Long-Term Follow-Up after Treatment of Intracranial Aneurysms with the Pipeline Embolization Device: Results from a Single Center

Discussion

The development of flow diverters for the thrombosis of wide-neck and giant aneurysms has elicited great enthusiasm in the neurointerventional community. Several early reports about the successful use of such devices, and the immediate technical and clinical outcomes, have been published.^5⇓–7 The reported periprocedural and midterm follow-up results have been impressive.^5⇓–7,10 Meanwhile, reports about the occurrence of late thrombosis, fatal hemorrhage, and delayed complications, such as stent migration, have also been published.^8,11,12 These publications have outlined the possibility of delayed aneurysm rupture in aneurysms treated with flow-diverter stents. Several possible causes for this phenomenon have been discussed, such as intra-aneurysmal flow modification, acute thrombosis of large or giant aneurysms, or inflammatory reactions.¹³ However, studies that carefully assess any potential early or late unexpected or undesirable effects related to the use of flow diverters are unavailable.

The current study is the first to report long-term angiographic and cross-sectional imaging results after placement of a PED for the treatment of wide-neck or otherwise untreatable aneurysms. The results demonstrate excellent technical success rates and immediate, midterm, and long-term results. No complications leading to permanent neurologic deficits occurred, and all but 2 treated aneurysms showed complete occlusion within the first 6 months after treatment. These results are consistent with previous studies that have reported 93–94% rates of complete aneurysm occlusion after 6 months.^6,7

In 1 of the 12 aneurysms, a delayed occlusion of an 8-mm aneurysm was observed, which was probably caused by the previous placement of 2 Neuroform stents. In this patient, CTA after 12 months showed complete occlusion of the aneurysm. The indwelling self-expandable stent may have impaired a contagious and homogeneous neointimal and endothelial coverage of the aneurysm neck, and thereby inhibited complete occlusion.⁵

One patient (8.3%) developed severe in-stent stenosis that was seen on the 6-month angiography. Although existing data about the development of in-stent stenosis in flow-diverting devices is sparse, potential stent occlusion due to exaggerated intimal hyperplasia may be relevant. An experimental investigation in 18 rabbits showed no cases of stenosis of the PED after up to 6 months.³ Another previous study reported moderate or severe stenosis in 4 out of 38 (10.5%) PED cases with angiographic follow-up of ≥3 months.⁵ All of these patients were clinically asymptomatic, and spontaneous regression of the stenoses was reported. Another study found mild stenosis in only 1 out of 30 patients at the 6-month angiography,⁷ while minimal lumen narrowing at 6-month angiography was seen in 1 of 19 (5.3%) patients of another report.⁶

In the case with severe in-stent stenosis, balloon dilation at 7 months was performed with the objective to prevent further progression of the stenosis and thus possible stent occlusion. At 13 months, angiographic follow-up revealed mild (>25%–50%) residual stenosis that was completely resolved at 31 months (Fig 3). It is questionable whether the stenosis should have been treated at all; the presence of a circular translucent layer on the inside of the PED (as depicted on the angiogram) likely was only the result of a transient inflammatory response leading to temporary changes at the vessel intima (Fig 3, F–G). Existing data about the development of intimal hyperplasia is derived mainly from the coronary literature. Intimal hyperplasia peaks at 12–16 weeks and very rarely progresses beyond 3–6 months after bare-metal stent implantation.^14⇓–16 In 1 study, 8 out of 24 patients developed asymptomatic in-stent stenosis after placement of a Silk stent (Balt, Montmorency, France).¹² Thus, progressive in-stent stenosis may be considered a transient finding that is not accompanied by clinical symptoms. However, at the time the in-stent stenosis was detected, the lack of long-term experience with the PED had led to the decision to balloon dilate the stenosis despite the absence of clinical symptoms. In light of the findings of the current study, the authors propose treatment of such a stenosis only if a progressive lumen narrowing is observed or the patient becomes clinically symptomatic.

Another possible complication after PED treatment is the development of late stent thrombosis. In a reported case of very late thrombosis after 23 months, the authors hypothesized whether the event was attributable to the placement of 3 PED devices or the additional use of polyglycolic/polylactic acid–covered bioactive coils.⁸ In another series, 1 of 19 patients developed stent thrombosis; retrospectively, it was found that the patient had not suitably been prescribed antiplatelet agents.⁶ The occluded arterial segment reopened later, while the patient was on proper medication. A similar case has been reported for the Silk stent, though no clear explanation for the event could be given.¹³ Acute thrombosis, inflammatory reactions or intra-aneurysmal flow changes were considered. Another study did not find any delayed in-construct stenoses, but the follow-up time was only 6 months.⁷ In our series, we did not observe late stent thrombosis.

The present study has the following limitations: First, the number of patients treated with the PED is small. Thus, the results may not be generalized. However, as this is the first investigation reporting long-term angiographic results, including information about the time courses of aneurysm occlusion and possibly transient in-stent stenosis, the presented data may be relevant. Second, the mean size of the treated aneurysms was relatively small and telescopic stent placement was performed only in 3 patients. The rate of in-stent stenosis may be higher if a larger number of patients with more than 1 inserted PED were evaluated.