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BACKGROUND AND PURPOSE The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. METHODS We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. RESULTS Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. CONCLUSIONS Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome.

Background: Severe hemorrhagic transformation (HT) after mechanical thrombectomy and intravenous thrombolysis predicts poor clinical outcome in acute ischemic stroke. The specific roles of microRNAs in the pathogenesis of HT, however, are still unclear. Thus, the aim of this study is to investigate miRNA expression profiles in the rat ischemic brain with HT after mechanical reperfusion. Methods: A model of reperfusion-induced HT was established in rats with hyperglycemic challenge and 5h middle cerebral artery occlusion (MCAO) followed by 19h reperfusion. Infarct volume, brain water content, HT, neurological score, and blood-brain barrier damage were determined at 24h after cerebral ischemia. The miRNA expression profiling of rat brain samples in the MCAO group and those in the sham-operated group was performed using the miRCURYLNA Array. The differentially expressed miRNAs were further validated by qRT-PCR. Then, after predicting their target genes from top-ranked miRNAs, the KEGG and GO analyses were further used to predict the associated significant cell signaling pathways and functions. Results: Reperfusion with 5h of MCAO induced HT in all hyperglycemic rats, and most of them were the parenchymal hematoma. The results from the miRNA array revealed that 57 miRNAs were significantly altered 24h after reperfusion in the ischemic brain with HT. The expressions of these 57 miRNAs were further verified using qRT-PCR, and 33 top-ranked miRNAs were confirmed. Among them, 30 miRNAs were significantly downregulated and 3 were significantly upregulated in rats with HT. The top-listed downregulated miRNAs included miR-383-5p, miR-335, miR-376a-5p, miR-212-5p, miR-219a, miR-126a-5p. Three miRNAs were significantly upregulated, including miR-125b, miR-195, miR-214. The most enriched pathways are associated with the Hippo signaling pathway which regulates cell survival and death. Twenty significantly regulated miRNAs involve into the Hippo signaling pathway, including miR-383-5p. Conclusions: Alteration of the miRNAs in the ischemic brain with HT may serve as biomarkers for HT after mechanical reperfusion in acute ischemic stroke. The role of reperfusion-inducible miR-383-5p and Hippo signaling pathway in the HT requires further investigation.

BackgroundInhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) pathway improves the neurological outcome in the transient middle cerebral artery occlusion (tMCAO) animal model. In this study we analyzed the microRNAs profile targeting NOX2 and NOX4 genes and its response to NOX2/4 inhibitor VAS2870 to understand the mechanisms of this protective effect.MethodsThe intraluminal filament tMCAO model was established in hyperglycemic rats (n=106) with 5 hours ischemia followed by 19 hours reperfusion. NOX inhibitor VAS2870 was delivered intravenously before reperfusion. Infarct volume, hemorrhagic transformation, and mortality were determined at 24 hours after cerebral ischemia. MicroRNAs profile targeting NOX2 and NOX4 genes were predicted by microRNA databases and further evaluated by microRNA microarray and quantitative RT-PCR.ResultsTen microRNAs potentially targeting NOX2 and NOX4 genes (including microRNA-29a, microRNA-29c, microRNA-126a, microRNA-132, microRNA-136, microRNA-138, microRNA-139, microRNA-153, microRNA-337, and microRNA-376a) were significantly downregulated in the ischemic hemisphere in the tMCAO group compared with the sham-operated group, as shown by microRNA microarray and quantitative RT-PCR (all pConclusionsSeveral microRNAs potentially targeting NOX2 and NOX4 genes displayed altered levels in hyperglycemic rats with the tMCAO model, suggesting their regulatory roles and targeting potentials for acute ischemic stroke treatment. Targeting specific microRNAs may represent a novel intervention opportunity to improve outcome and reduce hemorrhagic transformation after mechanical reperfusion for acute ischemic stroke.

Background: MicroRNAs are involved in regulating cerebral ischemia process, but its underlying mechanism is unclear. The removal of intraluminal filament in the transient middle cerebral artery occlusion (tMCAO) model resulted in instantaneous recanalization, similar to endovascular thrombectomy in stroke. We previously showed microRNA-376a down-regulation in the ischemic brain in rat tMCAO model with hemorrhagic transformation. This study investigated the role of miR-376a-5p in cerebral ischemia and reperfusion injury after mechanical reperfusion. Methods: The intraluminal filament tMCAO model was established in rats with 2 hour ischemia followed by reperfusion. The expression of miR-376a-5p in the ischemic brain and blood were quantified. Intravenous miR-376a-5p agomir was delivered before reperfusion or after reperfusion. Infarct volume, brain water content, neurological score, blood-brain barrier (BBB) damage, and levels of miR-376a-5p, NADPH oxidase (NOX) 4, Caspase-3 and aquaporin-4 were determined at 24-hour after ischemia. Results: MiR-376a-5p levels in the infarction core and peri-infarct cortex were decreased at 3 hours after reperfusion in tMCAO model. The decreased levels of miR-376a in ischemic brain and blood lasted for 24 hours after ischemia. Intravenous miR-376a-5p agomir before and after reperfusion increased the expression of miR-376a and suppressed the up-regulation of NOX4, Caspase-3 and AQP-4 in the infarction core and peri-infarct cortex compared with the tMCAO group (p Conclusions: MiR-376a-5p overexpression protects against cerebral ischemia and reperfusion injury via downregulating NOX4, Caspase-3 and AQP-4. Infusion of miR-376a-5p agomir represents a novel adjunctive therapeutic strategy to improve outcome after mechanical reperfusion for acute stroke.

Background: MicroRNA-29a (miR-29a) is involved in regulating cerebral ischemia process, but its underlying mechanism is unclear. We previously showed that inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX4) pathway improves the neurological outcome and increases the expression of miR-29a in transient middle cerebral artery occlusion (tMCAO) animal model. This study investigated the role of miR-29a in cerebral ischemia and reperfusion injury after mechanical reperfusion. Methods: The intraluminal filament tMCAO model was established in male rats with 2 hour ischemia followed by reperfusion. The expression of miR-29a and NOX4 in the infarction core and peri-infarct cortex were quantified at 0, 3, 12, and 24 hour after reperfusion. Permanent MCAO model was also evaluated after 2 hour and 24 hour ischemia. Intravenous miR-29a agomir was delivered immediately after reperfusion. Infarct volume, brain water content, neurological score, blood-brain barrier damage, and levels of miR-29a and NOX4 were determined at 24-hour after cerebral ischemia. Results: MiR-29a levels in the infarction core and peri-infarct cortex were significantly decreased at 3 hours after reperfusion in tMCAO group compared with the sham-operated group. The decreased levels of miR-29a lasted for 24 hours after cerebral ischemia. Dual-luciferase reporter system showed that NOX4 was the direct target gene of miR-29a. Intravenous miR-29a agomir increased the expression of miR-29a and suppressed NOX4 up-regulation in both the infarction core and peri-infarct cortex at 24-hour after ischemia compared with the tMCAO group (all p Conclusions: MiR-29a overexpression protects against cerebral ischemia and reperfusion injury via downregulating NOX4. Infusion of miR-29a agomir immediately after reperfusion represents a novel adjunctive therapeutic strategy to improve outcome after mechanical reperfusion for acute ischemic stroke.

Background and Purpose— High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy. Methods— We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization. Results— Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02–1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02–1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01–1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence. Conclusions— One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00318071, NCT01088672, and NCT01270867.

BackgroundThe influence of cerebral microbleeds (CMBs) on post-thrombolytic hemorrhagic transformation (HT) in patients with acute ischemic stroke remains controversial.ObjectiveTo investigate the association of CMBs with HT and clinical outcomes among patients with large-vessel occlusion strokes treated with mechanical thrombectomy.MethodsWe analyzed patients with acute stroke treated with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the association of the presence, burden, and distribution of CMBs with HT, procedural complications, in-hospital mortality, and clinical outcome.ResultsCMBs were detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were identified. Fourteen patients (6.8%) had ≥2 CMBs, only 1 patient had ≥5 CMBs. Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients, strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There were no significant differences between patients with CMBs and those without CMBs in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs 19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital mortality (16.2% vs 18.3%), and modified Rankin Scale score 0–3 at discharge. CMBs were not independently associated with HT or in-hospital mortality in patients treated with either thrombectomy or intravenous thrombolysis followed by thrombectomy.ConclusionsPatients with CMBs are not at increased risk for HT and mortality following mechanical thrombectomy for acute stroke. Excluding such patients from mechanical thrombectomy is unwarranted. The risk of HT in patients with ≥5 CMBs requires further study.

BackgroundSevere hemorrhagic transformation (HT) after mechanical thrombectomy predicts a poor clinical outcome in acute ischemic stroke. To better understand the mechanism of HT, we investigated the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in HT after reperfusion during acute stroke and whether NOX2/4 inhibitor VAS2870 reduces reperfusion-induced HT after mechanical recanalization.MethodsA model of reperfusion-induced HT was established in rats (n=182) with hyperglycemic challenge and 5 h middle cerebral artery occlusion followed by 19 h reperfusion. NOX inhibitor VAS2870 was delivered intravenously 30 min before reperfusion. Infarct volume, brain water content, HT, neurological score, mortality rate, blood–brain barrier (BBB) damage, neuronal apoptosis, and reactive oxygen species were determined at 24 h after cerebral ischemia. The expressions of NOX1, NOX2, NOX4, and BBB-associated proteins were measured.ResultsNOX2 and NOX4 upregulation and severe HT were observed in hyperglycemic rats after cerebral ischemia/reperfusion. VAS2870 suppressed oxidative stress, neuronal apoptosis, and NOX2/4 upregulation in the ischemic hemisphere. VAS2870 reduced infarct volume (17.2±5.3% vs 37.4±9.2%, pConclusionsNOX2 and NOX4 may mediate HT in rats with large vessel stroke after mechanical reperfusion. Infusion of NOX inhibitor VAS2870 before mechanical thrombectomy represents a novel adjunctive therapeutic strategy to prevent reperfusion-induced HT and improve outcome of acute stroke treatment.

Summary Aims To investigate the frequency and predictors of Merci device fracture in patients with acute ischemic stroke treated with mechanical thrombectomy and its impact on clinical outcome. Methods We retrospectively analyzed patients with acute ischemic stroke treated by thrombectomy with the Merci Retriever and identified the presence of device fracture. The predictors of device fracture were assessed. We evaluated the impact of device fracture on hemorrhage and clinical outcome. Results Of 136 patients treated by thrombectomy, 6 (4.4%) experienced intraprocedural Merci device fracture. Internal carotid artery occlusion was associated with device fracture. The fractured X and L series Merci Retrievers were successfully ensnared in four patients. Patients with fractured devices had similar rates of successful revascularization with those without. In patients with fractured devices, no parenchymal hematomas were found, while hemorrhagic infarction and subarachnoid hemorrhage were found in three and two patients, respectively. Patients with fractured devices tended to be more dependent (modified Rankin Scale ≥ 3) at discharge, but had similar rates of in-hospital mortality. Conclusions Merci device fracture is relatively infrequent in patients with acute ischemic stroke treated with thrombectomy. This complication may not increase the risk of parenchymal hematoma but tends to be associated with poor outcome.

BACKGROUND AND PURPOSE: DAVFs rarely involve the sphenoid wings and middle cranial fossa. We characterize the angiographic findings, treatment, and outcome of DAVFs within the sphenoid wings. MATERIALS AND METHODS: We reviewed the clinical and radiologic data of 11 patients with DAVFs within the sphenoid wing that were treated with an endovascular or with a combined endovascular and surgical approach. RESULTS: Nine patients presented with ocular symptoms and 1 patient had a temporal parenchymal hematoma. Angiograms showed that 5 DAVFs were located on the lesser wing of sphenoid bone, whereas the other 6 were on the greater wing of the sphenoid bone. Multiple branches of the ICA and ECA supplied the lesions in 7 patients. Four patients had cortical venous reflux and 7 patients had varices. Eight patients were treated with transarterial embolization using liquid embolic agents, while 3 patients were treated with transvenous embolization with coils or in combination with Onyx. Surgical disconnection of the cortical veins was performed in 2 patients with incompletely occluded DAVFs. Anatomic cure was achieved in all patients. Eight patients had angiographic and clinical follow-up and none had recurrence of their lesions. CONCLUSIONS: DAVFs may occur within the dura of the sphenoid wings and may often have a presentation similar to cavernous sinus DAVFs, but because of potential associations with the cerebral venous system, may pose a risk for intracranial hemorrhage. Curative embolization through a transarterial or transvenous approach is the primary therapeutic strategy for these lesions. In incompletely embolized patients, exclusion of any refluxing cortical veins is necessary.

Objective Carotid intraplaque hemorrhage may result in rapid worsening of stenosis and thrombus formation leading to stroke in patients with carotid atherosclerosis. The purpose of this study was to assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with carotid plaque and intraplaque hemorrhage in a swine model. Methods Carotid atherosclerosis was induced in miniswine using a combination of partial ligation and a high cholesterol diet. The carotid artery and rete mirabile were obtained for histopathological and immunohistochemical studies at 3 months. Atherosclerotic changes were classified by Stary stage according to the American Heart Association and the features of vulnerable carotid plaque were assessed. The association of MMP-9 expression in the carotid plaque with intraplaque hemorrhage was analyzed. Results One hundred and ninety-one carotid segments from 10 carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 had advanced plaque (Stary stage IV–VI). Atheroemboli were found in all 10 rete mirabili, confirming the presence of vulnerable ipsilateral carotid plaques. There was a trend to increased MMP-9 expression in the group with advanced plaque. Areas positive for MMP-9 were significantly greater in plaques with intraplaque hemorrhage than in those without intraplaque hemorrhage (11.84±1.22% vs 6.63±0.59%, p Conclusions Increased expression of MMP-9 is associated with intraplaque hemorrhage in a swine model of vulnerable carotid atherosclerosis.

Objectives Acute, simultaneous, concomitant internal carotid artery (ICA) and middle cerebral arteries (MCA) occlusions almost invariably lead to significant neurological disability if left untreated. Endovascular therapy is frequently the method of treatment in such situations but there remains a chance of incomplete recanalization. Successful recanalization of the proximal aspect of the occlusion may allow for endogenous thrombolysis and facilitate further endogenous recanalization of any residual MCA occlusion. Methods Consecutive patients with acute ischemic stroke undergoing endovascular therapy for tandem extracranial ICA–MCA or contiguous intracranial ICA–MCA occlusions were retrospectively analyzed. Rates of facilitated endogenous recanalization at 24 h (FER 24 ) were compared by imaging within the immediate post-intervention 5–24 h period in those with proximal recanalization and in those without. Results 17 patients were included in the analysis. 12 patients had good initial proximal recanalization but a residual partial or total occlusion of the MCA while five patients failed any recanalization. Seven patients (58.3%) in the first group and none in the second had FER 24 on interval imaging after intervention (p=0.04). The probability of death and disability at discharge was less in patients with FER 24 than those without (p=0.05). Conclusions More than half of all patients who present with both ICA and MCA occlusions who are only partially recanalized will undergo facilitated endogenous recanalization within the subsequent 24 h following intervention.

BACKGROUND AND PURPOSE: Endovascular therapy is an alternative for the treatment of AIS resulting from large intracranial arterial occlusions that depends on the use of iodinated RCM. The risk of RCM-mediated AKI following endovascular therapy for AIS may be different from that following coronary interventions because patients may not have identical risk factors. MATERIALS AND METHODS: All consecutive patients with large-vessel AIS undergoing endovascular therapy were prospectively recorded. We recorded the baseline kidney function, and RCM-AKI was assessed according to the AKIN criteria at 48 hours after RCM administration. We compared the rate of RCM-AKI 48 hours after the procedure and sought to determine whether any preexisting factors increased the risk of RCM-AKI. RESULTS: We identified 99 patients meeting inclusion criteria. The average volume of contrast was 189 ± 71 mL, and the average creatinine change was −4.6% at 48 hours postangiography. There were 3 patients with RCM-AKI. Although all 3 patients died as a result of their strokes, return to baseline creatinine levels occurred before death. There was a trend toward higher rates of premorbid diabetes mellitus, chronic renal insufficiency, preadmission statin and NSAID use, and a higher serum creatinine level on admission for the RCM-AKI group. The volume of procedural contrast was similar between groups (those with and those without RCM-AKI) (P = .5). CONCLUSIONS: In this small study, the rate of RCM-AKI following endovascular intervention for AIS was very low. A much larger study is required to determine its true incidence.

Background and Purpose— Intracranial mechanical thrombectomy is a therapeutic option for acute ischemic stroke patients failing intravenous tissue plasminogen activator (IV tPA). We compared patients treated by mechanical embolus removal in cerebral ischemia (MERCI) thrombectomy after failed IV tPA with those treated with thrombectomy alone. Methods— We pooled MERCI and Multi MERCI study patients, grouped them either as failed IV tPA or non–IV tPA, and assessed revascularization rates, procedural complications, symptomatic hemorrhage rates, clinical outcomes, and mortality. We also evaluated outcomes stratified by the occlusion site and final revascularization. Results— Among 305 patients, 48 failed, and 257 were ineligible for IV tPA. Nonresponders to IV tPA trended toward a higher revascularization rate (73% versus 63%) and less mortality (27.7% versus 40.1%) and had similar rates of symptomatic hemorrhage and procedural complications. Favorable 90-day outcomes were similar in failed and non–IV tPA patients (38% versus 31%), with no difference according to occlusion site. Among patients failing IV tPA, good outcomes tended to occur more frequently in revascularized patients (47.1% versus 15.4%), although this relationship was attributable solely to middle cerebral artery and not internal carotid artery occlusions, with no difference in mortality. Among IV tPA–ineligible patients, revascularization correlated with good outcome (47.4% versus 4.4%) and less mortality (28.5% versus 59.6%). Conclusions— The risks of hemorrhage and procedure-related complications after mechanical thrombectomy do not differ with respect to previous IV tPA administration. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with internal carotid artery occlusions in tPA-nonresponders.

BACKGROUND AND PURPOSE: Use of the Merci retriever is increasing as a means to reopen large intracranial arterial occlusions. We sought to determine whether there is an optimum number of retrieval attempts that yields the highest recanalization rates and after which the probability of success decreases. MATERIALS AND METHODS: All consecutive patients undergoing Merci retrieval for large cerebral artery occlusions were prospectively tracked at a comprehensive stroke center. We analyzed ICA, M1 segment of the MCA, and vertebrobasilar occlusions. We compared the revascularization of the primary AOL with the number of documented retrieval attempts used to achieve that AOL score. For tandem lesions, each target lesion was compared separately on the basis of where the device was deployed. RESULTS: We identified a total of 97 patients with 115 arterial occlusions. The median number of attempts per target vessel was 3, while the median final AOL score was 2. Up to 3 retrieval attempts correlated with good revascularization (AOL 2 or 3). When ≥4 attempts were performed, the end result was more often failed revascularization (AOL 0 or 1) and procedural complications ( P = .006). CONCLUSIONS: In our experience, 3 may be the optimum number of Merci retrieval attempts per target vessel occlusion. Four or more attempts may not improve the chances of recanalization, while increasing the risk of complications.

We present detailed results of using Neuroform stent-assisted coil embolization to treat complex cerebral aneurysms over a three-year period.Only patients who underwent Neuroform stent-assisted coil embolization were included in this study. We assessed patients' history, aneurysm morphology, indications for stenting, and technical details of the procedures, as well as complications and the midterm follow-up data.This study included 26 patients with 39 aneurysms. A total of 32 of 39 aneurysms were treated by Neuroform stent-assisted embolization (SAC), whereas 3 aneurysms were stented without coiling, 2 aneurysms coiled without stenting and 2 aneurysms surgically clipped. The indications for use of stent included broad-neck aneurysms (n = 28), giant or large aneurysms (n = 6), and fusiform aneurysms (n = 5). Of the 32 aneurysms treated with Neuroform SAC, we achieved complete (100%) and near complete (95%) occlusion in 27 aneurysms, and partial (95%) occlusion in 5 aneurysms. Follow-up angiographic data available in 22 of 32 aneurysms treated with Neuroform SAC (68.7%) demonstrated recanalization in 3 aneurysms (13.6%), and stable occlusion in 19 aneurysms (86.4%). There was no delayed progressive embolization or in-stent stenosis.Direct and midterm follow-up results confirmed that Neuroform stent-assisted coil embolization was a safe and effective technique in the treatment of complex cerebral aneurysms. Although clinically significant complications were uncommon and the evaluation at midterm follow-up is encouraging, further studies need to assess the long-term stability and durability of the stent.

Objective Our goal was to assess the long-term anatomic and clinical outcomes in patients with giant middle cerebral artery (MCA) aneurysms treated by endovascular coil embolization alone or in combination with cerebral revascularization. Methods One hundred twenty-six patients with giant intracranial aneurysms were endovascularly treated at the University of California, Los Angeles, between 1990 and 2007. Of these, 9 patients had partially thrombosed MCA aneurysms with incorporated branches. Five patients presented with symptoms of mass effect, 3 had seizures, 2 had episodes of brain ischemia, and 1 presented with acute subarachnoid hemorrhage. Results Three wide-neck saccular aneurysms were almost completely coil occluded, leaving only small neck remnants that were intended to preserve the patency of incorporated MCA branches. The other 6 fusiform aneurysms were effectively treated by superficial temporal artery-MCA or occipital artery-MCA bypass, followed by complete coil occlusion of these aneurysms. Immediate angiograms and mid- or long-term neuroradiological imaging follow-up examinations revealed complete obliteration or near-complete occlusion (90%-99%) of the aneurysms in all 9 patients. Seven patients had a favorable long-term clinical outcome, and 1 patient died as a result of unrelated congestive heart failure. One patient required emergent surgical aneurysm thrombectomy because of inadvertent coil occlusion of the frontal opercular artery, which was not protected by the bypass, and the patient subsequently sustained a moderate neurological disability. Conclusion Giant MCA aneurysms with branch incorporations and other unfavorable features such as intraluminal thrombus, mural calcification, and fusiform configuration can be effectively treated with a team approach, using coil embolization after protective surgical bypass. When aneurysms with MCA branches incorporated into the neck rather than the dome are treated by endovascular techniques alone, long-term angiographic follow-up is necessary to assess and further treat any significant remnant.

Background and Purpose— Use of mechanical thrombectomy for acute cerebrovascular occlusions is increasing. Preintervention MRI patterns may be helpful in predicting prognosis. Methods— We reviewed all Merci thrombectomy cases of either terminal ICA or M1 occlusions and classified them according to diffusion MRI patterns of (1) completed basal ganglia infarct (pure M1a), (2) near-completed basal ganglia infarct (incomplete M1a), and (3) relative sparing of deep MCA field (M1b). We compared the M1a and M1b patients with respect to neurological deficit on presentation, recanalization rates, hospital length of stay, and disability on discharge. We also determined whether deep MCA compromise predicted hematomal hemorrhagic transformation (HT) and whether this correlated with worse clinical outcome at discharge. Results— The M1a group had worse pre-Merci NIHSS (21 versus 14, P =0.004), worse discharge NIHSS (12 versus 4, P P =0.003), and higher rates of discharge mRS ≥3 (OR 8.4, 95% CI 2.1 to 44.7) despite equivalent recanalization rates when compared to the M1b group. The M1a group had a higher rate of parenchymal hematomal HT (OR 6.7, 95% CI 1.02 to 183.3). Patients with such hematomal HT had higher rates of death or dependency discharge (100% versus 60%, OR=infinite). Conclusions— Among patients with ICA and M1 occlusions, preintervention diffusion MRI evidence of advanced injury in the basal ganglia bodes worse dysfunction and disability at discharge, longer hospital stays, and higher rates of hemorrhage after intervention when compared to other diffusion patterns.

Object The authors report their preliminary experience using a balloon-assisted technique (BAT) in the transarterial embolization of intracranial dural arteriovenous fistulas (DAVFs). Methods The authors reviewed the prospectively collected data obtained in 7 consecutive patients with DAVFs in whom embolization was achieved using transarterially injected Onyx with either the venous or arterial BAT. Procedures were performed at the Division of Interventional Neuroradiology at the University of California at Los Angeles Medical Center between September 2005 and January 2008. Results Three patients presented with cortical venous reflux and 4 did not. Three patients underwent transarterial Onyx-based embolization combined with transvenous balloon protection; the balloon was inflated in the transverse sinus in 2 of these patients and in the superior sagittal sinus in the third. One of them underwent an additional transarterial Onyx embolization with arterial BAT, whereas 4 other patients were treated with arterial BAT alone. The occipital artery was temporarily occluded with the balloon in 4 of these cases, whereas in the fifth, the authors used temporary balloon occlusion of the middle meningeal artery. Angiograms obtained immediately after embolization demonstrated complete or near-complete obliteration of the fistula in 6 patients and partial occlusion in 1 patient. There were no immediate or postprocedural complications. Two patients who presented with intracranial hemorrhage never suffered a second hemorrhage, and all other patients experienced either complete resolution or significant improvement of their symptoms. Conclusions The BAT provides a new complementary method in the transarterial embolization of DAVFs that are not amenable to transvenous embolization. The venous BAT protects the patency of critical venous pathways, whereas the arterial BAT provides better control of the Onyx-based embolization.

Objective Dural arteriovenous fistulae (DAVFs) rarely involve the clivus. This report examines the clinical presentation, angiographic findings, endovascular management, and outcome of clival DAVFs. Particular attention was given to safety and efficacy of transarterial embolization using liquid embolic agents. Methods We reviewed the clinical and radiological data of 10 patients with spontaneous clival DAVFs who were treated endovascularly at the University of California at Los Angeles Medical Center between 1992 and 2006. Results Nine patients presented with ocular symptoms and one patient experienced pulsatile tinnitus. Cerebral angiograms showed that these clival DAVFs were supplied by multiple branches of the internal and external carotid arteries. The patterns of venous drainage were from the clival veins to the cavernous sinus and superior ophthalmic vein in nine patients and to the inferior petrosal sinus in two patients. Six clival DAVFs were embolized transarterially through the clival branches of the ascending pharyngeal artery. Onyx 18 (Micro Therapeutics Inc., Irvine, CA) was used in three patients and n-butyl cyanoacrylate was used in three patients. Immediate complete angiographic obliteration was achieved in three patients. All six patients experienced an angiographic and clinical cure without any complications at 3 months. Two patients were incompletely treated using particles and coils for the relief of the symptoms. Two other patients were completely treated after the recipient clival venous structures were occluded transvenously with coils. Conclusion Clival DAVFs can be misdiagnosed as dural cavernous sinus fistulae. The best treatment is transarterial embolization of the dural feeders using liquid embolic agents. Transvenous occlusion of the cavernous sinus is unnecessary in most cases.

The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome. We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2∗-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome. A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13–13.59; P

Purpose: Although various types of stents have been used to treat symptomatic intracranial stenosis, how stents interact with atherosclerotic plaques has not been evaluated. In this study, we demonstrate the utility of a swine carotid atherosclerotic model for the preclinical evaluation of intracranial stenting therapies. Methods: Advanced atherosclerotic plaques were induced in 28 carotid arteries of 14 Chinese miniswines using partial ligation and high cholesterol diet to create >70% stenosis. The plaques were characterized with three-dimensional rotational angiography, Doppler ultrasonography, MR scan and 18F-FDG PET/CT scans at three months and correlated with histopathological examination in 20 carotid arteries. Five Wingspan stents and one Paclitaxel-eluting balloon-mounted coronary stent were implanted into six diseased vessels. Two contralateral carotid arteries were used as controls. Dual-antiplatelet regimen with clopidogrel and aspirin was administrated 1 day prior to stenting and continued for 1 month. Stent and plaque interaction was evaluated with angiography, MR scan and 18F-FDG PET/CT scans at one month after stenting. Results: The diameter of proximal and distal segments of carotid arteries were 3.6±0.1 mm and 3.8±0.1 mm at post-ligation, and 3.6±0.1 mm and 3.7±0.1 mm at 3 months, respectively, similar to that of middle cerebral arteries in human (2.7-4.9 mm, average 3.7mm). Doppler waveforms showed features of low resistant vessels. Plaque rupture and distal embolism were observed, mimicking the mechanisms of stroke in human intracranial atherosclerosis. All stents were patent at one month but 25% restenosis was observed. Wingspan stents expanded beyond the arterial lumen whereas the coronary stent stayed in the intima. Conclusion: This swine model is suitable for the testing of devices for the endovascular treatment of intracranial atherosclerosis. It can be a useful tool for the study of mechanisms of in-stent restenosis.

Purpose: The imaging modality 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) has been recently used to identify inflammation in the atherosclerotic plaque. Increased uptake of 18 F-FDG in human atherosclerotic plaque on PET may predict plaque vulnerability, however, there is a lack of histological validation for PET imaging. The aim of this study is to evaluate the association of plaque vulnerability with FDG uptake on serial PET/CT scans in a swine model. Methods: Twenty carotid atherosclerotic models was induced in 10 miniswines using partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by carotid angiography. Serial 18 F-FDG PET/CT scans were performed at 0, 4, 8 and 12 weeks. MR scan for imaging-histologic correlation was performed at 12 weeks, and carotid artery sections were obtained for histopathological examination. The atherosclerotic lesions of AHA type IV to VI were defined as advanced plaques. Carotid arteries were evaluated for increased FDG uptake with a maximum standardized uptake value (SUV) and target-to-backgroud ratio (TBR). The association of carotid plaque vulerability with the serial FDG uptake was analyzed. Results: Various stages of atherosclerotic plaques were found in carotid segments from 20 carotid arteries. Most advanced plaque had the feature of vulnerability. FDG uptake in 100 carotid plaques were analyzed. Compared with carotid segments without atherosclerosis, significantly higher FDG uptake was observed in carotid segments with atherosclerosis at 4, 8 and 12 weeks (P Conclusion: Increased plaque metabolism revealed by PET persists with time and is associated with the complexity of carotid atherosclerotic plaque in a swine model. FDG PET/CT may be useful for identification of plaque vulnerability and monitoring the progress of atherosclerotic lesions.

Purpose: Fibrous cap rupture from atherosclerotic plaque can send distal emboli and lead to stroke in patients with carotid disease. The NADPH oxidases (Nox) family play an important role in the pathophysiology of atherosclerosis. However, the relationship of Nox expression with atherosclerotic plaque vulnerability remain elusive. We aim to assess the association of Nox4 and Nox5 expression with carotid plaque vulnerability in a swine model. Methods: Carotid atherosclerosis was induced in miniswines using partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography. Carotid artery sections were obtained for histologic examination and immunohistochemical study for Nox4 and Nox5 at 3 months. The atherosclerotic lesions of AHA type IV to VI were defined as advanced plaques. The association of Nox4 and Nox5 expression in the plaque with the feature of plaque vulnerability was analyzed. Results: Seventy-five carotid segments from ten carotid artery models had fibrous cap plaques with AHA type IV to VI. Distal embolism with the presence of atheroemboli was found in all rete mirabilis, and deemed to be from the ipsilateral carotid plaques. Positive staining of Nox4 and Nox5 were mostly distributed in the surrounding of lipid core, endothelium and plaque shoulder. Increased expression of Nox4 in the plaque was associated with the features of a large lipid core, marked foam cell and thin fibrous cap (p Conclusion: Nox4 and Nox5 are both expressed in carotid atherosclerotic plaques in a swine model, and their overexpression in carotid plaques are associated with thin fibrous cap and cap rupture. Upregulated Nox4 and Nox5 may participate in the process of vulnerable atherosclerotic plaque and may be used as a target for reducing the risk of distal embolism.

A swine model of carotid atherosclerosis may greatly facilitate the identification of imaging characteristics of vulnerable plaques and the preclinical evaluation of endovascular intervention. In this study we assess the association of matrix metalloproteinase (MMP)-9 expression and neovascularity in carotid atherosclerotic plaques with MRI patterns in a swine model.Carotid atherosclerosis models were created in miniswine using a combination of partial ligation and a high cholesterol diet. The animals were imaged in a 1.5 T MR scanner at 3 months and carotid arteries were obtained for histopathological and immunohistochemical examination. Contrast-enhanced T1-weighted imaging (T1WI) was used to match the histology findings. The contrast-to-noise ratio (CNR) of the plaques on T1WI and contrast-enhanced T1WI were measured and the association of MMP-9 expression and neovascularity in the carotid plaque with CNR on MRI was analyzed.Forty carotid artery segments were matched between MRI and histology. All segments were advanced carotid atherosclerotic plaques. The matched contrast-enhanced T1WI and histology slices showed good correlation for ratio of plaque size to lumen diameter (r=0.94, p0.001). Plaque CNR on contrast-enhanced T1WI was higher in plaques with strong MMP-9 expression than in those with weak MMP-9 expression (p=0.05). Plaque CNR on contrast-enhanced T1WI was also higher in plaques with marked neovascularization than in those without (p=0.02).Increased plaque CNR on contrast-enhanced T1WI is associated with MMP-9 expression and neovascularization in carotid atherosclerotic plaques and may be used to identify vulnerable plaques.

Background and purpose Successful revascularization can often improve functional outcome after large intracranial arterial occlusions. However, incomplete or unsuccessful recanalization is often the end result after attempted mechanical thrombectomy. A study was undertaken to determine whether partial recanalization of proximal isolated middle cerebral artery (MCA) occlusions facilitates endogenous thrombolysis and spontaneous recanalization. Methods We retrospectively analyzed consecutive patients with acute ischemic stroke undergoing mechanical thrombectomy using the Merci Retriever System for occlusions involving any portion of the M1 segment of the MCA. Only those patients with a residual obstruction of the proximal MCA segments were included. The rates of facilitated endogenous recanalization (FER 5 ) by imaging within the 5 h following intervention were compared in patients with partial proximal recanalization and those in whom recanalization was unsuccessful. Results Forty-two patients were included in the analysis. Twenty-six patients had good recanalization of the proximal aspect of the target lesion with an arterial occlusive lesion score of 2 or 3 but a residual partial or total occlusion of the MCA, while 16 patients failed to recanalize any portion of the target occlusion. Twelve patients (46%) in the first group and only one (5.9%) in the second group had facilitated endogenous recanalization on interval imaging 5 h after intervention (OR 12.9, 95% CI 1.5 to 112.2). Nine patients with proximal recanalization had good clinical outcomes at discharge (mRS ≤2) compared with none without recanalization (p=0.01), but FER did not have a relationship with clinical outcome. Conclusions Despite initially incomplete proximal mechanical thrombectomy, nearly half of all patients with residual M1 occlusions will undergo further endogenous recanalization within the subsequent 5 h.

Background and Purpose: Merci device fracture is an adverse event during mechanical thrombectomy for acute ischemic stroke. The purpose of this study was to describe the frequency and predictors of this complication in acute stroke patients after thrombectomy and its impact on clinical outcome. Methods: We retrospectively analyzed acute ischemic stroke patients treated by mechanical thrombectomy with the Merci Retriever and identified the presence of device fracture. The predictors of device fracture were assessed. We evaluated the impact of device fracture on potential hemorrhage and clinical outcome. Results: Of 136 patients treated by thrombectomy, 6 (4.4%) experienced intra-procedural device fracture. Internal carotid artery occlusion was associated with device fracture (OR 13.06; 95% CI 1.47 to 115.62, P =0.01). The fractured X and L series devices were successfully ensnared by a Merci device or a microsnare in 4 patients. Compared with patients with non-fractured devices, those with fractured devices had similar rates of Thrombolysis and Myocardial Infarction (TIMI) grade II and III revascularization (66.7% versus 72.3%; p =0.67), decreased rates of arterial occlusive lesion (AOL) grade III recanalization (0% versus 48.5%; p =0.03) and longer mean procedure time (2.5 hours versus 1.8 hours; p =0.03). In patients with fractured devices, no parenchymal hematomas were found, while hemorrhagic infarction and subarachnoid hemorrhage were found in 3 and 2 patients, respectively. Decompressive craniectomy following thrombectomy for malignant edema was associated with device fracture ( P =0.02). Patients with fractured devices had similar rates of independence at discharge (modified Rankin Scale≤2, 0% versus 25%; P =0.34) and in-hospital mortality (16.7% versus 23.4%; P >0.99). Conclusions: Device fracture is relatively infrequent in acute ischemic stroke patients treated by Merci thrombectomy. Target occlusion in the internal carotid artery is an independent predictor of intra-procedural device fracture. This complication is not associated with parenchymal hematomas or poor clinical outcomes after thrombectomy.

Purpose: The NADPH oxidases (Nox) are a family of reactive oxygen species generating enzymes, which play an important role in the pathophysiology of atherosclerosis. The relationship of Nox expression with carotid plaque vulnerability has not well been described. Vulnerable plaque with thin fibrous cap may be associated with the feature of distal emboli in a swine model of carotid atherosclerosis. The purpose of this study is to assess the association of Nox4 expression in vulnerable carotid plaque with thin fibrous cap in a swine model. Materials and Methods: Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for Nox4 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. The atherosclerotic lesions of AHA stage type IV to VI were defined as vulnerable plaques. The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of Nox4 expression in the plaque with the morphological features of plaque vulnerability was analyzed. Results: One hundred ninety-one carotid segments from ten carotid artery models were assessed. One hundred two segments had vulnerable plaque. Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal. Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. Areas positive for Nox4 tended to be greater in the plaques with the vulnerability features, including necrosis core, marked foam cells, plaque rupture, intraplaque hemorrhage and surface thrombus. The positive expression of Nox4 was associated with the feature of a large lipid core (p=0.035). Forty-eight segments were considered as thin fibrous cap plaques with the minimal thickness of fibrous cap less than 200 μ m. Areas positive for Nox4 were significantly greater in the plaque with thin fibrous cap than in the plaque with thick fibrous cap (p=0.005). On multivariate analysis, positive expression of Nox4 was an independent predictor of thin fibrous cap. Conclusion: Vulnerable carotid plaques with distal embolism were created in a swine model of carotid atherosclerosis. Increased expression of Nox 4 is associated with the feature of thin fibrous cap in vulnerable carotid plaques and may be used as a target for reducing the risk of distal embolism.

Purpose: The limited number of large animal carotid atherosclerotic models restricts the preclinical evaluation of endovascular therapies. Carotid intraplaque hemorrhage may be associated with a higher risk of ischemic stroke in patients with carotid disease. In this study, we assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with vulnerable atherosclerotic carotid plaque and intraplaque hemorrhage in a Swine model. Materials and Methods: Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for MMP-9 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. Atherosclerotic changes were classified by AHA/Stary stage (type I to VI). The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of MMP-9 expression in the plaque with the vulnerable plaque and intraplaque hemorrhage was further analyzed. Results: One hundred ninety-one carotid segments from ten carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 segments had vulnerable plaque (Stary IV to VI). Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal ( P Conclusion: Vulnerable carotid plaques with distal embolism were created in a Swine model of carotid atherosclerosis. Increased expression of MMP-9 may be associated with vulnerable carotid plaques, especially having the feature of intraplaque hemorrhage.

Background and Purpose— The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices. Methods— We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups. Results— Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days. Conclusions— Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.

We recently demonstrated that the preprocedural magnetic resonance imaging (MRI) pattern of deep middle cerebral artery (MCA) territory injury predicts poor prognosis. We postulate that the structures of the deep MCA field are particularly vulnerable to hemorrhagic transformation (HT) following reperfusion.We reviewed all cases of acute occlusions involving the M1 segment of the MCA with diffusion restriction of at least 50% of the deep MCA field on MRI (M1a pattern) that underwent endovascular therapy. We compared those with and without recanalization in regards to HT and disability on discharge.Thirty-five patients met inclusion criteria. The recanalized M1a group (n=27) had higher rates of HT (67% vs. 25%, P=0.05) and a trend toward more parenchymal HT (37% vs. 0%, P=0.07) and symptomatic HT (22% vs. 0%, P=0.12) than those M1a patients who failed to recanalize (n=8). Clinical improvement in the National Institutes of Health Stroke Scale by discharge was better in the survivors of the recanalized group.Among patients with the preintervention M1a MRI pattern of advanced basal ganglionic injury, successful recanalization predicts a higher risk of HT but better outcome.

The authors report their preliminary experience using a balloon-assisted technique (BAT) in the transarterial embolization of intracranial dural arteriovenous fistulas (DAVFs).The authors reviewed the prospectively collected data obtained in 7 consecutive patients with DAVFs in whom embolization was achieved using transarterially injected Onyx with either the venous or arterial BAT. Procedures were performed at the Division of Interventional Neuroradiology at the University of California at Los Angeles Medical Center between September 2005 and January 2008.Three patients presented with cortical venous reflux and 4 did not. Three patients underwent transarterial Onyx-based embolization combined with transvenous balloon protection; the balloon was inflated in the transverse sinus in 2 of these patients and in the superior sagittal sinus in the third. One of them underwent an additional transarterial Onyx embolization with arterial BAT, whereas 4 other patients were treated with arterial BAT alone. The occipital artery was temporarily occluded with the balloon in 4 of these cases, whereas in the fifth, the authors used temporary balloon occlusion of the middle meningeal artery. Angiograms obtained immediately after embolization demonstrated complete or near-complete obliteration of the fistula in 6 patients and partial occlusion in 1 patient. There were no immediate or postprocedural complications. Two patients who presented with intracranial hemorrhage never suffered a second hemorrhage, and all other patients experienced either complete resolution or significant improvement of their symptoms.The BAT provides a new complementary method in the transarterial embolization of DAVFs that are not amenable to transvenous embolization. The venous BAT protects the patency of critical venous pathways, whereas the arterial BAT provides better control of the Onyx-based embolization.

BACKGROUND AND PURPOSE: Distal embolism and acute thrombosis due to rupture of a vulnerable atherosclerotic plaque are the common mechanisms of stroke in patients with carotid disease. The purpose of this study was to develop the first animal model of vulnerable carotid atherosclerotic plaque. MATERIALS AND METHODS: Carotid atherosclerotic models were created in 12 Yucatan minipigs by using a combination of partial ligation and high cholesterol diet. Retia mirabilia from these animals were examined histopathologically to identify distal embolism. The association of distal embolism with advanced atherosclerosis and a thin fibrous cap was analyzed by using the Fisher exact test. RESULTS: Typical features of vulnerable plaques, including a thin fibrous cap, necrotic core, and intraplaque hemorrhage, were observed in this swine model of carotid atherosclerosis. Distal embolism was detected in retia mirabilia supplied by 7 of 10 carotid arteries with advanced atherosclerotic plaques, compared with 3 of 14 carotid arteries without advanced plaque (P < .05). CONCLUSIONS: This swine model of carotid atherosclerosis contains the salient features of vulnerable plaques, including plaque rupture and distal embolism.

To observe the clinical and pathological characteristics of brain arteriovenous malformations (BAVM) embolized with the non-adhesive aqueous embolic agent Onyx and evaluate its application in comprehensive treatment of BAVM.Thirty-four patients underwent BAVM embolization using Onyx, and their clinical manifestations, architecture of the malformed vessels, emblization procedure, and complications associated with the procedures were recorded. The resected tissues after embolization with Onyx were observed with electron microscope, and the prognosis of the patients was estimated with modified Rankin Score (mRS).These patients included 21 male and 13 female patients with a mean age of 30.45-/+11.81 years and an estimated mean size of the nidus of 3.98-/+1.43 cm. The patients received a total of 52 endovascular treatment procedures with Onyx to embolize 86 feeding pedicals, which resulted in an average estimated size reduction of the nidus of (72.35-/+21.26)%. Complications associated with the procedure occurred in 7 patients, and 23 patients received surgical resection or radiosurgery after embolization. Follow-up of the patients for 6 months to 4 years showed that the mRS was below 3 in 32 cases andor =3 in 2 cases. Vasodilatation, brain tissue edema surrounding the nidus, and inflammatory cell infiltration were observed in the resected tissues after embolization. In some major feeding pedicals, thrombus recanalization was observed after embolization with Onyx (diameteror =3 mm).Endovascular treatment of BAVM with Onyx can achieve high occlusion rate, enhance the safety of operation and radiosurgery, and improve the clinical prognosis of the patients.

Background Complex DAVFs involving both the clivus and cavernous sinus are rare, especially when associated with brainstem compression from a large varix. In this report, we describe the use of a covered stent in combination with a liquid embolic agent to cure a complex clival-cavernous DAVF. Methods A 46-year-old man presented with 6 months of dizziness, dysphagia, and progressive dysarthria. Magnetic resonance imaging showed tortuous and enlarged right cavernous and preclival flow voids. There were also bilateral prepontine varices compressing the ventral pons, which led to marked dorsal pontine edema. A cerebral angiogram revealed a clival DAVF supplied by multiple branches of the right ECA, as well as the MHT of the right ICA. Results An endovascular cure was achieved by deploying a covered stent in the right cavernous ICA, followed by transarterial embolization of the feeding arteries originating from the ECA with Onyx (ev3, Irvine, Calif). This combined approach resulted in complete occlusion of the fistula. His 1-month follow-up angiogram confirmed persistent occlusion of the fistula and preserved patency of the right ICA. The patient made a full recovery without any new symptoms, and he remained neurologically intact at 18-month follow-up. Conclusion The combined technique of covered stent placement and Onyx transarterial embolization is valuable for the management of complex DAVFs supplied by branches of both the external and internal carotid arteries.

Background Liquid embolic agents can achieve penetration of capillaries in tumors and thus may be even more effective at creating tumor necrosis than small particles. This study assesses the safety and efficacy of preoperative embolization of meningiomas with Onyx liquid embolic agent (Micro Therapeutics, Inc, Irvine, Calif) for delayed surgical resection. Methods Three cases of hypervascular intracranial meningiomas were treated by preoperative embolization with Onyx embolic agent using superselective catheterization of the feeding arteries from the ECA and the reflux-hold-reinjection technique. Results Meningiomas were devascularized successfully, and these patients did not present the symptoms of postembolization tumor swelling or hemorrhage before complete resection of the tumors 10 days later. Massive tumor necrosis was observed in all 3 cases of pathologic specimens, and shrinkage of tumor was seen by MRI as early as 8 days in 1 case. All patients had no recurrence of tumor at 12-month follow-up. Conclusion Preoperative embolization with Onyx may be a useful tool for treatment of meningiomas. Palliative embolization treatment of nonresectable hypervascular intracranial tumors with Onyx warrants future clinical investigation.