Raul G. Nogueira

Conscious Sedation Versus General Anesthesia During Endovascular Therapy for Acute Anterior Circulation Stroke: Preliminary Results From a Retrospective, Multicenter Study

Background and Purpose— Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT. Methods— A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death. Results— The mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13–20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63–3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23–2.30; P<0.0001) compared with conscious sedation. Conclusions— Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.

Preliminary Experience with Onyx Embolization for the Treatment of Intracranial Dural Arteriovenous Fistulas

BACKGROUND AND PURPOSE: Onyx was recently approved for the treatment of pial arteriovenous malformations, but its use to treat dural arteriovenous fistulas (DAVFs) is not yet well established. We now report on the treatment of intracranial DAVFs using this nonadhesive liquid embolic agent. MATERIALS AND METHODS: We performed a retrospective analysis of 12 consecutive patients with intracranial DAVFs who were treated with Onyx as the single treatment technique at our institution between March 2006 and February 2007. RESULTS: A total of 17 procedures were performed in 12 patients. In all of the cases, transarterial microcatheterization was performed, and Onyx-18 or a combination of Onyx-18/Onyx-34 was used. Eight patients were men. The mean age was 56 ± 12 years. Nine patients were symptomatic. There was an average of 5 feeders per DAVF (range, 1–9). Cortical venous reflux was present in all of the cases except for 1 of the symptomatic patients. Complete resolution of the DAVF on immediate posttreatment angiography was achieved in 10 patients. The remaining 2 patients had only minimal residual shunting postembolization, 1 of whom appeared cured on a follow-up angiogram 8 weeks later. The other patient has not yet had angiographic follow-up. Follow-up angiography (mean, 4.4 months) is currently available in 9 patients. There was 1 angiographic recurrence (asymptomatic), which was subsequently re-embolized with complete occlusion of the fistula and its draining vein. There was no significant morbidity or mortality. CONCLUSION: In our experience, the endovascular treatment of intracranial DAVFs with Onyx is feasible, safe, and highly effective with a small recurrence rate in the short-term follow-up.

Infarct Volume Is a Pivotal Biomarker After Intra-Arterial Stroke Therapy

Background and Purpose— Pretreatment infarct volume appears to predict clinical outcome after intra-arterial therapy. To confirm the importance of infarct size in patients undergoing intra-arterial therapy, we sought to characterize the relationship between final infarct volume (FIV) and long-term functional outcome in a prospective cohort of endovascularly treated patients. Methods— From our prospective intra-arterial therapy database, we identified 107 patients with acute ischemic stroke with anterior circulation proximal artery occlusions who underwent final infarct imaging and had 3-month modified Rankin Scale scores. Clinical, imaging, treatment, and outcome data were analyzed. Results— Mean age was 66.6 years. Median admission National Institutes of Health Stroke Scale score was 17. Reperfusion (Thrombolysis In Cerebral Infarction 2A–3) was achieved in 78 (72.9%) patients. Twenty-seven (25.2%) patients achieved a 3-month good outcome (modified Rankin Scale 0–2), and 30 (28.0%) died. Median FIV was 71.4 cm3. FIV independently correlated with functional outcome across the entire modified Rankin Scale. In receiver operating characteristic analysis, it was the best discriminator of both good outcome (area under the curve=0.857) and mortality (area under the curve=0.772). A FIV of approximately 50 cm3 demonstrated the greatest accuracy for distinguishing good versus poor outcome, and a FIV of approximately 90 cm3 was highly specific for a poor outcome. The interaction term between FIV and age was the only independent predictor of good outcome (P<0.0001). The impact of FIV was accentuated in patients <80 years. Conclusions— Among patients with anterior circulation acute ischemic stroke who undergo intra-arterial therapy, final infarct volume is a critical determinant of 3-month functional outcome and appears suitable as a surrogate biomarker in proof-of-concept intra-arterial therapy trials.

Malignant CTA Collateral Profile Is Highly Specific for Large Admission DWI Infarct Core and Poor Outcome in Acute Stroke

“Malignant” stroke features include a large core (>100 ml), little penumbra, and no collateral circulation, and portray a poor outcome. These authors studied patients with proximal intracranial arterial occlusions and assessed infarct core size and collateral circulation as seen on CTA. After analyzing 197 such patients, they determined that those with poor collateral grades (absent collateral circulation) had larger infarct cores, large lesions on DWI, and a poor functional outcome. Additionally, patients with poor collaterals had higher NIHSS scores at admission. BACKGROUND AND PURPOSE: Large admission DWI lesion volumes are associated with poor outcomes despite acute stroke treatment. The primary aims of our study were to determine whether CTA collaterals correlate with admission DWI lesion volumes in patients with AIS with proximal occlusions, and whether a CTA collateral profile could identify large DWI volumes with high specificity. MATERIALS AND METHODS: We studied 197 patients with AIS with M1 and/or intracranial ICA occlusions. We segmented admission and follow-up DWI lesion volumes, and categorized CTA collaterals by using a 5-point CS system. ROC analysis was used to determine CS accuracy in predicting DWI lesion volumes >100 mL. Patients were dichotomized into 2 categories: CS = 0 (malignant profile) or CS>0. Univariate and multivariate analyses were performed to compare imaging and clinical variables between these 2 groups. RESULTS: There was a negative correlation between CS and admission DWI lesion volume (ρ = −0.54, P < .0001). ROC analysis revealed that CTA CS was a good discriminator of DWI lesion volume >100 mL (AUC = 0.84, P < .001). CS = 0 had 97.6% specificity and 54.5% sensitivity for DWI volume >100 mL. CS = 0 patients had larger mean admission DWI volumes (165.8 mL versus 32.7 mL, P < .001), higher median NIHSS scores (21 versus 15, P < .001), and were more likely to become functionally dependent at 3 months (95.5% versus 64.0%, P = .003). Admission NIHSS score was the only independent predictor of a malignant CS (P = .007). CONCLUSIONS: In patients with AIS with PAOs, CTA collaterals correlate with admission DWI infarct size. A malignant collateral profile is highly specific for large admission DWI lesion size and poor functional outcome.

Endovascular Approaches to Acute Stroke, Part 1: Drugs, Devices, and Data

SUMMARY: Despite years of research and pioneering clinical work, stroke remains a massive public health concern. Since 1996, we have lived in the era of US Food and Drug Administration−approved intravenous (IV) recombinant tissue plasminogen activator (rtPA). This treatment, despite its promise, continues to exhibit its limitations. Endovascular therapy has several theoretic advantages over IV rtPA, including site specificity, longer treatment windows, and higher recanalization rates. In this article, we will review the various pharmacologic strategies for acute stroke treatment, providing both a historic context and the state of the art. The drugs will be classified on the basis of their theoretic rationale for therapy. Next, we will review the various devices and strategies for mechanical revascularization with an aim toward comprehensiveness. These range from wire disruption of thrombus to preclinical trials for novel mechanical solutions. This first installment of this 2-part series will end with an analysis of retrograde reperfusion techniques.

Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials

SUMMARY: Reperfusion remains the mainstay of acute ischemic stroke treatment. Endovascular therapy has become a promising alternative for patients who are ineligible for or have failed intravenous (IV) thrombolysis. The conviction that recanalization of properly selected patients is essential for the achievement of good clinical outcomes has led to the rapid and widespread growth in the adoption of endovascular stroke therapies. However, comparisons of the recent reperfusion studies have brought into question the strength of the association between revascularization and improved clinical outcome. Despite higher rates of recanalization, the mechanical thrombectomy studies have demonstrated substantially lower rates of good outcomes compared with IV and/or intra-arterial thrombolytic trials. However, such analyses disregard important differences in clot location and burden, baseline stroke severity, time from stroke onset to treatment, and patient selection in these studies. Many clinical trials are testing novel devices and drugs as well as the paradigm of physiology-based stroke imaging as a treatment-selection tool. The objective of this article is to provide a comprehensive review of the relevant past, current, and upcoming data on endovascular stroke therapy with a special focus on the prospective studies and randomized clinical trials.

Differentiation of Hemorrhage from Iodinated Contrast in Different Intracranial Compartments Using Dual-Energy Head CT

BACKGROUND AND PURPOSE: Identification of ICH, particularly after ischemic stroke therapy, is important for guiding subsequent antithrombotic management and is often confounded by contrast staining or extravasations within intracerebral or extra-axial compartments. This study evaluates the accuracy of DECT in distinguishing ICH from iodinated contrast in patients who received contrast via IA or IV delivery. MATERIALS AND METHODS: Forty patients who had received IA or IV contrast were evaluated using a DECT scanner at 80kV and 140kV to distinguish hyperdensities secondary to contrast staining or extravasation from those representing ICH. A 3-material decomposition algorithm was used to obtain virtual noncontrast images and iodine overlay images. Sensitivity, specificity, and accuracy of DECT in prospectively distinguishing intracranial contrast from hemorrhage within parenchymal, subarachnoid, extra-axial, intraventricular, and intra-arterial compartments were computed using routine clinical follow-up imaging as the standard of reference. RESULTS: A total of 148 foci of intracranial hyperattenuation were identified. Of these, 142 were correctly classified for the presence of hemorrhage by DECT. The sensitivity, specificity, and accuracy for identifying hemorrhage, depending on the compartment being considered, were 100%, 84.4%–100%, and 87.2%–100%, respectively. The only instances where DECT failed to correctly identify the source of hyperattenuation was in the presence of diffuse parenchymal calcification (n = 5) and a metallic streak artifact (n = 1). CONCLUSION: After IA and/or IV contrast administration, DECT can accurately differentiate all types of ICH from iodinated contrast without employing any additional radiation.

Case volumes of intra-arterial and intravenous treatment of ischemic stroke in the USA

Background and purpose Ischemic stroke is a major cause of disability and death in the USA. Intravenous tissue plasminogen activator (t-PA) remains underutilized. With the development of newer intra-arterial reperfusion therapies, there is increased opportunity to address the more devastating large-vessel occlusions. We seek to identify the numbers of patients with stroke treated with intravenous and intra-arterial therapies, as well as to estimate the potential number of intra-arterial cases in the foreseeable future. Methods We performed a literature search to determine case volumes of intravenous t-PA use. We extrapolated the current case volume of intra-arterial stroke therapies from the numbers of cases in which the Merci retrieval device was used. In order to estimate the potential numbers of intra-arterial stroke cases, we characterized the percentage of patients with stroke who received intra-arterial therapy at two leading stroke centers. We applied these percentages to the numbers of patients with stroke seen at the top 100, 200 and 500 stroke centers by volume. Results The rate of intravenous t-PA use is 2.4–3.6%, resulting in 15 000–22 000 cases/year in the USA. The estimated case volume of intra-arterial therapies is 3500–7200 in 2006. Based on data from St. Lukes Brain and Stroke Institute and Massachusetts General Hospital, approximately 5–20% of patients with ischemic stroke can be treated with intra-arterial therapies. Extrapolating this to the top 500 stroke centers by volume, the potential number of intra-arterial cases in the USA is 10 400–41 500/year. Conclusion Based on the current numbers of intra-arterial cases, our theoretical model identifies a potential for significant growth of this stroke therapy.

The Trevo device: preclinical data of a novel stroke thrombectomy device in two different animal models of arterial thrombo-occlusive disease

Background The currently available mechanical devices fail to achieve recanalization in as many as 20–40% of proximal arterial occlusion strokes. Objective The preclinical evaluation of the safety and efficacy of a novel thrombectomy device designed to achieve immediate flow restoration by quickly removing clot is reported. Methods Four confirmatory animal studies were performed with the Trevo device (Concentric Medical Inc, Mountain View, California, USA) in the swine (n=2) and canine (n=1) models of arterial thrombo-occlusive disease employing autologous thrombin generated thrombi. The angiographic response and the degree of device–clot incorporation were evaluated. High resolution flat panel three-dimensional CT was performed to further define the in vivo device–thrombus–vessel interaction. Finally, samples of three swine vessels treated with six passes of the device were explanted for histopathological analysis. Results A total of 16 clots of variable hardness and consistency were implanted in a variety of vascular settings, including the swine internal maxillary, lingual and forelimb arteries as well as the canine external carotid and vertebral arteries. Thrombolysis in Myocardial Infarction (TIMI) 2–3 reperfusion was achieved in all cases immediately after device deployment. All 16 clots were retrieved after one (n=15) or two (n=1) passes with the device. Histopathological analysis demonstrated severe disruption of the intima but no hemorrhage of media or adventitia. Conclusion The experimental data suggest that the Trevo device is highly effective at achieving immediate reperfusion of occluded arteries without causing any clinically significant disruption of vascular integrity.

CT Angiography-Source Image Hypoattenuation Predicts Clinical Outcome in Posterior Circulation Strokes Treated With Intra-Arterial Therapy

Background and Purpose— The aim of this study was to correlate CT angiography-source image (CTA-SI) parenchymal hypoattenuation with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis. Methods— In 16 patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis, we graded CTA-SI parenchymal hypoattenuation in the medulla, pons, midbrain, thalamus, cerebellum, occipital lobe, inferior parietal lobe, and medial temporal lobe. The grading scale was: 0, no hypoattenuation; 1, <50% hypoattenuation; and 2, >50% hypoattenuation. On CTA, we assessed clot location and length and collaterals. Outcome was measured with modified Rankin score. Results— Mean patient age was 68.3 years (range, 47 to 86 years), National Institutes of Health Stroke Scale was 28 (range, 11 to 40), time to CTA was 5.2 hours (range, 0.69 to 15.32), and time from CTA to intra-arterial thrombolysis was 5 hours (range, 2.25 to 10.38 hours). There were 4 basilar, 2 vertebral, and 10 combined occlusions. Eleven patients had near complete, 4 had partial, and one had no recanalization. Independent outcome predictors measured as modified Rankin score at 3 months were CTA-SI pons and midbrain scores(cumulative r=0.81, P<0.001). For outcome dichotomized into death versus survival, the CTA-SI pons score (P=0.0037) was the only independent predictor. Conclusion— Hypoattenuation in the pons and midbrain on pretreatment CTA-SI correlates highly with clinical outcome in patients with vertebrobasilar occlusion treated with intra-arterial thrombolysis.