Endovascular Treatment of Middle Cerebral Artery Aneurysms with Flow Modification with the Use of the Pipeline Embolization Device

Discussion

The PED represents the flow-diverting device designed to exclude the aneurysm from the circulation by disrupting intra-aneurysmal flow, yet allow enough flow through the side branches as well as small perforators arising along the parent vessel covered by the construct. In an experimental study in rabbits, Kallmes et al¹⁶ demonstrated that the vessels covered by the devices remained patent at long-term follow-up. On the other hand, in a recent clinical study,¹⁷ evaluating patency of the ophthalmic artery after treatment of paraclinoid aneurysms, it was demonstrated that nearly one-quarter of ophthalmic arteries covered by PEDs underwent occlusion; however, none of these patients had visual loss. This can be explained with the abundant distal collateral supply of the ophthalmic artery from the external carotid branches. Correspondingly, in another study including 46 aneurysms in which a branch originated from the sac (excluding the ophthalmic aneurysms), only in 5 aneurysms was the originating branch (exclusively posterior communicating artery in all 5) occluded, with the ipsilateral posterior cerebral artery filling from the posterior circulation.¹⁰ Other branches such as the anterior choroidal artery stayed open, which led us to postulate that the branches through which there is a flow demand because of insufficient distal collateral supply or toward which there is enough pressure gradient between the high-pressure parent arteries, are kept patent when covered by a flow diverter. Nevertheless, our findings in this previous study emerged with the use of a single device in the treatment of each aneurysm. Limited cases in the literature reported the use of more than 1 device in the treatment of aneurysms with the coverage of perforating arteries demonstrating occlusion of the lenticulostriate branches and infarction in the related territory.^11,18 In the present study, all aneurysms except for 2 were treated by use of a single PED. One of the 2 patients treated with 2 overlapping devices was admitted to the hospital in the fourth postoperative week. The MR imaging did not show any ischemic lesions, and CTA showed patency of the MCA branches, which was confirmed with 6-month control DSA. Furthermore, we prescribed low-molecular-weight heparin in addition to the antiplatelet therapy for 1 week, and the patient did not have a recurrent event. The remaining patient was the one with procedural SAH who had ischemic symptoms with unclear etiology as described above.

In this series, there was 1 PED placed within a pre-existing intraluminal construct (Enterprise stent), which had been placed during the previous endosaccular coiling. Lylyk et al¹⁹ postulated in their previous study that endoluminal constructs might represent potential impediments to the efficacy of the PED. In our patient, we did not experience any technical difficulty in deploying the PED. This was the patient in whom we discovered perianeurysmal edema 4 weeks after the procedure, which we think was unrelated to the pre-existing stent and PED combination. Six-month DSA control revealed complete occlusion of the aneurysm with patent bifurcating branches.

The main periprocedural and postprocedural complications of the use of flow diverters in the endovascular treatment of intracranial aneurysms are hemorrhagic and thromboembolic events. Early and delayed aneurysm ruptures^{20⇓⇓–23} and distal ipsilateral hemorrhage^10,14,24,25 have emerged as the hemorrhagic complications that are probably related to flow diversion. In this series, 1 hemorrhagic event occurred as an SAH with unknown origin during the procedure. No extravasation was observed in DSA images during the treatment; however, DynaCT revealed SAH. This bleeding may have been caused by a small, invisible dissection/wire perforation during catheterization of the MCA branch.

The only thromboembolic event (presented with transient ischemic attack 3 months after the procedure) with radiologic findings in this series occurred in 1 patient as the result of cessation of the antiplatelet drugs. There was no recurrent ischemic attack after antiplatelet and anticoagulant medication as described above. This result corroborates the importance of rigorously evaluating the thrombocyte inhibition level in response to clopidogrel or ticlopidine and safety of the PED use with the coverage of perforators and bifurcating branches, at least when a single device is used. We used whole-blood impedance platelet aggregation and the rapid platelet function assay VerifyNow P2Y12 (Accumetrics, San Diego, California) in all patients and performed the procedure only if there was no resistance to the drug and the value of Verify Now test was >30%.

In this series, all patients had at least 1 control angiographic study. According to the last angiographic follow-up, complete occlusion was revealed in 21 aneurysms (84%; 21/25). In our experience, we have observed that there are generally 3 phases, though not necessarily, in the occlusion process of aneurysms bearing a bifurcating branch by using the PED: 1) moderate to significant decrease in the aneurysm filling (1–3 months), 2) the infundibulum-like appearance resulting from the branch coming off the parent artery with a bulking origin caused by significant shrinkage of the aneurysm due to flow change, the so-called “remodeled artery” (3–12 months), and 3) complete occlusion (6–18 months) (Figs 1⇑–3). We recommend performing the first angiographic control at 6 months to evaluate the degree of occlusion as well as the patency of the device and the branch(es) covered by the device. When the device is patent, with cessation of clopidogrel or ticlopidine, and continuation of aspirin monotherapy, 18-month follow-up can be scheduled. According to the last follow-up, 12 of the branches originating from the aneurysms were patent, whereas 6 were filling in reduced caliber and 3 were occluded asymptomatically. In 1 patient, the bifurcating branch was filling in reduced caliber at 6-month and 1-year controls. Clopidogrel was not discontinued in this patient, and the branch was revealed to fill in normal caliber at 18 months (Fig 2). Our anticipation is that a branch is kept patent whenever there is a flow demand through it in the absence of rich distal collateral flow. Even so, the operator may extend the duration of dual antiplatelet treatment to 1 year or more.

Endovascular treatment of wide-neck bifurcation aneurysms, especially when the bifurcating branches emanate directly from the base of the aneurysm, is still challenging. With the introduction of the Y-stent placement technique with or without endosaccular coiling,^8,26,27 many of these difficult aneurysms have become amenable to treatment while preserving the parent arteries. However, in cases in which the branch has an acute angle relative to the main trunk, intra-aneurysmal maneuvers as well as exchange procedures are necessitated to catheterize this branch, increasing the risk of procedural hemorrhagic complications caused by aneurysmal rupture and wire perforation.

To date, to our knowledge, this series including 21 aneurysms located at the MCA bifurcations is the first study reporting specifically the use of the PED in bifurcation aneurysms. The PED, being technically more simple and straightforward, provides a safer procedure in cases of existing acutely angled branches. The difficult branch and the aneurysm sac are not to be catheterized; therefore, hemorrhagic risks caused by catheterization as well as endosaccular embolization can be avoided.

We acknowledge the limitations of our study, with the lack of longer follow-up data as well as the limited number of cases. Therefore, we do not advocate this treatment alternative for aneurysms that can be treated with conventional techniques, including clipping. However, the results of our preliminary experience of PED use in the endovascular management of challenging MCA aneurysms are encouraging, enabling the treatment of more complex aneurysms with less procedural risk.