Histological stroke clot analysis after thrombectomy: Technical aspects and recommendations.

The recent advent of endovascular procedures has created the unique opportunity to collect and analyze thrombi removed from cerebral arteries, instigating a novel subfield in stroke research. Insights into thrombus characteristics and composition could play an important role in ongoing efforts to improve acute ischemic stroke therapy. An increasing number of centers are collecting stroke thrombi. This paper aims at providing guiding information on thrombus handling, procedures, and analysis in order to facilitate and standardize this emerging research field.

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.

Safety and Efficacy of Aneurysm Treatment with the WEB: Results of the WEBCAST 2 Study.

BACKGROUND AND PURPOSE: Flow disruption with the Woven EndoBridge (WEB) device is an innovative technique for the endovascular treatment of wide-neck bifurcation aneurysms. The initial version of the device (WEB Double-Layer) was evaluated in the WEB Clinical Assessment of IntraSaccular Aneurysm Therapy (WEBCAST) study, whereas the French Observatory study evaluated both WEB Double-Layer and Single-Layer versions of the device. WEBCAST 2 was designed to evaluate the WEB Single-Layer with Enhanced Visualization. MATERIALS AND METHODS: Patients with wide-neck bifurcation aneurysms for which WEB treatment was possible were included. Clinical data including adverse events and clinical status at 1 month and 1 year were collected and analyzed. A core laboratory evaluated anatomic results at 1 year following the procedure. RESULTS: Ten European neurointerventional centers included 55 patients (38 women; 27-77 years of age; mean, 54.4 ± 10.0 years) with 55 aneurysms. Aneurysm locations were the middle cerebral artery in 25 aneurysms (45.5%), the anterior communicating artery in 16 (29.1%), the basilar artery in 9 (16.4%), and the internal carotid artery terminus in 5 (9.1%). Procedural morbidity and mortality at 1 month were, respectively, 1.8% (1/55 patients) and 0.0% (0/55 patients). Morbidity and mortality at 1 year were, respectively, 3.9% (2/51 patients) and 2.0% (1/51 patients). At 1 year, complete occlusion was observed in 27/50 aneurysms (54.0%); neck remnant, in 13/50 (26.0%); and aneurysm remnant, in 10/50 (20.0%) (adequate occlusion in 40/50, 80.0%). CONCLUSIONS: WEBCAST 2 confirms the high safety and efficacy of WEB aneurysm treatment demonstrated in the WEBCAST and French Observatory studies.

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.

Surpass Flow Diverter for Treatment of Posterior Circulation Aneurysms.

BACKGROUND AND PURPOSE: Flow diverters for the treatment of posterior circulation aneurysms remain controversial. We aimed to identify factors contributing to outcome measures in patients treated with the Surpass flow diverter for aneurysms in this location. MATERIALS AND METHODS: We conducted an observational study of 53 patients who underwent flow-diverter treatment for posterior circulation aneurysms at 15 centers. Key outcome measures were mortality, complete aneurysm occlusion, and modified Rankin Scale score at follow-up. RESULTS: At follow-up (median, 11.3 months; interquartile range, 5.9-12.7 months), 9 patients had died, resulting in an all-cause mortality rate of 17.3% (95% CI, 7%-27.6%); 7 deaths (14%) were directly related to the procedure and none occurred in patients with a baseline mRS score of zero. After adjusting for covariates, a baseline mRS of 3-5 was more significantly (P = .003) associated with a higher hazard ratio for death than a baseline mRS of 0-2 (hazard ratio, 17.11; 95% CI, 2.69-109.02). After adjusting for follow-up duration, a 1-point increase in the baseline mRS was significantly (P < .001) associated with higher values of mRS at follow-up (odds ratio, 2.93; 95% CI, 1.79-4.79). Follow-up angiography in 44 patients (median, 11.3 months; interquartile range, 5.9-12.7 months) showed complete aneurysm occlusion in 29 (66%; 95% CI, 50.1%-79.5%). CONCLUSIONS: Clinical results of flow-diverter treatment of posterior circulation aneurysms depend very much on patient selection. In this study, poorer outcomes were related to the treatment of aneurysms in patients with higher baseline mRS scores. Angiographic results showed a high occlusion rate for this subset of complex aneurysms.

Risk Factors for Ischemic Complications following Pipeline Embolization Device Treatment of Intracranial Aneurysms: Results from the IntrePED Study.

BACKGROUND AND PURPOSE: Risk factors for acute ischemic stroke following flow-diverter treatment of intracranial aneurysms are poorly understood. Using the International Retrospective Study of Pipeline Embolization Device (IntrePED) registry, we studied demographic, aneurysm, and procedural characteristics associated with postoperative acute ischemic stroke following Pipeline Embolization Device (PED) treatment. MATERIALS AND METHODS: We identified patients in the IntrePED registry with post-PED-treatment acute ischemic stroke. The rate of postoperative acute ischemic stroke was determined by demographics, comorbidities, aneurysm characteristics, and procedure characteristics (including anticoagulation use, platelet testing, number of devices used, sheaths, and so forth). Categoric variables were compared with χ(2) testing, and continuous variables were compared with the Student t test. Odds ratios and 95% confidence intervals were obtained by using univariate logistic regression. Multivariate logistic regression analysis was used to determine which factors were independently associated with postoperative stroke. RESULTS: Of 793 patients with 906 aneurysms, 36 (4.5%) patients had acute ischemic stroke. Twenty-six (72.2%) strokes occurred within 30 days of treatment (median, 3.5 days; range, 0-397 days). Ten patients died, and the remaining 26 had major neurologic morbidity. Variables associated with higher odds of acute ischemic stroke on univariate analysis included male sex, hypertension, treatment of MCA aneurysms, treatment of fusiform aneurysms, treatment of giant aneurysms, and use of multiple PEDs. However, on multivariate analysis, the only one of these variables independently associated with stroke was treatment of fusiform aneurysms (OR, 2.74; 95% CI, 1.11-6.75; P = .03). Fusiform aneurysms that were associated with stroke were significantly larger than those not associated with stroke (mean, 24.5 ± 12.5 mm versus 13.6 ± 6.8 mm; P < .001). CONCLUSIONS: Ischemic stroke following PED treatment is an uncommon-but-devastating complication. Fusiform aneurysms were the only variable independently associated with postoperative stroke.

Pipeline Embolization Device with or without Adjunctive Coil Embolization: Analysis of Complications from the IntrePED Registry.

Flow diversion to treat cerebral aneurysms has revolutionized neurointerventional surgery. Because the addition of coils potentially increases the time and complexity of endovascular procedures, we sought to determine whether adjunctive coil use is associated with an increase in complications. Patients in the International Retrospective Study of Pipeline Embolization Device registry were divided into those treated with the Pipeline Embolization Device alone (n = 689 patients; n = 797 aneurysms; mean aneurysm size, 10.3 ± 7.6 mm) versus those treated with the Pipeline Embolization Device and concurrent coil embolization (n = 104 patients; n = 109 aneurysms; mean aneurysm size, 13.6 ± 7.8 mm). Patient demographics and aneurysm characteristics were examined. Rates of neurologic morbidity and mortality were compared between groups. The Pipeline Embolization Device with versus without coiling required a significantly longer procedure time (135.8 ± 63.9 versus 96.7 ± 46.2 min; P < .0001) and resulted in higher neurological morbidity (12.5% versus 7.8%; P = .13). These data suggest that either strategy represents an acceptable risk profile in the treatment of complex cerebral aneurysms and warrants further investigation.

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.

Surpass flow diverter in the treatment of intracranial aneurysms: a prospective multicenter study.

BACKGROUND AND PURPOSE: Incomplete occlusion and recanalization of large and wide-neck brain aneurysms treated by endovascular therapy remains a challenge. We present preliminary clinical and angiographic results of an experimentally optimized Surpass flow diverter for treatment of intracranial aneurysms in a prospective, multicenter, nonrandomized, single-arm study. MATERIALS AND METHODS: At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and posterior circulations were enrolled. The primary efficacy end point was the percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The primary safety end point was neurologic death and any stroke through a minimum follow-up of 6 months. RESULTS: Successful flow-diverter delivery was achieved in 161 patients with 186 aneurysms (98%); the mean number of devices used per aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%), showed that the primary safety end point occurred in 18 subjects. Permanent neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and posterior circulation, respectively. Neurologic death during follow-up was observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the anterior and posterior circulation, respectively. Ischemic stroke at ≤30 days, SAH at ≤7 days, and intraparenchymal hemorrhage at ≤7 days were encountered in 3.7%, 2.5%, and 2.5% of subjects, respectively. No disabling ischemic strokes at >30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial aneurysms showed 100% occlusion in 75%. CONCLUSIONS: Clinical outcomes of the Surpass flow diverter in the treatment of intracranial aneurysms show a safety profile that is comparable with that of stent-assisted coil embolization. Angiographic results showed a high rate of intracranial aneurysm occlusion.

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 χ(2) 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.

WEB-DL endovascular treatment of wide-neck bifurcation aneurysms: short- and midterm results in a European study.

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.

Resolution of mass effect and compression symptoms following endoluminal flow diversion for the treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: Alleviation of aneurysm induced mass effect has been difficult with both conventional endovascular and surgical techniques. Our aim was to study the efficacy of endovascular flow modification on aneurysm-induced mass effect and compression syndrome, as demonstrated by cross-sectional imaging studies and clinical follow-up. MATERIALS AND METHODS: Thirty aneurysms larger than 10 mm were treated by flow diversion alone and previously had undergone pre- and posttreatment cross-sectional imaging. Pretreatment MR imaging or contrast CT, follow-up angiography at 6 months, and follow-up MR imaging studies between 6 and 18 months were retrospectively analyzed. The neurologic and neuro-ophthalmologic statuses of all patients were recorded before treatment and at the time of follow-up cross-sectional imaging. RESULTS: At 6 months, 28 aneurysms were completely occluded, 1 had a neck remnant, and 1 had residual filling on angiography. Between 6 and 18 months, 3 aneurysms decreased in size and 27 completely collapsed as demonstrated on MR imaging. Before treatment, 6 patients had vision loss, 10 had double vision due to a third or sixth nerve palsy or both, and 1 had hemiparesis due to brain stem compression. On MR imaging follow-up, vision loss had either improved or resolved in all except 1 patient, double vision had resolved completely (7/10) or partially (3/10), and the patient with brain stem compression became asymptomatic. There was no bleeding observed in this series. One parent artery thrombosis resulted in a major infarct. CONCLUSIONS: Endovascular flow diversion is a highly effective technique for resolving radiologic mass effect and clinical compression syndromes.

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.

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.

Thromboembolic complication induced stable occlusion of a ruptured basilar tip aneurysm. Case report and review of the literature.

We describe a case of a ruptured basilar bifurcation aneurysm that thrombosed during preparation for endovascular therapy as a complication of diagnostic angiogaphy, and showed a favorable evolution during long-term follow-up. Endogenous thrombosis of ruptured, non giant aneurysms is uncommon. The persistence of occlusion over time in such cases is not well established. Two weeks after rupture, a 6 x 8 mm basilar bifurcation aneurysm was referred for endovascular treatment. During preparation for endovascular coil occlusion, without having any endovascular material at the level of the basilar artery, a complete thrombotic occlusion of the basilar bifurcation and aneurysm was observed. Given the good collateral circulation for both posterior cerebral arteries no thrombolysis was undertaken. The early follow-up of seven days, three and six months showed a complete recanalization of the basilar artery and remodeling of the basilar bifurcation. The 20 months imaging follow-up demonstrated a small aneurysm regrowth at the prevoius location that remained stable during the follow-up of seven years. Unchanged biological and hemodynamic characteristics. however, may pose an elevated risk of a new aneurysm formation over time, making long-term imaging follow-up, and in case of progression, aneurysm occlusion necessary for the patient.