CT angiography and CT perfusion improve prediction of infarct volume in patients with anterior circulation stroke.

INTRODUCTION: We investigated whether baseline CT angiography (CTA) and CT perfusion (CTP) in acute ischemic stroke could improve prediction of infarct presence and infarct volume on follow-up imaging. METHODS: We analyzed 906 patients with suspected anterior circulation stroke from the prospective multicenter Dutch acute stroke study (DUST). All patients underwent baseline non-contrast CT, CTA, and CTP and follow-up non-contrast CT/MRI after 3 days. Multivariable regression models were developed including patient characteristics and non-contrast CT, and subsequently, CTA and CTP measures were added. The increase in area under the curve (AUC) and R (2) was assessed to determine the additional value of CTA and CTP. RESULTS: At follow-up, 612 patients (67.5%) had a detectable infarct on CT/MRI; median infarct volume was 14.8 mL (interquartile range (IQR) 2.8-69.6). Regarding infarct presence, the AUC of 0.82 (95% confidence interval (CI) 0.79-0.85) for patient characteristics and non-contrast CT was improved with addition of CTA measures (AUC 0.85 (95% CI 0.82-0.87); p < 0.001) and was even higher after addition of CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001) and combined CTA/CTP measures (AUC 0.89 (95% CI 0.87-0.91); p < 0.001). For infarct volume, adding combined CTA/CTP measures (R (2) = 0.58) was superior to patient characteristics and non-contrast CT alone (R (2) = 0.44) and to addition of CTA alone (R (2) = 0.55) or CTP alone (R (2) = 0.54; all p < 0.001). CONCLUSION: In the acute stage, CTA and CTP have additional value over patient characteristics and non-contrast CT for predicting infarct presence and infarct volume on follow-up imaging. These findings could be applied for patient selection in future trials on ischemic stroke treatment.

Relation between stroke severity, patient characteristics and CT-perfusion derived blood-brain barrier permeability measurements in acute ischemic stroke.

PURPOSE: Increased blood-brain barrier permeability (BBBP) can result from ischemia. In this study the relation between stroke severity, patient characteristics and admission BBBP values measured with CT-perfusion (CTP) was investigated in acute ischemic stroke patients. METHODS: From prospective data of the Dutch Acute Stroke Study 149 patients with a middle cerebral artery stroke and extended CTP were selected. BBBP values were measured in the penumbra and infarct core as defined by CTP thresholds, and in the contra-lateral hemisphere. The relation between stroke (severity) variables and patient characteristics, including early CT signs, dense vessel sign (DVS), time to scan and National Institute of Health Stroke Score (NIHSS), and BBBP parameters in penumbra and infarct core was quantified with regression analysis. RESULTS: Early CT signs were related to higher BBBP values in the infarct core (B = 0.710), higher ipsi- to contra-lateral BBBP ratios (B = 0.326) and higher extraction ratios in the infarct core (B = 16.938). Females were found to have lower BBBP values in penumbra and infarct core (B = - 0.446 and - 0.776 respectively) and lower extraction ratios in the infarct core (B = - 10.463). If a DVS was present the ipsi- to contra-lateral BBBP ratios were lower (B = - 0.304). There was no relation between NIHSS or time to scan and BBBP values. CONCLUSION: Early CT signs are related to higher BBBP values in the infarct core, suggesting that only severe ischemic damage alters BBBP within the first hours after symptom onset.

Quantification of structural cerebral abnormalities on MRI 18 months after aneurysmal subarachnoid hemorrhage in patients who received endovascular treatment.

INTRODUCTION: Volume measurements performed on brain MRI after aneurysmal subarachnoid hemorrhage (aSAH) may provide insight into the structural abnormalities that underlie the commonly occurring and persistent long-term functional deficits after aSAH. We examined the pattern of long-term cerebral structural changes on MRI in relation to known risk factors for poor functional outcome. METHODS: We studied MRI scans from 38 patients who received endovascular treatment and were not dependent for activities of daily life at 18 months after aSAH. Risk factors for poor functional outcome (clinical condition, Hijdra score, and bicaudate index on admission; occurrence of hydrocephalus or delayed cerebral infarction during hospitalization) were related to supratentorial cerebral parenchymal and lateral ventricular volumes on MRI with linear regression analyses adjusted for age, sex, and intracranial volume. RESULTS: Clinical condition, Hijdra score, and bicaudate index on admission were not related to cerebral parenchymal volume at 18 months. A higher bicaudate index on admission was related to lateral ventricular enlargement at 18 months after aSAH (Beta; 95%CI: 0.51; 0.14↔0.88). Delayed cerebral infarction was related to smaller cerebral parenchymal volumes (-0.14; -0.25↔-0.04) and to lateral ventricular enlargement (0.49; 0.16↔0.83) at 18 months. CONCLUSION: Volume measurements of the brain are able to quantify patterns of long-term cerebral damage in relation to different risk factors after aSAH. Application of volumetric techniques may provide more insight into the heterogeneous underlying pathophysiological processes. After confirmation of these results in larger studies, volumetric measures might even be used as outcome measures in future treatment studies.

Residual high-grade stenosis after recanalization of extracranial carotid occlusion in acute ischemic stroke.

BACKGROUND AND PURPOSE: Residual stenosis after recanalization of an acute symptomatic extracranial occlusion of the internal carotid artery (ICA) might be an indication for carotid endarterectomy. We evaluated the proportion of residual high-grade stenosis (≥70%, near occlusions not included) on follow-up imaging in a consecutive series of patients with an acute symptomatic occlusion of the extracranial ICA. METHODS: We included patients participating in the Dutch Acute Stroke Study (DUST), who had an acute symptomatic occlusion of the extracranial ICA that was diagnosed on computed tomographic angiography within 9 hours after onset of neurological symptoms. Follow-up imaging of the carotid artery had to be available within 7 days after admission. RESULTS: Of the 1021 patients participating in DUST between May 2009 and May 2013, an acute symptomatic occlusion of the extracranial ICA was found in 126 (12.3%) patients. Follow-up imaging was available in 86 (68.3%) of these patients. At follow-up, a residual stenosis of <30% was found in 15 (17.4%; 95% confidence interval, 10.8-26.9) patients, a 30% to 49% stenosis in 3 (3.5%; 95% confidence interval, 0.8-10.2) patients, a 50% to 69% stenosis in 2 (2.3%; 95% confidence interval, 0.1-8.6) patients, and a ≥70% stenosis in 14 (16.3%; 95% confidence interval, 9.8-25.6) patients. A near or persistent occlusion was present in the remaining 52 (60.5%) patients. CONCLUSIONS: A residual high-grade stenosis of the extracranial ICA occurs in 1 of 6 patients with a symptomatic occlusion in the acute stage of cerebral ischemia. Because this may have implications for secondary prevention, we recommend follow-up imaging in these patients within a week after the event. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00880113.

Prediction of outcome in patients with suspected acute ischaemic stroke with CT perfusion and CT angiography: the Dutch acute stroke trial (DUST) study protocol.

BACKGROUND: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated. METHODS/DESIGN: The DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests. DISCUSSION: This study will provide insight in the added prognostic value of CTP and CTA parameters in outcome prediction of acute stroke patients. The prediction models that will be developed in this study may help guide future treatment decisions in the acute stage of ischaemic stroke.

Admission hyperglycaemia and cerebral perfusion deficits in acute ischaemic stroke.

INTRODUCTION: Hyperglycaemia (HG) occurs in 30-40% of the patients with acute ischaemic stroke and is associated with larger infarct size and poor functional outcome. It is unknown whether HG is also associated with larger perfusion deficits in the acute stage of ischaemic stroke. As perfusion computed tomography (CT) is a reliable technique to determine the infarct core and ischaemic penumbra, we aimed to determine if patients with acute ischaemic stroke and HG have larger perfusion deficits or infarct cores on admission perfusion CT than patients with normoglycaemia (NG). METHODS: We identified 80 consecutive patients (mean age 69 ± 11 years, 58% men) with acute supratentorial non-lacunar ischaemic stroke in whom CT showed a perfusion deficit within 24 h after stroke onset. The size of the total perfusion deficit area (mean transit time of >145% compared to the contralateral hemisphere) and the infarct core area (cerebral blood volume of <2.0 ml/100 g) at the level of the basal ganglia (level 1) and at the level of the corona radiata (level 2) were compared between patients with HG (admission glucose ≥7.0 mM) and patients with NG with a MANOVA. Clinical outcome [modified Rankin Scale (mRS) score] after 6 months was correlated to glucose levels at admission. RESULTS: Admission HG was present in 33 of the 80 patients (41%). A perfusion deficit was present in 79 (40% HG) patients at level 1 and 75 (43% HG) at level 2. The total area with a perfusion deficit (level 1 HG 22.1 ± 11.3 and NG 23.3 ± 12.3 cm(2); level 2 HG 27.1 ± 12.3 and NG 25.4 ± 12.0 cm(2)) and the proportion of the infarct core (level 1 HG 31 ± 30% and NG 25 ± 22%; level 2 HG 33 ± 27% and NG 26 ± 23%) did not differ significantly between the groups. HG was associated with worse outcome (mRS ≥3) at 6 months (OR 2.6, 95% CI 0.72-9.1). CONCLUSIONS: As compared to patients with NG, patients with HG did not have larger perfusion deficits in the acute stage of ischaemic stroke. Nevertheless, functional outcome was worse in patients with HG, which means that poor clinical outcome in stroke patients with HG could not be explained by a larger perfusion deficit in the acute stage. Therefore, our study suggests that there might be a window of opportunity for glucose-lowering therapy in the future.

Diabetes, hyperglycaemia, and acute ischaemic stroke.

Diabetes and ischaemic stroke often arise together. People with diabetes have more than double the risk of ischaemic stroke after correction for other risk factors, relative to individuals without diabetes. Multifactorial treatment of risk factors for stroke-in particular, lifestyle factors, hypertension, and dyslipidaemia-will prevent a substantial number of these disabling strokes. Hyperglycaemia occurs in 30-40% of patients with acute ischaemic stroke, also in individuals without a known history of diabetes. Admission hyperglycaemia is associated with poor functional outcome, possibly through aggravation of ischaemic damage by disturbing recanalisation and increasing reperfusion injury. Uncertainty surrounds the question of whether glucose-lowering treatment for early stroke can improve clinical outcome. Achievement of normoglycaemia in the early stage of stroke can be difficult, and the possibility of hypoglycaemia remains a concern. Phase 3 studies of glucose-lowering therapy in acute ischaemic stroke are underway.

Symptomatic internal carotid artery occlusion: a long-term follow-up study.

BACKGROUND: Information on outcome of patients with occlusion of the internal carotid artery (ICA) is limited by the short duration of follow-up and lack of haemodynamic studies on the brain. METHODS: The authors prospectively investigated 117 consecutive patients with transient or moderately disabling cerebral or retinal ischaemia associated with ICA occlusion between September 1995 and July 1998, and followed them until June 2008. The authors determined the risk of recurrent ischaemic stroke and other vascular events and prognostic factors, including collateral pathways and transcranial Doppler CO(2) reactivity. RESULTS: Patients (mean age 61± 9 years; 80% male) were followed for a median time of 10.2 years; 22 patients underwent endarterectomy for contralateral ICA stenosis and 16 extracranial/intracranial bypass surgery. Recurrent ischaemic stroke occurred in 23 patients, resulting in an annual rate of 2.4% (95% CI 1.5 to 3.6). Risk factors for recurrent ischaemic stroke were age (HR 1.07, 1.02 to 1.13), cerebral rather than retinal symptoms (HR 8.0, 1.1 to 60), recurrent symptoms after documented occlusion (HR 4.4, 1.6 to 12), limb-shaking transient ischaemic attacks at presentation (HR 7.5, 2.6 to 22), history of stroke (HR 2.8, 1.2 to 6.7) and leptomeningeal collaterals (HR 5.2, 1.5 to 17) but not CO(2) reactivity (HR 1.01, 0.99 to 1.02). The composite event of any vascular event occurred in 57 patients, resulting in an annual rate of 6.4% (95% CI 4.9 to 8.2). CONCLUSION: The prognosis of patients with transient ischaemic attack or minor stroke and ICA occlusion depends on age, several clinical factors and the presence of leptomeningeal collaterals. The long-term risk of recurrent ischaemic stroke is much lower than that of other vascular events.

Hyperglycemia in aneurysmal subarachnoid hemorrhage: a potentially modifiable risk factor for poor outcome.

Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) occurs frequently and is associated with delayed cerebral ischemia (DCI) and poor clinical outcome. In this review, we highlight the mechanisms that cause hyperglycemia after aSAH, and we discuss how hyperglycemia may contribute to poor clinical outcome in these patients. As hyperglycemia is potentially modifiable with intensive insulin therapy (IIT), we systematically reviewed the literature on IIT in aSAH patients. In these patients, IIT seems to be difficult to achieve in terms of lowering blood glucose levels substantially without an increased risk of (serious) hypoglycemia. Therefore, before initiating a large-scale randomized trial to investigate the clinical benefit of IIT, phase II studies, possibly with the help of cerebral blood glucose monitoring by microdialysis, will first have to improve this therapy in terms of both safety and adequacy.

Fever after aneurysmal subarachnoid hemorrhage: relation with extent of hydrocephalus and amount of extravasated blood.

BACKGROUND AND PURPOSE: Fever after aneurysmal subarachnoid hemorrhage is associated with poor outcome. Because hydrocephalus and extravasated blood may influence thermoregulation, we determined whether these factors increase the risk for fever after subarachnoid hemorrhage. METHODS: Fever within 14 days (subdivided into infectious and noninfectious) was defined as a mean daily body temperature above 38.0 degrees C for at least 2 consecutive days in a prospectively collected cohort of 194 patients with subarachnoid hemorrhage. Hazard ratios were calculated to assess the impact of hydrocephalus (bicaudate index) and cisternal and intraventricular blood (Hijdra score) on the occurrence of fever. Adjusted hazard ratios were calculated in one multivariate model, including other possible confounding factors. RESULTS: Infectious fever occurred in 34% of patients and noninfectious fever in 9%. Adjusted hazard ratios of intraventricular blood were 2.2 (95% CI, 1.3 to 3.8) for any fever, 2.4 (95% CI, 1.3 to 4.4) for infectious fever, and 2.0 (95% CI, 0.7 to 5.9) for noninfectious fever. Adjusted hazard ratios of cisternal blood and hydrocephalus for infectious and noninfectious fever ranged from 0.6 to 1.5, all with wide CIs. CONCLUSIONS: Intraventricular blood is an independent risk factor for the development of fever. In this study, noninfectious fever was rare and not related to extravasated blood or hydrocephalus.