Endovascular therapy after intravenous t-PA versus t-PA alone for stroke.

BACKGROUND: Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS: We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS: The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83). CONCLUSIONS: The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.).

Relative Influence of Capillary Index Score, Revascularization, and Time on Stroke Outcomes From the Interventional Management of Stroke III Trial.

BACKGROUND AND PURPOSE: Until recently, acute ischemic stroke (AIS) trials have failed to show a benefit of endovascular therapy compared with standard therapy, leading some authors to recommend decreasing the time from ictus to revascularization to improve outcomes. We hypothesize that improving patient selection using the capillary index score (CIS) may also be a useful strategy. METHODS: CIS was calculated, blinded to outcome, from pretreatment diagnostic cerebral angiograms for 78 subjects in the Interventional Management of Stroke III database with internal carotid artery and middle cerebral artery trunk occlusion. The CIS was dichotomized into favorable (fCIS=2 or 3) and poor (pCIS=0 or 1). Outcomes were categorized based on the modified Rankin Scale score at 90 days (0-2 considered a good outcome). Modified thrombolysis in cerebral infarction score 2b or 3 was considered good revascularization. Multivariable logistic regression was performed to relate CIS, time from ictus to revascularization, modified thrombolysis in cerebral infarction score, and National Institue of Health Stroke Scale score to good outcomes. RESULTS: Only CIS and modified thrombolysis in cerebral infarction scores were correlated with good outcomes (P<0.01). Patients with fCIS and good revascularization achieved 71% modified Rankin Scale≤2, compared with 13% for patients with pCIS and good revascularization. CONCLUSIONS: In this subset of patients from the Interventional Management of Stroke III Trial, CIS and modified thrombolysis in cerebral infarction were strong predictors of outcome after endovascular reperfusion. Using the CIS to improve patient selection could be a powerful strategy to improve rate of good outcomes in endovascular therapy. A randomized trial is needed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Differential Effect of Baseline Computed Tomographic Angiography Collaterals on Clinical Outcome in Patients Enrolled in the Interventional Management of Stroke III Trial.

BACKGROUND AND PURPOSE: In the Interventional Management of Stroke (IMS) III trial, we sought to demonstrate evidence of a differential treatment effect of endovascular treatment of acute ischemic stroke compared with intravenous tissue-type plasminogen activator, according to baseline collateral status measured using computed tomographic angiography. METHODS: Of 656 patients enrolled in Interventional Management of Stroke III trial, 306 had baseline computed tomographic angiography. Of these, 185 patients had M1 middle cerebral artery ± intracranial internal carotid artery occlusion, where baseline collateral status could be measured. Collateral status was assessed by consensus using 3 different ordinal scales and categorized as good, intermediate, and poor. Multivariable modeling was used to assess the effect of collateral status and treatment type on clinical outcome by modified Rankin Scale (mRS 0-2, mRS 0-1, and the ordinal mRS). RESULTS: Of 185 patients, 126 randomized to endovascular therapy (87.6% recanalized, 41.3% 90-day mRS 0-2) and 59 to intravenous tissue-type plasminogen activator only (60.5% recanalized, 30.5% 90-day mRS 0-2). In multivariable modeling, collateral status was a significant predictor of all clinical outcomes (P<0.05). Maximal benefit with endovascular treatment across all clinical outcomes was seen in patients with intermediate collaterals, some benefit in patients with good collaterals, and none in patients with poor collaterals, although small sample size limited the power of the analysis to show a statistically significant interaction between collateral status and treatment type (P>0.05). CONCLUSION: Using data from a large randomized controlled trial (IMS III), we show that baseline computed tomographic angiography collaterals are a robust determinant of final clinical outcome and could be used to select patients for endovascular therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov/ct2/show/. Unique identifier: 0020NCT00359424.

Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial.

BACKGROUND AND PURPOSE: Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months, but data regarding outcomes at 12 months are currently lacking. METHODS: We compared functional and quality-of-life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous tissue-type plasminogen activator followed by endovascular treatment as compared with intravenous tissue-type plasminogen activator alone in the Interventional Management of Stroke III Trial. The key outcome measures were a modified Rankin Scale score ≤2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure. RESULTS: 656 subjects with moderate-to-severe stroke (National Institutes of Health Stroke Scale ≥8) were enrolled at 58 centers in the United States (41 sites), Canada (7), Australia (4), and Europe (6). There was an interaction between treatment group and stroke severity in the repeated measures analysis of modified Rankin Scale ≤2 outcome (P=0.039). In the 204 participants with severe stroke (National Institutes of Health Stroke Scale ≥20), a greater proportion of the endovascular group had a modified Rankin Scale ≤2 (32.5%) at 12 months as compared with the intravenous tissue-type plasminogen activator group (18.6%, P=0.037); no difference was seen for the 452 participants with moderately severe strokes (55.6% versus 57.7%). In participants with severe stroke, the endovascular group had 35.2 (95% confidence interval: 2.1, 73.3) more quality-adjusted-days over 12 months as compared with intravenous tissue-type plasminogen activator alone. CONCLUSIONS: Endovascular therapy improves functional outcome and health-related quality-of-life at 12 months after severe ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Data.

BACKGROUND AND PURPOSE: We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (National Institutes of Health Stroke Scale score, ≥20) after a prespecified analysis plan. METHODS: The pooled analysis of the Interventional Management of Stroke III (IMS III) and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trials included participants with an National Institutes of Health Stroke Scale score of ≥20 before intravenous tissue-type plasminogen activator (tPA) treatment (IMS III) or randomization (MR CLEAN) who were treated with intravenous tPA ≤3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy after intravenous tPA would have improved 90-day outcome (distribution of modified Rankin Scale scores), when compared with those who received intravenous tPA alone. RESULTS: Among 342 participants in the pooled analysis (194 from IMS III and 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared with the intravenous tPA group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.66). In the logistic regression model of the dichotomous outcome (modified Rankin Scale score, 0-2, or functional independence), the endovascular group had superior outcomes (adjusted odds ratio, 1.97; 95% confidence interval, 1.09-3.56). Functional independence (modified Rankin Scale score, ≤2) at 90 days was 25% in the endovascular group when compared with 14% in the intravenous tPA group. CONCLUSIONS: Endovascular therapy after intravenous tPA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424 (IMS III) and ISRCTN10888758 (MR CLEAN).

Time to angiographic reperfusion in acute ischemic stroke: decision analysis.

BACKGROUND AND PURPOSE: Our objective was to use decision analytic modeling to compare 2 treatment strategies of intravenous recombinant tissue-type plasminogen activator (r-tPA) alone versus combined intravenous r-tPA/endovascular therapy in a subgroup of patients with large vessel (internal carotid artery terminus, M1, and M2) occlusion based on varying times to angiographic reperfusion and varying rates of reperfusion. METHODS: We developed a decision model using Interventional Management of Stroke (IMS) III trial data and comprehensive literature review. We performed 1-way sensitivity analyses for time to reperfusion and 2-way sensitivity for time to reperfusion and rate of reperfusion success. We also performed probabilistic sensitivity analyses to address uncertainty in total time to reperfusion for the endovascular approach. RESULTS: In the base case, endovascular approach yielded a higher expected utility (6.38 quality-adjusted life years) than the intravenous-only arm (5.42 quality-adjusted life years). One-way sensitivity analyses demonstrated superiority of endovascular treatment to intravenous-only arm unless time to reperfusion exceeded 347 minutes. Two-way sensitivity analysis demonstrated that endovascular treatment was preferred when probability of reperfusion is high and time to reperfusion is small. Probabilistic sensitivity results demonstrated an average gain for endovascular therapy of 0.76 quality-adjusted life years (SD 0.82) compared with the intravenous-only approach. CONCLUSIONS: In our post hoc model with its underlying limitations, endovascular therapy after intravenous r-tPA is the preferred treatment as compared with intravenous r-tPA alone. However, if time to reperfusion exceeds 347 minutes, intravenous r-tPA alone is the recommended strategy. This warrants validation in a randomized, prospective trial among patients with large vessel occlusions.

Capillary Index Score in the Interventional Management of Stroke trials I and II.

BACKGROUND AND PURPOSE: The Capillary Index Score (CIS) is a simple angiography-based scale for assessing viable tissue in the ischemic territory. We retrospectively applied it to Interventional Management of Stroke (IMS) trials I and II to evaluate the predictive value for good outcomes. METHODS: CIS was calculated from pretreatment diagnostic cerebral angiograms blinded to outcome. IMS I and II diagnostic cerebral angiogram images of sufficient quality were reviewed and CIS calculated for treated subjects with internal carotid artery or M1 occlusion. CIS scoring (0-3) was dichotomized into favorable (f CIS; 2 or 3) and poor (p CIS; 0 or 1). Modified thrombolysis in cerebral infarction score 2b or 3 was considered good revascularization. CIS and modified thrombolysis in cerebral infarction scores were compared with good outcome, defined as modified Rankin Scale score≤2 at 90 days. RESULTS: Twenty-eight of 161 subjects met the inclusion criteria. Thirteen (46%) had f CIS. Good clinical outcome was significantly different between the 2 CIS groups (62% for f CIS versus 7% for p CIS; P=0.004). Good reperfusion correlated to good outcome (P=0.04). No significant differences in time to intravenous or intra-arterial treatment were identified between f CIS and p CIS groups (P>0.25). CONCLUSIONS: A f CIS was found in ≈50% of subjects and was a virtual prerequisite for good outcome in this study subgroup of IMS I and II. We call this the 50% barrier.

Alberta Stroke Program early computed tomography score to select patients for endovascular treatment: Interventional Management of Stroke (IMS)-III Trial.

BACKGROUND AND PURPOSE: The Interventional Management of Stroke (IMS)-III trial randomized patients with acute ischemic stroke to intravenous tissue-type plasminogen activator (tPA) plus endovascular therapy versus intravenous tPA therapy alone within 3 hours from symptom onset. A predefined secondary hypothesis was that subjects with significant early ischemic change on the baseline scan would not respond to endovascular therapy. METHODS: The primary outcome was 90-day modified Rankin Scale score 0 to 2. The baseline and follow-up computed tomographic (CT) scan images were reviewed centrally and blinded to any clinical information. We assessed whether the baseline Alberta Stroke Program Early CT Score (ASPECTS) predicted outcome and interacted with study treatment. We analyzed subgroups defined by time from onset to intravenous tPA initiation and baseline occlusion status at a prespecified α=0.01. RESULTS: Baseline demographic and clinical characteristics of 656 randomized patients were similar between subjects with a baseline ASPECTS 8 to 10 (58% of the study sample) versus 0 to 7. Subjects with ASPECTS 8 to 10 were almost twice as likely (relative risk, 1.8; 99% confidence interval, 1.4-2.4) to achieve a favorable outcome. There was insufficient evidence of a treatment-by-ASPECTS interaction. In those treated with onset to intravenous tPA <120 minutes, in CT angiography-proven internal carotid artery or middle cerebral artery occlusion, and in both, results were similar. The probability of achieving recanalization (arterial occlusion lesion, 2-3) of the primary arterial occlusive lesion (relative risk, 1.3; 99% confidence interval, 1.0-1.8) or achieving thrombolysis in cerebral ischemia score 2b/3 reperfusion (relative risk 2.0; 99% confidence interval, 1.2-3.2) was higher among subjects with higher ASPECTS. CONCLUSIONS: ASPECTS is a strong predictor of outcome and a predictor of reperfusion. ASPECTS did not identify a subpopulation of subjects that particularly benefitted from endovascular therapy immediately after routine intravenous tPA. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Collaterals at angiography and outcomes in the Interventional Management of Stroke (IMS) III trial.

BACKGROUND AND PURPOSE: Endovascular strategies provide unique opportunity to correlate angiographic measures of collateral circulation at the time of endovascular therapy. We conducted systematic analyses of collaterals at conventional angiography on recanalization, reperfusion, and clinical outcomes in the endovascular treatment arm of the Interventional Management of Stroke (IMS) III trial. METHODS: Prospective evaluation of angiographic collaterals was conducted via central review of subjects treated with endovascular therapy in IMS III (n=331). Collateral grade before endovascular therapy was assessed with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale, blinded to all other data. Statistical analyses investigated the association between collaterals with baseline clinical variables, angiographic measures of recanalization, reperfusion and clinical outcomes. RESULTS: Adequate views of collateral circulation to the ischemic territory were available in 276 of 331 (83%) subjects. Collateral grade was strongly related to both recanalization of the occluded arterial segment (P=0.0016) and downstream reperfusion (P<0.0001). Multivariable analyses confirmed that robust angiographic collateral grade was a significant predictor of good clinical outcome (modified Rankin Scale score≤2) at 90 days (P=0.0353), adjusted for age, history of diabetes mellitus, National Institutes of Health Stroke Scale strata, and Alberta Stroke Program Early CT Score. The relationship between collateral flow and clinical outcome may depend on the degree of reperfusion. CONCLUSIONS: More robust collateral grade was associated with better recanalization, reperfusion, and subsequent better clinical outcomes. These data, from the largest endovascular trial to date, suggest that collaterals are an important consideration in future trial design. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Evolution of practice during the Interventional Management of Stroke III Trial and implications for ongoing trials.

BACKGROUND AND PURPOSE: We explored changes in the patient population and practice of endovascular therapy during the course of the Interventional Management of Stroke (IMS) III Trial. METHODS: Changes in baseline characteristics, use of baseline CT angiography, treatment times and specifics, and outcomes were compared between the first 4 protocols and the fifth and final protocol. RESULTS: Compared with subjects treated in the first 4 protocol versions (n=610), subjects treated in fifth and final protocol (n=46) were older (75 versus 68 years, P<0.0002) and less likely to have a pretreatment Rankin of 0 (76% versus 89%, P=0.01), were more likely to have a pretreatment CT angiography (65% versus 45%, P=0.009), had quicker median times in the endovascular arm from onset to start of intra-arterial therapy (209 versus 250 minutes, P=0.002) and to reperfusion (269 versus 344 minutes, P<0.0001), had a higher mean dose of total tissue-type plasminogen activator in the endovascular arm (74.0 versus 63.7 mg, P<0.0001), and were less likely to receive intra-arterial tissue-type plasminogen activator as part of the endovascular procedure (16% versus 44%, P=0.015). There were no significant differences in functional and safety outcomes between subjects treated in the 2 treatments arms in either the first 4 protocols or fifth protocol although the small sample size in the fifth protocol provided limited power. CONCLUSIONS: Endovascular technology and diagnostic approaches to acute stroke patients changed substantially during the IMS III Trial. Efforts to decrease the time to delivery of endovascular therapy were successful.

Recanalization and clinical outcome of occlusion sites at baseline CT angiography in the Interventional Management of Stroke III trial.

PURPOSE: To use baseline computed tomographic (CT) angiography to analyze imaging and clinical end points in an Interventional Management of Stroke III cohort to identify patients who would benefit from endovascular stroke therapy. MATERIALS AND METHODS: The primary clinical end point was 90-day dichotomized modified Rankin Scale (mRS) score. Secondary end points were 90-day mRS score distribution and 24-hour recanalization. Prespecified subgroup was baseline proximal occlusions (internal carotid, M1, or basilar arteries). Exploratory analyses were subsets with any occlusion and specific sites of occlusion (two-sided α = .01). RESULTS: Of 656 subjects, 306 (47%) underwent baseline CT angiography or magnetic resonance angiography. Of 306, 282 (92%) had arterial occlusions. At baseline CT angiography, proximal occlusions (n = 220) demonstrated no difference in primary outcome (41.3% [62 of 150] endovascular vs 38% [27 of 70] intravenous [IV] tissue-plasminogen activator [tPA]; relative risk, 1.07 [99% confidence interval: 0.67, 1.70]; P = .70); however, 24-hour recanalization rate was higher for endovascular treatment (n = 167; 84.3% [97 of 115] endovascular vs 56% [29 of 52] IV tPA; P < .001). Exploratory subgroup analysis for any occlusion at baseline CT angiography did not demonstrate significant differences between endovascular and IV tPA arms for primary outcome (44.7% [85 of 190] vs 38% [35 of 92], P = .29), although ordinal shift analysis of full mRS distribution demonstrated a trend toward more favorable outcome (P = .011). Carotid T- or L-type occlusion (terminal internal carotid artery [ICA] with M1 middle cerebral artery and/or A1 anterior cerebral artery involvement) or tandem (extracranial or intracranial) ICA and M1 occlusion subgroup also showed a trend favoring endovascular treatment over IV tPA alone for primary outcome (26% [12 of 46] vs 4% [one of 23], P = .047). CONCLUSION: Significant differences were identified between treatment arms for 24-hour recanalization in proximal occlusions; carotid T- or L-type and tandem ICA and M1 occlusions showed greater recanalization and a trend toward better outcome with endovascular treatment. Vascular imaging should be mandated in future endovascular trials to identify such occlusions. Online supplemental material is available for this article.

Is intra-arterial thrombolysis beneficial for M2 occlusions? Subgroup analysis of the PROACT-II trial.

BACKGROUND AND PURPOSE: The role of endovascular therapy for acute M2 trunk occlusions is debatable. Through a subgroup analysis of Prolyse in Acute Cerebral Thromboembolism-II, we compared outcomes of M2 occlusions in treatment and control arms. METHODS: Solitary M2 occlusions were identified from the Prolyse in Acute Cerebral Thromboembolism-II database. Primary endpoints were successful angiographic reperfusion (TICI 2-3) at 120 minutes and functional independence (mRS 0-2) at 90 days. RESULTS: Forty-four patients with solitary M2 occlusions, 30 in the treatment arm and 14 in the control arm, were identified. Successful reperfusion (TICI 2-3) was achieved in 53.6% and 16.7% of patients in the treatment and control arms, respectively (P=0.04). A favorable clinical outcome (mRS 0-2) was observed in 53.3% and 28.6%, respectively (P=0.19). Baseline characteristics were similar between the 2 groups. CONCLUSIONS: Intra-arterial thrombolysis may lead to a 3-fold increase in the rate of early reperfusion of solitary M2 occlusions and could potentially double the chance of a favorable functional outcome at 90 days. Clinical Trial Registration- This trial was not registered because enrollment began before July 1, 2005.

Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial.

BACKGROUND AND PURPOSE: In a previous study, 0.3 and 0.45 mg/kg of intravenous recombinant tissue plasminogen activator (rt-PA) were safe when combined with eptifibatide 75 mcg/kg bolus and a 2-hour infusion (0.75 mcg/kg per minute). The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial sought to determine the safety of a higher-dose regimen and to establish evidence for a phase III trial. METHODS: CLEAR-ER was a multicenter, double-blind, randomized safety study. Ischemic stroke patients were randomized to 0.6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and a 2-hour infusion at 0.75 mcg/kg per minute) versus standard rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy outcome measure was the modified Rankin Scale (mRS) score ≤1 or return to baseline mRS at 90 days. Analysis of the safety and efficacy outcomes was done with multiple logistic regression. RESULTS: Of 126 subjects, 101 received combination therapy, and 25 received standard rt-PA. Two (2%) patients in the combination group and 3 (12%) in the standard group had symptomatic intracranial hemorrhage (odds ratio, 0.15; 95% confidence interval, 0.01-1.40; P=0.053). At 90 days, 49.5% of the combination group had mRS ≤1 or return to baseline mRS versus 36.0% in the standard group (odds ratio, 1.74; 95% confidence interval, 0.70-4.31; P=0.23). After adjusting for age, baseline National Institutes of Health Stroke Scale, time to intravenous rt-PA, and baseline mRS, the odds ratio was 1.38 (95% confidence interval, 0.51-3.76; P=0.52). CONCLUSIONS: The combined regimen of intravenous rt-PA and eptifibatide studied in this trial was safe and provides evidence that a phase III trial is warranted to determine efficacy of the regimen. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00894803.

Intra-arterial iodinated radiographic contrast material injection administration in a rat middle cerebral artery occlusion and reperfusion model: possible effects on intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Observations in human interventional stroke treatment led us to hypothesize that iodinated radiographic contrast material use may contribute to intracerebral hemorrhage. Effects of intra-arterial iodinated radiographic contrast material on hemorrhagic transformation after middle cerebral artery occlusion and reperfusion were studied in a placebo-controlled, blinded preclinical study in rats. METHODS: Four groups of male Sprague-Dawley rats were studied: saline group (n=8), contrast group (n=12), heparin group (n=9), and contrast+heparin group (n=9). The middle cerebral artery was occluded for 5 hours using suture placement. Heparin was infused before suture removal and reperfusion. Saline and/or contrast were infused immediately during reperfusion. Incidence, location, and size of hemorrhage were determined by brain necropsy inspection at 24 hours. RESULTS: There was a significant increase in incidence of cortical hemorrhage from control (37.5%), contrast (75.0%), heparin (77.8%) to contrast+heparin (100%; Cochran-Mantel-Haenszel correlation, P<0.01). Both pooled contrast groups (85.7%) and pooled heparin groups (88.9%) had higher rates of cortical intracerebral hemorrhage compared with the control group (P<0.05). Similar trends for increased cortical intracerebral hemorrhage were seen in the contrast-only (P=0.18) and heparin-only (P=0.18) groups. There was a trend for decreased infarct edema in rats receiving contrast versus those without (P=0.06). CONCLUSIONS: Intraarterial iodinated radiographic contrast material may increase cortical intracerebral hemorrhage, similar to heparin. Iodinated radiographic contrast material effect may be additive to heparin effect on the incidence of cortical intracerebral hemorrhage.

Performance and training standards for endovascular ischemic stroke treatment.

Stroke is the third-leading cause of death in the United States, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, 750,000 new strokes occur each year, resulting in 200,000 deaths (or 1 of every 16 deaths) per year in the United States alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intra-arterial (IA) thrombolysis in selected patients. IA thrombolysis has been studied in 2 randomized trials and numerous case series. Although 2 devices have been granted FDA 3 approval with an indication for mechanical stroke thrombectomy, none of these devices has demonstrated efficacy in improving patient outcomes. This report defines what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and identifies the performance standards that should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies that historically have been directly involved in the medical, surgical, and endovascular care of patients with acute stroke, including the Neurovascular Coalition and its participating societies: the Society of NeuroInterventional Surgery; American Academy of Neurology; American Association of Neurological Surgeons, Cerebrovascular Section; and Society of Vascular & Interventional Neurology.

Microcatheter contrast injections during intra-arterial thrombolysis may increase intracranial hemorrhage risk.

BACKGROUND AND PURPOSE: During intra-arterial revascularization, either guide catheter injections of contrast in the neck or microcatheter contrast injections (MCIs) at or beyond the site of an occlusion, can be used to visualize intracranial vasculature. Neurointerventionalists vary widely in their use of MCIs for a given circumstance. We tested the hypothesis that MCIs are a risk factor for intracranial hemorrhage (ICH) in the Interventional Management of Stroke (IMS) I and II trials of combined intravenous/IA recombinant tissue plasminogen activator therapy. METHODS: All arteriograms with M1, M2, and ICA terminus occlusions were reanalyzed (n=98). The number of MCIs within or distal to the target occlusion was assigned. Postprocedure CTs were reviewed for contrast extravasation and ICH. Contrast extravasation was defined as a hyperdensity suggestive of contrast (Hounsfield unit >90) seen at 24 hours or present before 24 hours and persisting or replaced by ICH at 24 hours. RESULTS: In this IMS subset, the rate of any ICH was 58% (57 of 98). More MCIs were seen in the ICH group (median=2 versus 1; P=0.04). Increased MCIs were associated with higher ICH rates (P=0.03). MCIs remained associated with ICH in multivariable analysis (P=0.01) as did baseline CT edema/mass effect, atrial fibrillation, time to intravenous recombinant tissue plasminogen activator initiation, and Thrombolysis in Cerebral Infarction reperfusion score. MCIs were also associated with contrast extravasation in unadjusted and adjusted analyses. CONCLUSIONS: MCIs may risk ICH in the setting of combined intravenous/intra-arterial recombinant tissue plasminogen activator therapy, possibly due to contrast toxicity or pressure transmission by injections. MCIs should be minimized whenever possible. These findings will be tested prospectively in the IMS III trial.