The Pipeline embolization device (PED, ev3 Endovascular, Plymouth, MN, USA) and Silk flow-diverting stent (Balt Extrusion, Montmorency, France) is a widely utilized flow diverter in the treatment of intracranial aneurysms, particularly those with unfavorable configurations.
It is a braided, platinum and nickel-cobalt chromium alloy, wire mesh cylindrical implanted device.
An aneurysm treated with a flow diverter is expected to involute over time, contrary to the immediate obliteration expected by surgical clipping or coiling. Yet, which aneurysms will respond to PED therapy and the time frame to expect full obliteration remains unclear 1).
It works by causing progressive flow redirection leading to thrombosis within the aneurysm.
Close to one-fifth of aneurysms, however, fail to occlude after PED placement. It offers an acceptable alternative for the treatment of difficult aneurysms according to their morphologies, including giant, wide-necked, fusiform, complex, and blister types.
PED was initially approved for adults with large or giant wide-necked (≥4 mm or no discernible neck) internal carotid artery aneurysms from the petrous to the superior hypophyseal segments. Studies have shown a superior aneurysm occlusion rate of 85 % at 6 months for the PED and mortality ranging from 2.6 to 4 %. There appears to be a knowledge gap in terms of the duration of dual antiplatelet therapy and efficacy of assessing platelet inhibition. However, increasing operator experience and favorable longer-term outcome data have led to the exploration of PED for a wide array of off-label uses. Given the paucity of good-quality studies comparing PED with other endovascular/surgical treatment options, several multicenter randomized trials are currently underway to answer these important questions 2).
Pipeline embolization device (PED) can be utilized in the treatment of distal anterior circulation aneurysms with difficult anatomy for conventional surgical or endovascular techniques. Larger-scale studies with long-term follow-up are needed to further elucidate the durability of PED treatment and its effect on perforator-rich vascular segments 3).
Use of the Pipeline embolization device (PED) in the posterior circulation is of some controversy. Publications have described adverse outcomes associated with the PED for vertebral artery and/or basilar artery pathology. In a case series publication of Albuquerque et al. stated that patient selection is essential for safe and effective PED treatment of posterior circulation aneurysms. The PED is equally effective in achieving aneurysm obliteration with an acceptable risk profile as it is in the anterior circulation. Dolichoectatic aneurysms were not included in this treatment cohort. PED may be a preferable alternative to open surgical treatment of posterior circulation aneurysms 4).
The main concern with the use of the pipeline embolization device (PED) in treating cerebral aneurysms is the risk of hemorrhagic and thromboembolic complications, including several cases of branch artery occlusion and delayed occlusion of the stented parent vessel shortly after antiplatelet medications were discontinued, highlighting the potential need for long-term antiplatelet therapy, and disastrous bleeding complications in unruptured aneurysm.
In addition, these microcell stents are difficult to use in distal aneurysms located over the ICA bifurcation and basilar tip because of the stiffness of the device, and perforating vessel occlusion is more likely to occur due to the characteristics of the stent. Before the era of flow-diverting microcell stents, large cell intracranial stents like the Neuroform stent (Boston Scientific/Target Therapeutic, Fremont, CA, USA) and Enterprise stent without coiling were used to provide flow-diverting effects for complex intracranial aneurysms.
Aneurysm treatment with the Pipeline Embolization Device is associated with the lowest complication rates when used to treat small ICA aneurysms. Procedure-related morbidity and mortality are higher in the treatment of posterior circulation and giant aneurysms 5).
In-Pipeline stenosis (IPS) is a common, early, and mostly benign complication. Patients with internal carotid artery aneurysms are more likely to develop IPS. Aspirin plays a key role in preventing IPS 6).
Aneurysm clips placed on canine parent arteries bearing a Pipeline flow diverter were unable to reliably stop blood flow. Application of aneurysm clips can cause mild damage to the device and neointima, which might translate into thromboembolic risks. If possible, vascular control should be sought beyond the terminal ends of the implanted device 7).
Acute embolism following use of the PED for treatment of intracranial aneurysms is more common than hypothesized. The only identifiable risk factor for embolism appears to be greater aneurysm size, perhaps indicating significant disturbed flow across the aneurysm neck with ingress and egress through the PED struts. The strength of antiplatelet therapy, as measured by residual platelet aggregation, did not appear to be associated with cases of procedural embolism. Further work is needed to determine the implications of these findings and whether anticoagulation regimens can be altered to lower the rate of complications following PED deployment 8).
Significant heterogeneity in dual antiplatelet therapy regimens following Pipeline Embolization Device (PED) placement and associated costs, exists at major academic neurovascular centers. The most commonly used first line dual antiplatelet regimen consists of aspirin and clopidogrel. Two major alternate protocols involving ticagrelor and prasugrel, are administered to clopidogrel hypo-responders. The optimal dual antiplatelet regimen for patients with cerebrovascular conditions has not been established, given limited prospective data within the neurointerventional literature 9).
The study cohort was comprised of 109 patients. The mean aneurysm size was, 20.2% were located in the posterior circulation, and 11.9% were ruptured. The most common reasons for off-label use were aneurysm size (50.5%), location (25.7%) or both (10.1%). The mean follow-up was 9 months. Complete occlusion was achieved in 82.5% of cases at last angiographic follow-up and mRS decline was found in 18.8% of the cases. On univariate analysis, age, aneurysm size aneurysm morphology, aneurysm location, and the reason for off label use as well as the rupture status were not associated with clinical decline or aneurysm occlusion on angiography. On multivariate analysis PED treatment of a ruptured aneurysm was found to be an independent predictor of a postoperative decline in mRS, and size as the only reason for off-label PED use was found to be an independent predictor of complete occlusion on final angiography.
The off-label use of the PED has a reasonable risk to benefit profile for appropriately selected aneurysms. Posterior circulation location and fusiform morphology do not appear to be associated with worse clinical or angiographic outcomes 10).
Records of patients with distal internal carotid artery (ICA) aneurysms treated with PED at our institution between 2012 and 2017 were retrospectively reviewed. Regions of interest were selected proximally to PED over the cavernous ICA and distally over the middle cerebral artery (MCA), and then transit times were determined using syngo iFlow software (Siemens). Ratio of MCA to ICA transit time was compared before, after treatment, and at follow-up. Ratios were also compared between DIPH+ and DIPH- subgroups. Correlations between aneurysm size, age, and ratios were investigated. Results Fifty-three patients were included. The ratio of MCA to ICA transit time decreased significantly after PED deployment (1.13 vs. 1.22, p < 0.01). The ratio in the DIPH + subgroup ( n = 4) was significantly lower (1.00 vs. 1.14, p = 0.01) and decreased significantly more (21% vs. 4.4%, p = 0.02) compared to the DIPH- subgroup ( n = 49). The ratio tended to be higher in larger aneurysms at baseline ( r = 0.25, p = 0.07) but not after PED treatment ( r = 0.11, p = 0.15). Age did not correlate with ratio. Conclusion The ratio of MCA to ICA transit time decreases following PED treatment and decreases more in patients with DIPH. These contrast transit time changes can be detected in real time immediately after PED deployment 11).
Kan et al., report on a cohort of 15 patients with 16 cerebral aneurysms that incorporated an end vessel with no significant distal collaterals, which were treated with the PED. The cohort includes 7 posterior communicating artery aneurysms, 5 ophthalmic artery aneurysms, 1 superior cerebellar artery aneurysm, 1 anterior inferior cerebellar artery aneurysm, and 2 middle cerebral artery aneurysms. None of the aneurysms achieved significant occlusion at the last follow-up evaluation (mean 24 months). Based on these observations, the authors do not recommend the use of flow diverters for the treatment of this subset of cerebral aneurysms 12).
Thirty-three patients who underwent treatment with the PED of a recurrent previously coiled aneurysm were retrospectively identified. Efficacy was assessed in terms of angiographic occlusion at the latest cerebral angiogram, recurrence and retreatment rates after PED placement, and clinical outcome at the latest follow-up. Safety was assessed by looking at the complications, morbidity, and mortality after PED treatment.
The mean patient age was 53 years. The mean percent recurrence from coiling to PED placement was 34%. The mean time from coiling to PED placement was 40 months. PED treatment resulted in complete aneurysm occlusion in 76.7% of patients and near-complete aneurysm occlusion (≥90%) in 10%, for a total rate of complete and near-complete aneurysm occlusion of 86.7%. All patients, including those with incomplete aneurysm occlusion, had a significant reduction in aneurysm size. Two aneurysms required another retreatment after PED placement (6.2%). Ninety-seven percent of patients had a good clinical outcome. Complications were observed in 1 patient (3%), who suffered an intracerebral hemorrhage. There were no mortalities.
The use of the PED in the management of recurrent, previously coiled aneurysms is safe and effective in achieving aneurysm occlusion 13).
Xiang et al. performed computational modeling of 3 PED-treated complex aneurysm cases. The patient in Case 1 had a fusiform vertebral aneurysm treated with a single PED. In Case 2 the patient had a giant internal carotid artery (ICA) aneurysm treated with 2 PEDs. Case 3 consisted of tandem ICA aneurysms (III-a and III-b) treated by a single PED. The authors' recently developed high-fidelity virtual stenting (HiFiVS) technique was used to recapitulate the clinical deployment process of PEDs in silico for these 3 cases. Pretreatment and posttreatment aneurysmal hemodynamics studies performed using CFD simulation were analyzed. Changes in aneurysmal flow velocity, inflow rate, wall shear stress (WSS), and turnover time were calculated and compared with the clinical outcome.
In Case 1 (occluded within the first 3 months), the aneurysm had the most drastic flow reduction after PED placement; the aneurysmal average velocity, inflow rate, and average WSS were decreased by 76.3%, 82.5%, and 74.0%, respectively, whereas the turnover time was increased to 572.1% of its pretreatment value. In Case 2 (occluded at 6 months), aneurysmal average velocity, inflow rate, and average WSS were decreased by 39.4%, 38.6%, and 59.1%, respectively, and turnover time increased to 163.0%. In Case 3, Aneurysm III-a (occluded at 6 months) had a decrease by 38.0%, 28.4%, and 50.9% in average velocity, inflow rate, and average WSS, respectively, and turnover time increased to 139.6%, which was quite similar to Aneurysm II. Surprisingly, the adjacent Aneurysm III-b had more substantial flow reduction (a decrease by 77.7%, 53.0%, and 84.4% in average velocity, inflow rate, and average WSS, respectively, and an increase to 213.0% in turnover time) than Aneurysm III-a, which qualitatively agreed with angiographic observation at 3-month follow-up. However, Aneurysm III-b remained patent at both 6 months and 9 months. A closer examination of the vascular anatomy in Case 3 revealed blood draining to the ophthalmic artery off Aneurysm III-b, which may have prevented its complete thrombosis.
This proof-of-concept study demonstrates that HiFiVS modeling of flow diverter deployment enables detailed characterization of hemodynamic alteration by PED placement. Posttreatment aneurysmal flow reduction may be correlated with aneurysm occlusion outcome. However, predicting aneurysm treatment outcome by flow diverters also requires consideration of other factors, including vascular anatomy 14).
Between March 2012 and September 2014, 130 patients with 139 intracranial aneurysms (8 ruptured) were treated with the PED under CS at the Departments of Neurosurgery, Radiology, and Neurology, School of Medicine and Biomedical Sciences Gates Vascular Institute at Kaleida Health, and Toshiba Stroke and Vascular Research Center, University at Buffalo, State University of New York; Jacobs Institute, Buffalo, New York.
Procedure details and time (including duration, radiation exposure, and fluoroscopy) and procedure-related complications were retrospectively reviewed.
A total of 155 PED deployment procedures were performed under CS. Treatment was successfully completed in all cases. Anesthesia was converted from CS to general anesthesia during 5 procedures. Mean interval from patient entry at the endovascular suite to procedure initiation was 18 minutes (range, 5 minutes-1 hour 10 minutes). Mean procedure length was 1 hour 25 minutes (range, 30 minutes-3 hours 51 minutes). Mean ± SD values for fluoroscopy time and radiation exposure were 36.17 ± 18.4 minutes and 1367 ± 897 mGy, respectively. The mean amount of contrast material administered was 211.37 ± 83.5 mL. Permanent neurological complications were seen in 4 patients (3%).
CS for PED placement for intracranial aneurysm treatment is feasible and safe. Procedure and fluoroscopy times and amount of radiation exposure are similar to or less than described in reports of PED placement under general anesthesia. CS allows direct neurological evaluation and earlier detection of and response to intraprocedural complications 15).
30 patients harboring 30 aneurysms were analyzed. 39 devices were placed properly. Multiple Pipeline embolization devices (PEDs) were used in 7 cases. In 28 devices the distal end opened fully from the beginning with a complete wall apposition. In the remaining 11 devices, distal-end opening of the devices was instant but partial, but fully opened easily after recapture. Among the 30 procedures, recapture and reposition of the Pipeline Flex was performed four times owing to proximal migration/malposition of the device during delivery. Four intraprocedural/periprocedural complications occurred, of which 2 resulted in major complications, with neurologic deficits persisting for longer than 7 days. The 30-day morbidity rate was 6.6%, with no deaths. No aneurysm rupture or parenchymal hemorrhage was seen 16).
29 anterior circulation unruptured saccular aneurysms with a mean size of 6.99 mm treated with the PED in a single center were retrospectively studied. The overall occlusion rate was 79.3% after a mean follow-up of 9.2 months. Four aneurysms were related to the fetal-type posterior communicating artery (PComA), and all were refractory to flow diverter treatment. Female gender was significantly associated with a higher occlusion rate. We present the anatomical features and propose possible pathophysiological mechanisms of these PComA aneurysms that failed flow diverter treatment.
A PComA aneurysm with persistent fetal-type circulation appears to be particularly refractory to flow diverter treatment, especially when the aneurysm incorporates a significant portion of the PComA. Our experience suggested that flow diverting stents alone may not be the ideal treatment for this subgroup of aneurysms, and alternative modalities should be considered. Female patients were found to have a significantly higher rate of treatment success 17).
Navarro et al. describe their early experience in treating 3 unruptured pediatric brain aneurysms using the Pipeline embolization device (PED). The first patient, a girl with Majewski osteodysplastic primordial dwarfism Type II who was harboring multiple intracranial aneurysms, underwent two flow diversion procedures for a vertebrobasilar aneurysm and a supraclinoid internal carotid artery aneurysm. The second patient underwent PED placement on a previously coiled but enlarging posterior communicating artery aneurysm. All procedures were uneventful, with no postsurgical complications, and led to complete angiographic obliteration of the aneurysms. To the authors' knowledge, this is the first series of flow diversion procedures in children reported in the medical literature. While flow diversion is a new and relatively untested technology in children, outcomes in adults have been promising. For challenging lesions in the pediatric population, flow diversion may have a valuable role as a well-tolerated, safe treatment with durable results. Many issues remain to be addressed, such as the durability of flow diverters over a very long follow-up and vessel response to growth in the presence of an endoluminal device 18).
Eleven patients with 13 aneurysms were included in this study. All patients had an ipsilateral posterior cerebral artery arising from the basilar artery (P1). In the immediate post-procedural setting, four patients (36%) had diminished Pcomm flow rates. After a mean follow-up of 12.6±6.7 months, three Pcomm arteries (27%) were occluded and two Pcomm arteries (18%) had diminished flow. Of patients with diminished flow/occluded Pcomm at follow-up, 80% (4/5) had diminished flow at initial post-procedure angiography compared to none of the six patients without diminished/occluded flow immediately post treatment. No patients suffered new neurologic symptoms at follow-up.
Approximately one half of Pcomm arteries demonstrated occlusion or decreased flow at follow-up if the ostia are covered with a flow diversion device. Covering the Pcomm ostium in patients with a P1 did not result in any neurologic deficits 19)
108 patients with recently unruptured large and giant wide-necked aneurysms were enrolled in the study. The primary effectiveness endpoint was angiographic evaluation that demonstrated complete aneurysm occlusion and absence of major stenosis at 180 days. The primary safety endpoint was occurrence of major ipsilateral stroke or neurologic death at 180 days.
PED placement was technically successful in 107 of 108 patients (99.1%). Mean aneurysm size was 18.2 mm; 22 aneurysms (20.4%) were giant (>25 mm). Of the 106 aneurysms, 78 met the study's primary effectiveness endpoint (73.6%; 95% posterior probability interval: 64.4%-81.0%). Six of the 107 patients in the safety cohort experienced a major ipsilateral stroke or neurologic death (5.6%; 95% posterior probability interval: 2.6%-11.7%).
PED offers a reasonably safe and effective treatment of large or giant intracranial internal carotid artery aneurysms, demonstrated by high rates of complete aneurysm occlusion and low rates of adverse neurologic events; even in aneurysms failing previous alternative treatments 20).
Bowers et al. report the microsurgical rescue and removal of a Pipeline stent embolization of a giant internal carotid artery aneurysm. After the initial placement of a Pipeline Embolization Device (PED), it migrated proximally to the cavernous carotid with the distal end free in the middle of the aneurysm, resulting in only partial aneurysm neck coverage. The patient underwent microsurgical rescue with trapping, bypass, and opening of the aneurysm with PED removal. The vessel remained patent in the proximal segment previously covered by the Pipeline stent. Microsurgical rescue for definitive aneurysm treatment with PED removal can be safe and effective for aneurysms unsuccessfully treated with PED 21).
A 40-year-old woman who had left facial pain and orbit discomfort. Angiography showed a giant fusiform aneurysm located in the cavernous segment of the left internal carotid artery. A PED was successfully deployed across the aneurysm. The procedure and post-procedural course were uneventful. After 3 months, angiography showed complete obliteration of the aneurysm with good patency of the branching vessels originating from the deployed segment. The patient's symptoms improved completely without complications 22).