Extra-Aneurysmal Flow Modification Following Pipeline Embolization Device Implantation: Focus on Regional Branches, Perforators, and the Parent Vessel

Side Branches and Perforators Covered by the PED

In our overall cohort, delayed occlusion of the ophthalmic artery, covered by the PED, occurred in 2 cases (5.9%) but was clinically silent. In the literature, patency of collateral branches is rarely reported. Concerning the ophthalmic artery, Szikora et al⁶ reported immediate occlusion in 1 case, resulting in a retinal branch occlusion and a small visual field deficit, and delayed occlusion at 6 months in 2 other cases, which were clinically silent. This finding is consistent with a rate of delayed ophthalmic artery occlusion of 11.7%. More recently, Puffer et al¹⁸ observed that 21% of the ophthalmic artery covered by a PED appeared occluded in subsequent angiographic follow-up. All reported cases of ophthalmic artery occlusion were clinically silent, perhaps due to the good collateral circulation.¹⁸ In another study, Yu et al²⁰ did not report any occlusions among 107 ophthalmic arteries covered by the PED. Overall, the placement of 1 or multiple PEDs across the ophthalmic artery appears safe.

In our study, as well as in the article by Szikora et al,⁶ we did not report other side branch occlusions (anterior choroidal artery, posterior inferior cerebellar artery, superior cerebellar artery, posterior communicating artery, anterior spinal artery, ACA, or MCA). Brinjikji et al²¹ reported an occlusion rate of 27% in cases of posterior communicating artery coverage without neurologic deficit. In all these cases, the P1 segment was patent on the initial angiogram.

In our series, slow flow was observed immediately after PED implantation in all cases of ACA coverage and in 3 of 5 cases of M2-MCA coverage. Most interesting, territorial infarction resulting in a transient aphasia was observed in only 1 case of M2-MCA slow flow.

In our series, 16.2% of collateral branches covered by the PED had arterial narrowing on the 12-month follow-up angiogram. In no case was it associated with a neurologic deficit. All cases of ACA coverage presented with delayed arterial narrowing. All patients had a patent anterior communicating artery and contralateral A1 on the initial imaging. Late narrowing or occlusion was observed in 38% (5/13) after initial slow flow and was observed in only 14.5% (8/55) when slow flow was not reported just after stent placement (P < .05), suggesting that peroperative slow flow is a strong predictor of late branch occlusion. In the literature, narrowing of collateral branches is rarely reported. Preclinical studies^{9,22⇓⇓⇓–26} reported that flow within collateral arteries was maintained after the placement of a flow diverter. However, these arteries were considered end vessels without distal collaterals. In a clinical study, Brinjikji et al²¹ observed a decreased flow in 18% of posterior communicating arteries covered by a flow diverter with a patent P1. These findings suggest that the placement of a flow diverter is probably responsible for a vascular and hemodynamic remodeling of regional branches covered by the device, which can lead to arterial narrowing at midterm follow-up. This vascular remodeling is probably favored by flow competition from communicating arteries. The narrowing or occlusion of such arteries remains clinically silent due to good collaterality. In our practice, we now check the patency of the anterior communicating artery before placing a flow diverter in this segment.

Among the 5 cases of lenticulostriate coverage, we reported 1 case of infarction. This patient was treated for a dissecting MCA aneurysm with the placement of 1 PED, and it is not possible to conclude whether the infarct was due to extension of the dissection to the lenticulostriate arteries or due to the device. Overall, PED placement across perforating lenticulostriate arteries remains safe, probably due to the discrepancy between the wire size of the PED (30 μm) and the diameter of lenticulostriate arteries (mean, 480 μm; range, 100-1280 μm).²⁷ Furthermore, in a computational model, Appanaboyina et al²⁵ observed that the coverage of 90% of the perforating vessel ostium reduced <10% of the flow through the inlet. These data suggest that even if 3 wires cross a perforator ostium with a diameter of 100 μm, the coverage of the orifice area will never be >90%. However, tiny thrombi can develop on the surface of the PED and then migrate distally. A recent in vitro study observed that flow reduction within side branches was higher in cases of tight mesh or overlapping stents²⁴; however, previous preclinical studies^9,22,28 did not observe side branch occlusion in rabbit models even when small branches, similar in diameter to human perforating arteries, were covered by 1 or multiple overlapped PEDs. In our study, the number of overlapped PEDs implanted covering the lenticulostriate arteries was not a predictor of perforator infarction. Patency of perforating arteries in human clinical studies is rarely reported in the literature. van Rooij and Sluzewski²⁹ observed a case of perforator infarction in the territory of the lenticulostriate arteries covered by the flow diverter. Phillips et al³⁰ reported 3 cases of perforator infarction in the vertebrobasilar territory. Overall, the risk of occlusion of perforating arteries appears low, assuming an effective antiplatelet therapy.

Parent Artery Flow Modification

We did not observe any cases of delayed intraparenchymal hemorrhage,¹⁷ but we reported 2 cases of reperfusion cerebral syndrome. In both cases, the patients were older than 75 years (78 and 82 years of age) and the aneurysms treated were large (13 and 15 mm) and involved a tortuous carotid artery. This syndrome has been described as a minor manifestation of the classic cerebral hyperperfusion syndrome.³¹ This syndrome is a rare but well-described phenomenon occurring after a carotid endarterectomy, angioplasty, stent placement,³² or aneurysm clipping.^33⇓–35 It is related to a sudden increase in regional cerebral blood flow secondary to loss of cerebrovascular autoregulation.^31,32,36 The symptoms can range from headache and neurologic deficit (without any ischemic lesion on MR imaging) to intracerebral hemorrhage.³⁷ Several risk factors have been reported, including hypertension, diabetes, age older than 75 years, recent carotid surgery/intervention within 3 months, high-grade ipsilateral or contralateral stenosis, female sex, vascular malformation, and cerebrovascular reactivity.³²

Recently, Chiu and Wenderoth³⁸ reported a case of hyperperfusion syndrome following flow-diverter treatment of a large paraclinoid aneurysm for which the clinical presentation and MR imaging findings were similar to those of our patients except that in this case, there was hyperperfusion on CT perfusion. In our study, there was no evidence of hyperperfusion on PWI-MR imaging; hence, we have to use the term “reperfusion syndrome”.^31,39 Murakami et al⁴⁰ hypothesized that before treatment, giant aneurysms are responsible for the reduction in blood flow through the distal parent artery and might cause relative hypoperfusion in the ipsilateral cerebral cortex. Following aneurysm clipping, blood flow through the parent vessel suddenly increases, exceeding cerebral autoregulatory abilities, leading to cerebral hyperperfusion. One may hypothesize a similar phenomenon in aneurysms treated by surgical clipping or flow diverters, in which the stent redirects most of the blood flow into the parent artery. These data were reported in a computational fluid dynamics model,⁴¹ in which an increase in blood flow was observed in the parent artery after PED placement. As in previous studies,^17,42 we hypothesized that these hemodynamic modifications after flow diversion could lead to delayed intraparenchymal hemorrhage.

Two patients died in unclear circumstances, and we strongly suspect delayed aneurysm rupture. These fatal events occurred a few days or weeks following flow diversion. Similar events have already been reported for the PED and Silk flow diverter (Balt Extrusion, Montmorency, France).^{14⇓–16,43,44} The reason for delayed aneurysm rupture is still uncertain. In computational models, Cebral et al¹⁴ observed, after the placement of a flow diverter, an increase of intra-aneurysmal pressure, which could lead to rupture, especially in cases of giant aneurysms, tortuous vessels, or pre-existing proximal parent artery stenosis. Most of these ruptures have been described in cases of large or giant aneurysms treated by flow diverters alone. Hence, some authors recommend the combined use of coils^15,43 for large and giant aneurysms and suggest a modest reduction of systemic blood pressure in the postoperative period.

Limitations

A limitation of this study is the relatively small number of aneurysms treated and side branches covered by the device, which can diminish the differences between groups. Thus, we did not perform any statistical analyses. Another limitation is the follow-up period, which may be too short to assess the long-term patency of side branches, especially those with narrowing on the midterm follow-up.