation. Early clinical experiences with 2 such devices, the Silk stent (Balt Extrusion, Montmorency, France)²⁸ and the PED,^29–31 have recently been reported. Nine of the 18 cases reported here are part of the first clinical trial designed to study the safety and efficacy of a flow-diverter device, the PED (the PITA trial).

Because our intention was to find an effective treatment technique for aneurysms otherwise difficult to treat, large, giant, fusiform, or wide-neck (as defined by a neck >4 mm or a neck-to-sac ratio <1:2) lesions were treated exclusively. Overall, the aneurysms were larger compared with those in most endovascular series, having a mean diameter of 16 mm and a mean volume of 1.26 cm³. The PED is a single layer of woven wire mesh design with a pore size of 0.020–0.052 mm². Its flexibility and conformability to the implanted parent arteries were satisfactory. All devices were successfully navigated into position with moderate effort by using standard microcatheters. Two of 41 PEDs could not be deployed due to friction and were easily removed together with the microcatheter. Introduction and gentle inflation of a microballoon was necessary to release and fully open the distal tip of 1 PED that failed to detach from its delivery wire. This, too, was related to friction due to proximal tortuosity. Thirty-nine devices were acceptably deployed across the target lesion and apposed to the parent artery wall.

The exact degree of flow reduction sufficient for aneurysm thrombosis and its importance in achieving ultimate aneurysm occlusion are unclear and are likely to remain subjective in each case until flow and thrombosis simulations become incorporated into routine clinical practice. The aim is to prolong circulation time (contrast residence) within the aneurysm. Intra-aneurysmal circulation (vorticity) has been shown to be directly related to the surface area of the orifice^32–34 and can be reduced by decreasing the free surface available for fluid exchange. PED provides approximately 30%–35% surface coverage at a nominal opening as a single layer, but its design allows the overlapping of multiple devices, which can be used to strategically increase the degree of aneurysm coverage, providing 2 options for significantly reducing intra-aneurysmal circulation: the primary use of multiple coaxial PEDs or (particularly where perforator branches restrict the number of PEDs that can safely be used) reducing intra-aneurysmal flow with adjunctive coiling of the aneurysm.¹⁰ In this series, we used both approaches.

In very large and giant aneurysms, in which it is difficult to achieve a significant effect on flow with coils, we elected to use multiple PED coverage. Aneurysms covered by ≥3 devices were practically twice as large as those treated with single or double PED coverage (On-line Table and Tables 1 and 2). To avoid occlusion of important side branches, we first used a single long bridging PED to create a stable scaffold, followed by shorter devices placed strategically over the aneurysm neck to enhance coverage of the orifice but minimize that of the parent artery proximal and distal to the aneurysm.

For smaller aneurysms, at the beginning, additional coiling was performed if complete stasis to the subjective satisfaction of the operator was not achieved. Technically, coil packing following PED coverage of the neck was very easy. With growing experience, we learned that complete stasis is not required for ultimate aneurysm occlusion; if the flow is visibly reduced by angiography, the aneurysm is likely to thrombose, and aneurysm packing is discontinued. Applying both techniques provided an opportunity for retrospective comparison of aneurysms that had additional coiling with those that were treated with PED coverage alone. Analysis of the 6-month follow-up results demonstrated that, in general, the coil-packing density was very low. Further, even though unpacked aneurysms had significantly larger volume than those that were adjunctively coiled (On-line Table and Tables 1 and 2), aneurysms of similar size and location occluded equally, regardless of coil packing (On-line Table and Tables 1 and 2, Figs 4 and 5). On the other hand, all but 1 coiled aneurysm was treated with a single PED, while unpacked aneurysms were covered by multiple overlapping devices. We concluded that for many aneurysms, PED coverage itself is an effective treatment, and for the future, we restricted additional coil packing to cases in which there is an increased risk of aneurysm rupture (such as multiple aneurysms) or the need to restrict PED coverage to a single device due to the vicinity of significant side branches.

Patency of side branches is a significant concern for the application of multilayer high-mesh-attenuation stents. In our study, 1 acute occlusion was attributed to severe catheter-induced ICA vasospasm rather than stent coverage. This was supported by the reopening of the ophthalmic artery at 6 months. Both branches that had delayed occlusion were covered by either 2 or 4 overlapping devices. A single-layer PED did not cause any side branch thrombosis. Having this positive experience in the relatively forgiving area of the supraclinoid ICA encouraged us to use the technique of targeted multilayer PED coverage in a large fusiform basilar trunk aneurysm, which was treated by 5 coaxial PEDs. In this case, coverage of the SCA and AICA segments was limited to single anchoring devices, while 3 additional short PEDs were overlapped across the aneurysm neck. No visible branches of the BA occluded, and no clinical signs of perforator-related ischemia were detected within 8 months of follow-up (Fig 3).

Another significant concern regarding high-metal-surface-area stents is their potential thrombogenicity, particularly if multiple devices are used. In-stent thrombosis occurred in 1 case in a patient retrospectively found not to have been suitably covered with antiplatelet agents. The occluded ICA reopened later, while the patient was on proper medication (Fig 2). This suggests that the PED has an acceptable thrombotic profile, but rigorous antiplatelet periprocedural medication is necessary.

Similar to the application of other intracranial stents, the necessity of aggressive antiaggregation raises further concerns about potential bleeding complications. In our study, a patient died due to diffuse SAH. This patient had a very small aneurysm on the ipsilateral ICA bifurcation distal to her giant multilobulated target aneurysm on the proximal ICA. Control angiography failed to demonstrate a source of bleeding; however, an autopsy suggested rupture of the small distal aneurysm, likely related to wire perforation. This suggests that patients having an additional aneurysm distal to the target lesion carry higher risk because perforation of the distal aneurysm may occur during the exchange maneuver or PED placement. While such perforation might otherwise remain clinically silent, it may become catastrophic under double antiaggregation. Treatment of the distal aneurysm before the target lesion should be considered.

The PED device demonstrated high efficacy, inducing complete occlusion in all but 1 aneurysm at 6 months. This was seen in the patient who had transient ICA occlusion and, for this reason, was kept on double antiplatelets for 6 months. She is due for further follow-up (Fig 2). All other aneurysms completely occluded at 6 months, with reconstruction of the lumen of the parent artery (Figs 1, 3, and 4). A minimal (15%) diameter narrowing was detected by follow-up angiography at 6 months in a single case without any flow restriction. The patient is being followed clinically and by MR imaging and MRA.

Effective treatment of mass effect is difficult with intrasaccular aneurysm packing. Treatment with flow diversion resulted not only in angiographic aneurysm occlusion but also in reduction of mass effect. This result is proved by the elimination or improvement of cranial nerve neuropathies and headaches as well as by involution of the aneurysmal mass and resolution of the mass effect at 6 months by CT or MR imaging (Figs 1 and 3).

The long-term results are yet to be studied. We do not have angiographic results for more than 6 months; however, time-of-flight MRA in 11 patients (12 aneurysms at 18–24 months) indicated persistent occlusion of the aneurysms and good flow within the parent arteries proximal and distal to the treated segments. Patients have been clinically followed for ≤12–18 months so far. No further clinical events have been recorded.

This article summarizes short-term results of only a small cohort of patients. On the basis of these results, application of this technology seems to be beneficial for patients with large and giant proximal aneurysms, particularly those having mass effect. Further studies are warranted to collect longer term follow-up data and to investigate the potential of the technique for treatment of more distally located aneurysms.