István Szikora

The Pipeline Embolization Device for the Intracranial Treatment of Aneurysms Trial

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow diverting devices represents a novel constructive technique for the treatment of cerebral aneurysms. We present the results of the first prospective multicenter trial of a flow-diverting construct for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with unruptured aneurysms that were wide-necked (>4 mm), had unfavorable dome/neck ratios (<1.5), or had failed previous therapy were enrolled in the PITA trial between January and May 2007 at 4 (3 European and 1 South American) centers. Aneurysms were treated with the PED with or without adjunctive coil embolization. All patients underwent clinical evaluation at 30 and 180 days and conventional angiography 180 days after treatment. Angiographic results were adjudicated by an experienced neuroradiologist at a nonparticipating site. RESULTS: Thirty-one patients with 31 intracranial aneurysms (6 men; 42–76 years of age; average age, 54.6 years) were treated during the study period. Twenty-eight aneurysms arose from the ICA (5 cavernous, 15 parophthalmic, 4 superior hypophyseal, and 4 posterior communicating segments), 1 from the MCA, 1 from the vertebral artery, and 1 from the vertebrobasilar junction. Mean aneurysm size was 11.5 mm, and mean neck size was 5.8 mm. Twelve (38.7%) aneurysms had failed (or recurred after) a previous endovascular treatment. PED placement was technically successful in 30 of 31 patients (96.8%). Most aneurysms were treated with either 1 (n = 18) or 2 (n = 11) PEDs. Fifteen aneurysms (48.4%) were treated with a PED alone, while 16 were treated with both PED and embolization coils. Two patients experienced major periprocedural stroke. Follow-up angiography demonstrated complete aneurysm occlusion in 28 (93.3%) of the 30 patients who underwent angiographic follow-up. No significant in-construct stenosis (≥50%) was identified at follow-up angiography. CONCLUSIONS: Intracranial aneurysm treatment with the PED is technically feasible and can be achieved with a safety profile analogous to that reported for stent-supported coil embolization. PED treatment elicited a very high rate (93%) of complete angiographic occlusion at 6 months in a population of the most challenging anatomic subtypes of cerebral aneurysms.

Treatment of Intracranial Aneurysms by Functional Reconstruction of the Parent Artery: The Budapest Experience with the Pipeline Embolization Device

BACKGROUND AND PURPOSE: Aneurysm treatment by intrasaccular packing has been associated with a relatively high rate of recurrence. The use of mesh tubes has recently gained traction as an alternative therapy. This article summarizes the midterm results of using an endoluminal sleeve, the PED, in the treatment of aneurysms. MATERIALS AND METHODS: A total of 19 wide-neck aneurysms were treated in 18 patients: 10 by implantation of PEDs alone and 9 by a combination of PED and coils. Angiographic and clinical results were recorded immediately and at 6 months following treatment. RESULTS: Immediate angiographic occlusion was achieved in 4 and flow reduction, in another 15 aneurysms. Angiography at 6 months demonstrated complete occlusion in 17 and partial filling in 1 of 18 patients. There was no difference between coil-packed and unpacked aneurysms. Of 28 side branches covered by ≥1 device, the ophthalmic artery was absent immediately in 1 and at 6 months in another 2 cases. One patient experienced abrupt in-stent thrombosis resulting in a transient neurologic deficit, and 1 patient died due to rupture of a coexisting aneurysm. All giant aneurysms treated with PED alone were demonstrated by follow-up cross-sectional imaging to have involuted by 6 months. CONCLUSIONS: Treatment of large, wide-neck, or otherwise untreatable aneurysms with functional reconstruction of the parent artery may be achieved with relative safety using dedicated flow-modifying devices with or without adjunctive use of intrasaccular coil packing.

Pipeline for Uncoilable or Failed Aneurysms: Results from a Multicenter Clinical Trial

PURPOSE To evaluate the safety and effectiveness of the Pipeline Embolization Device (PED; ev3/Covidien, Irvine, Calif) in the treatment of complex intracranial aneurysms. MATERIALS AND METHODS The Pipeline for Uncoilable or Failed Aneurysms is a multicenter, prospective, interventional, single-arm trial of PED for the treatment of uncoilable or failed aneurysms of the internal carotid artery. Institutional review board approval of the HIPAA-compliant study protocol was obtained from each center. After providing informed consent, 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. RESULTS 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 studys 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%). CONCLUSION 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.

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.

Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16–18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).

Curative cerebrovascular reconstruction with the Pipeline embolization device: the emergence of definitive endovascular therapy for intracranial aneurysms

Endovascular, endosaccular, coil embolization has emerged as an established therapy for both ruptured and unruptured cerebral aneurysms. However, many aneurysms are not cured using conventional endovascular techniques. Coil embolization often results in incomplete aneurysm occlusion or recanalization in the ensuing months after treatment. The Pipeline embolization device (PED; Chestnut Medical) represents a new generation endoluminal implant which is designed to treat aneurysms by reconstructing the diseased parent artery. Immediately after implantation, the PED functions to divert flow from the aneurysm, creating an environment conducive to thrombosis. With time, the PED is incorporated into the vessel wall as neointimal–endothelial overgrowth occurs along the construct. Ultimately, this process results in the durable complete exclusion of the aneurysm from the cerebrovasculature and a definitive endoluminal reconstruction of the diseased parent artery.

Hemodynamics of cerebral aneurysm initiation: the role of wall shear stress and spatial wall shear stress gradient.

BACKGROUND AND PURPOSE: Cerebral aneurysms are preferentially located at arterial curvatures and bifurcations that are exposed to major hemodynamic forces, increasingly implicated in the life cycle of aneurysms. By observing the natural history of aneurysm formation from its preaneurysm state, we aimed to examine the hemodynamic microenvironment related to aneurysm initiation at certain arterial segments later developing an aneurysm. MATERIALS AND METHODS: The 3 patients included in the study underwent cerebral angiography with 3D reconstruction before a true aneurysm developed. The arterial geometries obtained from the 3D-DSA models were used for flow simulation by using finite-volume modeling. The WSS and SWSSG at the site of the future aneurysm and the flow characteristics of the developed aneurysms were analyzed. RESULTS: The analyzed regions of interest demonstrated significantly increased WSS, accompanied by an increased positive SWSSG in the adjacent proximal region. The WSS reached values of >5 times the temporal average values of the parent vessel, whereas the SWSSG approximated or exceeded peaks of 40 Pa/mm in all 3 cases. All patients developed an aneurysm within 2 years, 1 of which ruptured. CONCLUSIONS: The results of this hemodynamic study, in accordance with the clinical follow-up, suggest that the combination of high WSS and high positive SWSSG focused on a small segment of the arterial wall may have a role in the initiation process of aneurysm formation.

Endovascular WEB flow disruption in middle cerebral artery aneurysms: preliminary feasibility, clinical, and anatomical results in a multicenter study.

BACKGROUND The endovascular treatment of middle cerebral artery (MCA) aneurysms with unfavorable anatomy (wide neck, unfavorable morphology) is frequently challenging. Flow disruption with the WEB is a potentially interesting endovascular treatment for this type of aneurysm. OBJECTIVE To report in a multicenter series the preliminary treatment experience of MCA aneurysms with flow disruption by the WEB. METHODS Thirty-three patients with 34 MCA aneurysms were treated with the WEB in 5 European centers. The ability to successfully deploy the WEB, procedure- and device-related adverse events, morbidity and mortality of the treatment, and short-term angiographic follow-up results were analyzed. RESULTS Most treated aneurysms were unruptured (85.3%) and were between 5 and 10 mm (85.3%) with a neck size ≥  4 mm (88.2%). The treatment failed in 1 of the 34 aneurysms (2.9%) owing to a lack of appropriate device size. Treatment was performed exclusively with the WEB in 29 of 33 aneurysms (87.9%). Additional treatment (coiling and/or stenting) was used in 4 of 33 aneurysms (12.1%). Mortality of the treatment was 0.0% and morbidity was 3.1% (intraoperative rupture with modified Rankin Scale score of 3 at the 1-month follow-up). In short-term follow-up (range, 2-12 months), adequate occlusion (total occlusion or neck remnant) was observed in 83.3% of aneurysms. CONCLUSION WEB flow disruption seems to be a promising technique for the treatment of complex MCA aneurysms, particularly those with a wide neck or unfavorable dome-to-neck ratio.

WEB-DL Endovascular Treatment of Wide-Neck Bifurcation Aneurysms: Short- and Midterm Results in a European Study

Short- and midterm results of endovascular aneurysm treatment with the new WEB-DL device were assessed in 45 patients from 12 European centers. Of these, 42 aneurysms were unruptured and most were located either in the MCA bifurcation or the posterior circulation. Adequate occlusion was observed in 81% and 90% of aneurysms at 6 and 13 months, respectively. Results suggest that WEB endovascular treatment of wide-neck bifurcation aneurysms offers stable occlusion in a class of aneurysms that are historically unstable. BACKGROUND AND PURPOSE: Flow disruption with the WEB-DL device has been used safely for the treatment of wide-neck bifurcation aneurysms, but the stability of aneurysm occlusion after this treatment is unknown. This retrospective multicenter European study analyzed short- and midterm data in patients treated with WEB-DL. MATERIALS AND METHODS: Twelve European neurointerventional centers participated in the study. Clinical data and pre- and postoperative short- and midterm images were collected. An experienced interventional neuroradiologist independently analyzed the images. Aneurysm occlusion was classified into 4 grades: complete occlusion, opacification of the proximal recess of the device, neck remnant, and aneurysm remnant. RESULTS: Forty-five patients (34 women and 11 men) 35–74 years of age (mean, 56.3 ± 9.6 years) with 45 aneurysms treated with the WEB device were included. Aneurysm locations were the middle cerebral artery in 26 patients, the posterior circulation in 13 patients, the anterior communicating artery in 5 patients, and the internal carotid artery terminus in 1 patient. Forty-two aneurysms were unruptured. Good clinical outcome (mRS < 2) was observed in 93.3% of patients at the last follow-up. Adequate occlusion (complete occlusion, opacification of the proximal recess, or neck remnant) was observed in 30/37 patients (81.1%) in short-term follow-up (median, 6 months) and in 26/29 patients (89.7%) in midterm follow-up (median, 13 months). Worsening of the aneurysm occlusion was observed in 2/28 patients (7.1%) at midterm follow-up. CONCLUSIONS: The results suggest that the WEB endovascular treatment of wide-neck bifurcation aneurysms offers stable occlusion in a class of aneurysms that are historically unstable. Additionally, our data show that opacification of the WEB recess can be delineated from true neck or aneurysm remnants.

Endovascular Treatment of Experimental Aneurysms with Liquid Polymers: The Protective Potential of Stents

Liquid polymers have previously been used to treat experimental and human aneurysms. However, the delivery of a liquid embolic material into the cerebral circulation involves a high risk of irreversible vessel occlusion and stroke. To evaluate methods for the safe and effective treatment of experimental aneurysms with liquid polymer injection, we tested four different techniques to deliver cellulose acetate polymer (CAP) or N-hexyl-cyanoacrylate into canine side-wall carotid artery aneurysms. The animals were observed for 1 to 10 weeks after treatment. Two aneurysms were treated without protection of the distal circulation, one with CAP and another with N-hexyl-cyanoacrylate. In four cases, an angioplasty balloon was inflated within the parent artery during endosaccular injection of CAP. In two of these cases, the balloon was placed adjacent to the aneurysm orifice, resulting in simultaneous occlusion of both the aneurysm and the parent artery, and in the other two cases, the balloon was positioned proximal to the aneurysm, resulting in temporary flow arrest. Three aneurysms were treated with either CAP or N-hexyl-cyanoacrylate after implantation of a balloon-expandable tantalum stent within the parent artery across the aneurysm orifice. Complete angiographic obliteration was achieved in all but one case. One aneurysm ruptured. Another partially occluded aneurysm reopened 10 weeks after treatment. In all cases treated without stents, distal migration of the polymer resulted in either stenosis or occlusion of the parent arteries. The combination of stent implantation and polymer injection resulted in permanent aneurysm occlusion without detectable polymer migration. An intravascular stent deployed within the parent artery across the aneurysm orifice acted as a safety net during endosaccular polymer injection by allowing blood to flow from the aneurysm cavity while preventing distal migration of liquid polymer.