Gord Gubitz

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study

BACKGROUND 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. METHODS 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. FINDINGS 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 (p<0·001). 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 (p<0·001). 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 (p<0·001). 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). INTERPRETATION 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. FUNDING Canadian Stroke Consortium and NovoNordisk Canada.

Gender Differences in Stroke Examined in a 10-Year Cohort of Patients Admitted to a Canadian Teaching Hospital

Background and Purpose— Studies suggest that women with stroke are investigated less aggressively and receive tissue plasminogen activator less frequently than men. We tested whether gender differences in the investigation, treatment, and outcome of stroke are due to confounding factors. Methods— Gender differences in the use of investigations, trial enrollment, treatment with intravenous tissue plasminogen activator, and in-hospital outcomes were examined in data from our prospective registry using multivariate analysis to adjust for age, prestroke functional status, stroke subtype and severity, and atrial fibrillation. Results— Of 2725 consecutive hospitalized patients (1996 to 2006), 88% had ischemic stroke and 48% were women. Women were older (median age, 77 versus 70 years), had more severe strokes, and were less likely to be independent prestroke (78% versus 87%) compared with men (all P<0.001). The proportion of women, but not men, aged ≥80 years, increased significantly between 1996 to 1997 and 2005 to 2006. After adjustment for confounding, women were less likely to have infratentorial strokes (OR, 0.78; 95% CI, 0.62 to 0.97), be able to walk unaided on admission (OR, 0.69; 95% CI, 0.54 to 0.87), be treated with tissue plasminogen activator (OR, 0.51; 95% CI, 0.35 to 0.72), experience pneumonia (OR, 0.38; 95% CI, 0.26 to 0.55), achieve a discharge Barthel Index of ≥95 (OR, 0.75; 95% CI, 0.61 to 0.94, and were more likely to experience a urinary tract infection (OR, 2.06; 95% CI, 1.61 to 2.64). There was no gender difference in adjusted use of investigations. Conclusion— The majority of the gender differences in stroke were explained by confounding. More research is required to understand gender differences in stroke pathophysiology and the utilization of thrombolytic therapy.

Canadian Stroke Best Practice Recommendations: Hyperacute Stroke Care Guidelines, Update 2015

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.

Canadian Stroke Best Practice Recommendations: secondary prevention of stroke guidelines, update 2014

Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals. The 2014 update of the Canadian Secondary Prevention of Stroke guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. Notable changes in this 5th edition include an emphasis on treating the highest risk patients who present within 48 h of symptom onset with transient or persistent motor or speech symptoms, who need to be transported to the closest emergency department with capacity for advanced stroke care; a recommendation for brain and vascular imaging (of the intra- and extracranial vessels) to be completed urgently using computed tomography/computed tomography angiography; prolonged cardiac monitoring for patients with suspective cardioembolic stroke but without evidence for atrial fibrillation on electrocardiogram or holter monitoring; and de-emphasizing the need for routine echocardiogram. The Canadian Stroke Best Practice Recommendations include a range of supporting materials such as implementation resources to facilitate the adoption of evidence to practice, and related performance measures to enable monitoring of uptake and effectiveness of the recommendations using a standardized approach. The guidelines further emphasize the need for a systems approach to stroke care, involving an interprofessional team, with access to specialists regardless of patient location, and the need to overcome geographical barriers to ensure equity in access within a universal health-care system.

Prevention of ischaemic stroke

Recent advances in the treatment of acute ischaemic stroke have focused largely on drug treatments, and yet the number of effective and widely practicable treatments remains limited. After a spate of trials with negative results, no neuroprotective agents have yet been licensed for acute stroke. Although thrombolysis with tissue plasminogen activator is now available in the United States and Canada, most eligible patients are not treated, and thrombolysis remains the subject of considerable debate in the international research community. 1 2 Other important interventions for people with acute stroke include organised care in multidisciplinary stroke units and routine use of aspirin in acute ischaemic stroke. 3 4 Stroke is the second most common cause of death worldwide, and with no major panacea for acute stroke imminent, we must not ignore stroke prevention.5 Medical and surgical treatments to prevent stroke carry some risk (and some cost). These preventive strategies should be targeted at those who are at the highest absolute risk of stroke, because these individuals are likely to derive the greatest absolute benefit.6 These patients generally have a history of occlusive vascular diseases with symptoms— that is, prior ischaemic stroke or transient ischaemic attack, coronary heart disease, or peripheral vascular disease. Among the 80% of patients who survive an acute stroke, the risk of recurrent stroke is highest within the first few weeks and months; about 10% in the first year and about 5% per year thereafter. These patients are also at a major risk of other vascular disease, including myocardial infarction, emphasising the need for early preventive treatments.7 Individual risk factors such as a history of hypertension, smoking, hyperlipidaemia, increased blood glucose concentration, and obesity are important considerations for all patients, especially those at high risk. #### Summary points Reduction of blood pressure is effective at preventing a first …

Predicting functional outcome after stroke by modelling baseline clinical and CT variables

BACKGROUND we aimed to assess whether the performance of stroke outcome models comprising simple clinical variables could be improved by the addition of more complex clinical variables and information from the first computed tomography (CT) scan. METHODS 538 consecutive acute ischaemic and haemorrhagic stroke patients were enrolled in a Stroke Outcome Study between 2001 and 2002. Independent survival (modified Rankin scale <or=2) was assessed at 6 months. Models based on clinical and radiological variables from the first assessment were developed using multivariate logistic regression analysis. RESULTS three models were developed (I-III). Model I included age, pre-stroke independence, arm power and a stroke severity score (area under a receiver operating characteristic curve, AUC = 0.882) but performed no better than Model II, which comprised age, pre-stroke independence, normal verbal component of the Glasgow coma score, arm power and being able to walk without assistance (AUC 0.876). Model III, including two radiological variables and clinical variables, was not statistically superior to model II (AUC 0.901, P = 0.12). Model II was externally validated in two independent datasets (AUCs of 0.773 and 0.787). CONCLUSION this study demonstrates an externally validated stroke outcome prediction model using simple clinical variables. Outcome prediction was not significantly improved with CT-derived radiological variables or more complex clinical variables.

Spot Sign Number Is the Most Important Spot Sign Characteristic for Predicting Hematoma Expansion Using First-Pass Computed Tomography Angiography: Analysis From the PREDICT Study

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<0.05 each) and demonstrated near perfect interobserver agreement (&kgr;=0.82 and &kgr;=0.85, respectively). Incremental risk of hematoma expansion among spot-positive patients was not identified for SSS (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.

Acute ischaemic stroke

Definition Stroke is characterised by rapidly developing clinical symptoms and signs of focal, and at times global, loss of cerebral function lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin.1 Ischaemic stroke is defined as stroke due to vascular insufficiency (such as cerebrovascular thromboembolism) rather than haemorrhage. #### Interventions Acute ischaemic stroke ##### Beneficial: Stroke units Aspirin ##### Trade-off between benefits and harms: Thrombolytic treatment ##### Likely to be ineffective or harmful: Immediate systemic anticoagulation Acute reduction of blood pressure Intracerebral haematomas ##### Unknown effectiveness: Evacuation Incidence/prevalence Stroke is the third most common cause of death in most developed countries.2 It is a worldwide problem: about 4.5 million people die from stroke each year. Stroke can occur at any age, but half of all strokes occur in people over 70 years old.3 Aetiology About 80% of all acute strokes are caused by cerebral infarction, usually resulting from thrombotic or embolic occlusion of a cerebral artery4; the remainder are caused either by intracerebral or subarachnoid haemorrhage. Prognosis About 10% of all people with acute ischaemic strokes will die within 30 days of stroke onset.5 Of those who survive the acute event, about 50% will experience some level of disability after six months.6 Aims To achieve rapid restoration and maintenance of blood supply to the ischaemic area in the brain, and to minimise brain damage and hence impairment, disability, and secondary complications. Outcomes Risk of death or dependency (generally assessed as the proportion of people dead or requiring physical assistance for transfers, mobility, dressing, feeding, or toileting three to six months after stroke onset7); quality of life. Clinical Evidence researchers searched the Cochrane Library and the Cochrane Stroke Review Group database in 1998 and performed an update search and appraisal for systematic reviews and subsequent randomised controlled trials (RCTs) in June 1999. Question: What …

Intracerebral Hematoma Morphologic Appearance on Noncontrast Computed Tomography Predicts Significant 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.

Venous Phase of Computed Tomography Angiography Increases Spot Sign Detection, but Intracerebral Hemorrhage Expansion Is Greater in Spot Signs Detected in Arterial Phase

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.