Vascular injury

While these complications can occur in any neurointerventional procedure, there are certain aspects unique to this device which may predispose to vessel or aneurysm injury. Because of the unique design of the PED, deployment of the device often requires a stiffer triaxial support platform than other neurointerventional treatments for aneurysms.20 The PED can be deployed through a Marksman microcatheter (eV3/Covidien; 2.8 F outer diameter, 0.027 inch inner diameter) or a microcatheter of similar size.

During deployment the PED is alternately unsheathed with a ‘left to right’ hand motion withdrawing the catheter over the PED, ‘packed’ to increase the density of the lumenal coverage at the neck of the aneurysm with a ‘right to left’ motion, and ‘wagged’ by advancing and withdrawing the delivery wire and microcatheter together to allow for deployment of the device around arterial curvatures. While the lead wire is designed to be as atraumatic as possible, there is still considerable movement of the wire during the deployment process. We described one case in particular where the lead wire of a second PED was retained within the posterior cerebral artery during treatment of a recurrent mid-basilar artery aneurysm (figure 2). Following initial balloon-assisted coiling of the recurrent aneurysm, the first PED was deployed in the basilar artery. However, the device did not fully cover the neck of the aneurysm and the decision was made to add a second device. During the course of deploying the second PED the lead wire was noted to travel in an extralumenal position. Because the PED is not retrievable, the decision was made to continue with deployment of the PED and address the complication afterwards. There was no contrast extravasation noted on immediate post-deployment angiography. After unsuccessful attempts to remove the wire, the distal portion of the wire was fractured off by torquing the delivery wire and left in place. Thrombus was also noted within the origins of the superior cerebellar arteries and treated with intra-arterial abciximab infusion. Immediate post-procedure CT of the head did not demonstrate any evidence of contrast extravasation, subarachnoid hemorrhage, or infarcts. We suspect that the lead wire became trapped and stuck within a perforator rather than perforating through the posterior cerebral artery, given the lack of contrast extravasation or subarachnoid hemorrhage. The patient remained neurologically intact following the procedure and was discharged home several days later.

The use of a triaxial catheter system and/or the stiffness of the PED may contribute to the increased rate of vessel injury which we encountered in our series. Particularly with more tortuous anatomy, the navigation of the device to the target lesion becomes increasingly more difficult and may result in treatment failures.7 In the PITA series the authors describe six instances where they were unable to deliver the initial device through the microcatheter due to excessive friction.5 However, in all six cases the procedure was ultimately successful with subsequent attempts.

Thromboembolic events and device occlusion

There are several unique attributes of the PED which may play a role in the increased occurrence of complications in our series. The bimetallic cobalt chromium and platinum tungsten PED provides 30–35% wall coverage using a novel 48-strand braided construction. The microcell architecture provides increased wall coverage and is essential for its function as a FDS. However, the increased amount of metallic surface of the stent may increase the thrombogenicity of the device.

We identified device thrombosis in both an acute and delayed fashion in our cohort. Very late device occlusions 23 months after initial treatment have also been described in the literature.21 The use of coils with the PED may also increase the thrombogenicity of the ultimate construct. Siddiqui et al22 hypothesized that extensive packing of aneurysms with coils may have affected the delayed PED occlusion in their case report.

As with all intracranial stents, it is imperative that the patient is on dual antiplatelet coverage for the procedure.23–25 Patient compliance with the drug regimen plays an integral role in the ultimate success of the procedure because, as in our series, early termination of the dual antiplatelet medications or discontinuation of chronic aspirin therapy can have significant deleterious effects.

Tan et al24 reported thromboembolic complications in 5/74 patients (6.8%) treated with the PED for on-label and off-label indications. They noted that patients who responded to dual antiplatelet therapy with P2Y12 reaction unit (PRU) values >208 were more likely to have thromboembolic complications (12.8%, 5/39) than those with PRU values <208 (0%, 0/35). However, this difference did not reach statistical significance (p=0.06) in their series. Similarly, Delgado Almandoz et al23 identified low or high PRU values (<60 or >240) as the only independent risk factor in multivariate analysis of all and major complications in their series of 48 PED procedures in 44 patients. The only major thromboembolic complication occurred in one of two procedures where the last recorded PRU was >240. Interestingly, their one instance of delayed asymptomatic PED occlusion occurred in an individual within the safe therapeutic PRU range.

Another possible source for thrombosis of the PED involves the increasing recognition of resistance to clopidogrel in certain patients.25 ,26 Despite the real risk of thromboembolic complications, there is no uniform consensus on antiplatelet medication use or monitoring among centers and practitioners following neuroendovascular procedures.27 Faught et al27 noted that less than half (46.8%) of responders to an email study used point of care testing for antiplatelet response during their procedures. Furthermore, the extent of antiplatelet response necessary for risk mitigation is still a matter of some controversy without a uniform definition across all centers.

Whether or not device occlusion results in significant neurological morbidity is solely related to the extent of collateral circulation. Although four of our patients who developed delayed device occlusion while on proper antiplatelet coverage remained clinically asymptomatic, this will certainly not be the case for every individual.

Contralateral intracranial hemorrhages

While the phenomenon of delayed ipsilateral intracranial hemorrhage after the use of the PED has been described in the literature, in our series there was only one instance of delayed intracranial hemorrhage following PED use on the contralateral side of treatment.8 ,28 Our patient initially experienced a contralateral CVA following the procedure with delayed hemorrhagic conversion probably influenced by the need for dual antiplatelet medications. Unfortunately, there was no identifiable cause for the contralateral CVA in this individual.

Chitale et al8 described two patients who experienced contralateral hemorrhages following PED placement. One patient in their series was noted to have an occult contralateral cervical ICA dissection which was not observed on previous studies. Their second patient had no known explanation for the contralateral intraparenchymal hemorrhage. Unfortunately, these events represent a particularly challenging diagnostic and management dilemma since there is no clear etiology for this potentially devastating complication, as noted by Chitale et al.8 Certainly, use of dual antiplatelet medications in the setting of an intracranial hemorrhage will only exacerbate an already difficult situation.

Perforator/side branch occlusion

We encountered two instances of perforator or side vessel occlusion at the time of treatment. In one patient a basilar trunk aneurysm was treated with two PEDs and coil embolization. A large mid-basilar perforator was occluded by the PED, but flow was re-established following the administration of intra-arterial abciximab. A second patient developed occlusion of an A1 vessel after placement of a single PED for treatment of an ICA blister aneurysm. Flow was re-established following aspiration of the thrombus using the Penumbra thromboaspiration system (Penumbra, Alameda, California, USA) and administration of intra-arterial abciximab. Fortunately, in both cases there were no untoward long-term neurological deficits. Similarly, Lall et al29 reported three cases of acute side branch/perforator occlusion following placement of a PED for treatment of two giant posterior circulation aneurysms and one previously clipped and coiled middle cerebral artery aneurysm in patients with an adequate preprocedural response to dual antiplatelet therapy. In all three instances vessel patency was restored following intra-arterial administration of abciximab without neurological sequelae.

In one of our cases an ophthalmic artery occluded in a delayed fashion following treatment of an ophthalmic artery aneurysm without incident.30 Similarly, Puffer et al31 described four delayed occlusions of the ophthalmic artery in 19 patients treated with the PED. They theorized that side branches with distal collateral flow (ie, ophthalmic artery) may be more predisposed to occlusion than side branches which are end arteries (ie, anterior choroidal or lenticulostriate arteries). Szikora et al7 described one acute ophthalmic artery occlusion resulting in a small visual field deficit and two delayed occlusions without clinical sequelae.

In other instances in the literature, monocular visual loss following PED use was not associated with ophthalmic artery occlusion. Chitale et al8 described one patient who presented with delayed monocular blindness 29 days following treatment and 8 days after a follow-up angiogram demonstrated patency of the ophthalmic artery. Fortunately, the vision was recovered to baseline within 6 months. Likewise, Sise et al32 described delayed monocular visual loss with distal retinal artery branch occlusion on ophthalmological examination with fluoroscein angiography following use of two telescoping PEDs for a small supraclinoid ICA aneurysm. A follow-up cerebral angiogram noted patency of the ophthalmic artery with preserved retinal blush and the patient's vision returned to baseline. The authors suggest that emboli may have formed on the PED as a result of the procedure with migration and occlusion of distal branches.

Other complications

Certainly the overall percentage of complications (31.7%) appears much higher than that reported in the medical literature. However, our series differs from other previously described series in its inclusion of all complications experienced by our patients following the initial procedure, rather than limiting complications solely to neurological events.2 ,4 ,6 ,8 ,18 In one of the few studies to look at non-neurological complications Lylyk et al9 cites minor complications in six of 53 patients (11%), five of whom had groin site hematomas.

We also identified three patients with significant gastrointestinal bleeds following institution of dual antiplatelet therapy. This is of particular concern given the risk of thrombosis of the PED without proper pharmacological coverage and presents a management dilemma should the bleeding be of sufficient concern. There were also three groin hematomas, two urinary tract infections, and one significant urethral trauma during Foley catheter insertion requiring placement of a suprapubic catheter in our series. These complications, while not directly related to the use of the PED, may be encountered in any neurointerventional procedure. If we eliminate all minor non-neurological complications from our series, the overall complication rate would decrease by half, bringing it in line with reported complications in other series.8 ,9 Even though it may seem somewhat trivial to include these types of complications in our series, it will probably become more important to identify these issues in the changing healthcare landscape of accountability and outcomes.