Imanuel Dzialowski

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.

Extent of Early Ischemic Changes on Computed Tomography (CT) Before Thrombolysis, Prognostic Value of the Alberta Stroke Program Early CT Score in ECASS II

Background and Purpose— The significance of early ischemic changes (EICs) on computed tomography (CT) to triage patients for thrombolysis has been controversial. The Alberta Stroke Program Early CT Score (ASPECTS) semiquantitatively assesses EICs within the middle cerebral artery territory using a10-point grading system. We hypothesized that dichotomized ASPECTS predicts response to intravenous thrombolysis and incidence of secondary hemorrhage within 6 hours of stroke onset. Methods— Data from the European-Australian Acute Stroke Study (ECASS) II study were used in which 800 patients were randomized to recombinant tissue plasminogen activator (rt-PA) or placebo within 6 hours of symptom onset. We retrospectively assessed all baseline CT scans, dichotomized ASPECTS at ≤7 and >7, defined favorable outcome as modified Rankin Scale score 0 to 2 after 90 days, and secondary hemorrhage as parenchymal hematoma 1 (PH1) or PH2. We performed a multivariable logistic regression analysis and assessed for an interaction between rt-PA treatment and baseline ASPECTS score. Results— We scored ASPECTS >7 in 557 and ≤7 in 231 patients. There was no treatment-by-ASPECTS interaction with dichotomized ASPECTS (P=0.3). This also applied for the 0- to 3-hour and 3- to 6-hour cohorts. However, a treatment-by-ASPECTS effect modification was seen in predicting PH (0.043 for the interaction term), indicating a much higher likelihood of thrombolytic-related parenchymal hemorrhage in those with ASPECTS ≤7. Conclusion— In ECASS II, the effect of rt-PA on functional outcome is not influenced by baseline ASPECTS. Patients with low ASPECTS have a substantially increased risk of thrombolytic-related PH.

Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score.

Background In ischemic stroke, functional outcomes vary depending on site of intracranial occlusion. We tested the prognostic value of a semiquantitative computed tomography angiography-based clot burden score. Methods Clot burden score allots major anterior circulation arteries 10 points for presence of contrast opacification on computed tomography angiography. Two points each are subtracted for thrombus preventing contrast opacification in the proximal M1, distal M1 or supraclinoid internal carotid artery and one point each for M2 branches, A1 and infraclinoid internal carotid artery. We retrospectively studied patients with disabling neurological deficits (National Institute of Health Stroke Scale score ≥ 5) and computed tomography angiography within 24-hours from symptom onset. We analyzed percentages independent functional outcome (modified Rankin Scale score ≤ 2), final infarct Alberta Stroke Program Early Computed Tomography Score and parenchymal hematoma rates across categorized clot burden score groups and performed multivariable analysis. Results We identified 263 patients (median age 73-years, National Institute of Health Stroke Scale score 10, onset-to-computed tomography angiography time 165 min). Clot burden score < 10 was associated with reduced odds of independent functional outcome (odds ratio 0.09 for clot burden score ≤5; odds ratio 0.22 for clot burden score 6–7; odds ratio 0.48 for clot burden score 8–9; all versus clot burden score 10; P <0.02 for all). Lower clot burden scores were associated with lower follow-up Alberta Stroke Program Early CT Scores (P <0.001) and higher parenchymal hematoma rates (P = 0.008). Inter-rater reliability for clot burden score was 0.87 (lower 95% confidence interval 0.71) and intra-rater reliability 0.96 (lower 95% confidence interval 0.92). Conclusion The quantification of intracranial thrombus extent with the clot burden score predicts functional outcome, final infarct size and parenchymal hematoma risk acutely. The score needs external validation and could be useful for patient stratification in stroke trials.

Asymptomatic Hemorrhage After Thrombolysis May Not Be Benign. Prognosis by Hemorrhage Type in the Canadian Alteplase for Stroke Effectiveness Study Registry

Background and Purpose— There is ongoing controversy about the impact of hemorrhagic transformation after thrombolysis on long-term functional outcome. We sought to study the relation between the type of hemorrhagic transformation on CT scans and functional outcome. Methods— Data were obtained from the Canadian Alteplase for Stroke Effectiveness Study. This study was established as a registry to prospectively collect data for acute stroke patients receiving intravenous alteplase within 3 hours from stroke onset between February 1999 and June 2001. Follow-up was completed at 90 days, and good functional outcome was defined as a modified Rankin Scale score of 0 or 1. Copies of head CT scans obtained at 24 to 48 hours after starting treatment were read in consensus by a central reading panel consisting of 1 neuroradiologist and 1 stroke neurologist. According to European Cooperative Acute Stroke Study criteria, hemorrhagic transformation was classified as none, hemorrhagic infarction (HI-1 and HI-2), or parenchymal hematoma (PH-1 and PH-2). We compared outcome across groups and performed a multivariable analysis including previously determined important predictors of good outcome in acute ischemic stroke. Results— From 1135 patients enrolled at 60 centers across Canada, 954 follow-up CT scans were assessable. We observed some hemorrhagic transformation in 259 of 954 (27.1%) patients (110 HI-1, 57 HI-2, 48 PH-1, and 44 PH-2). Proportions of patients with good outcome were 41% with no hemorrhagic transformation, 30% with HI-1, 17% with HI-2, 15% with PH-1, and 7% with PH-2 (P<0.0001, &khgr;2 test). After adjustment for age, baseline serum glucose, baseline Alberta Stroke Program Early CT score, and baseline National Institutes of Health Stroke Scale score, HI-1 was not a predictor of outcome. However, HI-2 (odds ratio=0.38, 95% CI=0.17 to 0.83), PH-1 (odds ratio=0.32, 95% CI=0.12 to 0.80), and PH-2 (odds ratio=0.14, 95% CI=0.04 to 0.48) were all negative predictors of outcome. Conclusions— The likelihood of a poor outcome after thrombolysis was proportional to the extent of hemorrhage on CT scans. HI grades of hemorrhagic transformation may not be benign.

Extent of Hypoattenuation on CT Angiography Source Images Predicts Functional Outcome in Patients With Basilar Artery Occlusion

Background and Purpose— Quantification of early ischemic changes (EIC) may predict functional outcome in patients with basilar artery occlusion (BAO). We tested the validity of a novel CT score, the posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS). Methods— Pc-ASPECTS allots the posterior circulation 10 points. Two points each are subtracted for EIC in midbrain or pons and 1 point each for EIC in left or right thalamus, cerebellum or PCA-territory, respectively. We studied 2 different populations: (1) patients with suspected vertebrobasilar ischemia and (2) patients with BAO. We applied pc-ASPECTS to noncontrast CT (NCCT), CT angiography source images (CTASI), and follow-up image by 3-reader consensus. We calculated sensitivity for ischemic changes and analyzed the predictivity of pc-ASPECTS for independent (modified Rankin Scale [mRS] score ≤2) and favorable (mRS score ≤3) outcome. Results— Of 130 patients with suspected vertebrobasilar ischemia, 72% (94) had posterior circulation stroke, 8% (10) transient ischemic attack, and 20% (26) nonischemic etiology. Sensitivity for ischemic changes was improved with CTASI compared to NCCT (65% [95% CI, 57% to 73%] versus 46% [95% CI, 37% to 55%], respectively). Pc-ASPECTS score on CTASI but not NCCT predicted functional independence (OR 1.58; P=0.005 versus 1.22; P=0.42, respectively). Of 46 patients with BAO, 52% (12/23) with CTASI pc-ASPECTS score ≥8 but only 4% (1/23) with a score <8 had favorable functional outcome (RR 12.1; 95% CI, 1.7 to 84.9). This difference was consistent in 21 patients with angiographic recanalization (RR 7.7; 95% CI, 1.1 to 52.1). Conclusion— The CTASI pc-ASPECTS score may identify BAO patients unlikely to have a favorable outcome despite recanalization.

The Alberta Stroke Program Early CT Score in Clinical Practice: What have We Learned?

The introduction of brain imaging with computed tomography revolutionised the treatment of patients with acute ischaemic stroke. With the visual differentiation of haemorrhagic stroke from ischaemic stroke, thrombolytic therapy became feasible. The Alberta Stroke Program Early CT Score was devised to quantify the extent of early ischaemic changes in the middle cerebral artery territory on noncontrast computed tomography. With its systematic approach, the score is simple and reliable. However, the assessment of early ischaemic changes and Alberta Stroke Program Early CT scoring require training. The Alberta Stroke Program Early CT Score is a strong predictor of functional outcome. Furthermore, the effectiveness of intraarterial thrombolysis in patients with middle cerebral artery occlusion shows effect modification by the Alberta Stroke Program Early CT Score. This review summarises the Alberta Stroke Program Early CT Score methodology. We illustrate current knowledge regarding Alberta Stroke Program Early CT Score applied to clinical trials and comment on how Alberta Stroke Program Early CT Score may facilitate clinical treatment decision making and future trial design. Moreover, we introduce a modification of the Alberta Stroke Program Early CT Score methodology that disregards isolated cortical swelling, i.e. focal brain swelling without associated parenchymal hypoattenuation, as early ischaemic changes in the Alberta Stroke Program Early CT Score system.

Brain Tissue Water Uptake after Middle Cerebral Artery Occlusion Assessed with CT

Background and Purpose. To study whether computed tomography (CT) can measure the water content of early ischemic edema. Methods. The authors obtained cranial CT in 5 groups of rats subjected to 1 hour (n = 8),2 hours (n = 11),3 hours (n = 13),4 hours (n = 13), or 6 hours (n = 14) of right middle cerebral artery (MCA) occlusion. Immediately after CT, the authors removed the rats’ brains and determined tissue water content by the dry‐wet weight method. They correlated brain x‐ray attenuation with brain tissue water content. Results. Mean brain tissue water content remained constant in the nonischemic left hemispheres at 77.9%± 0.6% and increased up to 79.3%± 1.0% in the right hemispheres after 6 hours of permanent right MCA occlusion. X‐ray attenuation remained constant in the left hemispheres at 75.6 ± 2.2 Hounsfield units (HU) and decreased to 71.7 ± 3.4 HU in the right hemispheres after 6 hours of right MCA occlusion. The decrease in x‐ray attenuation correlated significantly with the increase in ischemic brain tissue water content (y= 217.3 – 1.8 ×x; r= .55, P < .0001). That means that a 1% increase in hemispheric tissue water content causes a decrease in x‐ray attenuation of 1.8 HU. Conclusions. After MCA occlusion, immediate brain tissue net water uptake is associated with a decrease in x‐ray attenuation. CT can monitor ischemic edema in an acute stroke.

Incidence of radiocontrast nephropathy in patients undergoing acute stroke computed tomography angiography

Background and Purpose— Minimal research has evaluated the renal safety of emergent computed tomography angiography (CTA) procedures, consecutive contrast medium application, and the long-term outcome in acute stroke patients. We investigated the incidence of contrast-induced renal impairment in these populations. Methods— We retrospectively reviewed patients with acute stroke syndrome who received a CTA of the brain with or without the neck within 24 hours from onset of symptoms. All creatinine results and additional conventional angiography findings were recorded. With a positive history of renal disease, contrast administration was delayed until creatinine results were available. Radiocontrast nephropathy (RCN) was defined as a ≥25% increase in serum creatinine from the baseline value up to 5 days after CTA. Results— Four hundred eighty-one patients were reviewed, and 224 met the inclusion criteria. There were 7 of 224 (3%) who fulfilled the criteria for RCN. A number of patients underwent emergent CTA without knowledge of their creatinine value; 2 of 93 (2%) developed RCN. There were 36 patients who received an additional digital subtraction angiogram, and none of these developed subsequent RCN. No patients required dialysis, and 9 of 68 (13%) had a >25% increase in their creatinine levels at a late (>30 days) follow-up. Conclusions— Overall, these results illustrate that there is a low incidence of RCN in acute stroke patients undergoing emergency CTA.

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.

CT Angiographic Source Images Predict Outcome and Final Infarct Volume Better Than Noncontrast CT in Proximal Vascular Occlusions

Background and Purpose— Alberta Stroke Programme Early CT Score (ASPECTS) is widely used for assessment of early ischemic changes in acute stroke. We hypothesized that CT angiography source image (CTA-SI) ASPECTS correlates better with baseline National Institutes of Health Stroke Scale score, final ASPECTS and neurological outcomes when compared with noncontrast CT ASPECTS. Methods— We studied patients presenting with acute ischemic stroke and identified proximal arterial occlusions (internal carotid artery, middle cerebral artery M1, and proximal middle cerebral artery M2) from the Calgary CT Angiography database. CT scans were independently read by 3 observers for baseline noncontrast CT ASPECTS, CT angiography source image ASPECTS, and follow-up ASPECTS. Details of demographics and risk factors were noted. A modified Rankin Scale score ⩽2 at 3 months was considered a favorable outcome. Results— We identified 261 patients with proximal occlusions for analysis. We found a better correlation between CT angiography source image ASPECTS and follow-up ASPECTS (Spearman correlation coefficient r=0.65; 95% CI, 0.58 to 0.72; P<0.001) than between noncontrast CT ASPECTS and follow-up CT ASPECTS (r=0.46; 95% CI, 0.36 to 0.55; P<0.001). CT angiography source image ASPECTS correlated better with baseline National Institutes of Health Stroke Scale and 24-hour National Institutes of Health Stroke Scale when compared with noncontrast CT ASPECTS (P<0.001). In an adjusted model including both CT angiography source image ASPECTS and noncontrast CT ASPECTS, CT angiography source image ASPECTS was associated with good outcome (OR, 2.30; 95%, CI, 1.16 to 4.53), whereas noncontrast CT ASPECTS was not (OR, 1.54; 95% CI, 0.84 to 2.82). Among imaging parameters, CT angiography source image ASPECTS was the only independent predictor of good outcome (OR, 2.29; 95% CI, 1.16 to 4.53). Conclusions— CT angiography source image ASPECTS correlates better with baseline stroke severity, is a better predictor of final infarct extension, and independently predicts neurological outcome than noncontrast CT ASPECTS.