Pipeline Embolization Device in the Treatment of Recurrent Previously Stented Cerebral Aneurysms

BACKGROUND AND PURPOSE:The use of the Pipeline Embolization Device in the management of recurrent previously stented cerebral aneurysms is controversial. The aim of this study was to evaluate the efficacy and safety of the Pipeline Embolization Device in the treatment of recurrent, previously stented aneurysms.MATERIALS AND METHODS:Twenty-one patients with previously stented recurrent aneurysms who later underwent Pipeline Embolization Device placement (group 1) were retrospectively identified and compared with 63 patients who had treatment with the Pipeline Embolization Device with no prior stent placement (group 2). Occlusion at the latest follow-up angiogram, recurrence and retreatment rates, clinical outcome, complications, and morbidity and mortality observed after treatment with the Pipeline Embolization Device were analyzed.RESULTS:Patient characteristics were similar between the 2 groups. The mean time from stent placement to recurrence was 25 months. Pipeline Embolization Device treatment resulted in complete aneurysm occlusion in 55.6% of patients in group 1 versus 80.4% of patients in group 2 (P = .036). The retreatment rate in group 1 was 11.1% versus 7.1% in group 2 (P = .62). The rate of good clinical outcome at the latest follow-up in group 1 was 81% versus 93.2% in group 2 (P = .1). Complications were observed in 14.3% of patients in group 1 and 9.5% of patients in group 2 (P = .684).CONCLUSIONS:The use of the Pipeline Embolization Device in the management of previously stented aneurysms is less effective than the use of this device in nonstented aneurysms. Prior stent placement can worsen the safety and efficacy profile of this device.

Since the introduction of detachable coils, cerebral aneurysm management has shifted considerably toward endovascular treatment. One of the main weaknesses of cerebral aneurysm coiling lies in the treatment of patients with large^1,2 wide-neck or fusiform aneurysms.³ These aneurysms tend to have higher recurrence and retreatment rates after coiling. To make up for this deficiency, intracranial stents have emerged as an alternative in the management of this type of aneurysm. The most widely used stents include the Neuroform (Stryker Neurovascular, Kalamazoo, Michigan) and Enterprise self-expanding (Codman & Shurtleff, Raynham, Massachusetts) stents, which were approved for use as Humanitarian Use Devices in 2002 and 2007, respectively. Several techniques can be used with stents, including stent placement alone and stent-assisted coiling. Recanalization and retreatment rates are lower with stent placement and stent-assisted coiling than with coiling alone.^4–6 However, the initial occlusion rates are suboptimal, particularly in large aneurysms.^7,8The management of recurrent previously stented aneurysms remains controversial. There are no recommendations to indicate the most appropriate management strategy, to our knowledge. In 2011, the Pipeline Embolization Device (PED; Covidien, Irvine, California) was FDA-approved for the treatment of large and giant wide-neck aneurysms in the internal carotid artery, from the petrous to the superior hypophyseal segments.⁹ The PED belongs to a family of devices known as flow diverters, which work by acting as a scaffold for endothelial overgrowth of the aneurysm neck.¹⁰ The main structural differences from previous stents are the higher metal surface area coverage compared with previous stents and the low porosity, which allows more flow reduction into the aneurysm neck.^11,12 The overall use of the PED has gained popularity mainly because of its high success rate in achieving aneurysm occlusion and low aneurysm recurrence and retreatment rates, especially compared with other endovascular interventions.^13,14 Early reports have questioned the efficacy and safety of the PED in treating previously stented aneurysms.^15–17 The aim of this study was to evaluate the role of the PED, both its efficacy and safety, in the treatment of recurrent, previously stented cerebral aneurysms.     

Patency of the Anterior Choroidal Artery after Flow-Diversion Treatment of Internal Carotid Artery Aneurysms

BACKGROUND AND PURPOSE:Treatment of cerebral aneurysms with flow diverters often mandates placement of the device across the ostia of major branches of the internal carotid artery. We determined the patency rates of the anterior choroidal artery after placement of flow-diversion devices across its ostium.MATERIALS AND METHODS:We analyzed a consecutive series of patients in whom a Pipeline Embolization Device was placed across the ostium of an angiographically visible anterior choroidal artery while treating the target aneurysm. Patency of the anterior choroidal artery after Pipeline Embolization Device placement was determined at immediate postoperative and follow-up angiography. Data on pretreatment aneurysm rupture status, concomitant coiling, number of Pipeline Embolization Devices used, neurologic status at follow-up, and follow-up MR imaging/CT findings were collected.RESULTS:Fifteen patients with 15 treated aneurysms were included in this study. In the immediate postprocedural setting, the anterior choroidal artery was patent on posttreatment angiography for all 15 patients. Of the 14 patients with follow-up angiography at least 6 months after Pipeline Embolization Device placement, 1 (7%) had occlusion of the anterior choroidal artery and 14 had a patent anterior choroidal artery (93%). No patients had new neurologic symptoms or stroke related to anterior choroidal artery occlusion at follow-up. Of the 9 patients with follow-up CT or MR imaging, none had infarction in the vascular territory of the anterior choroidal artery.CONCLUSIONS:In this small study, placement of a Pipeline Embolization Device across the anterior choroidal artery ostium resulted in occlusion of the artery in only 1 patient. It was not associated with ischemic changes in the distribution of the anterior choroidal artery in any patient.

Flow-diverter devices such as the Pipeline Embolization Device (PED; Covidien, Irvine, California) are increasingly being used in the embolization of intracranial aneurysms as both alternatives and adjuncts to endovascular coiling.^1–4 Flow diverters limit aneurysmal blood flow but maintain blood flow into large vessels and perforating vessels covered by the device.⁵ Although many in vitro and experimental models have demonstrated long-term patency rates of branch vessels covered by the PED, the long-term patency of major branch vessels is not well-established.^6–8 In this study, we assessed the immediate and long-term patency rates of the anterior choroidal artery (AchoA) in patients following the placement of a PED across the AchoA ostium.     

Anterior Choroidal Artery Patency and Clinical Follow-Up after Coverage with the Pipeline Embolization Device

BACKGROUND AND PURPOSE:Endoluminal reconstruction with the Pipeline Embolization Device is an effective treatment option for select intracranial aneurysms. However, concerns for the patency of eloquent branch arteries covered by the Pipeline Embolization Device have been raised. We aimed to examine the patency of the anterior choroidal artery and clinical sequelae after ICA aneurysm treatment.MATERIALS AND METHODS:We prospectively analyzed all patients among our first 157 patients with ICA aneurysms treated by the Pipeline Embolization Device who required placement of at least 1 device across the ostium of the anterior choroidal artery. The primary outcome measure was angiographic patency of the anterior choroidal artery at last follow-up. Age, sex, type of aneurysm, neurologic examination data, number of Pipeline Embolization Devices used, relationship of the anterior choroidal artery to the aneurysm, and completeness of aneurysm occlusion on follow-up angiograms were also analyzed.RESULTS:Twenty-nine aneurysms requiring placement of at least 1 Pipeline Embolization Device (median = 1, range = 1–3) across the anterior choroidal artery ostium were identified. At angiographic follow-up (mean = 15.1 months; range = 12–39 months), the anterior choroidal artery remained patent, with antegrade flow in 28/29 aneurysms (96.5%), while 24/29 (82.7%) of the target aneurysms were angiographically occluded by 1-year follow-up angiography. Anterior choroidal artery occlusion, with retrograde reconstitution of the vessel, was noted in a single case. A significant correlation between the origin of the anterior choroidal artery from the aneurysm dome and failure of the aneurysms to occlude following treatment was found.CONCLUSIONS:After placement of 36 Pipeline Embolization Devices across 29 anterior choroidal arteries (median = 1 device, range = 1–3 devices), 1 of 29 anterior choroidal arteries was found occluded on angiographic follow-up. The vessel occlusion did not result in persistent clinical sequelae. Coverage of the anterior choroidal artery origin with the Pipeline Embolization Device, hence, may be considered reasonably safe when deemed necessary for aneurysm treatment.

Flow diversion with the Pipeline Embolization Device (PED; Covidien, Irvine, California) has been shown to be an effective treatment option for complex intracranial aneurysms of the internal carotid artery.^1–4 Fundamentally, the safety and effectiveness of the device in the cerebral vasculature depends on its ability to differentially facilitate aneurysm occlusion without symptomatically compromising branch vessel patency. Branch vessel flow depends on the arterial-venous pressure gradient and composite impedance of the vascular territory subserved by the branch.⁵ Although placement of single PEDs across the origins of branch vessels is not expected to affect vascular resistance in the jailed (covered) artery,^6,7 the intrinsic thrombogenicity of the implant has caused concern for the patency of jailed branch arteries.^5,6,8 Several studies have shown that coverage of the ophthalmic artery is clinically safe,^9,10 but coverage of the anterior choroidal artery (AchoA) has not yet been systematically evaluated. Several reports have suggested that >50% compromise of the luminal cross-sectional area is required before flow in branch arteries is diminished significantly,^11,12 reflecting a degree of branch ostial coverage lower than that expected from deployment of a single PED (between 18% and 36% surface metal coverage) as determined from benchtop analysis.¹³ Even when PEDs are overlapped, metal coverage is not reasonably expected to exceed 40% for any 2 devices.¹⁴ We therefore hypothesized that coverage of the AchoA with PED is unlikely to cause occlusion of this eloquent vessel territory.     

Last-Recorded P2Y12 Reaction Units Value Is Strongly Associated with Thromboembolic and Hemorrhagic Complications Occurring Up to 6 Months after Treatment in Patients with Cerebral Aneurysms Treated with the Pipeline Embolization Device

BACKGROUND AND PURPOSE:A recent study identified a preprocedural P2Y12 reaction units value of <60 or >240 as a strong independent predictor of perioperative thromboembolic and hemorrhagic complications after treatment of cerebral aneurysms with the Pipeline Embolization Device. This study aimed to determine whether a last-recorded P2Y12 reaction units value of <60 or >240 predicts thromboembolic and hemorrhagic complications up to 6 months after treatment of cerebral aneurysms with the Pipeline Embolization Device in the same patient cohort.MATERIALS AND METHODS:We recorded patient and aneurysm characteristics, P2Y12 receptor antagonist administered, P2Y12 reaction units value with VerifyNow, procedural variables, and thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures at our institution during an 8-month period. Complications causing a permanent disabling neurologic deficit or death were considered major. Multivariate regression analysis was performed to identify independent predictors of thromboembolic and hemorrhagic complications.RESULTS:Forty-four patients underwent 48 Pipeline Embolization Device procedures at our institution during the study period. There were 11 thromboembolic and hemorrhagic complications up to 6 months after treatment in our cohort (22.9%), 5 of which were major (10.4%). A last-recorded P2Y12 reaction units value of <60 or >240 was the only independent predictor of all (P = .002) and major (P = .03) thromboembolic and hemorrhagic complications in our cohort. Most patients (71%) required, on average, 2 adjustments to the dose or type of P2Y12 receptor antagonist to remain within the 60–240 target P2Y12 reaction units range.CONCLUSIONS:In our cohort, a last-recorded P2Y12 reaction units value of <60 or >240 was the only independent predictor of all and major thromboembolic and hemorrhagic complications up to 6 months after Pipeline Embolization Device procedures.

Endovascular treatment of cerebral aneurysms with the Pipeline Embolization Device (PED; Covidien/ev3, Irvine, California) requires its deployment within the lumen of the parent artery to allow the vessel to endothelialize along the PED and exclude the aneurysm from the circulation. This process carries the risk of thromboembolic complications because platelets could become activated, adhere to the PED, form thrombus, and cause either in situ PED thrombosis or distal thromboembolization. Hence, PED procedures are usually performed under dual antiplatelet therapy (DAT) with aspirin and a P2Y12 receptor antagonist such as clopidogrel, prasugrel, or ticagrelor. However, DAT carries the risk of hemorrhagic complications, with parenchymal intracerebral hemorrhage (ICH) being the most potentially devastating.Case series of 12–191 patients with cerebral aneurysms treated with the PED have reported a wide range of thromboembolic and hemorrhagic complications, with the risk of cerebral infarction ranging from 0% to 14% and the risk of ICH ranging from 0% to 11%.^1–16 Among other factors, the variability in thromboembolic and hemorrhagic complications after PED procedures could be due to differences in patient responses to the P2Y12 receptor antagonists administered while the PED endothelializes.The P2Y12 receptor plays a central role in platelet activation and aggregation. Clopidogrel and prasugrel cause irreversible inhibition of the P2Y12 receptor, while ticagrelor causes reversible inhibition of this receptor. VerifyNow (Accumetrics, San Diego, California) is a point-of-care platelet function test that measures the degree of P2Y12 receptor inhibition after stimulation with adenoside diphosphate, a P2Y12 receptor agonist. This assay has been found to correlate strongly with light transmittance aggregometry, the criterion standard for quantification of platelet reactivity, in patients treated with clopidogrel, prasugrel, or ticagrelor.^17–20 VerifyNow results are reported in P2Y12 reaction units (PRUs), with a lower PRU value corresponding to a higher degree of P2Y12 receptor inhibition and, hence, a decreased likelihood of platelet activation and aggregation; and a higher PRU value corresponding to a lower degree of P2Y12 receptor inhibition and, hence, an increased likelihood of platelet activation and aggregation. A recent study of 44 patients who underwent 48 PED procedures for treatment of cerebral aneurysms at our institution found that a preprocedural PRU value of <60 or >240 measured with VerifyNow was the strongest independent predictor of perioperative thromboembolic and hemorrhagic complications occurring up to postoperative day 30.¹⁶The aim of this study was to determine whether a last-recorded PRU value of <60 or >240 (up to the occurrence of a complication, if any) predicts thromboembolic and hemorrhagic complications occurring up to 6 months after treatment in the same cohort of patients with cerebral aneurysms treated with the PED at our institution.     

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

BACKGROUND AND PURPOSE:The Pipeline Embolization Device was reported to be safe and effective in the treatment of sidewall aneurysms, preserving the patency of the vessels covered by the construct. However, to date, the safety and efficacy of this device in treating bifurcation aneurysms remains unknown. We report our preliminary experience with the use of the Pipeline Embolization Device in the management of MCA aneurysms located at the bifurcations, including mid- and long-term follow-up data.MATERIALS AND METHODS:Wide-neck MCA aneurysms, which give rise to a bifurcating or distal branch in which other endovascular techniques are thought to be unfeasible or more risky, were included. Data including demographics, aneurysm features, antiplatelet therapy, complications, and angiographic follow-up results for up to 30 months were recorded.RESULTS:Twenty-five aneurysms located at the MCA bifurcation (n = 21) or distal (n = 4) were treated. Of these, 22 were small and 3 were large. A single device was used in all but 2. No deaths occurred in the series. All patients had at least 1 control angiographic study, 21 of which were DSA (3–30 months), which showed that 12 of the rising branches were patent whereas 6 were filling in reduced caliber and 3 were occluded asymptomatically. According to the last angiographic follow-up, complete occlusion was revealed in 21 of 25 aneurysms (84%).CONCLUSIONS:The Pipeline Embolization Device provides a safe and effective treatment alternative for wide-neck MCA aneurysms that give rise to a bifurcating or distal branch when other endovascular techniques are thought to be unfeasible or more risky.

Providing diseased parent artery reconstruction in addition to exclusion of the aneurysm from the circulation by means of flow disruption, spontaneous aneurysm thrombosis, and endothelialization mechanisms, flow diversion is a new but widely accepted endovascular treatment technique for intracranial aneurysms. The use of self-expandable neurovascular stents (designed to be used in conjunction with coil embolization) as a monotherapy was previously reported with the implantation of 1 or more stents.^1–5 A few case series with the use of the sole stent placement technique in the treatment of complex fusiform MCA aneurysms also exist in the literature.^6,7 Additionally, Y-stent flow diversion by use of self-expandable stents with a closed-cell design without endosaccular coiling has also been reported to be effective in a small, selected case series, including 5 MCA bifurcation aneurysms with complete occlusion in the follow-up.⁸The introduction of the Pipeline Embolization Device (PED) (Covidien/ev3, Irvine, California) as a dedicated flow diverter added a new dimension to this treatment strategy, with its being porous enough to preserve the patency of the branch vessels covered by the construct.⁹ The previous experience with the PED in the treatment of saccular aneurysms revealed that when a branch was originating directly from the aneurysm sac, this branch was kept patent when there was a flow demand through it.¹⁰ Although, to date, the safety and efficacy of this device in treating bifurcation aneurysms remains unknown. This inspired us to use the PED for treatment of MCA bifurcation or M2 aneurysms in which one of the bifurcating branches or a distal branch originate directly from the aneurysm sac, when other endovascular techniques were deemed unfeasible or more risky. There have been limited numbers of MCA aneurysms reported to be treated with the PED within different case series^11–15; however, none included bifurcation aneurysms. We report, to our knowledge, the first case series focused on the use of the PED in the management of MCA aneurysms, in which a bifurcating or a distal branch emanates directly from the aneurysm sac.     

Contrast-Enhanced Time-Resolved MRA for Follow-Up of Intracranial Aneurysms Treated with the Pipeline Embolization Device

BACKGROUND AND PURPOSE:Endovascular reconstruction and flow diversion by using the Pipeline Embolization Device is an effective treatment for complex cerebral aneurysms. Accurate noninvasive alternatives to DSA for follow-up after Pipeline Embolization Device treatment are desirable. This study evaluated the accuracy of contrast-enhanced time-resolved MRA for this purpose, hypothesizing that contrast-enhanced time-resolved MRA will be comparable with DSA and superior to 3D-TOF MRA.MATERIALS AND METHODS:During a 24-month period, 37 Pipeline Embolization Device–treated intracranial aneurysms in 26 patients underwent initial follow-up by using 3D-TOF MRA, contrast-enhanced time-resolved MRA, and DSA. MRA was performed on a 1.5T unit by using 3D-TOF and time-resolved imaging of contrast kinetics. All patients underwent DSA a median of 0 days (range, 0–68) after MRA. Studies were evaluated for aneurysm occlusion, quality of visualization of the reconstructed artery, and measurable luminal diameter of the Pipeline Embolization Device, with DSA used as the reference standard.RESULTS:The sensitivity, specificity, and positive and negative predictive values of contrast-enhanced time-resolved MRA relative to DSA for posttreatment aneurysm occlusion were 96%, 85%, 92%, and 92%. Contrast-enhanced time-resolved MRA demonstrated superior quality of visualization (P = .0001) and a higher measurable luminal diameter (P = .0001) of the reconstructed artery compared with 3D-TOF MRA but no significant difference compared with DSA. Contrast-enhanced time-resolved MRA underestimated the luminal diameter of the reconstructed artery by 0.965 ± 0.497 mm (27% ± 13%) relative to DSA.CONCLUSIONS:Contrast-enhanced time-resolved MRA is a reliable noninvasive method for monitoring intracranial aneurysms following flow diversion and vessel reconstruction by using the Pipeline Embolization Device.

Surgical clipping or endovascular coil embolization is generally the preferred treatment for intracranial aneurysms.¹ The Pipeline Embolization Device (PED; Covidien, Irvine, California) is an endovascular device that has redefined the scope of treatment for large, giant, wide-neck, or fusiform aneurysms or aneurysms having failed coil embolization, by reconstructing the parent artery and restoring its natural course.² The PED is designed for 85% reduction of blood flow within an aneurysm, which induces thrombosis² while keeping perforators and/or side branch vessels patent.³ Results from a multicenter prospective trial for treatment of uncoilable or failed large and giant ICA aneurysms with the PED demonstrated 99% technical success and 74% complete occlusion with 6% major ipsilateral stroke or death.⁴ Flow diversion with the PED has also been reported in the treatment of HIV vasculopathy, with fusiform cerebral aneurysms precluding parent vessel sacrifice or surgical bypass.⁵Digital subtraction angiography is the reference standard for the evaluation of aneurysms after endovascular treatment due to its unsurpassed spatial resolution; however, DSA is invasive and not without risks of puncture site and neurologic complications.⁶ Posttreatment follow-up of intracranial aneurysms after coil embolization with MRA by using 3D-TOF or contrast-enhanced techniques is a potential noninvasive alternative to DSA for the evaluation of PED-treated aneurysms without the use of ionizing radiation.⁷ Contrast-enhanced time-resolved MRA (CE-TR MRA) uses acquisition schemes aimed at accelerated data collection, primarily using parallel imaging algorithms and novel k-space trajectories to achieve high temporal resolution for multiphasic MRA examinations. This technique provides consistent, technologist-independent, optimal arterial enhancement for contrast-enhanced MRA and provides information on temporal contrast kinetics.^8,9 Use of CE-TR MRA has been reported in the evaluation of intracranial lesions such as arteriovenous malformations and dural arteriovenous fistulas and for assessment of stenosis of the extracranial carotid artery, and it seems to be a promising technique for evaluating aneurysms after stent-assisted coil embolization.^9–11We hypothesized that TR-CE MRA could provide information comparable with DSA and would be superior to 3D-TOF MRA in the evaluation of intracranial aneurysms and the parent artery following flow diversion and parent vessel reconstruction with the PED.     

Intravenous C-Arm Conebeam CT Angiography following Long-Term Flow-Diverter Implantation: Technologic Evaluation and Preliminary Results

BACKGROUND AND PURPOSE:A noninvasive investigation with high spatial resolution and without metal artifacts is necessary for long-term imaging follow-up after flow-diverter implantation. We aimed to evaluate the diagnostic value of conebeam CT angiography with intravenous contrast enhancement in the assessment of vascular status following implantation of the Pipeline Embolization Device and to analyze the preliminary results of vascular status following long-term Pipeline Embolization Device implantation.MATERIALS AND METHODS:This was an ongoing prospective study of consecutive patients with intracranial aneurysms treated with the Pipeline Embolization Device. Patients with a modified Rankin Scale score of 4–5 were excluded. The median and interquartile range of the time interval of Pipeline Embolization Device implantation to conebeam CT angiography with intravenous contrast enhancement were 56.6 and 42.9–62.4 months, respectively. Conebeam CT angiography with intravenous contrast enhancement was performed with the patient fully conscious, by using a C-arm CT with a flat panel detector.RESULTS:There were 34 patients and 34 vascular segments. In all 34 cases, contrast effect and image quality were good and not substantially different from those of intra-arterial conebeam CTA. Metal artifacts occurred in all 14 cases with coil masses; the Pipeline Embolization Device was obscured in 3 cases. In all 34 cases, there was no residual aneurysm, no vascular occlusion, 1 vascular stenosis (50%), good Pipeline Embolization Device apposition to the vessel, and no Pipeline Embolization Device–induced calcification. All 28 Pipeline Embolization Device–covered side branches were patent.CONCLUSIONS:Conebeam CT angiography with intravenous contrast enhancement is potentially promising and useful for effective evaluation of the vascular status following intracranial flow diverters. The Pipeline Embolization Device for intracranial aneurysms is probably safe and promising for long-term placement, with favorable morphologic outcome and without delayed complications.

The Pipeline Embolization Device (PED; Covidien, Irvine, California) as a flow diverter has been introduced for the treatment of intracranial aneurysms.^1–6 To date, knowledge on the anatomic status of the post-PED vascular segment as revealed on DSA is mainly limited to within 6–12 months.^1,2,4,5,7,8 Follow-up DSA with a longer duration of 18–24 months has been reported in only 2 studies.^6,9 Beyond 24 months, post-PED vascular status has been studied only with MR imaging,¹⁰ but CT angiography or MR angiography is not desirable for this purpose owing to metal artifacts from the PED and suboptimal spatial resolution.^11,12 The long-term status of the post-PED vascular segment and the covered side branches beyond 24 months remains unknown. The use of DSA to assess long-term post-PED vascular status is probably not practical because patients tend to refuse an invasive investigation when they do not see an immediate clinical need; such limitations could be an important cause of lack of long-term angiographic data. There is, therefore, a need for a noninvasive technique with multiplanar cross-sectional imaging capability for simultaneous visualization of the PED and the vessel lumen, to allow adequate examination of the PED-paved vascular segment.The use of conebeam CT angiography with intravenous contrast enhancement (IVCBCTA) for patient monitoring following placement of flow diverters has been reported and found to be feasible and potentially useful.^13–15 We aimed to evaluate the diagnostic value of IVCBCTA in the assessment of post-PED vascular status and to analyze the preliminary results of vascular status following long-term PED implantation.     

Lack of Association between Statin Use and Angiographic and Clinical Outcomes after Pipeline Embolization for Intracranial Aneurysms

BACKGROUND AND PURPOSE:Use of statin medications has been demonstrated to improve clinical and angiographic outcomes in patients receiving endovascular stent placement for coronary, peripheral, carotid, and intracranial stenoses. We studied the impact of statin use on long-term angiographic and clinical outcomes after flow-diverter treatment of intracranial aneurysms.MATERIALS AND METHODS:We performed a post hoc analysis from pooled patient-level datasets from 3 Pipeline Embolization Device studies: the International Retrospective Study of the Pipeline Embolization Device, the Pipeline for Uncoilable or Failed Aneurysms Study, and the Aneurysm Study of Pipeline in an Observational Registry. We analyzed data comparing 2 subgroups: 1) patients on statin medication, and 2) patients not on statin medication at the time of the procedure and follow-up. Angiographic and clinical outcomes were compared by using the χ² test, Fisher exact test, or Wilcoxon rank sum test.RESULTS:We studied 1092 patients with 1221 aneurysms. At baseline, 226 patients were on statin medications and 866 patients were not on statin medications. The mean length of clinical and angiographic follow-up was 22.1 ± 15.1 months and 28.3 ± 23.7 months, respectively. There were no differences observed in angiographic outcomes at any time point between groups. Rates of complete occlusion were 82.8% (24/29) versus 86.4% (70/81) at 1-year (P = .759) and 93.3% (14/15) versus 95.7% (45/47) at 5-year (P = 1.000) follow-up for statin-versus-nonstatin-use groups, respectively. There were no differences in any complication rates between groups, including major morbidity and neurologic mortality (7.5% versus 7.1%, P = .77).CONCLUSIONS:Our study found no association between statin use and angiographic or clinical outcomes among patients treated with the Pipeline Embolization Device.

Statin medications are among the most commonly prescribed in the adult population and have been found beneficial in improving clinical and angiographic outcomes of a number of endovascular neurovascular, cardiovascular, and peripheral vascular stent-placement procedures.^1–3 Both experimental and clinical studies have demonstrated that statin use is associated with improved endothelialization of implanted stents, which can reduce the rates of delayed in-stent thrombosis and in-stent stenosis.^4–6 In the treatment of aneurysms with flow diverters such as the Pipeline Embolization Device (PED; Covidien, Irvine, California), stent endothelialization has been shown to play a key role in aneurysm occlusion rates and in reducing the risk of delayed in-stent thrombosis.⁷Given the widespread acceptance and use of flow-diverter therapy in the treatment of intracranial aneurysms, it is important to know what effect, if any, statins have on clinical and angiographic outcomes. To gain a better understanding of the impact of statins on short- and long-term outcomes after flow diversion for intracranial aneurysms, we studied angiographic and clinical outcomes of patients included in 3 large clinical studies of the PED: the Pipeline for Uncoilable or Failed Aneurysms Study (PUFS),⁸ the International Retrospective Study of the Pipeline Embolization Device (IntrePED),⁹ and the Aneurysm Study of Pipeline in an Observational Registry (ASPIRe),¹⁰ dividing patients into 2 groups: 1) those who were on a statin medication at the time and following treatment with the PED, and 2) those who were not on statin medications.^8,9 The goal of this study was to determine whether statin use is associated with angiographic occlusion and major neurologic morbidity and mortality after PED treatment. We hypothesized that patients on statin medications would have a lower rate of in-stent stenosis and morbidity and mortality rates and improved angiographic occlusion rates.     

International Retrospective Study of the Pipeline Embolization Device: A Multicenter Aneurysm Treatment Study

BACKGROUND AND PURPOSE:Flow diverters are increasingly used in the endovascular treatment of intracranial aneurysms. Our aim was to determine neurologic complication rates following Pipeline Embolization Device placement for intracranial aneurysm treatment in a real-world setting.MATERIALS AND METHODS:We retrospectively evaluated all patients with intracranial aneurysms treated with the Pipeline Embolization Device between July 2008 and February 2013 in 17 centers worldwide. We defined 4 subgroups: internal carotid artery aneurysms of ≥10 mm, ICA aneurysms of <10 mm, other anterior circulation aneurysms, and posterior circulation aneurysms. Neurologic complications included spontaneous rupture, intracranial hemorrhage, ischemic stroke, permanent cranial neuropathy, and mortality. Comparisons were made with t tests or ANOVAs for continuous variables and the Pearson χ² or Fisher exact test for categoric variables.RESULTS:In total, 793 patients with 906 aneurysms were included. The neurologic morbidity and mortality rate was 8.4% (67/793), highest in the posterior circulation group (16.4%, 9/55) and lowest in the ICA <10-mm group (4.8%, 14/294) (P = .01). The spontaneous rupture rate was 0.6% (5/793). The intracranial hemorrhage rate was 2.4% (19/793). Ischemic stroke rates were 4.7% (37/793), highest in patients with posterior circulation aneurysms (7.3%, 4/55) and lowest in the ICA <10-mm group (2.7%, 8/294) (P = .16). Neurologic mortality was 3.8% (30/793), highest in the posterior circulation group (10.9%, 6/55) and lowest in the anterior circulation ICA <10-mm group (1.4%, 4/294) (P < .01).CONCLUSIONS: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.

Endoluminal flow-diverter therapy has gained widespread acceptance for the treatment of intracranial aneurysms.^1–4 High rates of complete aneurysm occlusion have been reported, even in large and giant aneurysms, with the use of endoluminal flow diverters.^1–7 The Pipeline Embolization Device (PED; Covidien, Irvine, California) received CE mark approval in 2008 for the embolization of cerebral aneurysms and received US FDA approval in 2011 (PMA P100018) for the treatment of large and giant wide-neck aneurysms in the internal carotid artery, from the petrous to the superior hypophyseal segments. While numerous previous studies have reported overall rates of adverse events similar to those in other endovascular procedures, case reports and small case series documenting severe and “unexpected” complications have raised questions about the safety of these devices.^1,3,8,9 Severe and unexpected adverse events include spontaneous rupture of treated aneurysms and intraparenchymal intracranial hemorrhage unrelated to aneurysm rupture.^8,10–12 These reports led to policies in some regions mandating concomitant coil embolization with flow-diverter therapy to mitigate the risk of spontaneous aneurysm rupture.¹³Most previous literature on flow-diversion therapy comprised single-center case series, either retrospective or prospective, and has substantial selection bias, which may affect the rates of severe and unexpected adverse events. These biases may be diminished through pooling of consecutive patients treated at multiple centers in a “real-world” setting, with homogeneous end points and methods of data analysis. The International Retrospective Study of Pipeline Embolization Device (IntrePED) registry was designed for this purpose and to determine rates of important neurologic safety events following PED placement for intracranial aneurysm treatment.     

Treatment of Tandem Internal Carotid Artery Aneurysms Using a Single Pipeline Embolization Device: Evaluation of Safety and Efficacy

BACKGROUND AND PURPOSE:Tandem aneurysms are defined as multiple aneurysms located in close proximity on the same parent vessel. Endovascular treatment of these aneurysms has rarely been reported. Our aim was to evaluate the safety and efficacy of a single Pipeline Embolization Device for the treatment of tandem aneurysms of the internal carotid artery.MATERIALS AND METHODS:A retrospective analysis of consecutive aneurysms treated with the Pipeline Embolization Device between 2009 and 2016 at 3 institutions in the United States was performed. Cases included aneurysms of the ICA treated with a single Pipeline Embolization Device, and they were divided into tandem versus solitary. Angiographic and clinical outcomes were compared.RESULTS:The solitary group (median age, 58 years) underwent 184 Pipeline Embolization Device procedures for 184 aneurysms. The tandem group (median age, 50.5 years) underwent 34 procedures for 78 aneurysms. Aneurysms were primarily located along the paraophthalmic segment of the ICA in both the single and tandem groups (72.3% versus 78.2%, respectively, P = .53). The median maximal diameters in the solitary and tandem groups were 6.2 and 6.7 mm, respectively. Complete occlusion on the last angiographic follow-up was achieved in 75.1% of aneurysms in the single compared with 88.6%% in the tandem group (P = .06). Symptomatic thromboembolic complications were encountered in 2.7% and 8.8% of procedures in the single and tandem groups, respectively (P = .08).CONCLUSIONS:Tandem aneurysms of the ICA can be treated with a single Pipeline Embolization Device with high rates of complete occlusion. While there appeared to be a trend toward higher thromboembolic complication rates, this did not reach statistical significance.

Multiple intracranial aneurysms account for 14%–34% of the distribution of all intracranial aneurysms.^1–5 When these aneurysms are located in close proximity to each another on the same parent vessel, they are referred to as “tandem aneurysms.” The treatment of tandem aneurysms has rarely been reported in the literature. These aneurysms are most commonly found along the internal carotid artery and may arise within the same anatomic segment or involve adjacent segments. Rarely, they are identified in the posterior circulation.^1,6–9 Flow diversion with the Pipeline Embolization Device (PED; Covidien, Irvine, California) was initially approved by the US Food and Drug Administration for treatment of large or giant, wide-neck cerebral aneurysms of the ICA from the petrous to superior hypophyseal segments.¹⁰ Numerous studies have since demonstrated the safety and efficacy of the PED in the treatment of aneurysms with varying morphologies and anatomic locations.^11–16 Currently, only a few studies with small numbers of patients have evaluated endovascular treatment of tandem aneurysms with coil embolization,⁸ stent-assisted coiling,⁹ or flow diversion.⁹ In this study, we compare the outcomes following deployment of a single PED in 2 groups of patients, those with solitary ICA aneurysms and those with tandem ICA aneurysms.     

Effect of Structural Remodeling (Retraction and Recoil) of the Pipeline Embolization Device on Aneurysm Occlusion Rate

BACKGROUND AND PURPOSE:During endovascular treatment of unruptured aneurysms with the Pipeline Embolization Device, an oversized device is often selected to achieve better wall apposition; however, this device oversizing could be related to overelongation and possible delayed enlargement of the stented region. The purpose of this study is to investigate the relationship between oversize and treatment outcome.MATERIALS AND METHODS:The DynaCT images of 14 aneurysms treated by a single Pipeline Embolization Device were retrospectively analyzed. 3D images of the deployed device were compared with those acquired at the 6-month follow-up for qualitative and quantitative evaluation. The diameter and length of the Pipeline Embolization Device were measured at both time points and compared for determination of the device changes.RESULTS:Structural changes of the device have been observed, and it was found that the Pipeline Embolization Device influences the vessel curvature in some cases. On average, it increases its diameter by 0.23 mm and decreases its length by 2.88 mm within 6 months of initial deployment. Excessive elongation beyond its nominal length is correlated with a lower aneurysm occlusion rate at the 6-month follow-up.CONCLUSIONS:Not only does a Pipeline Embolization Device reconstruct the aneurysm and parent artery, but its entire structure goes through a gradual remodeling process. The relative deformation between the device and the artery indicates suboptimal wall apposition. Device oversizing does not have a direct effect on shortening or recoil. The aneurysm occlusion rate, however, is lowered by overelongation of the Pipeline Embolization Device.

Growing enthusiasm for the Pipeline Embolization Device (PED; Covidien, Irvine, California) has prompted a dramatic shift in how unruptured aneurysms are managed since approval of the device.¹ The PED diverts blood away from the aneurysm and reduces rupture risk by stimulating formation of intra-aneurysmal thrombus and lowering hemodynamic forces on the aneurysm dome.Few aneurysms treated by flow diversion are thrombosed acutely; the aneurysm occlusion rate varies from center to center, but in general, it increases with time, from 68% at the 3-month,² 65%–91% at the 6-month,^3,4 90%–93% at the 12-month,⁵ and 84% at the 18-month follow-up.⁶ Nevertheless, it is not uncommon for aneurysms to remain patent >2 years after treatment, and the risk of delayed hemorrhage persists.^7,8Intracranial stents are known to alter vessel curvature⁹; similarly, the parent artery may cause deformation of a flow diverter and influence the device porosity.¹⁰ Vessel tortuosity often renders a nonuniform distribution of the porosity and allows potentially less metal coverage at the aneurysm neck; as a result, prediction of the timing of complete aneurysm occlusion after flow diversion can be a challenge. The PED is a braided self-expanding stent with 12 platinum and 36 cobalt-chromium alloy strands. Radio-opacity of the platinum strands in a PED can be used as a marker and offers an opportunity to visualize the PED in greater detail to reveal suboptimal deployment, which may require further intervention.^11,12 In this study, we investigated the temporal change of the PED structure in situ after deployment and examined its relationship with the aneurysm occlusion rate.     

New ischemic brain lesions on diffusion-weighted MRI after carotid artery stenting with filter protection: frequency and relationship with plaque morphology

BACKGROUND AND PURPOSE:CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms. Our purpose was to evaluate the frequency of new ischemic lesions found on DWI after protected CAS placement and to determine its association with plaque morphology.MATERIALS AND METHODS:Fifty patients (mean age 65.13 ± 7.08 years) with moderate and severe internal carotid artery stenosis underwent CAS with distal filter protection. Fibrolipid and fibrocalcified plaque morphology was determined by sonography according to the relative contribution of echogenic and echolucent material, and by multisection CT using plaque attenuation. There were 46.81% of patients with fibrolipid and 53.19% with fibrocalcified plaques. DWI was performed before and 24 hours after CAS.RESULTS:Seven (14.89%) patients showed new lesions. Four (8.51%) had 6 new lesions inside the treated vascular territory. Three had a single lesion and 1 patient had 3 lesions (mean: 1.5 ± 1). Most lesions (66.66%) were subcortical, with a mean diameter of 9 mm (range 5–15 mm). All lesions occurred in the area supplied by the middle cerebral artery and were clinically silent. A significant relationship was found between plaque morphology and the appearance of new lesions. Patients with fibrolipid plaques had a significantly higher number of new lesions compared with patients with fibrocalcified plaques (P = .041). The absolute risk of new lesions in the fibrolipid group was 18.18%.CONCLUSIONS:New ischemic lesions were observed in the treated vascular territory in 8.51% of patients. The appearance of new ischemic lesions was significantly related to the plaque morphology. Fibrolipid plaques were associated with higher numbers of new lesions.

CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms.^1–4 This has led to the development and widespread application of cerebral protection devices.^5,6 The most widely used devices are those based on distal filter placement that capture emboli dislodged from plaque; however, their application may result in additional complications.^7–12Several reviews have reported contradictory data concerning the rate of stroke and ischemia after protected versus unprotected stent placement.^3,13–15 The frequency of new ischemic lesions after CAS may be associated with numerous factors, such as clinical status, vascular anatomy, plaque morphology, and complexity. Therefore, the need to identify patients at risk for embolic events has become increasingly important. The morphologic characteristics of atherosclerotic carotid plaques may be useful in heralding embolic potential in the carotid arteries. Several authors have reported that plaques in the carotid arteries that are associated with large lipid pools or soft extracellular lipid are more prone to rupture and production of emboli.¹⁶ DWI is the most sensitive tool for the detection of neurologically silent or asymptomatic infarcts at a very early stage.^17–19The aim of this study was to determine the frequency of new ischemic DWI lesions in patients with moderate and severe ICA stenosis after protected CAS using a filter device, and to determine its potential association with plaque morphology.     

Symptom Differences and Pretreatment Asymptomatic Interval Affect Outcomes of Stenting for Intracranial Atherosclerotic Disease

BACKGROUND AND PURPOSE:Different types of symptomatic intracranial stenosis may respond differently to interventional therapy. We investigated symptomatic and pathophysiologic factors that may influence clinical outcomes of patients with intracranial atherosclerotic disease who were treated with stents.MATERIALS AND METHODS:A retrospective analysis was performed of patients treated with stents for intracranial atherosclerosis at 4 centers. Patient demographics and comorbidities, lesion features, treatment features, and preprocedural and postprocedural functional status were noted. χ² univariate and multivariate logistic regression analysis was performed to assess technical results and clinical outcomes.RESULTS:One hundred forty-two lesions in 131 patients were analyzed. Lesions causing hypoperfusion ischemic symptoms were associated with fewer strokes by last contact [χ² (1, n = 63) = 5.41, P = .019]. Nonhypoperfusion lesions causing symptoms during the 14 days before treatment had more strokes by last contact [χ² (1, n = 136), 4.21, P = .047]. Patients treated with stents designed for intracranial deployment were more likely to have had a stroke by last contact (OR, 4.63; P = .032), and patients treated with percutaneous balloon angioplasty in addition to deployment of a self-expanding stent were less likely to be stroke free at point of last contact (OR, 0.60; P = .034).CONCLUSIONS:More favorable outcomes may occur after stent placement for lesions causing hypoperfusion symptoms and when delaying stent placement 7–14 days after most recent symptoms for lesions suspected to cause embolic disease or perforator ischemia. Angioplasty performed in addition to self-expanding stent deployment may lead to worse outcomes, as may use of self-expanding stents rather than balloon-mounted stents.

Intracranial atherosclerotic disease (ICAD) causes considerable morbidity and mortality, accounting for up to one-third of ischemic strokes in some series, particularly in certain populations.^1–3 Some lesions prove recalcitrant to first-line medical management, and, in recent decades, endovascular treatments have emerged and evolved as complementary therapies.^4,5 Early series demonstrated technical feasibility and acceptable safety for percutaneous transluminal angioplasty (PTA) and then stent placement of lesions in ICAD.^5–17 Initially, intracranial procedures were performed with devices designed and approved for coronary interventions, with subsequent release of angioplasty balloons specifically engineered for intracranial use.^5,12,17–33 In 2005, the Wingspan stent system with Gateway PTA balloon catheter (Stryker, Kalamazoo, Michigan) became the first stent approved for treatment of ICAD in the United States.^{5,12,18–22,25,34} Numerous studies reported progressively improved outcomes and low complication rates, but randomized data proving efficacy were lacking.^{5,12,18,20,24,25,35,36} In 2011, enrollment in the first randomized, controlled trial to evaluate stent placement versus medical management of ICAD, the Stent placement and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, was halted early due to high complication rates in the stent placement group as compared with the medical management group.⁴The results of SAMMPRIS have elicited strong responses from both proponents and detractors of stent placement, with clinical decisions now changing.⁵ This current study retrospectively analyzes results of stent placement procedures performed for ICAD at 4 centers, with attention given to factors not specifically assessed in SAMMPRIS that may help guide further investigations of endovascular ICAD management.     

Preoperative Embolization of Intracranial Meningiomas: Efficacy,Technical Considerations,and Complications

BACKGROUND AND PURPOSE:Preoperative embolization for intracranial meningiomas offers potential advantages for safer and more effective surgery. However, this treatment strategy has not been examined in a large comparative series. The purpose of this study was to review our experience using preoperative embolization to understand the efficacy, technical considerations and complications of this technique.MATERIALS AND METHODS:We performed a retrospective review of patients undergoing intracranial meningioma resection at our institution (March 2001 to December 2012). Comparisons were made between embolized and nonembolized patients, including patient and tumor characteristics, embolization method, operative blood loss, complications, and extent of resection. Logistic regression analyses were used to identify factors predictive of operative blood loss and extent of resection.RESULTS:Preoperatively, 224 patients were referred for embolization, of which 177 received embolization. No complications were seen in 97.1%. There were no significant differences in operative duration, extent of resection, or complications. Estimated blood loss was higher in the embolized group (410 versus 315 mL, P = .0074), but history of embolization was not a predictor of blood loss in multivariate analysis. Independent predictors of blood loss included decreasing degree of tumor embolization (P = .037), skull base location (P = .005), and male sex (P = .034). Embolization was not an independent predictor of gross total resection.CONCLUSIONS:Preoperative embolization is a safe option for selected meningiomas. In our series, embolization did not alter the operative duration, complications, or degree of resection, but the degree of embolization was an independent predictor of decreased operative blood loss.

Preoperative embolization has been an option for adjunctive treatment of intracranial meningiomas for almost 4 decades, but it remains used in only a minority of cases.¹ Meningiomas are commonly supplied by the middle meningeal, accessory meningeal, ascending pharyngeal, or occipital branches of the external carotid artery (ECA), which are easily accessible by selective microcatheterization.² Branches of the internal carotid artery and pial feeders supplying the tumor may also be embolized,^3–6 though these vessels are typically more difficult to access and are associated with a higher risk of parenchymal infarct. In an attempt to change the tumor characteristics to increase the likelihood of a gross total resection and minimize operative morbidity, a variety of embolization materials have been used, including polyvinyl alcohol (PVA) particles,^7,8 large-caliber microspheres,^8,9 ethylene-vinyl alcohol (Onyx; Covidien, Irvine, California),^10,11 detachable coils,¹² fibrin glue¹³ and hyperosmolar mannitol.¹⁴ The potential advantages of preoperative embolization include decreased operative duration, reduced operative blood loss, and alteration of tumor consistency, all of which decrease the technical difficulty of surgical resection and increase the likelihood of achieving a more complete resection. Embolization likely causes histopathologic changes within the meningioma, including necrosis, ischemic changes, and microvascular fibrinoid changes.¹⁵ Hypoxia caused by disruption of tumoral blood supply also causes changes in protein expression consistent with angiogenesis and promotion of growth,¹⁶ along with cytologic changes, including infiltration of macrophages.¹⁷ The combination of these changes may make histologic examination of embolized meningiomas more difficult because they may histopathologically resemble higher grade tumors.^15,18–20 Embolization also carries with it the risk of procedural complications, including large-vessel dissection, microcatheter fracture, and unintended arterial or venous occlusion resulting in hemorrhagic or ischemic infarct.^1,7,21–28Series of meningiomas that were preoperatively embolized have been recently published,⁷ but the operative findings and postoperative course for embolized tumors have not been compared with nonembolized tumors in a large modern series. In this study, we sought to review our outcomes following preoperative angiography, embolization when possible, and resection of intracranial meningiomas for the following objectives: 1) to assess the effect of preoperative embolization on operative time, surgical blood loss, and extent of resection; 2) to compare outcomes and complications between resection of embolized and nonembolized meningiomas; and 3) to determine predictors of objective utility of meningioma embolization.     

Long-Term Follow-Up Results following Elective Treatment of Unruptured Intracranial Aneurysms with the Pipeline Embolization Device

BACKGROUND AND PURPOSE:Numerous reports of treatment of wide-neck aneurysms by flow diverters have been published; however, long-term outcomes remain uncertain. This article reports the imaging results of unruptured aneurysms treated electively with the Pipeline Embolization Device for up to 56 months and clinical results for up to 61 months.MATERIALS AND METHODS:One hundred nineteen aneurysms in 98 patients from 3 centers admitted between August 2009 and June 2011 were followed at 6-month, 1-year, and 2+-year postprocedural timeframes. Analyses on the effects of incorporated vessels, previous stent placement, aneurysm size, and morphology on aneurysm occlusion were performed.RESULTS:The 1- and 2+-year imaging follow-ups were performed, on average, 13 and 28 months postprocedure. At 2+-year follow-up, clinical data were 100% complete and imaging data were complete for 103/116 aneurysms (88.8%) with a 93.2% occlusion rate. From 0 to 6 months, TIA, minor stroke, and major stroke rates were 4.2%, 3.4%, and 0.8% respectively. After 6 months, 1 patient had a TIA of uncertain cause, with an overall Pipeline Embolization Device–related mortality rate of 0.8%. An incorporated vessel was significant for a delay in occlusion (P = .009) and nonocclusion at 6 months and 1 year, with a delayed mean time of occlusion from 9.1 months (95% CI, 7.1–11.1 months) to 16.7 months (95% CI, 11.4–22.0 months). Other factors were nonsignificant.CONCLUSIONS:The Pipeline Embolization Device demonstrates continued very high closure rates at 2+ years, with few delayed clinical adverse sequelae. The presence of an incorporated vessel in the wall of the aneurysm causes a delay in occlusion that approaches sidewall closure rates by 2 years.

The endovascular treatment of wide-neck aneurysms by flow-diverting devices has been previously been evaluated for both small and large aneurysms. The midterm results of implantation of the Pipeline Embolization Device (PED; Covidien, Irvine, California) have been previously reported.^1–6 Data collection is now complete for up to 56 months with a mean of 28 months, and we report the results in patients who have previously undergone elective treatment with the PED.     

Can Doppler Flow Parameters of Carotid Stenosis Predict the Occurrence of New Ischemic Brain Lesions Detected by Diffusion-Weighted MR Imaging after Filter-Protected Internal Carotid Artery Stenting?

BACKGROUND AND PURPOSE:Carotid angioplasty and stent placement are increasingly being used for the treatment of symptomatic and asymptomatic carotid artery disease. Carotid angioplasty and stent placement carry an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms. Our purpose was to evaluate the frequency of new ischemic lesions found on diffusion-weighted imaging after protected carotid angioplasty and stent placement and to determine the association of new lesions with ICA Doppler flow parameters.MATERIALS AND METHODS:Fifty-two patients (mean age, 68 ± 11 years) with 50%–69% (n = 20, group 1) and ≥70% (n = 32, group 2) internal carotid artery stenosis underwent carotid angioplasty and stent placement with distal filter protection. DWI was performed before and 48 hours after carotid angioplasty and stent placement.RESULTS:Thirty-three (63.4%) patients showed new lesions. The average number of new postprocedural lesions was 3.4 per patient. Most of the postprocedural lesions were <5 mm (range, 3–23 mm), cortical and corticosubcortical, and clinically silent. Group 2 had a significantly higher number of new lesions compared with group 1 (P < .001). A significant relationship was found between ICA Doppler flow parameters and the appearance of new lesions.CONCLUSIONS:The appearance of new ischemic lesions was significantly related to the Doppler flow parameters, particularly peak systolic velocity.

Stroke is the most common life-threatening neurologic disorder and the most important single cause of disability.^1,2 Carotid artery stenosis, a major risk factor for stroke, and distal embolization, arising from degenerative breakdown or thrombotic occlusion of complex plaques, are important mechanisms of stroke in patients with atherosclerotic internal carotid artery stenosis.^3–6 Duplex sonography is currently the principal and, undoubtedly, the most accurate noninvasive and inexpensive diagnostic technique available for the evaluation of internal carotid artery stenosis. It provides information about the presence and severity of carotid stenosis, the velocity and characteristics of blood flow, and plaque morphology.^7–10Carotid angioplasty and stent placement for severe internal carotid artery stenosis have been introduced as a safe alternative to medical and/or surgical treatment in patients at high risk for surgical procedures.^11,12 However, there is still a major concern regarding its safety because of the risk of distal cerebral embolization during the procedure. Recent technical refinements, therefore, have led to the widespread use of carotid artery stenting (CAS) with cerebral-protection devices, markedly reducing thromboembolic complication rates.¹³ Diffusion-weighted MR imaging is a very sensitive and specific technique for diagnosing cerebral ischemia.^14,15 It has been used to detect structural damage of the brain due to cerebral embolism after cerebral angiography, neurointerventional procedures, and carotid endarterectomy.^16,17The purpose of our study was to assess, with DWI, the number, size, and location of new brain lesions after protected CAS and to evaluate the association of these new lesion deficits and Doppler flow parameters of ICA.     

Novel Human Acute Ischemic Stroke Blood Clot Analogs for In Vitro Thrombectomy Testing

BACKGROUND AND PURPOSE:Previous studies have successfully created blood clot analogs for in vitro endovascular device testing using animal blood of various species. Blood components vary greatly among species; therefore, creating clot analogs from human blood is likely a more accurate representation of thrombi formed in the human vasculature.MATERIALS AND METHODS:Following approval from the Mayo Clinic institutional review board, human whole-blood and platelet donations were obtained from the blood transfusion service. Twelve clot analogs were created by combining different ratios of red blood cells + buffy coat, plasma, and platelets. Thrombin and calcium chloride were added to stimulate coagulation. Clot composition was assessed using histologic and immunohistochemical staining. To assess the similarities of mechanical properties to patient clots, 3 types of clot analogs (soft, elastic, and stiff) were selected for in vitro thrombectomy testing.RESULTS:The range of histopathologic compositions produced is representative of clots removed during thrombectomy procedures. The red blood cell composition ranged from 8.9% to 91.4%, and fibrin composition ranged from 3.1% to 53.4%. Platelets (CD42b) and von Willebrand Factor ranged from 0.5% to 47.1% and 1.0% to 63.4%, respectively. The soft clots had the highest first-pass effect and successful revascularization rates followed by the elastic and stiff clots. Distal embolization events were observed when clot ingestion could not be achieved, requiring device pullback. The incidence rate of distal embolization was the highest for the stiff clots due to the weak clot/device integration.CONCLUSIONS:Red blood cell–rich, fibrin-rich, and platelet-rich clot analogs that mimic clots retrieved from patients with acute ischemic stroke were created in vitro. Differing retrieval outcomes were confirmed using in vitro thrombectomy testing in a subset of clots.

In the treatment of acute ischemic stroke (AIS), the achievement of complete revascularization from a single mechanical thrombectomy attempt, termed first-pass effect (FPE), is associated with significantly improved outcomes for patients.^1,2 Removing the clot in a fragmented manner increases the potential of embolization to new territories, a major contributing factor to poor neurologic outcomes due to additional brain infarction.^3-5 Despite the advancement in the second-generation mechanical thrombectomy devices, the rates of FPE remain low, as low as 29% in the recently reported Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) trial.⁶Previous studies have demonstrated that a wide variety of occlusive clots can cause large-vessel occlusion,^7-11 and clot composition has been shown to have a significant impact on the success of mechanical thrombectomy procedures.^7,12,13 These findings suggest that to further advance the success rates of stroke intervention, we must turn our attention to clot composition and compare treatment strategies using in vitro thrombectomy models of the cerebral vasculature. Previous studies have successfully created blood clot analogs for in vitro testing using animal blood of various species, which have significantly advanced our understanding of clot biomechanics and imaging characteristics.^13-19 However, blood components and blood groups vary among species;²⁰ thus, creating clot analogs with human blood is likely a more accurate representation of thrombi formed in the human vasculature.The hypothesis of the study was that the diverse range of clots retrieved from patients with AIS can be accurately replicated using human blood by mimicking the process by which clots form in vivo. The rationale for this study is that because the success of mechanical thrombectomy procedures is influenced by the composition of the clot, creating human clot analogs that accurately represent the different phenotypes retrieved from patients and testing them in an in vitro thrombectomy system will allow us to compare the performance of different thrombectomy devices and techniques. We will be able to determine the optimum treatment approach for each clot phenotype, thereby optimizing the chances of achieving the desired first-pass TICI 3 outcome in the clinical setting.¹ To assess the similarities of mechanical properties to patient clots, we selected 3 types of clot analogs (soft, elastic, and stiff) for in vitro thrombectomy testing.     

Predictors of Incomplete Occlusion following Pipeline Embolization of Intracranial Aneurysms: Is It Less Effective in Older Patients?

BACKGROUND AND PURPOSE:Flow diversion with the Pipeline Embolization Device (PED) for the treatment of intracranial aneurysms is associated with a high rate of aneurysm occlusion. However, clinical and radiographic predictors of incomplete aneurysm occlusion are poorly defined. In this study, predictors of incomplete occlusion at last angiographic follow-up after PED treatment were assessed.MATERIALS AND METHODS:A retrospective analysis of consecutive aneurysms treated with the PED between 2009 and 2016, at 3 academic institutions in the United States, was performed. Cases with angiographic follow-up were selected to evaluate factors predictive of incomplete aneurysm occlusion at last follow-up.RESULTS:We identified 465 aneurysms treated with the PED; 380 (81.7%) aneurysms (329 procedures; median age, 58 years; female/male ratio, 4.8:1) had angiographic follow-up, and were included. Complete occlusion (100%) was achieved in 78.2% of aneurysms. Near-complete (90%–99%) and partial (<90%) occlusion were collectively achieved in 21.8% of aneurysms and defined as incomplete occlusion. Of aneurysms followed for at least 12 months (211 of 380), complete occlusion was achieved in 83.9%. Older age (older than 70 years), nonsmoking status, aneurysm location within the posterior communicating artery or posterior circulation, greater aneurysm maximal diameter (≥21 mm), and shorter follow-up time (<12 months) were significantly associated with incomplete aneurysm occlusion at last angiographic follow-up on univariable analysis. However, on multivariable logistic regression, only age, smoking status, and duration of follow-up were independently associated with occlusion status.CONCLUSIONS:Complete occlusion following PED treatment of intracranial aneurysms can be influenced by several factors related to the patient, aneurysm, and treatment. Of these factors, older age (older than 70 years) and nonsmoking status were independent predictors of incomplete occlusion. While the physiologic explanation for these findings remains unknown, identification of factors predictive of incomplete aneurysm occlusion following PED placement can assist in patient selection and counseling and might provide insight into the biologic factors affecting endothelialization.

The flow-diverting Pipeline Embolization Device (PED; Covidien, Irvine, California) has become a mainstay for the treatment of intracranial aneurysms.¹ The device was approved by the US Food and Drug Administration in 2011 for the treatment of large or giant, wide-neck brain aneurysms along the internal carotid artery in adults.² Numerous studies have since demonstrated the safety and efficacy of the PED in treating aneurysms with varying morphologies in different anatomic locations.^3–8 As the clinical indications for PED placement expand, predictors of radiographic outcomes have become a topic of ongoing investigation. Although 1 study found that fusiform aneurysm morphology and shorter follow-up length were independent predictors of incomplete occlusion, this study was limited by a small sample size and a mean follow-up of 6.1 months.⁹ The expanding use of PEDs for treating intracranial aneurysms necessitates an evaluation of predictors of incomplete occlusion.     

Delayed ipsilateral parenchymal hemorrhage following flow diversion for the treatment of anterior circulation aneurysms

BACKGROUND AND PURPOSE:The PED is a flow-diverting stent designed for the treatment of cerebral aneurysms. We report 4 cases of delayed ipsilateral IPH following the technically successful treatment of anterior circulation aneurysms with the PED.MATERIALS AND METHODS:Clinical and imaging data from all patients undergoing aneurysm treatment with the PED at 2 institutions were analyzed to assess the incidence of delayed IPH after treatment with the PED.RESULTS:A total of 66 patients (47 anterior circulation) with cerebral aneurysms underwent treatment with a PED between January 2008 and November 2010. Four patients experienced delayed periprocedural IPH, all after the treatment of anterior circulation aneurysms (8.5%, 4/47). The aneurysm size ranged from 5 to 21 mm. All IPHs occurred within the cerebral hemisphere, ipsilateral to the treated aneurysm, and were anatomically remote from the treated aneurysms. All procedures were uncomplicated, and patients emerged from general anesthesia at neurologic baseline. The hemorrhages became clinically evident between 1 and 6 days after the procedure. Two patients had unfavorable outcomes (mRS scores, 4 and 6).CONCLUSIONS:Delayed IPH may occur after the treatment of anterior circulation aneurysms with flow diverters. This complication does not seem to be restricted to a specific aneurysm subtype and does not seem to be related to an intraprocedural complication or solely attributable to DAT.

Flow diverters have recently received full European Conformity Mark approval for commercialization within the European Union and FDA approval for their use within the United States. To date, the reported periprocedural and midterm follow-up results have been extremely impressive,^1–5 with very high rates of complete aneurysm occlusion and relatively low rates of postoperative morbidity and mortality. However, as more experience is accrued, their potential limitations and optimal applications are becoming increasingly evident.^6–12We report 4 cases of delayed ipsilateral IPH following the treatment of anterior circulation aneurysms with the PED.     

Selective-versus-Standard Poststent Dilation for Carotid Artery Disease: A Systematic Review and Meta-Analysis

BACKROUND:The safety and efficacy of standard poststent angioplasty in patients undergoing carotid artery stent placement have not been well-established.PURPOSE:We conducted a systematic review of the literature to evaluate the safety and efficacy of carotid artery stent placement and analyzed outcomes of standard-versus-selective poststent angioplasty.DATA SOURCES:A systematic search of MEDLINE, EMBASE, Scopus, and the Web of Science was performed for studies published between January 2000 and January 2015.STUDY SELECTION:We included studies with >30 patients describing standard or selective poststent angioplasty during carotid artery stent placement.DATA ANALYSIS:A random-effects meta-analysis was used to pool the following outcomes: periprocedural stroke/TIA, procedure-related neurologic/cardiovascular morbidity/mortality, bradycardia/hypotension, long-term stroke at last follow-up, long-term primary patency, and technical success.DATA SYNTHESIS:We included 87 studies with 19,684 patients with 20,378 carotid artery stenoses. There was no difference in clinical (P = .49) or angiographic outcomes (P = .93) in carotid artery stent placement treatment with selective or standard poststent balloon angioplasty. Both selective and standard poststent angioplasty groups had a very high technical success of >98% and a low procedure-related mortality of 0.9%. There were no significant differences between both groups in the incidence of restenosis (P = .93) or procedure-related complications (P = .37).LIMITATIONS:No comparison to a patient group without poststent dilation could be performed.CONCLUSIONS:Our meta-analysis demonstrated no significant difference in angiographic and clinical outcomes among series that performed standard poststent angioplasty and those that performed poststent angioplasty in only select patients.

Endovascular therapy of carotid artery disease has advanced during the past decade and is now considered a valuable treatment alternative to surgery in appropriately selected patients.^1–5 The indications for carotid endarterectomy were initially established in the North American Symptomatic Carotid Endarterectomy Trial⁶ in 1991, which expanded treatment indications to patients with symptomatic severe or moderate carotid stenoses. Formerly, patients who were not eligible for surgery were treated with percutaneous transluminal balloon angioplasty,^7,8 first described by Kerber et al in 1980.⁹ Although procedure-related complication rates were similar/comparable for both treatment modalities,^7,8,10 some potential drawbacks and specific problems occurred due to the endovascular approach, including luminal compromise from catheters and guidewires crossing the stenotic lesions and/or during balloon inflation (temporary carotid occlusion by a balloon and/or wire catheter), intraprocedural thromboembolic events, elastic vessel recoil, or intimal dissection.¹¹ After the carotid artery stent placement technique was developed, stent-assisted balloon angioplasty showed better results in event-free survival and even lower repeat angioplasty rates.¹¹ The primarily used balloon-expandable stents were increasingly replaced by self-expanding stents,^11,12 exhibiting an intrinsic radial expansion force with memory on the stenotic vessel wall. Poststent balloon angioplasty may then be performed to closely appose the stent and intima and, moreover, to expand regions of residual stent narrowing.¹¹Supporters of standard poststent balloon angioplasty (per protocol) indicated that poststent ballooning decreased the incidence of restenosis by re-establishing the normal luminal diameter. However, numerous studies^13–15 have suggested that poststent balloon dilation increases the likelihood of postprocedural emboli. Moreover, poststent ballooning can increase the probability of reflex bradycardia and hypotension, which might be associated with higher rates of periprocedural and postprocedural complications.^16–19Some authors claim that poststent dilation should be performed on a selective, case-by-case basis to maximize patient benefits and limit complications. However, to the best of our knowledge, there is no evidence in the recently published literature supporting the superiority of either of these techniques. Standard poststent balloon angioplasty has become the standard of care in many vascular centers,^20–35 and only some interventionalists^19,36–41 prefer performing poststent angioplasty on a selective base. On the basis of the latter studies, standard poststent balloon angioplasty may be associated with additional risks in patients with acceptable angiographic results, without additional post–carotid artery stent placement (CAS) angioplasty.To evaluate the safety and efficacy of standard poststent angioplasty versus selective poststent angioplasty, we conducted a systematic review and meta-analysis and analyzed outcomes by a series that performed standard poststent balloon angioplasty per protocol on all patients versus those that performed selective poststent balloon angioplasty on only a subset of patients.