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Background: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 μg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. Methods: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. Results: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2–2.6). Median time from baseline CT to study drug was 62.5 (55–80) minutes, and from study drug to early post-dose CT was 19 (14.5–30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (−0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8–8.3) in the placebo arm ( P =0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (−2.6 to 8.3) in the rFVIIa arm and 0.7 mL (−1.6 to 2.1) in the placebo arm ( P =0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71–1.43]; P =0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994–1.003]; P =0.50; Table 3). Conclusions: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01359202.

Background and Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0–3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2–3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0–1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0–2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72–20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21–5.51]). Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.

Background and Purpose— Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods— Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4–6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results— Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8–54.7) and 82.9% (95% CI, 75.3–88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8–72.1) and specificity of 75.2% (95% CI, 66.8–82.4). Overall accuracy was significantly improved with the revised definition ( P =0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31–4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6–65.5]; specificity, 78.3% [95% CI, 40.2–85.1]; aOR, 2.40 [95% CI, 1.23–4.69]). Conclusions— In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.

Background and Purpose— Patients with intracerebral hemorrhage (ICH) are often subject to rapid deterioration due to hematoma expansion. Current prognostic scores are largely based on the assessment of baseline radiographic characteristics and do not account for subsequent changes. We propose that calculation of prognostic scores using delayed imaging will have better predictive values for long-term mortality compared with baseline assessments. Methods— We analyzed prospectively collected data from the multicenter PREDICT study (Prediction of Hematoma Growth and Outcome in Patients With Intracerebral Hemorrhage Using the CT-Angiography Spot Sign). We calculated the ICH Score, Functional Outcome in Patients With Primary Intracerebral Hemorrhage (FUNC) Score, and modified ICH Score using imaging data at initial presentation and at 24 hours. The primary outcome was mortality at 90 days. We generated receiver operating characteristic curves for all 3 scores, both at baseline and at 24 hours, and assessed predictive accuracy for 90-day mortality with their respective area under the curve. Competing curves were assessed with nonparametric methods. Results— The analysis included 280 patients, with a 90-day mortality rate of 25.4%. All 3 prognostic scores calculated using 24-hour imaging were more predictive of mortality as compared with baseline: the area under the curve was 0.82 at 24 hours (95% CI, 0.76–0.87) compared with 0.78 at baseline (95% CI, 0.72–0.84) for ICH Score, 0.84 at 24 hours (95% CI, 0.79–0.89) compared with 0.76 at baseline (95% CI, 0.70–0.83) for FUNC, and 0.82 at 24 hours (95% CI, 0.76–0.88) compared with 0.74 at baseline (95% CI, 0.67–0.81) for modified ICH Score. Conclusions— Calculation of the ICH Score, FUNC Score, and modified ICH Score using 24-hour imaging demonstrated better prognostic value in predicting 90-day mortality compared with those calculated at presentation.

The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign. We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression. A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01–1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57–0.71). Youden’s method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09–3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61–5.42) were similar to HEP scores ≥ 4. The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

To compare the association of different measures of intracranial thrombus permeability on non-contrast computerized tomography (NCCT) and computed tomography angiography (CTA) with recanalization with or without intravenous alteplase.Patients with anterior circulation occlusion from the INTERRSeCT study were included. Thrombus permeability was measured on non-contrast CT and CTA using the following methods: [1] automated method, mean attenuation increase on co-registered thin (2.5 mm) CTA/NCCT; [2] semi-automated method, maximum attenuation increase on non-registered CTA/NCCT (ΔHUmax); [3] manual method, maximum attenuation on CTA (HUmax); and [4] visual method, residual flow grade. Primary outcome was recanalization with intravenous alteplase on the revised AOL scale (2b/3). Regression models were compared using C-statistic, Akaike (AIC), and Bayesian information criterion (BIC).Four hundred eighty patients were included in this analysis. Statistical models using methods 2, 3, and 4 were similar in their ability to discriminate recanalizers from non-recanalizers (C-statistic 0.667, 0.683, and 0.634, respectively); method 3 had the least information loss (AIC = 483.8; BIC = 492.2). A HUSimple methods that measure thrombus permeability are as reliable as complex image processing methods in discriminating recanalizers from non-recanalizers.

The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack. The recommendations are intended for use by a interdisciplinary team of clinicians across a wide range of settings and highlight key elements involved in prehospital and Emergency Department care, acute treatments for ischemic stroke, and acute inpatient care. The most notable changes included in this 6th edition are the renaming of the module and its integration of the formerly separate modules on prehospital and emergency care and acute inpatient stroke care. The new module, Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care is now a single, comprehensive module addressing the most important aspects of acute stroke care delivery. Other notable changes include the removal of two sections related to the emergency management of intracerebral hemorrhage and subarachnoid hemorrhage. These topics are covered in a new, dedicated module, to be released later this year. The most significant recommendation updates are for neuroimaging; the extension of the time window for endovascular thrombectomy treatment out to 24 h; considerations for treating a highly selected group of people with stroke of unknown time of onset; and recommendations for dual antiplatelet therapy for a limited duration after acute minor ischemic stroke and transient ischemic attack. This module also emphasizes the need for increased public and healthcare provider’s recognition of the signs of stroke and immediate actions to take; the important expanding role of paramedics and all emergency medical services personnel; arriving at a stroke-enabled Emergency Department without delay; and launching local healthcare institution code stroke protocols. Revisions have also been made to the recommendations for the triage and assessment of risk of recurrent stroke after transient ischemic attack/minor stroke and suggested urgency levels for investigations and initiation of management strategies. The goal of this updated guideline is to optimize stroke care across Canada, by reducing practice variations and reducing the gap between current knowledge and clinical practice.

Background and Purpose— Previous studies reported Fabry disease in 0% to 4% of young patients with cryptogenic ischemic stroke (IS). We sought to determine the prevalence of Fabry and outcomes among young Canadians with cryptogenic IS or transient ischemic attack (TIA). Methods— We prospectively enrolled individuals aged 18 to 55 with IS or speech or motor TIA, and no cause identified despite predetermined investigation. α-galactosidase-A gene was sequenced for Fabry diagnosis. National Institutes of Health Stroke Scale score was measured at presentation to quantify stroke severity. Modified Rankin Scale determined functional outcomes ≤7 days after presentation and 6 months later. Results— We enrolled 365 patients with IS and 32 with TIA. α-galactosidase-A sequencing identified a single carrier of a genetic variant of unknown significance (p.R118C) and no well-recognized pathogenic variants. Mean National Institutes of Health Stroke Scale score was 3.1. Proportion of patients with modified Rankin Scale of 0 to 2 was 70.7% at ≤7 days and 87.4% at 6 months. National Institutes of Health Stroke Scale score at presentation and diabetes mellitus predicted 6-month modified Rankin Scale. Thirteen patients experienced 5 recurrent IS and 9 TIA during follow-up. No patient died. Most patients (98.7%) returned home. Among previous workers, 43% had residual working limitations. Conclusions— In this Canadian cohort of patients with cryptogenic IS or TIA, the prevalence of Fabry was 0.3% if p.R118C variant is considered as pathogenic. This suggests that more cost-effective methods should be applied for diagnosis of Fabry rather than systematic genetic screening in this population. Overall, cryptogenic IS in young adults is associated with favorable outcomes.

Background and Purpose— The computed tomographic angiography spot sign as a predictor of hematoma expansion is limited by its modest sensitivity and positive predictive value. It is possible that hematoma expansion in spot-positive patients is missed because of decompression of intracerebral hemorrhage (ICH) into the ventricular space. We hypothesized that revising hematoma expansion definitions to include intraventricular hemorrhage (IVH) expansion will improve the predictive performance of the spot sign. Our objectives were to determine the proportion of ICH nonexpanders who actually have IVH expansion, determine the proportion of false-positive spot signs that have IVH expansion, and compare the known predictive performance of the spot sign to a revised definition incorporating IVH expansion. Methods— We analyzed patients from the multicenter PREDICT ICH spot sign study. We defined hematoma expansion as ≥6 mL or ≥33% ICH expansion or >2 mL IVH expansion and compared spot sign performance using this revised definition with the conventional 6 mL/33% definition using receiver operating curve analysis. Results— Of 311 patients, 213 did not meet the 6-mL/33% expansion definition (nonexpanders). Only 13 of 213 (6.1%) nonexpanders had ≥2 mL IVH expansion. Of the false-positive spot signs, 4 of 40 (10%) had >2 mL ventricular expansion. The area under the curve for spot sign to predict significant ICH expansion was 0.65 (95% confidence interval, 0.58–0.72), which was no different than when IVH expansion was added to the definition (area under the curve, 0.66; 95% confidence interval, 0.58–0.71). Conclusions— Although IVH expansion does indeed occur in a minority of ICH nonexpanders, its inclusion into a revised hematoma expansion definition does not alter the predictive performance of the spot sign.

The computed tomography angiography (CTA) spot sign is widely used to assess the risk of hematoma expansion following acute intracerebral hemorrhage (ICH). However, not all patients can receive intravenous contrast nor are all hospital systems equipped with this technology. We aimed to independently validate the Hematoma Expansion Prediction (HEP) Score, an 18-point non-contrast prediction scale, in an external cohort and compare its diagnostic capability to the CTA spot sign.We performed a retrospective analysis of the predicting hematoma growth and outcome in intracerebral hemorrhage using contrast bolus CT (PREDICT) Cohort Study. Primary outcome was significant hematoma expansion (≥ 6 mL or ≥ 33%). We generated a receiver operating characteristic (ROC) curve comparing the HEP score to significant expansion. We calculated sensitivity, specificity, positive and negative predictive values (PPV/NPV) for each score point. We determined independent predictors of significant hematoma expansion via logistic regression.A total of 292 patients were included in primary analysis. Hematoma growth of ≥ 6 mL or ≥ 33% occurred in 94 patients (32%). The HEP score was associated with significant expansion (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.01-1.30). ROC curves comparing HEP score to significant expansion had an area under the curve of 0.64 (95% CI 0.57-0.71). Youden's method showed an optimum score of 4. HEP Scores ≥ 4 (n = 100, sensitivity 49%, specificity 73%, PPV 46%, NPV 75%, aOR 1.99, 95% CI 1.09-3.64) accurately predicted significant expansion. PPV increased with higher HEP scores, but at the cost of lower sensitivity. The diagnostic characteristics of the spot sign (n = 82, Sensitivity 49%, Specificity 81%, PPV 55%, NPV 76%, aOR 2.95, 95% CI 1.61-5.42) were similar to HEP scores ≥ 4.The HEP score is predictive of significant expansion (≥ 6 mL or ≥ 33%) and is comparable to the spot sign in diagnostic accuracy. Non-contrast prediction tools may have a potential role in the recruitment of patients in future intracerebral hemorrhage trials.

Introduction: There is interest in understanding thrombus dynamics from IV TPA prior to endovascular thrombectomy (EVT) given the possible dichotomy amongst sites of occlusion for IV TPA benefit/harm. Kaesmacher et al reported beneficial 5+% rates of early TICI > 2a reperfusion in distal M1 or M2 MCA occlusions with IV TPA. However in more proximal occlusions this was rare; and potentially harmful worsening of perfusion seen with change of occlusion site. We aimed to examine IV TPA related thrombus dynamics including migration further across both proximal and distal occlusions in a multicenter prospective cohort study INTERRSeCT. Methods: Acute ischemic stroke patients with intracranial occlusion who had baseline CTA and follow-up CTA or initial run angio in INTERRSeCT and IV TPA were reviewed. We evaluated change of occlusion site (COS) and classified patients into 4 categories: Complete Recanalization (CR) of primary occlusive lesion with no remaining thrombus; definite Thrombus Migration (dTM) with primary occlusion site moved to a distal artery and occlusion site patent on baseline CTA; probable Thrombus Migration (pTM) with COS evident but initial occlusion extent not visualized; or No Change of occlusion site (NC). Results: A total of 462 IV TPA patients were enrolled, 41% received EVT. Median time from TPA to follow-up imaging was 133 minutes. COS was seen in 50% of cases with CR in 15% and TM in 35% (dTM 12%, pTM 23%). Distal artery occlusion and longer interval of TPA to imaging were independent predictors for COS. In 62 proximal occlusion (ICA and proximal-mid M1 MCA) patients with follow-up imaging within 60 mins after TPA (receiving EVT in 94%), any TM showed a lower rate of 90-day mRS≤2 than NC (47% vs 78%, adjusted OR 0.21, 95%CI 0.04-0.87). No CR was seen in this early group. Conclusions: Thrombus migration is common after IV TPA. Thrombus instability from IV TPA may worsen clinical outcome in proximal occlusions despite early EVT initiation, possibly due to migration of thrombus to distal arteries accelerating infarction or more challenging thrombectomy due to thrombus dispersion. The benefit of IV TPA prior to EVT at comprehensive stroke centers for ICA or prox-mid M1 occlusions require more study in randomized clinical trials.

ObjectiveTo describe the relationship between intraventricular hemorrhage (IVH) expansion and long-term outcome and to use this relationship to select and validate clinically relevant thresholds of IVH expansion in 2 separate intracerebral hemorrhage (ICH) populations.MethodsWe used fractional polynomial analysis to test linear and nonlinear models of 24-hour IVH volume change and clinical outcome with data from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT)-ICH study. The primary outcome was poor clinical outcome (modified Rankin Scale [mRS] score 4–6) at 90 days. We derived dichotomous thresholds from the selected model and calculated diagnostic accuracy measures. We validated all thresholds in an independent single-center ICH cohort (Massachusetts General Hospital).ResultsOf the 256 patients from PREDICT, 127 (49.6%) had an mRS score of 4 to 6. Twenty-four–hour IVH volume change and poor outcome fit a nonlinear relationship, in which minimal increases in IVH were associated with a high probability of an mRS score of 4 to 6. IVH expansion ≥1 mL (n = 53, sensitivity 33%, specificity 92%, adjusted odds ratio [aOR] 2.68, 95% confidence interval [CI] 1.11–6.46) and development of any new IVH (n = 74, sensitivity 43%, specificity 85%, aOR 2.53, 95% CI 1.22–5.26) strongly predicted poor outcome at 90 days. The dichotomous thresholds reproduced well in a validation cohort of 169 patients.ConclusionIVH expansion as small as 1 mL or any new IVH is strongly predictive of poor outcome. These findings may assist clinicians with bedside prognostication and could be incorporated into definitions of hematoma expansion to inform future ICH treatment trials.

Objective: To determine the association of ultraearly hematoma growth (uHG) with the CT angiography (CTA) spot sign, hematoma expansion, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: We analyzed data from 231 patients enrolled in the multicenter Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT study. uHG was defined as baseline ICH volume/onset-to-CT time (mL/h). The spot sign was used as marker of active hemorrhage. Outcome parameters included significant hematoma expansion (>33% or >6 mL, primary outcome), rate of hematoma expansion, early neurologic deterioration, 90-day mortality, and poor outcome. Results: uHG was higher in spot sign patients ( p p 4.7 mL/h ( p = 0.002) and the CTA spot sign ( p = 0.030) showed effects on rate of hematoma expansion but not its interaction (2-way analysis of variance, p = 0.477). uHG >4.7 mL/h improved the sensitivity of the spot sign in the prediction of significant hematoma expansion (73.9% vs 46.4%), early neurologic deterioration (67.6% vs 35.3%), 90-day mortality (81.6% vs 44.9%), and poor outcome (72.8% vs 29.8%), respectively. uHG was independently related to significant hematoma expansion (odds ratio 1.06, 95% confidence interval 1.03–1.10) and clinical outcomes. Conclusions: uHG is a useful predictor of hematoma expansion and poor clinical outcomes in patients with acute ICH. The combination of high uHG and the spot sign is associated with a higher rate of hematoma expansion, highlighting the need for very fast treatment in ICH patients.

Background Hematoma expansion is a major predictor of morbidity and mortality after intracerebral hemorrhage (ICH). Both baseline hematoma volume and the CT-angiogram (CTA) spot sign predict hematoma expansion. Because the CTA spot sign may represent foci of active hemorrhage, we hypothesized that patients with smaller baseline hematoma volumes are less likely to be spot sign positive, and therefore less likely to expand. Aim We sought to validate our prior finding that small hematomas are unlikely to expand, and to determine the relationship between baseline hematoma volume, spot sign status, and risk of hematoma expansion. Methods Data were from the prospective PREDICT ICH study. Patients presenting within 6 h of symptom onset with completed baseline CT, CTA, and follow-up CT were included. Baseline hematoma volume was categorized a priori (20 mL). The primary outcome was significant hematoma expansion (≥6 mL, ≥12.5 mL or ≥33%) and secondary outcomes were early neurological worsening, good clinical outcome (modified Rankin Scale 0–3), and mortality at 90 days. Results Among 315 patients meeting the inclusion criteria, baseline hematoma volume category predicted absolute hematoma expansion ( p Conclusion Very small hematomas are unlikely to expand and have a low spot sign prevalence. Hemostatic therapy trials may be best targeted at hemorrhages >3 mL in volume.

Background and Purpose— Nine- and 24-point prediction scores have recently been published to predict hematoma expansion (HE) in acute intracerebral hemorrhage. We sought to validate these scores and perform an independent analysis of HE predictors. Methods— We retrospectively studied 301 primary or anticoagulation-associated intracerebral hemorrhage patients presenting Results— The 9- and 24-point HE scores demonstrated acceptable discrimination for HE>6 mL or 33% and >6 mL, respectively (area under the curve of 0.706 and 0.755, respectively). The 24-point score demonstrated appropriate calibration in the PREDICT cohort (χ 2 statistic, 11.5; P =0.175), whereas the 9-point score demonstrated poor calibration (χ 2 statistic, 34.3; P 1.5, Glasgow Coma Scale, and National Institutes of Health Stroke Scale and were included in PREDICT A/B scores. PREDICT A showed improved discrimination compared with both existing scores, whereas performance of PREDICT B varied by definition of expansion. Conclusions— The 9- and 24-point expansion scores demonstrate acceptable discrimination in an independent multicenter cohort; however, calibration was suboptimal for the 9-point score. The PREDICT A score showed improved discrimination for HE prediction but requires independent validation.

Importance Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design. Objective To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase. Design, Setting, and Participants Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA). Exposures Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA. Main Outcomes and Measures Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]). Results Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]). Conclusions and Relevance In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.

Importance Early treatment of patients with transient ischemic attack (TIA) reduces the risk of stroke. However, many patients present with symptoms that have an uncertain diagnosis. Patients with motor, speech, or prolonged symptoms are at the highest risk for recurrent stroke and the most likely to undergo comprehensive investigations. Lower-risk patients are much more likely to be cursorily investigated. Objective To establish the frequency of acute infarct defined by diffusion restriction detected on diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) scan (DWI positive). Design, Setting, and Participants The Diagnosis of Uncertain-Origin Benign Transient Neurological Symptoms (DOUBT) study was a prospective, observational, international, multicenter cohort study of 1028 patients with low-risk transient or minor symptoms referred to neurology within 8 days of symptom onset. Patients were enrolled between June 1, 2010, and October 31, 2016. Included patients were 40 years or older and had experienced nonmotor or nonspeech minor focal neurologic events of any duration or motor or speech symptoms of short duration (≤5 minutes), with no previous stroke. Exposures Patients underwent a detailed neurologic assessment prior to undergoing a brain MRI within 8 days of symptom onset. Main Outcomes and Measures The primary outcome was restricted diffusion on a brain MRI scan (acute stroke). Results A total of 1028 patients (522 women and 506 men; mean [SD] age, 63.0 [11.6] years) were enrolled. A total of 139 patients (13.5%) had an acute stroke as defined by diffusion restriction detected on MRI scans (DWI positive). The final diagnosis was revised in 308 patients (30.0%) after undergoing brain MRI. There were 7 (0.7%) recurrent strokes at 1 year. A DWI-positive brain MRI scan was associated with an increased risk of recurrent stroke (relative risk, 6.4; 95% CI, 2.4-16.8) at 1 year. Absence of a DWI-positive lesion on a brain MRI scan had a 99.8% negative predictive value for recurrent stroke. Factors associated with MRI evidence of stroke in multivariable modeling were older age (odds ratio [OR], 1.02; 95% CI, 1.00-1.04), male sex (OR, 2.03; 95% CI, 1.39-2.96), motor or speech symptoms (OR, 2.12; 95% CI, 1.37-3.29), ongoing symptoms at assessment (OR, 1.97; 95% CI, 1.29-3.02), no prior identical symptomatic event (OR, 1.87; 95% CI, 1.12-3.11), and abnormal results of initial neurologic examination (OR, 1.71; 95% CI, 1.11-2.65). Conclusions and Relevance This study suggested that patients with transient ischemic attack and symptoms traditionally considered low risk carry a substantive risk of acute stroke as defined by diffusion restriction (DWI positive) on a brain MRI scan. Early MRI is required to make a definitive diagnosis.

Background Patients with proximal arterial M2-segment of the Middle Cerebral Artery (M2-MCA) occlusions were largely excluded from endovascular stroke trials. Current American Stroke guidelines are conservative in recommending thrombectomy for such patients. We sought to assess the natural history of medically- treated M2-MCA occlusion patients. Methods This is a prospective multi-central international cohort study of all acute ischemic stroke patients with intracranial occlusions on baseline imaging. Patients with M2-MCA occlusions were identified on baseline CT angiography and non-endovascular-treated patients were included. The M2-MCA segment was defined as the first-order branch of the proximal MCA, excluding the anterior temporal artery. The M2-MCA was further classified according to its visually-assessed diameter relative to the M1-MCA into: M1-equivalent (>90% of the diameter of the M1-MCA), Major (50%–90%), Minor ( Results Out of 575 patients in the entire study, there were a total of 184 M2-MCA occlusions seen. Of those, 104 patients were NOT treated with endovascular therapy: 90 patients (86.5%) received IV TPA and 14 (23.5%) patients conservative management. Among those, 23.1% (24/104) M1-equivalent, 66.4% (69/104) major, and 9.6% (10/104) minor M2-MCA. The median age was 76 years (interquartile range 19 years). The median (IQR) baseline NIHSS score of the cohort was 9 (9): M1-equivalent 12(10), major 9 (9), minor 7 (8). The median baseline ASPECTS was 9 overall and in all M2 groups. Successful recanalization was observed in 44.2% (46/104) of the medical M2 occlusion cohort overall. TPA group was 47.8% (43/90) and conservative group 21.4% (3/14). With IV TPA successful recanalization occurred in 30% (6/20) of M1-equivalent, 50% (31/62) of major, and 75% (6/8) of minor M2-MCA occlusions. In conservative management group successful recanalization occurred in 25% (1/4) of M1-equivalent, 14.3% (1/7) of major, and 50% (1/2) of minor M2-MCA occlusions. Good functional outcome (mRS 0–2) at 90 day was observed in 62.1% (64/104) of the cohort overall. Among those with successful recanalization, 76.1% (35/46) achieved good outcome. With IV TPA, the proportion of patients achieving independent functional outcome was 45% (9/20) with M1-equivalent, 70.5% (43/61) of major, and 62.5% (5/8) of minor M2-MCA occlusions. In the conservative management group, the proportion of patients achieving independent functional outcome at 90 day was 25% (1/4) with M1-equivalent, 71.4% (5/7) of major, and 50% (1/2) of minor M2-MCA occlusions. In logistic regression analyses, successful recanalization predicted independent functional outcome (OR 2.9, 95% CI 1.02 to 8.1, p 0.046). Age (OR 0.89, 95% CI 0.84 to 0.94, p Conclusion While over one half of medically-treated patients with M2-MCA segment occlusions achieve independent outcome, a subset of patients suffers poor functional outcomes at 90 days. Successful recanalization are associated with higher odds of independent functional outcome. Disclosures B. Menon: None. M. Najm: None. F. Al-Ajlan: None. M. Almekhlafi: None. J. Puig: None. M. Castellanos: None. D. Dowlatshahi: None. A. Calleja: None. S. Sohn: None. S. Ahn: None. A. Poppe: None. R. Mikulik: None. N. Asdaghi: None. T. Field: None. A. Jin: None. T. Asil:None. J. Boulanger: None. E. Smith: None. S. Coutts: None. P. Barber: None. S. Bal: None. S. Subramanian: None. S. Mishra: None. A. Trivedi: None. S. Dey: None. M. Eesa: None. T. Sajobi: None. M. Goyal: None. M. Hill: None. A. Demchuk: None.

Introduction: Multiple studies have correlated larger final infarct volume (FIV) with worse clinical outcomes. In INTERRSeCT , an international multicenter prospective cohort study, we sought to determine the favorable intracranial clot characteristics predicting smaller infarct volumes. Methods: FIV was measured (24 ±12 hours after baseline imaging) in 605 patients from INTERRSeCT study by blinded readers using Quantomo (Cybertrial Inc, Calgary). Clot Burden Score (CBS) is a 10-point scale with 10 referring to a completely patent ipsilateral anterior circulation from ICA to both M2 arteries, whereas 0 refers to a completely occluded ipsilateral anterior circulation. Residual Flow Grade (RFG) assesses the radiological permeability of the clot to contrast, with grade 0, 1, and 2 defined as no contrast, diffuse ghosting, and hairline lumen, respectively. Both of these scores were assessed by a blinded reader to the FIV. Using ordinal logistic regression, FIV was divided into deciles as the outcome. CBS and RFG were analyzed from 0 to 10, and 0 to 2, respectively. Two models were used, the first has no recanalization status, while the second included it. Results: The median FIVs with and without recanalization were 12.34 ml (IQR: 32.3 ml) and 22.15 ml (IQR: 60.12ml), respectively. CBS and RFG were independently predictive of FIV (p-value= Conclusions: Residual flow grade and clot burden score are fast and practical techniques for practitioners treating acute ischemic stroke patients. Favorable RFG and CBS independently, predict lower infarct volumes regardless of whether recanalization achieved.

Background: While recent endovascular therapy trials have had a minimal number of adverse events, intracerebral hemorrhage (ICH) still occurs. The predictors of ICH with endovascular therapy remain unclear. We assessed predictors of hemorrhage following endovascular thrombectomy using data from the prospectively collected, multicenter INTERRSeCT study. Methods: Patients undergoing endovascular therapy +/- intravenous alteplase (tPA) were enrolled and received baseline CT/CTA, follow-up CTA/Angiogram and 24-hr CT or MRI images. Primary outcome was any ICH as per the ECASS classification of hemorrhage. Secondary outcome was PH1/PH2 hemorrhages. We assessed the relations between ICH and baseline ASPECTS scoring, thrombus location, residual flow, collateralization, tPA use, and final recanalization state. Multivariable regression with stepwise selection was used to adjust for relevant covariates. Results: Of 242 patients who met inclusion criteria, 58 (24%) had an ICH at 24 hours (HI1 53%, HI2 19%, PH1 7%, PH2 21%). Post-procedure hemorrhage was associated with lower ASPECTS scores (p Conclusion: Early ischemia defined by imaging, mid-M1 thrombus location, and increased serum glucose are associated with increased risk of hemorrhage in patients undergoing combination tPA and endovascular therapy.

Background and Aims: TIA and minor stroke offer a massive opportunity for stroke prevention. Patients with motor or speech symptoms have a higher risk of early recurrent stroke. Many patients with transient or mild neurological deficits do not have high-risk features (eg sensory symptoms). The aim of the DOUBT study was to assess what proportion of these lower risk patients have true brain ischemia and secondarily to establish whether clinically we can predict what clinical factors predict a higher risk of brain ischemia. Method: DOUBT was a multicentre, international, prospective, observational, cohort study assessing the diagnosis and prognosis of patients with lower risk focal neurological symptoms. Patients aged ≥ 40, with no previous stroke, with either very brief ( Results: 1047 patients in Canada, Europe and Australia were prospectively enrolled in the study. All patients had a detailed neurological assessment prior to undergoing MRI brain. Preliminary analysis shows 13% true brain schema rate (DWI positive). Patients were less likely to have a DWI lesion if their symptoms were fully resolved at assessment (RR 0.57, 95%CI: 0.38-0.79, p Conclusion: We found a low but real risk of true brain ischemia in these lower risk patients. Further analysis is needed to explain why woman are more likely to have DWI lesions with low risk symptoms. Detailed neurological assessment may help us stratify these patients further.

Objectives: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. Design: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). Validation: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). Setting: Neurocritical and ICUs. Patients: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. Interventions: None. Measurements and Main Results: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4–6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2–6, 3–6, 5–6, 6). We employed Youden’s J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four–hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden’s method showed an optimum cut point at –0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25–7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08–36.66]). All definitions reproduced well in the validation cohort. Conclusions: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials.

The 2015 update of the Canadian Stroke Best Practice Recommendations Hyperacute Stroke Care guideline highlights key elements involved in the initial assessment, stabilization, and treatment of patients with transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and acute venous sinus thrombosis. The most notable change in this 5th edition is the addition of new recommendations for the use of endovascular therapy for patients with acute ischemic stroke and proximal intracranial arterial occlusion. This includes an overview of the infrastructure and resources required for stroke centers that will provide endovascular therapy as well as regional structures needed to ensure that all patients with acute ischemic stroke that are eligible for endovascular therapy will be able to access this newly approved therapy; recommendations for hyperacute brain and enhanced vascular imaging using computed tomography angiography and computed tomography perfusion; patient selection criteria based on the five trials of endovascular therapy published in early 2015, and performance metric targets for important time-points involved in endovascular therapy, including computed tomography-to-groin puncture and computed tomography-to-reperfusion times. Other updates in this guideline include recommendations for improved time efficiencies for all aspects of hyperacute stroke care with a movement toward a new median target door-to-needle time of 30 min, with the 90th percentile being 60 min. A stronger emphasis is placed on increasing public awareness of stroke with the recent launch of the Heart and Stroke Foundation of Canada FAST signs of stroke campaign; reinforcing the public need to seek immediate medical attention by calling 911; further engagement of paramedics in the prehospital phase with prehospital notification to the receiving emergency department, as well as the stroke team, including neuroradiology; updates to the triage and same-day assessment of patients with transient ischemic attack; updates to blood pressure recommendations for the hyperacute phase of care for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The goal of these recommendations and supporting materials is to improve efficiencies and minimize the absolute time lapse between stroke symptom onset and reperfusion therapy, which in turn leads to better outcomes and potentially shorter recovery times.

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Background: Early Neurological Worsening (ENW) is common after ICH, and predicts poor outcome. However, there is limited data as to what degree of ENW best relates to outcome. We used two ICH cohorts to refine and validate a definition of ENW that best predicted 90-day outcomes. Methods: We generated receiver operating characteristic (ROC) curves for the association between 24-hour NIHSS change and ICH outcomes using data from the VISTA collaboration. Primary outcome was poor outcome at 90 days (mRS 4-6); secondary outcomes were other mRS cutpoints (mRS 2-6, 3-6, 5-6, 6). We tested the commonly used NIHSS≥4 definition and in addition employed Youden’s J Index to select optimal cutpoints and calculated sensitivity, specificity, and predictive values. Independent predictors of poor outcome were determined via multivariable logistic regression. Definitions were validated in the prospectively collected PREDICT-ICH cohort. Results: Using 552 patients from the VISTA cohort, ROC curves of 24hr NIHSS change had an area under the curve of 0.75. NIHSS change of ≥0 at 24hrs was seen in 46.4%. Youden’s method showed an optimum cutoff at -0.5. Based on this, ENW defined as >0 (Sens 43%, Spec 91%, PPV 83%, aOR 7.13 [CI:4.05-12.55]), ≥0 (Sens 65%, Spec 73%, PPV 70%, aOR 5.05 [CI:3.25-7.85]), or ≥-1 (Sens 78%, Spec 59%, PPV 65%, aOR 6.04 [CI:3.75-9.71]) all accurately predicted poor outcome. PPV increased with higher NIHSS cutoffs, but at the cost of lower sensitivities. Regression confirmed that all definitions independently predicted outcome at all mRS cutpoints. ENW definitions reproduced well in the validation cohort of 275 patients. Conclusion: All NIHSS cut-offs for ENW predict clinical outcome, regardless of outcome definition. In particular, lack of clinical improvement at 24 hours (i.e. NIHSS is the same or higher) robustly predicted poor outcome, but may not be sufficiently reliable to determine clinical management.

Introduction: Decisions to transport patients from primary to comprehensive stroke centre would be influenced by info on likelihood/timing of spontaneous or IV tPA recanalization (recan). We examined recan rates by time for a wide range of occlusion sites in the INTERRSeCT multicenter prospective cohort study. Methods: Acute stroke patients consented/enrolled at 12 centers/5 countries if intracranial occlusion present on baseline CTA; eGFR≥60 ml/min. CTA was repeated 2-6 hrs later for recan unless patient taken for EVT (first run of angio used instead). Primary outcome was successful recan (rAOL scale score 2b/3) interpreted by central core lab. Results: 619 patients enrolled, 81.6% received IV tPA. 59.9% recan by follow-up CTA and 40.1% by first run angio. Median baseline NIHSS 14 (IQR 11); mean age 70.1 yrs (SD 13); median onset to baseline CTA 115 mins (IQR 108). Recan assessment imaging median 162 mins (IQR 198) from IV tPA bolus or baseline CTA (if no IV tPA). Successful recan (rAOL 2b-3) rates comparing baseline to repeat imaging shown in Figure 1a (IV tPA red; no IV tPA blue). IV tPA had much higher recan than non-IV tPA group (30.5% vs 11%, p Conclusions: Early recan rates were low across all occlusion sites. Beyond 6 hrs post tPA, recan rates approached EVT levels except for ICA. Imaging factors such as residual flow may further refine transport/triage decisions.

Background and Purpose— Variability in computed tomography angiography (CTA) acquisitions may be one explanation for the modest accuracy of the spot sign for predicting intracerebral hemorrhage expansion detected in the multicenter Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study. This study aimed to determine the frequency of the spot sign in intracerebral hemorrhage and its relationship with hematoma expansion depending on the phase of image acquisition. Methods— PREDICT study was a prospective observational cohort study of patients with intracerebral hemorrhage presenting within 6 hours from onset. A post hoc analysis of the Hounsfield units of an artery and venous structure were measured on CTA source images of the entire PREDICT cohort in a core laboratory. Each CTA study was classified into arterial or venous phase and into 1 of 5 specific image acquisition phases. Significant hematoma expansion and total hematoma enlargement were recorded at 24 hours. Results— Overall (n=371), 77.9% of CTA were acquired in arterial phase. The spot sign, present in 29.9% of patients, was more frequently seen in venous phase as compared with arterial phase (39% versus 27.3%; P =0.041) and the later the phase of image acquisition ( P =0.095). Significant hematoma expansion ( P =0.253) and higher total hematoma enlargement ( P =0.019) were observed more frequently among spot sign–positive patients with earlier phases of image acquisition. Conclusions— Later image acquisition of CTA improves the frequency of spot sign detection. However, spot signs identified in earlier phases may be associated with greater absolute enlargement. A multiphase CTA including arterial and venous acquisitions could be optimal in patients with intracerebral hemorrhage.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2013. This year's update includes 2 new recommendations. First, among nonhypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise does not adversely influence blood pressure (BP) (Grade D). Thus, such patients need not avoid this type of exercise for fear of increasing BP. Second, and separately, for very elderly patients with isolated systolic hypertension (age 80 years or older), the target for systolic BP should be150 mm Hg (Grade C) rather than140 mm Hg as recommended for younger patients. We also discuss 2 additional topics at length (the pharmacological treatment of mild hypertension and the possibility of a diastolic J curve in hypertensive patients with coronary artery disease). In light of several methodological limitations, a recent systematic review of 4 trials in patients with stage 1 uncomplicated hypertension did not lead to changes in management recommendations. In addition, because of a lack of prospective randomized data assessing diastolic BP thresholds in patients with coronary artery disease and hypertension, no recommendation to set a selective diastolic cut point for such patients could be affirmed. However, both of these issues will be examined on an ongoing basis, in particular as new evidence emerges.

Background and Purpose— The spot sign score (SSS) provides risk stratification for hematoma expansion in acute intracerebral hemorrhage; however, external validation is needed. We sought to validate the SSS and assess prognostic performance of individual spot characteristics associated with hematoma expansion from a prospective multicenter intracerebral hemorrhage study. Methods— Two hundred twenty-eight intracerebral hemorrhage patients within 6 hours after ictus were enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study, a multicenter prospective intracerebral hemorrhage cohort study. Patients were evaluated with baseline noncontrast computerized tomography, computerized tomography angiography, and 24-hour follow-up computerized tomography. Primary outcome was significant hematoma expansion (>6 mL or >33%) and secondary outcome was absolute and relative expansion. Blinded computerized tomography angiography spot sign characterization and SSS calculation were independently performed by 2 neuroradiologists and a radiology resident. Diagnostic performance of the SSS and individual spot characteristics were examined with multivariable regression, receiver operating characteristic analysis, and tests for trend. Results— SSS and spot number independently predicted significant, absolute, and relative hematoma expansion ( P P trend=0.720) but was demonstrated for spot number ( P trend=0.050). Spot number and SSS demonstrated similar area under the curve (0.69 versus 0.68; P =0.306) for hematoma expansion. Conclusions— Multicenter external validation of the SSS demonstrates that the spot number alone provides similar prediction but improved risk stratification of hematoma expansion compared with the SSS.

Background:Stroke thrombolysis is limited by the “last-seen well” principle, which defines stroke onset time. A significant minority of stroke patients (~15%) awake with their symptoms and are by definition ineligible for thrombolysis because they were “last-seen well” at the time they went to bed implying an interval that is most often greater than three hours.Methods:A single-centre prospective, safety study was designed to thrombolyse 20 subjects with stroke-on-awakening. Patients were eligible for inclusion if they were last seen well less than 12 hours previously, specifically including those who awoke from sleep with their stroke deficits. They had a baseline computed tomogram (CT) scan with an ASPECTS score greater than 5, no evidence of well-evolved infarction and a CT angiogram / Trans-cranial Doppler ultrasound study demonstrating an intracranial arterial occlusion. Patients fulfilled all other standard criteria for stroke thrombolysis. The primary outcome was safety defined by symptomatic ICH or death.Results:Among 89 screened patients, 20 were treated with thrombolysis. Two patients (10%) died due to massive carotid territory stroke and two patients (10%) died of stroke complications. Two patients (10%) showed asymptomatic intracerebral hemorrhage (ICH) (petechial hemorrhage) and none symptomatic ICH. Reasons for exclusion were: (a) ASPECTS ≤ 5 (29); (b) well-evolved infarcts on CT (19); (c) historical mRS > 2 (17); (d) no demonstrable arterial occlusion or were too mild to warrant treatment (10).Conclusions:Patients who awake with their deficits can be safely treated with thrombolysis based upon a tissue window defined by NCCT and CTA/TCD.

Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a β-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2012. The new recommendations are: (1) use of home blood pressure monitoring to confirm a diagnosis of white coat syndrome; (2) mineralocorticoid receptor antagonists may be used in selected patients with hypertension and systolic heart failure; (3) a history of atrial fibrillation in patients with hypertension should not be a factor in deciding to prescribe an angiotensin-receptor blocker for the treatment of hypertension; and (4) the blood pressure target for patients with nondiabetic chronic kidney disease has now been changed to < 140/90 mm Hg from < 130/80 mm Hg. We also reviewed the recent evidence on blood pressure targets for patients with hypertension and diabetes and continue to recommend a blood pressure target of less than 130/80 mm Hg.

In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion.PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis.We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47–73) for the positive predictive value and 78% (71–84) for the negative predictive value, with 51% (39–63) sensitivity and 85% (78–90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002).These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH.Canadian Stroke Consortium and NovoNordisk Canada.

Contexte: Selon certaines etudes, il existerait une association entre l'hypocholesterolemie et l'hemorragie intracerebrale (HIC). Dans l'essai clinique SPARCL, l'utilisation d'une statine augmentait le risque d'HIC. Nous avons verifie l'hypothese selon laquelle l'utilisation de statines influence le volume de l'HIC spontanee et contribue a la progression du volume de l'HIC a la tomodensitometrie cerebrale initiale et de suivi. Methodes: Des cas consecutifs d'HIC spontanee ont ete revises. Les causes secondaires ont ete exclues. Nous avons mesure le volume de l'HIC a la tomodensitometrie initiale et a celle de suivi au moyen de la formule AxBxC/2. L'analyse multivariee et la regression logistique ont ete utilisees pour l'analyse des donnees. L'issue primaire etait le volume de l'HIC a la tomodensitometrie initiale. Les issues secondaires etaient la variation du volume entre la tomodensitometrie initiale et la premiere effectuee au cours du suivi et le deces. Resultats: Soixante et onze des 303 sujets prenaient une statine au moment de l'HIC (23%). Les sujets qui prenaient une statine avaient une plus forte probabilite d'etre plus jeunes, d'avoir des comorbidites et de prendre des anticoagulants ou des antiplaquettaires. Ils avaient egalement un volume initial d'HIC plus grand que ceux qui ne prenaient pas de statines (mediane 31,2 10,82,1] ml versus 16 [4, 43,8] ml ; p = 0,006). Apres ajustement pour les variables confondantes possibles, les statines demeuraient associees a un volume plus grand d'HIC (p = 0,007). Il y avait une progression significative du volume de l'HIC entre la premiere et la seconde tomodensitometrie chez les sujets qui prenaient une statine (+10,8 versus +0,9 ml; p = 0,03; IC a 95%: -1 a +22,6 et -2,5 a +4,3 respectivement). Nous n'avons pas observe de difference de mortalite entre les deux groupes. Conclusion: Le traitement par les inhibiteurs de l'HMG-CoA reductase pourrait constituer un facteur de risque d'un plus grand volume d'HIC dans les hemorragies cerebrales spontanees et pourrait contribuer a la progression du volume de l'hemorragie.

Background and Purpose— Microembolic signals (MES) found on transcranial Doppler range from harmless air bubbles to large, solid, particulate emboli from the heart and large vessels. The presence of MES is not always associated with poor clinical outcome. The purpose of our study was to determine whether the relative energy index of MES measured by power M-mode Doppler can distinguish malignant from benign MES and to identify patients with worse prognosis. Methods— We prospectively collected transcranial Doppler emboli monitoring data from patients with symptomatic carotid stenosis presenting with TIA or ischemic stroke. For each patient, we calculated the relative energy index of MES and categorized those >1.0 as malignant MES. We compared the clinical characteristics, number, and volume of diffusion-weighted imaging lesions, and degree of stenosis and plaque characteristics on CT angiogram of patients with malignant and benign MES. Results— We enrolled 92 patients, 29 with TIA and 63 with stroke, within 48 hours of symptom onset. Twenty-six patients had a total of 319 MES; of these, 82.4% were benign and were 17.6% malignant. Malignant MES traveled further within intracranial vessels than benign MES. The 9 patients with >1 malignant MES had significantly larger baseline diffusion-weighted imaging lesion volume, had a higher prevalence of intraluminal thrombus on CT angiogram of the neck and plaque ulceration, and were more likely to have a poor clinical outcome (modified Rankin Score ≥2) than those with benign MES (OR, 6.5; 95% CI, 1.47–28.68). The presence of malignant MES led to the institution of more aggressive secondary prevention measures. Conclusions— Power M-mode transcranial Doppler identifies a subgroup of patients with malignant MES. These signals are more frequent in longer arterial trajectory. Patients with malignant MES have larger baseline infarcts, a higher prevalence of intraluminal thrombus or ulcerated plaque in the carotid artery, and worse clinical outcome.

Introduction Abnormalities on acute magnetic resonance imaging predict outcome in minor stroke and transient ischaemic attack patients. We hypothesised that noncontrast computed tomography and computed tomography angiography findings in minor stroke and transient ischaemic attack patients would also predict functional outcome. Methods We analysed consecutive patients with a transient ischaemic attack or a minor stroke with an National Institute of Health Stroke Scale ≤3 who were assessed with a noncontrast computed tomography and CT angiography of the circle of Willis and neck within 24 h of symptom onset. We assessed the association between clinical or imaging features and functional impairment on the modified Rankin Scale (mRS≥2) at 90 days. Results Among 457 patients, the median baseline National Institute of Health Stroke Scale score was 1. Median time from symptom onset to noncontrast computed tomography was 278 min (interquartile range 151–505) and median delay from noncontrast computed tomography to CT angiography was 3 min (interquartile range 0–13). At 90 days, 57 patients (12·5%) had a mRS ≥2. Clinical factors that were associated with functional impairment were age ≥60 years (RR 2·05 CI95 1·16–3·64) and baseline National Institute of Health Stroke Scale score >0 (RR 3·23 1·72–6·06). All the assessed computed tomography parameters (acute stroke on noncontrast computed tomography and intracranial or extracranial stenosis or occlusion) were individually predictive of functional impairment. A composite computed tomography imaging ‘at risk’ metric, defined by acute stroke on noncontrast computed tomography, Circle of Willis intracranial vessel occlusion or ≥50% stenosis, extracranial occlusion or ≥50% stenosis, was associated with poorer outcome (RR 2·92 CI95 1·81–4·71). Conclusions The presence of an acute stroke on noncontrast computed tomography or an intracranial or extracranial occlusion or stenosis was associated with an increased risk of functional impairment. Multi-modal computed tomography could be used to identify high-risk transient ischaemic attack or minor stroke patients.

BACKGROUND AND PURPOSE Single gate transcranial Doppler spectrogram (sgTCD) has a high variability in the detection of microembolic signals (MES), Adding Power M-mode Doppler (PMD) information may improve MES detection. Our study's aim is to derive combined PMD/sgTCD microemboli criteria to overcome this limitation. METHODS Patients with symptomatic carotid disease were prospectively enrolled within 24 h of symptom onset underwent 1 hour TCD emboli monitoring. We reviewed disparity between PMD MES criteria and sgTCD MES criteria. We compared combined PMD/sgTCD criteria to sgTCD alone criteria by measuring the intraclass correlation coefficient (ICC). RESULTS Of 92 patients, 28 patients had evidence of MES on sgTCD or PMD. Total MES count was 269 based on sgTCD criteria, and 326 based on combined PMD/sgTCD criteria (P= 0.005). Combined PMD/sgTCD criteria revealed 17 MESs (4.8%) based on sgTCD criteria to represent artifacts and 57 MESs (17.5%) not to be detected by sgTCD criteria. Overall ICC based on sgTCD criteria was 0.67 [95% confidence interval (CI): 0.58–0.74]; however, introducing combined PMD/sgTCD criteria resulted in a significant increase in the ICC, 0.91 (95% CI: 0.88–0.93). CONCLUSION Our combined PMD/sgTCD criteria for MES appeared to improve the yield of MES detection. Reliability in MES detection interpretation was improved when combined PMD/sgTCD criteria was applied.

Background and Purpose— There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients. Methods— We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by ≥4 points, temporally related to a parenchymal hematoma on follow-up-imaging. Results— A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with ≥5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs ( P =0.170, Fisher’s exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, −2.0 to 8.3). Conclusions— The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.

Objective To provide updated, evidence-based recommendations for the prevention and management of hypertension in adults. Options and Outcomes For lifestyle and pharmacological interventions, evidence was reviewed from randomized controlled trials and systematic reviews of trials. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. For treatment of patients with kidney disease, the progression of kidney dysfunction was also accepted as a clinically relevant primary outcome. Evidence A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to update the 2006 Canadian Hypertension Education Program recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. Recommendations Dietary lifestyle modifications for prevention of hypertension, in addition to a well-balanced diet, include a dietary sodium intake of less than 100mmol/day. In hypertensive patients, the dietary sodium intake should be limited to 65mmol/day to 100mmol/day. Other lifestyle modifications for both normotensive and hypertensive patients include: performing 30min to 60 min of aerobic exercise four to seven days per week; maintaining a healthy body weight (body mass index of 18.5kg/m2 to 24.9kg/m2) and waist circumference (less than 102cm in men and less than 88 cm in women); limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women; following a diet reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and considering stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and any comorbid conditions: blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients require more than one agent to achieve these blood pressure targets. In adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor plus diuretic combination is preferred; in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered. Validation All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.

Objectives: To evaluate whether the presence of leukoaraiosis or multiple lacunes is associated with symptomatic intracerebral hemorrhage (ICH) and 90-day outcome after thrombolytic treatment with tissue plasminogen activator (tPA).Methods: Data were from a Canadian national registry of thrombolyzed patients with ischemic stroke. A total of 820 scans were assessed, blind to clinical features, for the presence of severe vs no/moderate leukoaraiosis, and of multiple (>2) vs no/single lacunar infarcts. Logistic regression was used to determine if an independent interaction existed between the presence and degree of leukoaraiosis/lacunes and risk of symptomatic ICH, and to evaluate the predictive role of leukoaraiosis and lacunes in relation to 90-day outcome.Results: An overall symptomatic ICH rate of 3.5% was observed. The rate of symptomatic ICH increased up to 10% in patients with severe leukoaraiosis and multiple lacunes. A significant association was observed between ICH risk and either severe leukoaraiosis (RR = 2.7 [95% CI 1.1 to 6.5]) or multiple lacunes (RR = 3.4 [95% CI 1.5 to 7.6]). Patients with multiple lacunes, but not leukoaraiosis, had higher mortality at 90 days compared to those with one or no lacunes (OR = 2.9, 95% CI 1.3 to 6.2, p = 0.008). No difference was observed in the good outcome rate among patients with and without leukoaraiosis or lacunes or both.Conclusion: The presence of small vessel disease on CT scan does not affect overall clinical outcome at 3 months in routine community use of tPA for ischemic stroke. A significant increase in the risk of symptomatic ICH is observed.

Background and Purpose— Perihematomal edema volume may be related to intracerebral hemorrhage (ICH) volume at baseline and, consequently, with hematoma expansion. However, the relationship between perihematomal edema and hematoma expansion has not been well established. We aimed to investigate the relationship among baseline perihematomal edema, the computed tomographic angiography spot sign, hematoma expansion, and clinical outcome in patients with acute ICH. Methods— Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) was a prospective observational cohort study of ICH patients presenting within 6 hours from onset. Patients underwent computed tomography and computed tomographic angiography scans at baseline and 24-hour computed tomography scan. A post hoc analysis of absolute perihematomal edema and relative perihematomal edema (absolute perihematomal edema divided by ICH) volumes was performed on baseline computed tomography scans (n=353). Primary outcome was significant hematoma expansion (>6 mL or >33%). Secondary outcomes were early neurological deterioration, 90-day mortality, and poor outcome. Results— Absolute perihematomal edema volume was higher in spot sign patients (24.5 [11.5–41.8] versus 12.6 [6.9–22] mL; P ρ =0.905; P P P =0.400). Absolute perihematomal edema volume and poorer outcomes were higher by tertiles of ICH volume, and perihematomal edema volume did not independently predict significant hematoma expansion. Conclusions— Perihematomal edema volume is greater at baseline in the presence of a spot sign. However, it is strongly correlated with ICH volume and does not independently predict hematoma expansion.

Background and Purpose— Hematoma expansion in intracerebral hemorrhage is associated with higher morbidity and mortality. The computed tomography (CT) angiographic spot sign is highly predictive of expansion, but other morphological features of intracerebral hemorrhage such as fluid levels, density heterogeneity, and margin irregularity may also predict expansion, particularly in centres where CT angiography is not readily available. Methods— Baseline noncontrast CT scans from patients enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study were assessed for the presence of fluid levels and degree of density heterogeneity and margin irregularity using previously validated scales. Presence and grade of these metrics were correlated with the presence of hematoma expansion as defined by the PREDICT study on 24-hour follow-up scan. Results— Three hundred eleven patients were included in the analysis. The presence of fluid levels and increasing heterogeneity and irregularity were associated with 24-hour hematoma expansion ( P =0.021, 0.003 and 0.049, respectively) as well as increases in absolute hematoma size. Fluid levels had the highest positive predictive value (50%; 28%–71%), whereas margin irregularity had the highest negative predictive value (78%; 71%–85). Noncontrast metrics had comparable predictive values as spot sign for expansion when controlled for vitamin K, antiplatelet use, and baseline National Institutes of Health Stroke Scale, although in a combined area under the receiver-operating characteristic curve model, spot sign remained the most predictive. Conclusions— Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign.

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed.

Background: Atrial fibrillation (AF) is a cause of ischemic stroke and is associated with recurrence and with acute multi-vessel territory non lacunar stroke. Many cryptogenic strokes could be secondary to undiagnosed paroxystic AF. As left atrium (LA) dilatation is a risk factor of AF, we sought to determine if moderate or severe LA dilatation was associated with multiple vascular territory infarcts on magnetic resonance imaging (MRI) in patients with acute ischemic stroke without known AF. Normal LA diameter values are ≤4.0 cm for men and ≤3.8 for women. Methods: Patients who presented at our center between 2006 and 2011 with a diagnosis of acute ischemic stroke (AIS) or transient ischemick attack (TIA) who had a transthoracic echocardiography and a brain MRI were included. Patients with known or de novo AF diagnosed within 3 months of the event were excluded. The main outcome was the presence of acute multi-vessel territory infarct(s) on MRI.Results: 356 patients were included. The mean LA diameter was 37 mm in the control group (normal or mildly dilated LA) and 49 mm in those with moderately to severely enlarged LA (pConclusions: LA dilatation (at least moderate) is associated with acute non lacunar multiple vascular territory infarcts on MRI in patients with AIS or TIA without known AF or a confirmed diagnosis of AF. Further studies are necessary to determine if this population might benefit from anticoagulation therapy.

L'hypertension est la cause modifiable la plus importante de l'accident vasculaire cerebral (AVC). L'hypertension est la cause principale de l'AVC. Le Groupe de travail du Programme educatif canadien sur l'hypertension (PECH) est forme d'experts canadiens dans le domaine de l'hypertension. Il publie a chaque annee des recommandations fondees sur des donnees probantes sur le diagnostic et le traitement de l'hypertension. Methodes: Nous presentons les recommandations 2005 du PECH sur la prise en charge de l'hypertension chez les patients ayant subi un AVC. Resultats: Le diagnostic de l'hypertension doit etre accelere chez les patients ayant subi un AVC. Il peut meme etre fait a la deuxieme visite d'evaluation de la pression arterielle chez ces patients. Le traitement de choix chez ces patients est l'association d'un inhibiteur de l'enzyme de conversion de l'angiotensine (ECA) et d'un diuretique, a moins qu'il n'existe des contre-indications a ce traitement. Les valeurs cibles de pression arterielle sont de moins de 140/90 mmHg chez les patients qui ne sont pas diabetiques, de moins de 130/80 mmHg chez les diabetiques et de moins de 125/75 mmHg chez les patients atteints de nephropathie ayant une proteinurie (> 1 gr par jour). Les interventions axees sur le mode de vie peuvent etre aussi efficaces que la medication et devraient etre utilisees en association avec la medication. Le tour de taille devrait etre de moins de 102 cm chez l'homme et de moins de 88 cm chez la femme. La prise en charge d'une pression arterielle elevee dans le contexte d'un AVC aigu demeure controversee. Conclusions: L'association d'un ECA et d'un diuretique est recommandee chez les patients ayant subi un AVC et la pression arterielle devrait etre maintenue sous 140/90 mmHg.

Introduction: The PREDICT study confirmed that the spot sign was a valid predictor of expansion in intracerebral hemorrhage (ICH) at 24h, with a positive predictive value (PPV) of 61%. This technique requires access to computed tomography angiography (CTA). Other markers may enhance the ability to predict expansion in ICH, or be useful in cases where multimodal imaging is not available. Previous studies have suggested that markers on non-contrast computed tomography (NCCT) such as density heterogeneity within the hematoma, irregularity of external margins, or internal fluid levels are associated with hematoma expansion (HE). Methods: Baseline NCCT scans of patients enrolled in PREDICT were examined for the presence of internal fluid levels (defined as a change within the hematoma resulting in a linear interface between two discrete fluid densities) and for the presence of hematoma density heterogeneity and margin irregularity (using an ordinal scale of 1-5 defined, published and validated previously). The association of each marker with median 24h absolute growth and with significant HE (defined as an increase in hematoma size of 6 mL or 33% measured 24h from baseline) were determined. Results: Fluid levels were present in 29 (8.3%) of 351 eligible patients. The presence of fluid levels were associated with significant HE at 24h (χ2 =7.64, df=1, p Conclusions: Density heterogeneity and fluid levels are associated with significant HE at 24h, and margin irregularity is associated with increased median hematoma size. These markers may be useful for predicting significant HE in ICH in cases where CTA is unavailable to identify the presence of a spot sign. They may also provide additional variables to incorporate into risk scores for hematoma expansion.

Background/Aims: Cognitive impairment is frequent in cerebrovascular disease but often remains undetected. The Montreal Cognitive Assessment (MoCA) has been proposed in this context. Our aim was to evaluate the MoCA and its subtests in cerebrovascular disease. Methods: We assessed 386 consecutive patients with minor stroke (National Institutes of Health Stroke Score 1. Results: The prevalence of cognitive impairment (cutoff of 26) was 55% using the MoCA and 13% using the MMSE. In a multivariate analysis, MoCA Conclusion: This study extends the utility of the MoCA to milder forms of cerebrovascular disease. The MoCA is associated with the 3-month functional outcome. Five subtests may constitute an optimal brief tool in vascular cognitive impairment.