Philip A. Barber

Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy

Summary Background Computed tomography (CT) must be done before thrombolytic treatment of hyperacute ischaemic stroke, but the significance of early ischaemic change on CT is unclear. We tested a quantitative CT score, the Alberta Stroke Programme Early CT Score (ASPECTS). Methods 203 consecutive patients with ischaemic stroke were treated with intravenous alteplase within 3 h of symptom onset in two North American teaching hospitals. All pretreatment CT scans were prospectively scored. The score divides the middle-cerebral-artery territory into ten regions of interest. Primary outcomes were symptomatic intracerebral haemorrhage and 3-month functional outcome. The sensitivity and specificity of ASPECTS for the primary outcomes were calculated. Logistic regression was used to test the association between the score on ASPECTS and the primary outcomes. Findings Ischaemic changes on the baseline CT were seen in 117 (75%) of 156 treated patients with anteriorcirculation ischaemia included in the analysis (23 had ischaemia in the posterior circulation and 24 were treated outside the protocol). Baseline ASPECTS value correlated inversely with the severity of stroke on the National Institutes of Health Stroke Scale (r=� 0·56, p<0·001). Baseline ASPECTS value predicted functional outcome and symptomatic intracerebral haemorrhage (p<0·001, p=0·012, respectively). The sensitivity of ASPECTS for functional outcome was 0·78 and specificity 0·96; the values for symptomatic intracerebral haemorrhage were 0·90 and 0·62. Agreement between observers for ASPECTS, with knowledge of the affected hemisphere, was good (� statistic 0·71–0·89). Interpretation This CT score is simple and reliable and identifies stroke patients unlikely to make an independent recovery despite thrombolytic treatment.

High Rate of Complete Recanalization and Dramatic Clinical Recovery During tPA Infusion When Continuously Monitored With 2-MHz Transcranial Doppler Monitoring

Background and Purpose—Clot dissolution with tissue plasminogen activator (tPA) can lead to early clinical recovery after stroke. Transcranial Doppler (TCD) with low MHz frequency can determine arterial occlusion and monitor recanalization and may potentiate thrombolysis. Methods—Stroke patients receiving intravenous tPA were monitored during infusion with portable TCD (Multigon 500M; DWL MultiDop-T) and headframe (Marc series; Spencer Technologies). Residual flow signals were obtained from the clot location identified by TCD. National Institutes of Health Stroke Scale (NIHSS) scores were obtained before and after tPA infusion. Results—Forty patients were studied (mean age 70±16 years, baseline NIHSS score 18.6±6.2, tPA bolus at 132±54 minutes from symptom onset). TCD monitoring started at 125±52 minutes and continued for the duration of tPA infusion. The middle cerebral artery was occluded in 30 patients, the internal carotid artery was occluded in 11 patients, the basilar artery was occluded in 3 patien...

Importance of Early Ischemic Computed Tomography Changes Using ASPECTS in NINDS rtPA Stroke Study

Background and Purpose— The importance of early ischemic change (EIC) on baseline computed tomography (CT) in the decision to thrombolyze the patient with acute ischemic stroke has been controversial. ASPECTS is a semiquantitative scale that scores the extent of EIC within the middle cerebral artery territory. We examined whether ASPECTS could be a treatment modifier by systematically reviewing the CT scans in the NINDS rtPA Stroke Study. Methods— Six hundred eight of the 624 CT scans were available and of sufficient quality. One of 2 teams (n=3 each) of expert ASPECTS readers evaluated each scan for an ASPECTS value using a consensus score approach. Each team was blind to all clinical information except symptom side and blind to follow-up imaging and outcome information. ASPECTS values were stratified before analysis. Multivariable logistic regression was used to determine if an ASPECTS by treatment interaction existed on treatment response, outcome, and intracerebral hemorrhage risk. Results— A total of 57.2% (348 of 608) of scans showed EIC with an ASPECTS <10. ASPECTS dichotomized into 8 to 10 and <8 did not have a treatment-modifying effect on good outcome but showed a trend to lower mortality at 90 days with tPA (relative risk 0.67, 95% confidence interval 0.41 to 1.06, P=0.10). ASPECTS 8 to 10 were associated with a trend to larger benefit of tPA with a number needed to treat (NNT) of 5 versus ASPECTS 3 to 7 with a NNT of 8. Conclusion— There was no evidence of treatment effect modification by the baseline ASPECTS value in the NINDS rtPA Stroke Study. Therefore, exclusion of patients for thrombolysis within 3 hours of symptom onset based on EIC is not supported by our data. There is a trend to reduced mortality and increased benefit to rtPA if the baseline CT scan is favorable (ASPECTS >7).

Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging.

We examined whether the presence of diffusion‐weighted imaging (DWI) lesions and vessel occlusion on acute brain magnetic resonance images of minor stroke and transient ischemic attack patients predicted the occurrence of subsequent stroke and functional outcome. 120 transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale ≤ 3) patients were prospectively enrolled. All were examined within 12 hours and had a magnetic resonance scan within 24 hours. Overall, the 90‐day risk for recurrent stroke was 11.7%. Patients with a DWI lesion were at greater risk for having a subsequent stroke than patients without and risk was greatest in the presence of vessel occlusion and a DWI lesion. The 90‐day risk rates, adjusted for baseline characteristics, were 4.3% (no DWI lesion), 10.8% (DWI lesion but no vessel occlusion), and 32.6% (DWI lesion and vessel occlusion) (p = 0.02). The percentages of patients who were functionally dependent at 90 days in the three groups were 1.9%, 6.2%, and 21.0%, respectively (p = 0.04). The presence of a DWI lesion and a vessel occlusion on a magnetic resonance image among patients presenting acutely with a transient ischemic attack or minor stroke is predictive of an increased risk for future stroke and functional dependence. Ann Neurol 2005;57:848–854

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.

Effectiveness of t-PA in acute ischemic stroke: Outcome relates to appropriateness

Objective: To examine whether the demonstrated efficacy of tissue-type plasminogen activator (t-PA) for acute ischemic stroke can be effective in a community setting. Methods: Sixty-eight consecutive patients with acute ischemic stroke treated with IV t-PA within 3 hours of symptom onset by attending general neurologists in a busy teaching hospital. Outcome measures at 3 months were the National Institute of Health Stroke Scale (NIHSS), functional outcome (independence [modified Rankin score 0–2], dependence [modified Rankin score 3–5], and death), and symptomatic hemorrhage. Appropriately treated patients were defined by adherence to the National Institute of Neurological Disorders and Stroke (NINDS) guidelines. Effectiveness is expressed as the absolute risk reduction in which the baseline risk is assumed to be similar to that of the NINDS control group. Results: Of 68 consecutively treated patients (with a mean baseline NIHSS score of 15 ± 6), 26 (38%) made a full recovery and 39 (57%) made an independent recovery. The 11 patients who violated protocol had a lower probability of independence (p < 0.02) and full neurologic recovery (p < 0.02) and a higher probability of symptomatic hemorrhage (p < 0.05) and death (p < 0.01) compared with those of 57 patients treated according to NINDS guidelines. Conclusions: The use of t-PA for stroke in this community is effective with a number needed to treat of six. The risk of symptomatic hemorrhage is similar to that noted in randomized trials. Treating patients who violate protocol results in excess risk with no observable benefit.

Hyperdense Sylvian Fissure MCA “Dot” Sign A CT Marker of Acute Ischemia

Background and Purpose— The hyperdense appearance of the main middle cerebral artery (HMCA) is now a familiar early warning of large cerebral infarction, brain edema, and poor prognosis. This article describes the hyperdensity associated with embolic occlusion of branches of the middle cerebral artery in the sylvian fissure (MCA “dot” sign). We define it and determine its incidence, diagnostic value, and reliability. Methods— CT scans performed on patients with acute ischemic stroke within 3 hours of symptom onset were analyzed for signs of thromboembolic stroke and evidence of early CT ischemia. Two neuroradiologists and 2 stroke neurologists initially blinded to all clinical information and then with knowledge of the affected hemisphere evaluated scans for the presence of the MCA dot sign, the HMCA sign, and early MCA territory ischemic changes. Results— Of 100 consecutive patients who presented within 3 hours of symptom onset, 91 were considered at symptom onset to have anterior circulation stroke syndromes. Early CT ischemia was seen in 74% of these baseline CT scans. The HMCA sign was seen in 5% of CT scans, whereas the MCA dot sign was seen in 16%. All patients then received intravenous tissue plasminogen activator. All 5 patients with an HMCA sign, including 2 with an associated MCA dot sign, were either dead or dependent at 3 months. The 14 patients with an MCA dot sign alone were independent at 3 months in 64% of cases, compared with 50% without the sign (Fisher’s exact test P =0.79). Balanced &kgr; statistics for both the HMCA and the MCA dot sign were in the moderate to good range when the stroke symptom side was given. Conclusions— The MCA dot sign is an early marker of thromboembolic occlusion of the distal MCA branches seen in the sylvian fissure and is associated with better outcome than the HMCA sign.

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.

MR molecular imaging of early endothelial activation in focal ischemia.

Focal ischemia followed by reperfusion initiates a harmful P‐ and E‐selectin–mediated recruitment of leukocytes in brain microvasculature. In this study, we tested whether a novel magnetic resonance (MR) contrast agent (Gd‐DTPA‐sLex A), which is designed to bind to activated endothelium could be detected by MR imaging (MRI) in a focal stroke mouse model. MRIs (9.4T) of the brain were acquired 24 hours after transient middle cerebral artery occlusion. T1 maps were acquired repeatedly before and up to 1.5 hours after the intravenous injection of either Gd‐DTPA or Gd‐DTPA‐sLex A. Analysis of images included a pixel‐by‐pixel subtraction of T1 maps from the precontrast T1 maps and quantification of T1 within the ischemic area. After injection of Gd‐DTPA‐sLex A, T1 decreased compared with precontrast levels, and an interhemispheric difference between the pre–post contrast T1 developed within the stroke lesion at a mean time of 52 minutes after injection (p < 0.05). Animals injected with Gd‐DTPA did not exhibit changes in T1 signal intensity between regions of the ipsilateral and contralateral hemispheres, indicating that the reductions in T1 observed with Gd‐DTPA‐sLex A were unrelated to blood–brain barrier breakdown. Fluorescent‐labeled sLex A administered intravenously was observed to bind to the endothelium of injured but not control brain. The study suggests that the contrast agent Gd‐DTPA‐sLex A can be used to visualize early endothelial activation after transient focal ischemia in vivo with MRI. Ann Neurol 2004;56:116–120