M Marosfoi

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.

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.

Long-Term Clinical and Angiographic Outcomes Following Pipeline Embolization Device Treatment of Complex Internal Carotid Artery Aneurysms: Five-Year Results of the Pipeline for Uncoilable or Failed Aneurysms Trial

BACKGROUND Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies. OBJECTIVE To present 5-yr follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial. METHODS In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded. RESULTS The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed. CONCLUSION Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events.

Impact of aneurysmal geometry on intraaneurysmal flow: a computerized flow simulation study.

IntroductionThis study was performed to assess the effect of aneurysm geometry on parameters that may have an impact on the natural history of intracranial aneurysms, such as intraaneurysmal flow pressure and shear stress.MethodsFlow was simulated in 21 randomly selected aneurysms using finite volume modeling. Ten aneurysms were classified as side-wall aneurysms, with either single-sided or circumferential involvement of the parent artery wall, and 11 as bifurcation aneurysms (symmetric or asymmetric), with an axis either perpendicular or parallel to the parent artery. The flow patterns were classified as either jet or vortex types (with regular or irregular vortex flow). Pressures and shear stresses were characterized as evenly or unevenly distributed over the aneurysm wall and neck.ResultsAll side-wall and four of the bifurcation aneurysms with a perpendicular axis had a vortex type flow pattern and seven bifurcation aneurysms with a parallel axis (four symmetric and two asymmetric) had a jet flow pattern. Jet type flow was associated with an uneven pressure distribution in seven out of seven aneurysms. Vortex type flow resulted in an even pressure distribution in five out of six aneurysms with an irregular flow pattern and six out of eight with a regular flow pattern. No firm relationship could be established between any geometrical type and shear stress distribution. Only 1 of 14 aneurysms with a perpendicular axis, but 4 of 7 aneurysms with a parallel axis, had ruptured.ConclusionAneurysm geometry does have an impact on flow conditions. Aneurysms with a main axis parallel to the parent artery have a tendency to have a jet flow pattern and uneven distribution of unsteady pressure. These aneurysms may have a higher rate of rupture as than those with a main axis perpendicular to the parent artery.

Pipeline for uncoilable or failed aneurysms: 3-year follow-up results

OBJECTIVE The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. METHODS The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data. RESULTS At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0-1 were demonstrated in 80 subjects. CONCLUSIONS Pipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth. Clinical trial registration no.: NCT00777088 (clinicaltrials.gov).

Neuroophthalmological outcomes associated with use of the Pipeline Embolization Device: analysis of the PUFS trial results

OBJECT Neuroophthalmological morbidity is commonly associated with large and giant cavernous and supraclinoid internal carotid artery (ICA) aneurysms. The authors sought to evaluate the neuroophthalmological outcomes after treatment of these aneurysms with the Pipeline Embolization Device (PED). METHODS The Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial was an international, multicenter prospective trial evaluating the safety and efficacy of the PED. All patients underwent complete neuroophthalmological examinations both before the PED procedure and at a 6-month follow-up. All examinations were performed for the purpose of this study and according to study criteria. RESULTS In total, 108 patients were treated in the PUFS trial, 98 of whom had complete neuroophthalmological follow-up. Of the patients with complete follow-up, 39 (40%) presented with a neuroophthalmological baseline deficit that was presumed to be attributable to the aneurysm, and patients with these baseline deficits had significantly larger aneurysms. In 25 of these patients (64%), the baseline deficit showed at least some improvement 6 months after PED treatment, whereas in 1 patient (2.6%), the deficits only worsened. In 5 patients (5%), new deficits had developed at the 6-month follow-up, while in another 6 patients (6%), deficits that were not originally assumed to be related to the aneurysm had improved by that time. A history of diabetes was associated with failure of the baseline deficits to improve after the treatment. The aneurysm maximum diameter was significantly larger in patients with a new deficit or a worse baseline deficit at 6 months postprocedure. CONCLUSIONS Patients treated with the PED for large and giant ICA aneurysms had excellent neuroophthalmological outcomes 6 months after the procedure, with deficits improving in most of the patients, very few deficits worsening, and few new deficits developing.

Evolution of Flow-Diverter Endothelialization and Thrombus Organization in Giant Fusiform Aneurysms after Flow Diversion: A Histopathologic Study

BACKGROUND AND PURPOSE: Treatment of giant fusiform aneurysms with flow diverters has been associated with a relatively high rate of complications. Our goal was to study the evolution of flow-diverter endothelialization and thrombus organization at different time points after flow-diverter treatment in giant fusiform aneurysms to better understand reasons for flow-diverter thrombosis and delayed aneurysm ruptures. MATERIALS AND METHODS: Two giant anterior and 2 posterior circulation aneurysms, all of which had partially thrombosed before treatment, were studied. An unruptured, untreated posterior circulation aneurysm was used as a control. Each specimen was removed at 7 days or at 6, 9, or 13 months after flow-diverter treatment. The 3 patients who survived longer than 7 days were followed up by angiography and MR imaging. Formaldehyde-fixed paraffin-embedded sections were stained by using H&E, Van Gieson elastic, CD34, h-Caldesmon, and Picrosirius stains and studied by light microscopy. RESULTS: According to angiography, aneurysms were found to be obliterated partially at 6 and 9 months and completely at 13 months. MR imaging revealed that mass effect remained unchanged in each case. Sections of the flow diverter within the normal parent artery were covered by an endothelialized fibrous layer as early as 6 months, but there was no tissue coverage or endothelialization seen even at 13 months inside the aneurysm itself. Each treated aneurysm had a thin wall with complete lack of smooth muscle cells. No signs of thrombus organization were found at any of the time points studied. CONCLUSIONS: Endothelialization of the flow diverter in giant fusiform aneurysms may not occur and thrombus organization may not be initiated inside these aneurysms for as long as 1 year, which explains delayed flow-diverter thrombosis and the possibility of delayed ruptures.

Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

Background and Purpose— The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement. Methods— A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy. Results— Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001). Conclusions— A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.

Imaging Inflammation in Cerebrovascular Disease

Imaging inflammation in large intracranial artery pathology may play an important role in the diagnosis of and risk stratification for a variety of cerebrovascular diseases. Looking beyond the lumen has already generated widespread excitement in the stroke community, and the potential to unveil molecular processes in the vessel wall is a natural evolution to develop a more comprehensive understanding of the pathogenesis of diseases, such as ICAD and brain aneurysms.