S B Coutts

Identification of Penumbra and Infarct in Acute Ischemic Stroke Using Computed Tomography Perfusion–Derived Blood Flow and Blood Volume Measurements

Background and Purpose— We investigated whether computed tomography (CT) perfusion–derived cerebral blood flow (CBF) and cerebral blood volume (CBV) could be used to differentiate between penumbra and infarcted gray matter in a limited, exploratory sample of acute stroke patients. Methods— Thirty patients underwent a noncontrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) scan within 7 hours of stroke onset, NCCT and CTA at 24 hours, and NCCT at 5 to 7 days. Twenty-five patients met the criteria for inclusion and were subsequently divided into 2 groups: those with recanalization at 24 hours (n=16) and those without (n=9). Penumbra was operationally defined as tissue with an admission CBF <25 mL · 100 g−1 · min−1 that was not infarcted on the 5- to 7-day NCCT. Logistic regression was applied to differentiate between infarct and penumbra data points. Results— For recanalized patients, CBF was significantly lower (P<0.05) for infarct (13.3±3.75 mL · 100 g−1 · min−1) than penumbra (25.0±3.82 mL · 100 g−1 · min−1). CBV in the penumbra (2.15±0.43 mL · 100 g−1) was significantly higher than contralateral (1.78±0.30 mL · 100 g−1) and infarcted tissue (1.12±0.37 mL · 100 g−1). Logistic regression using an interaction term (CBF×CBV) resulted in sensitivity, specificity, and accuracy of 97.0%, 97.2%, and 97.1%, respectively. The interaction term resulted in a significantly better (P<0.05) fit than CBF or CBV alone, suggesting that the CBV threshold for infarction varies with CBF. For patients without recanalization, CBF and CBV for infarcted regions were 15.1±5.67 mL · 100 g−1 · min−1 and 1.17±0.41 mL · 100 g−1, respectively. Conclusions— We have shown in a limited sample of patients that CBF and CBV obtained from CTP can be sensitive and specific for infarction and should be investigated further in a prospective trial to assess their utility for differentiating between infarct and penumbra.

Addition of brain and carotid imaging to the ABCD² score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study.

BACKGROUND The ABCD² score improves stratification of patients with transient ischaemic attack by early stroke risk. We aimed to develop two new versions of the score: one that was based on preclinical information and one that was based on imaging and other secondary care assessments. METHODS We analysed pooled data from patients with clinically defined transient ischaemic attack who were investigated while in secondary care. Items that contribute to the ABCD² score (age, blood pressure, clinical weakness, duration, and diabetes), other clinical variables, carotid stenosis, and abnormal acute diffusion-weighted imaging (DWI) were recorded and were included in multivariate logistic regression analysis of stroke occurrence at early time intervals after onset of transient ischaemic attack. Scores based on the findings of this analysis were validated in patients with transient ischaemic attack from two independent population-based cohorts. FINDINGS 3886 patients were included in the study: 2654 in the derivation sample and 1232 in the validation sample. We derived the ABCD³ score (range 0-9 points) by assigning 2 points for dual transient ischaemic attack (an earlier transient ischaemic attack within 7 days of the index event). C statistics (which indicate discrimination better than chance at >0·5) for the ABCD³ score were 0·78 at 2 days, 0·80 at 7 days, 0·79 at 28 days, and 0·77 at 90 days, compared with C statistics for the ABCD² score of 0·71 at 2 days (p=0·083), 0·71 at 7 days (p=0·012), 0·71 at 28 days (p=0·021), and 0·69 at 90 days (p=0·018). We included stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points) in the ABCD³-imaging (ABCD³-I) score (0-13 points). C statistics for the ABCD³-I score were 0·90 at 2 days (compared with ABCD² score p=0·035), 0·92 at 7 days (p=0·001), 0·85 at 28 days (p=0·028), and 0·79 at 90 days (p=0·073). The 90-day net reclassification improvement compared with ABCD² was 29·1% for ABCD³ (p=0·0003) and 39·4% for ABCD³-I (p=0·034). In the validation sample, the ABCD³ and ABCD³-I scores predicted early stroke at 7, 28, and 90 days. However, discrimination and net reclassification of patients with early stroke were similar with ABCD³ compared with ABCD². INTERPRETATION The ABCD³-I score can improve risk stratification after transient ischaemic attack in secondary care settings. However, use of ABCD³ cannot be recommended without further validation. FUNDING Health Research Board of Ireland, Irish Heart Foundation, and Irish National Lottery.

An improved scoring system for identifying patients at high early risk of stroke and functional impairment after an acute transient ischemic attack or minor stroke

Background Risk of a subsequent stroke following an acute transient ischemic attack (TIA) or minor stroke is high. The ABCD2 tool was proposed as a method to triage these patients using five clinical factors. Modern imaging of the brain was not included. The present study quantified the added value of magnetic resonance imaging (MRI) factors to the ABCD2 tool. Methods Patients with TIA or minor stroke were examined within 12 h and had a brain MRI within 24 h of symptom onset. Primary outcomes were recurrent stroke and functional impairment at 90 days. A new tool, ABCD2+ MRI, was created by adding diffusion-weighted imaging lesion and vessel occlusion status to the ABCD2 tool. The predictive accuracy of both tools was quantified by the area under the curve (AUC). Results One hundred and eighty patients were enrolled and 11·1% had a recurrent stroke within 90 days. The predictive accuracy of the ABCD2+MRI was significantly higher than ABCD2 (AUC of 0·88 vs. 0·78, P = 0·01). Those with a high score (7–9) had a 90-day recurrent stroke risk of 32·1%, moderate score (5–6) risk of 5·4%, and low score (0-4) risk of 0·0%. The ABCD2 tool did not predict risk of functional impairment at 90 days (P = 0·33), unlike the ABCD2+MRI (P = 0·02): high score (22·9%), moderate (7·5%), low (7·7%). Conclusions Risk of recurrent stroke and functional impairment after a TIA or minor stroke can be accurately predicted by a scoring system that utilizes both clinical and MRI information. The ABCD2+MRI score is simple and its components are commonly available during the time of admission.

Reliability of Assessing Percentage of Diffusion-Perfusion Mismatch

Background and Purpose— Emergent neurovascular imaging holds promise in identifying new and optimum target populations for thrombolysis in stroke. Recent research has focused on patients with diffusion-weighted MRI (DWI)-perfusion-weighted MRI (PWI) mismatch as a marker of tissue at risk of infarction and a means to select the most suitable candidates for thrombolysis. The present study sought to estimate the reliability of assessing the percentage of DWI-PWI mismatch. Methods— Thirteen patients with acute strokes had DWI and PWI within 7 hours of symptom onset. Six raters independently created relative mean transit time (rMTT) maps and then compared them with DWI images to assess the percentage of mismatch (PWI>DWI) in 10% increments. The MR scans were reassessed by 4 raters, tracing around the lesions to calculate the volume percentage of mismatch. Results— Visual assessment had an interrater reliability of 0.68 (95% CI, 0.52 to 1.0; SEM=21.6%) and an intrarater reliability of 0.80 (95% CI, 0.47 to 1.0; SEM=16.9%). Hand-drawn assessment had an interrater reliability of 0.66 (95% CI, 0.45 to 1.0; SEM=26.2%) and an intrarater reliability of 0.94 (95% CI, 0.81 to 1.0; SEM=10.9%). Conclusions— Results from the present study suggest that quantifying mismatch by the human eye is reproducible but not reliable among observers. This raises doubts about using mismatch for clinical decision making and clinical trial enrollment.

Impact of a Stroke Unit on Length of Hospital Stay and In-Hospital Case Fatality

Background and Purpose— Randomized trials have demonstrated reduced morbidity and mortality with stroke unit care; however, the effect on length of stay, and hence the economic benefit, is less well-defined. In 2001, a multidisciplinary stroke unit was opened at our institution. We observed whether a stroke unit reduces length of stay and in-hospital case fatality when compared to admission to a general neurology/medical ward. Methods— A retrospective study of 2 cohorts in the Foothills Medical Center in Calgary was conducted using administrative databases. We compared a cohort of stroke patients managed on general neurology/medical wards before 2001, with a similar cohort of stroke patients managed on a stroke unit after 2003. The length of stay was dichotomized after being centered to 7 days and the Charlson Index was dichotomized for analysis. Multivariable logistic regression was used to compare the length of stay and case fatality in 2 cohorts, adjusted for age, gender, and patient comorbid conditions defined by the Charlson Index. Results— Average length of stay for patients on a stroke unit (n=2461) was 15 days vs 19 days for patients managed on general neurology/medical wards (n=1567). The proportion of patients with length of stay >7 days on general neurology/medical wards was 53.8% vs 44.4% on the stroke unit (difference 9.4%; P<0.0001). The adjusted odds of a length of stay >7 days was reduced by 30% (P<0.0001) on a stroke unit compared to general neurology/medical wards. Overall in-hospital case fatality was reduced by 4.5% with stroke unit care. Conclusions— We observed a reduced length of stay and reduced in-hospital case-fatality in a stroke unit compared to general neurology/medical wards.

Role of Recanalization in Acute Stroke Outcome: Rationale for a CT Angiogram-Based “Benefit of Recanalization” Model

BACKGROUND AND PURPOSE: In acute middle cerebral artery (MCA) stroke, CT angiographic (CTA) source images (CTA-SI) identify tissue likely to infarct despite early recanalization. This pilot study evaluated the impact of recanalization status on clinical and radiologic predictors of patient outcomes. MATERIALS AND METHODS: Of 44 patients undergoing CT/CTA within 6 hours of developing symptoms of proximal MCA ischemia, 19 patients achieved complete proximal MCA (MCA M1) recanalization. Admission National Institutes of Health Stroke Scale (NIHSS) score, onset-to-imaging time, CTA-SI Alberta Stroke Program Early CT Score, MCA M1 occlusion, cerebrovascular collaterals score, and CTA-SI lesion volume were correlated with 3- to 6-month follow-up modified Rankin Scale (mRS). We developed 2 stepwise regression models: one for patients with complete MCA M1 recanalization and one for patients without complete recanalization. RESULTS: Complete and incomplete recanalization groups had similar median admission NIHSS scores (19 versus 19) and mean onset-to-imaging times (2.3 versus 1.9 hours) but different proportions of patients achieving mRS scores 0–2 (74% versus 40%; P = .04). The only independent predictors of clinical outcome in patients with complete recanalization were onset-to-imaging time and admission CTA-SI lesion volume (total model R2 = 0.75; P = .01). The only independent predictors of outcome in patients with incomplete recanalization were admission CTA-SI lesion volume and NIHSS score (total model R2 = 0.66; P = .007). CONCLUSION: Regardless of recanalization status, admission CTA-SI lesion volume was associated with clinical outcome. Recanalization status did, however, affect which variables in addition to CTA-SI volume significantly impacted clinical outcome: time with complete recanalization and NIHSS with incomplete recanalization. This finding may support the development of a model predicting the potential clinical benefit expected with early successful recanalization.

Acute ischemic lesions of varying ages predict risk of ischemic events in stroke/TIA patients

Background: Multiple ischemic lesions identified by diffusion-weighted imaging (DWI) have been shown to predict high risk of future ischemic events. However, the importance of lesion age has not been factored into this risk. Our goal was to evaluate whether the presence of ischemic lesions of varying ages identified by DWI and apparent diffusion coefficient (ADC) suggests a higher risk of future ischemic events. Methods: Patients with acute stroke and TIA presenting within 12 hours of symptom onset who had a baseline and 1-month follow-up MRI were enrolled in the study. Acute ischemic lesions were divided into DWI positive with ADC low lesions and DWI positive with ADC normalized lesions. The baseline MRI and the presence of new lesions on the follow-up MRI were analyzed. Results: A total of 360 patients were prospectively enrolled, and all had appropriate imaging. Two hundred twenty-three were excluded as there were no DWI lesions, they received recombinant tissue plasminogen activator, or they did not have the 30-day follow-up MRI. One hundred seventeen patients had DWI lesions of one age (DWI positive with either ADC low lesions or ADC normalized lesions alone) and 20 had lesions of varying ages (DWI positive lesions with reduced and normalized ADC) on the baseline MRI. Patients with multiple DWI lesions of varying ages were at more risk of having new lesions on the 30-day MRI compared with those having lesions of the same age (relative risk = 3.6; 95% CI 1.9 to 6.8). Multiple DWI lesions of varying ages (odds ratio [OR] 6.6; 95% CI 2.3 to 19.1) and cardioembolic stroke subtype (OR 3.2; 95% CI 1.1 to 8.7) were independently associated with new lesion recurrence by multiple logistic regression analysis. Conclusion: The presence of multiple diffusion-weighted imaging lesions of varying ages suggests very active early recurrence over time and portends a higher early risk of future ischemic events.

Normal Magnetic Resonance Perfusion-Weighted Imaging in Lacunar Infarcts Predicts a Low Risk of Early Deterioration

Background: Current clinical tools to identify lacunar infarct patients at risk of deterioration are inadequate, and imaging techniques to predict fluctuation and deterioration would be of value. We sought to determine the occurrence of MRI perfusion-weighted imaging (PWI) abnormalities in lacunes, and whether they help predict clinical and radiological outcome. Methods: Patients with lacunar stroke or TIA were selected from a prospective MR imaging study. MRI was performed within 24 h of the event and follow-up imaging completed at 30 or 90 days. Baseline perfusion maps were qualitatively assessed and infarct volumes measured. Early clinical deterioration (NIHSS worsening of ≥3 points within 72 h of event) and 90-day modified Rankin Scale score (mRS) were recorded. Results: Twenty-two patients were included. Fifteen (68.2%) had abnormal PWI at the site of the diffusion-weighted imaging lesion. Patients with abnormal PWI were more likely to have stroke than TIA as their index event (RR 2.2, 95% CI 0.9–5.2, p = 0.02). Early clinical deterioration occurred in 4 patients (18.2%), all of whom had abnormal PWI. PWI lesions were not associated with a higher 90-day NIHSS or mRS score, nor did they predict infarct volume growth. Conclusions: MR-PWI abnormalities are seen in two thirds of lacunar infarcts, and are associated with stroke rather than TIA. Normal PWI identifies patients at low risk of early clinical deterioration.

Computed tomography and computed tomography angiography findings predict functional impairment in patients with minor stroke and transient ischaemic attack.

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.

CT Angiography Source Images Predict Final Infarct Extent in Patients with Basilar Artery Occlusion

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) is a 10-point grading system to quantify ischemic changes in the posterior circulation. We analyzed whether pc-ASPECTS on CT angiography (CTA) source images (CTASI) predicted the final infarct extent and hemorrhagic transformation (HT) rate in patients with basilar artery occlusion. MATERIALS AND METHODS: A pc-ASPECTS score of 10 indicates absence of visible ischemic changes in the posterior circulation, and pc-ASPECTS score of 0 indicates ischemic changes in the midbrain, pons, and bilateral thalami, posterior circulation territories, and cerebellar hemispheres. We retrospectively studied patients with basilar artery occlusion on CTA within 24 hours from symptom onset. We applied pc-ASPECTS to noncontrast CT (NCCT), CTASI, and follow-up images by 3-reader-consensus and assessed HT on follow-up images. We calculated Spearman correlation coefficients and performed linear regression analysis. Final infarct extent and HT rates were compared across dichotomized CTASI pc-ASPECTS groups (≥ 8 vs < 8). RESULTS: Among 43 patients, median (range) onset to CTA time was 5.0 hours (range, 0.7–24 hours). Pc-ASPECTS on CTASI (r = 0.75; P < .001) but not NCCT (r = 0.29; P = .063) correlated with pc-ASPECTS on follow-up scans. Linear regression demonstrated a significant positive relationship between pc-ASPECTS on CTASI and follow-up scans (R2 = 0.58; P < 01). Median follow-up pc-ASPECTS was lower in patients with a CTASI pc-ASPECTS < 8 compared with patients with a CTASI pc-ASPECTS of 8 or more, respectively (P < .001). HT rates were 27.3% vs 9.5%, respectively (P = .24). None of 8 patients without thrombolysis had HT on follow-up scans. CONCLUSIONS: The extent of hypoattenuation on CTASI predicts the final infarct extent in patients with basilar artery occlusion.