Intracranial Large Artery Occlusion Research Articles

Leukoaraiosis and Sex Predict the Hyperacute Ischemic Core Volume

Leukoaraiosis (LA) and male sex have been associated with decreased cerebrovascular reactivity, which potentially adversely affects tissue viability in acute stroke. Therefore, we aimed to elucidate the contribution of LA-severity and sex to the extent of the hyperacute ischemic core volume after intracranial large artery occlusion. We analyzed data from 87 patients with acute intracranial large artery occlusion who had acute multimodal computed tomography-imaging. LA-severity was assessed using the van Swieten scale on noncontrast computed tomography. Computed tomography perfusion data were analyzed using automatic calculation of the mean transit time and hyperacute cerebral blood volume defects. Multivariate linear and logistic regression analyses were used to identify independent predictors of the hyperacute infarct-volume. Severe LA (van Swieten Scale, 3-4; odds ratio, 43.22; 95% CI, 6.26-298.42; P<0.001) and male sex (odds ratio, 7.52; 95% CI, 1.38-40.86; P=0.020) were independently associated with a hyperacute cerebral blood volume-lesion >25 mL on multivariate logistic regression analysis. Multivariate linear regression analysis confirmed the association between severe LA (P<0.001) and male sex (P=0.01) with larger cerebral blood volume-lesions. There was no significant difference in the absolute or relative mean transit time-lesion volumes when stratified by LA-severity or sex. Women had significantly smaller cerebral blood volume-lesion volumes compared with men (P=0.036). Severe LA and male sex are associated with larger infarct cores, which adds to the notion that sex and LA alter the brain's intrinsic susceptibility to acute cerebral ischemia. Future, larger studies are needed to confirm our observation that women have smaller core volumes and its significance.

E-024 The Mindframe Capture LP 3 mm and 4 mm thrombectomy device. Early clinical results

IntroductionMechanical thrombectomy is effective in restoring blood flow to the brain in patients with occlusion of large intracranial arteries. Most devices require a 0.021 or 0.027 microcatheter. However, in some...

Leukoaraiosis Predicts Poor 90-Day Outcome after Acute Large Cerebral Artery Occlusion

Background: To date limited information regarding outcome-modifying factors in patients with acute intracranial large artery occlusion (ILAO) in the anterior circulation is available. Leukoaraiosis (LA) is a common finding among patients with ischemic stroke and has been associated with poor post-stroke outcomes but its association with ILAO remains poorly characterized. This study sought to clarify the contribution of baseline LA and other common risk factors to 90-day outcome (modified Rankin Scale, mRS) after stroke due to acute anterior circulation ILAO. Methods: We retrospectively analyzed 1,153 consecutive patients with imaging-confirmed ischemic stroke during a 4-year period (2007–2010) at a single academic institution. The final study cohort included 87 patients with acute ILAO subjected to multimodal CT imaging within 24 h of symptom onset. LA severity was assessed using the van Swieten scale on non-contrast CT. Leptomeningeal collaterals were graded using CT angiogram source images. Hemorrhagic transformation (HT) was determined on follow-up CT. Multivariate logistic regression controlling for HT, treatment modality, demographic, as well as baseline clinical and imaging characteristics was used to identify independent predictors of a poor outcome (90-day mRS >2). Results: The median National Institutes of Health Stroke Scale (NIHSS) at baseline was 15 (interquartile range 9–21). Twenty-four percent of the studied patients had severe LA. They were more likely to have hypertension (p = 0.028), coronary artery disease (p = 0.015), poor collaterals (p < 0.001), higher baseline NIHSS (p = 0.003), higher mRS at 90 days (p < 0.001), and were older (p = 0.002). Patients with severe LA had a uniformly poor outcome (p < 0.001) irrespective of treatment modality. Poor outcome was independently associated with higher baseline NIHSS (p < 0.001), worse LA (graded and dichotomized, p < 0.001), reduced leptomeningeal collaterals (graded and dichotomized, p < 0.001), presence of HT (p < 0.001), presence of parenchymal hemorrhages (p = 0.01), baseline mRS (p = 0.002), and older age (p = 0.043). The association between severe LA (p = 0.0056; OR 13.86; 95% CI 1.94–∞) and baseline NIHSS (p = 0.0001; OR 5.11; 95% CI 2.07–14.49 for each 10-point increase) with poor outcome maintained after adjustment for confounders in the final regression model. In this model, there was no significant association between presence of HT and poor outcome (p = 0.0572). Conclusion: Coexisting LA may predict poor functional outcome in patients with acute anterior circulation ILAO independent of other known important outcome predictors such as comorbid state, admission functional deficit, collateral status, hemorrhagic conversion, and treatment modality.

Abstract 2269: Leukoaraiosis Predicts 90-day Outcome After Intracranial Large Artery Occlusion

Background: Intracranial large artery occlusion (ILAO) accounts for a significant number of ischemic strokes and predicts a poor outcome. However, factors modifying the outcome following ILAO remain incompletely characterized. Leukoaraiosis (LA), which is a frequent finding in stroke patients, has been associated with poor post-stroke outcomes. However, its contribution to patient outcome after ILAO remains to be clarified. We sought to determine the association between LA-severity and 90-day outcomes in patients following anterior circulation ILAO. Methods: We retrospectively analyzed 1153 consecutive patients with imaging confirmed ischemic stroke during a 4-year period (2007-2010). The final study cohort included 87 patients with acute ILAO subjected to multimodal CT-imaging within 24 hours of symptom onset. LA-severity was assessed using the van Swieten scale on non-contrast CT. Leptomeningeal collaterals were graded using CT-angiogram source images. Hemorrhagic infarction was determined on follow-up CT. Multivariate logistic regression controlling for hemorrhagic infarction, treatment modality, demographic, as well as baseline clinical and imaging characteristics was used to identify independent predictors for outcome. Results: Factors independently associated with poor outcome (90-day mRS≥3) were admission NIHSS (p=0.0001; OR 5.11; 95% CI, 2.07-14.49 for each 10-point increase) and severe LA (p=0.0056; OR 13.86; 95% CI, 1.94-∞; Figure ). There was a trend for an association between presence of hemorrhagic conversion and poor outcome (p=0.0572; OR 4.82; CI 0.96-32.65). Compared to patients with none-to-moderate LA, patients with severe LA were more likely to have hypertension (p=0.027), coronary artery disease (p=0.008), poor collaterals (p&lt;0.001), higher admission NIHSS (p=0.003), higher mRS at 90 days (p&lt;0.001), and they were older (p=0.002). Patients with severe LA had a uniformly poor outcome (p&lt;0.001). Conclusion: In addition to NIHSS, the severity of pre-existing LA has substantial impact on outcome in patients with acute ILAO and may prove to be an important factor to guide clinical decision making. Figure: Functional outcome by Leukoaraiosis grades Functional outcome at 90 days (modified Rankin Score, mRS) stratified by severity of Leukoaraiosis (LA) grades (van Swieten Score 0-2 vs. 3-4, P&lt;0.001). Numbers indicate n per mRS-category.

Prevention of cardioembolic stroke.

Cardiac causes of ischemic stroke lead to severe neurological deficits from large intracranial artery occlusion compared to small vessel ischemic stroke. The most common cause of cardioembolic stroke is atrial fibrillation (AF), which has an increasing incidence with age. AF stroke trials demonstrate that anti-coagulation is superior to anti-platelet therapy in terms of ischemic stroke prevention. Recently, warfarin was compared with dabigatran, an oral, direct thrombin inhibitor, and was found to be at least equally effective in reducing ischemic stroke with less intracranial bleeding risk. Future research is investigating other direct thrombin inhibitors as potential alternatives to warfarin, which has a narrow therapeutic index, requires frequent blood monitoring, has multiple drug interactions, and a higher rate of intracranial bleeding. Other causes of cardioembolic stroke include myocardial infarction, left ventricular thrombus, reduced ejection fraction, valvular abnormalities, and endocarditis. Patent foramen ovale is a common finding on echocardiograms in patients with and without stroke (up to 20% of the population), and it is a controversial source of cryptogenic stroke. The best way to prevent cardioembolic stroke remains early detection and treatment of AF, and treating the underlying stroke mechanism. Cardiac magnetic resonance imaging is an emerging technology and reveals some sources of cardiac embolism missed by echocardiography, and might provide an additional diagnostic tool in investigating cardioembolic stroke.

Does intra‐arterial thrombolysis have a role as first‐line intervention in acute ischaemic stroke?

Minimization of the clinical impact of acute ischaemic stroke depends largely on prompt restoration of blood flow to underperfused regions of the brain. Intravenous thrombolysis (IVT) is currently the first-line intervention for acute ischaemic stroke, with proven efficacy in randomized controlled trials. There are several major limitations associated with IVT, in particular, the relatively poor outcomes in large artery occlusions. A major emerging modality in acute stroke management is intra-arterial thrombolysis (IAT), whereby clot-retrieval or thrombolytics are applied under angiographic guidance to the site of the clot. Strong arguments exist for the use of IAT as first-line ischaemic stroke management in preference of IVT, especially with large intracranial artery occlusion. Despite these arguments, the lack of data from randomized controlled studies in IAT means that it is appropriate to continue the current practice of IVT as first-line treatment for the majority of acute ischaemic strokes at this stage. Advanced neuroimaging techniques, in particular a 'multimodal' computed tomography (CT) approach combining non-contrast CT, CT angiography and perfusion CT, may serve as a valuable triage tool for patient selection. Ongoing research is required in endovascular approaches to stroke; in particular, randomized controlled trials with a focus on clinical outcomes and tackling the inherent delays between symptom onset and treatment.

Is mechanical clot removal or disruption a cost-effective treatment for acute stroke?

It is unclear whether the costs and risks of mechanical therapies make them cost-effective. We examined whether interventions such as mechanical clot removal or disruption with angioplasty are cost-effective for acute ischemic stroke compared with best medical therapy. We performed a cost-utility analysis of patients with acute stroke due to large intracranial artery occlusion presenting beyond the 3-hour window for IV tPA. Model inputs for the mechanical arm were derived from Multi MERCI trial data and a recent meta-analysis. For best medical therapy, we used rates of spontaneous recanalization, ICH, and functional outcomes based on a systematic literature review. Discounted QALYs were determined by using the Markov modeling for 65-year-old patients with acute ischemic stroke. On the basis of a systematic literature review, we modeled an 84% rate of recanalization with mechanical intervention and a 6.3% rate of symptomatic ICH. For best medical therapy, we modeled a spontaneous recanalization rate of 24% with a 2% rate of symptomatic ICH. Mechanical therapies were associated with a $7718 net cost and a gain of a 0.82 QALYs for each use, thus yielding a net of $9386/QALY gained. In sensitivity analyses, results were dependent on the rates of recanalization, symptomatic ICH rates, and costs of treatment. On the basis of available data, mechanical therapies in qualified patients with acute stroke beyond the window for IV tPA appear to be cost-effective. However, the inputs are not derived from randomized trials, and results are sensitive to several assumptions.

Gender Differences in Outcomes after Ischemic Stroke: Role of Ischemic Lesion Volume and Intracranial Large-Artery Occlusion

Background: The reasons for gender disparities in stroke outcome remain unclear, and little is known about the value of acute neuroimaging characteristics in elucidating differential stroke outcomes between the sexes. Methods: We prospectively evaluated consecutive patients with acute ischemic stroke. CT angiography (CTA) was performed in all patients within 24 h of symptom onset. CTA source images were used to evaluate lesion volume. The primary outcome measure was a modified Rankin scale (mRS) score ≧3 at 6 months. Results: We evaluated 676 consecutive patients (322 women). Women were older than men (p < 0.01), more frequently had a prestroke mRS >0 (p < 0.01), and had higher admission National Institutes of Health Stroke scale scores (p = 0.01). More women had intracranial artery occlusions than men (46 vs. 33.1%, p = 0.01), but there was no significant difference between ischemic lesion volumes (p = 0.21). Using multiple regression, female gender remained an independent predictor of poor mRS scores at 6 months (odds ratio 1.57; 95% confidence interval 1.02–2.36) after adjustment for clinical and imaging covariates. Conclusion: Compared with men, women are less likely to achieve independence after acute ischemic stroke. The disparity in stroke outcome is not explained by differences in ischemic lesion volume or the presence of intracranial artery occlusions.

D-dimers increase in acute ischemic stroke patients with the large artery occlusion, but do not depend on the time of artery recanalization

D-dimers are one of the basic laboratory markers of fibrinolytic system activity. The aim of this prospective study was to detect changes in D-dimer levels in acute stroke patients as a function of the time of artery recanalization and the therapy used. During a 12-month period, 80 acute ischemic stroke patients admitted to the hospital within a 6-h time window were consecutively enrolled in the study. The clinical neurologic examination, brain computed tomography, neurosonologic examination, and biochemical and hematological blood tests (including D-dimers and fibrinogen) were performed on all patients on admission. The control examinations of D-dimer and fibrinogen blood levels were performed 3 (optional), 6, and 24 h after stroke onset. The Mann-Whitney test, Kruskal-Wallis test, ANOVA test, multiple comparison test, and Pearson test were used for statistical evaluation. Application of intravenous thrombolysis significantly increased the D-dimer levels and decreased the fibrinogen level 6 h after stroke onset in comparison with patients treated with antiplatelets or anticoagulants (P < 0.01), with normalization of blood levels over a 24 h period. The use of sonothrombotripsy showed a tendency to increase the D-dimer levels (P = 0.09) with a significant decrease of the fibrinogen level 6 h after stroke onset (P < 0.05). A significant increase in the D-dimer levels was detected in patients with strokes of cardioembolic and atherothrombotic etiologies, and patients with occlusion of cervical or large intracranial arteries (P < 0.05). There was no correlation between the changes in D-dimer or fibrinogen levels and age, gender, time to artery recanalization, risk factors, and the seriousness of neurologic deficits on admission (P > 0.05). D-dimer levels significantly increased during the first 6 h after stroke onset in patients with large artery occlusion and patients treated using intravenous thrombolysis. However, this increase was independent on the time of artery recanalization thus cannot be used as its marker.

Significance of Susceptibility Vessel Sign on T2*-Weighted Gradient Echo Imaging for Identification of Stroke Subtypes

In contrast to platelet-rich white thrombi, red thrombi in the heart are rich in fibrin and trapped erythrocytes. The magnetic susceptibility effect of deoxygenated hemoglobin in red thrombi may result in hypointense signals on T2*-weighted gradient echo imaging (GRE). We tested the hypothesis that a GRE susceptibility vessel sign (SVS) is specific for cardioembolic stroke. This retrospective study examined data from acute ischemic stroke patients who underwent diffusion-weighted imaging, GRE and magnetic resonance angiography (MRA) within 24 hours of stroke onset and who had symptomatic occlusion of large intracranial arteries in the circle of Willis. Hypointense signals within vascular cisterns on GRE corresponding to symptomatic vascular occlusion were termed "GRE SVS." Recanalization was assessed on follow-up MRA performed within 7 days of onset. The relationships between GRE SVS and stroke subtypes and subsequent recanalization were explored. Of the 95 patients who met the inclusion criteria, GRE SVS was observed in 45 (47.4%). GRE SVS was more commonly associated with cardioembolic stroke patients (31 of 40, 77.5%) than with other stroke subtypes (14 of 55, 25.5%; P<0.001). In 66 patients who underwent follow-up MRA, GRE SVS was associated with subsequent recanalization (P<0.001). Multivariate analysis showed that GRE SVS was an independent predictor of cardioembolic stroke and subsequent recanalization (odds ratio, 10.75 and 4.26; 95% CI, 3.68 to 31.47 and 1.12 to 16.30). GRE SVS may predict cardioembolic stroke and subsequent recanalization. Identifying clot composition may be important in choosing the optimal treatment based on clot characteristics.

Mechanical Embolus Removal. A New Day Dawning

Mechanical Embolus Removal. A New Day Dawning

Approval of the MERCI Clot Retriever

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …

Improving the Assessment of Outcomes in Stroke: Use of a Structured Interview to Assign Grades on the Modified Rankin Scale

Improving the Assessment of Outcomes in Stroke: Use of a Structured Interview to Assign Grades on the Modified Rankin Scale