Original Paper Received: July 2, 2013 Accepted: December 30, 2013 Published online: May 20, 2014
Eur Neurol 2014;72:45–53 DOI: 10.1159/000358297
Increased Blood-Brain Barrier Permeability on Perfusion Computed Tomography Predicts Hemorrhagic Transformation in Acute Ischemic Stroke Ozlem Ozkul-Wermester a Evelyne Guegan-Massardier a Aude Triquenot a Alaina Borden a Guillaume Perot b Emmanuel Gérardin b Departments of a Neurology and b Radiology, Rouen University Hospital, Rouen, France
Abstract Background/Purpose: Perfusion computed tomography (CT) is capable of measuring the permeability surface product (PS). PS reflects the permeability of the blood-brain barrier, involved in the pathophysiology of hemorrhagic transformation (HT) of ischemic stroke. The aim of our study was to determine if an increased PS can predict HT. Methods: A total of 86 patients with ischemic stroke were included. They underwent multimodality CT, including the measurement of PS. We compared the clinical and radiological characteristics of patients who developed HT to those who did not, using univariate analysis. Multivariate regression analyses were then used to determine HT predictors. Results: HT was observed in 27 patients (31%). Infarct PS was significantly associated with HT (p = 0.047), as were atrial fibrillation (p = 0.03), admission National Institute of Health Stroke Scale score (p = 0.02), infarct volume (p = 0.0004), presence of large-vessel occlusion (p = 0.0005) and a poorer collateral status (p = 0.003). Using logistic regression modeling, an infarct PS >0.84 ml/100 g/min was an independent predictor
© 2014 S. Karger AG, Basel 0014–3022/14/0722–0045$39.50/0 E-Mail [email protected] www.karger.com/ene
of HT (OR 28, 95% CI 1.75–452.98; p = 0.02). Other independent predictors of HT were infarct volume and a history of atrial fibrillation. Conclusions: Our findings suggest that infarct PS can be a predictor of HT and may help clinicians to improve patient care around thrombolysis decisions in the acute phase of ischemic stroke. © 2014 S. Karger AG, Basel
Introduction
Hemorrhagic transformation (HT) of acute ischemic stroke is associated with increased mortality and a poor clinical outcome [1]. It is difficult to predict a given patient’s probability of experiencing HT. Currently, several clinical parameters are known to be associated with an increased HT risk, such as age, baseline National Institute of Health Stroke Scale (NIHSS) score, previous antithrombotic treatment and thrombolytic treatment [1]. Imaging criteria can provide additional help to stratify HT risk. Early ischemic changes on cerebral noncontrast computed tomography (NCT) quantified using the Alberta Stroke Programme Early CT Score (ASPECTS), the presence of leukoaraiosis and admission diffusion-weighted imaging (DWI) have been preliminarily studied [2, 3]. Dr. O. Ozkul-Wermester Department of Neurology, Rouen University Hospital 1 rue de Germont FR–76031 Rouen Cedex (France) E-Mail ozlem.ozkul-wermester @ chu-rouen.fr
Downloaded by: UCSF Library & CKM 169.230.243.252 - 2/16/2015 12:58:57 PM
Key Words Blood-brain barrier · Perfusion computed tomography · Hemorrhagic transformation
Patients and Methods Patient Selection and Clinical Data This standard-of-care protocol received approval from the local ethics committee (CPP Nord NORD-OUEST I: CPPSC2009/001). We prospectively analyzed clinical, laboratory and imaging data in a consecutive series of patients admitted to the emergency room of the Rouen University Hospital with a clinical presentation suggesting hemispheric stroke within 6 h after symptom onset between June 2009 and December 2010. Inclusion criteria were as follows: patients older than 18 years, stroke symptom onset 145% of this contralateral-side mean MTT value and was outlined on MTT maps by hand-drawn ROIs in every slice separately and multiplied by slice thickness to obtain MTT-derived ischemic lesion volume in milliliters. We created mirror ROIs by reflecting the ischemic ROI across the midline in the unaffected hemisphere (fig. 1a).
Ozkul-Wermester et al.
Downloaded by: UCSF Library & CKM 169.230.243.252 - 2/16/2015 12:58:57 PM
Multimodal CT, including NCT, perfusion CT (PCT) and CT angiography (CTA), contributes to the evaluation of acute stroke patients with an accuracy similar to that of DWI [3, 4]. Large-vessel occlusions and poor collateral vessels on CTA have been demonstrated to be associated with an increased rate of HT and poor clinical outcomes [5–7]. PCT can distinguish between the infarct core and the penumbra using quantitative assessments of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT). Ischemic lesion volume derived from MTT maps and admission values for CBV have been reported to be strongly associated with HT [3, 8, 9]. Recently, several authors have described methods of quantifying blood-brain barrier (BBB) integrity with PCT to predict HT risk [10–14]. Loss of BBB integrity is believed to be a precursor of HT [15, 16]. Using the Johnson-Wilson model, PCT enables radiologists to calculate the permeability surface area product (PS), which assesses the rate of contrast material extravasation from the intravascular to the extravascular space through a disrupted BBB [17]. Aviv et al. [10] and Hom et al. [11] reported that patients with an increased PS have a higher risk of developing HT after acute ischemic stroke. Predicting HT in ischemic stroke patients could have essential implications for acute management, especially for recombinant tissue plasminogen activator (rtPA) administration [18]. The aim of this prospective study was to determine whether admission PCT-derived PS can predict HT after ischemic stroke.
Color version available online
a
b
c
d
with sudden onset of right hemiplegia and aphasia. a MTT map showing hypoperfusion with left middle cerebral artery acute ischemic stroke (arrow). b PS map showing abnormally high infarct PS with a mean value of 1 ml/100 g/min (arrow). c CTA with a collateral filling score of 1 (arrow). d Follow-up DWI showing PH-2 HT (arrow).
The hypoperfused areas on CBV maps with a threshold at 50% but
Eur Neurol 2014;72:45–53 DOI: 10.1159/000358297
Increased Blood-Brain Barrier Permeability on Perfusion Computed Tomography Predicts Hemorrhagic Transformation in Acute Ischemic Stroke Ozlem Ozkul-Wermester a Evelyne Guegan-Massardier a Aude Triquenot a Alaina Borden a Guillaume Perot b Emmanuel Gérardin b Departments of a Neurology and b Radiology, Rouen University Hospital, Rouen, France
Abstract Background/Purpose: Perfusion computed tomography (CT) is capable of measuring the permeability surface product (PS). PS reflects the permeability of the blood-brain barrier, involved in the pathophysiology of hemorrhagic transformation (HT) of ischemic stroke. The aim of our study was to determine if an increased PS can predict HT. Methods: A total of 86 patients with ischemic stroke were included. They underwent multimodality CT, including the measurement of PS. We compared the clinical and radiological characteristics of patients who developed HT to those who did not, using univariate analysis. Multivariate regression analyses were then used to determine HT predictors. Results: HT was observed in 27 patients (31%). Infarct PS was significantly associated with HT (p = 0.047), as were atrial fibrillation (p = 0.03), admission National Institute of Health Stroke Scale score (p = 0.02), infarct volume (p = 0.0004), presence of large-vessel occlusion (p = 0.0005) and a poorer collateral status (p = 0.003). Using logistic regression modeling, an infarct PS >0.84 ml/100 g/min was an independent predictor
© 2014 S. Karger AG, Basel 0014–3022/14/0722–0045$39.50/0 E-Mail [email protected] www.karger.com/ene
of HT (OR 28, 95% CI 1.75–452.98; p = 0.02). Other independent predictors of HT were infarct volume and a history of atrial fibrillation. Conclusions: Our findings suggest that infarct PS can be a predictor of HT and may help clinicians to improve patient care around thrombolysis decisions in the acute phase of ischemic stroke. © 2014 S. Karger AG, Basel
Introduction
Hemorrhagic transformation (HT) of acute ischemic stroke is associated with increased mortality and a poor clinical outcome [1]. It is difficult to predict a given patient’s probability of experiencing HT. Currently, several clinical parameters are known to be associated with an increased HT risk, such as age, baseline National Institute of Health Stroke Scale (NIHSS) score, previous antithrombotic treatment and thrombolytic treatment [1]. Imaging criteria can provide additional help to stratify HT risk. Early ischemic changes on cerebral noncontrast computed tomography (NCT) quantified using the Alberta Stroke Programme Early CT Score (ASPECTS), the presence of leukoaraiosis and admission diffusion-weighted imaging (DWI) have been preliminarily studied [2, 3]. Dr. O. Ozkul-Wermester Department of Neurology, Rouen University Hospital 1 rue de Germont FR–76031 Rouen Cedex (France) E-Mail ozlem.ozkul-wermester @ chu-rouen.fr
Downloaded by: UCSF Library & CKM 169.230.243.252 - 2/16/2015 12:58:57 PM
Key Words Blood-brain barrier · Perfusion computed tomography · Hemorrhagic transformation
Patients and Methods Patient Selection and Clinical Data This standard-of-care protocol received approval from the local ethics committee (CPP Nord NORD-OUEST I: CPPSC2009/001). We prospectively analyzed clinical, laboratory and imaging data in a consecutive series of patients admitted to the emergency room of the Rouen University Hospital with a clinical presentation suggesting hemispheric stroke within 6 h after symptom onset between June 2009 and December 2010. Inclusion criteria were as follows: patients older than 18 years, stroke symptom onset 145% of this contralateral-side mean MTT value and was outlined on MTT maps by hand-drawn ROIs in every slice separately and multiplied by slice thickness to obtain MTT-derived ischemic lesion volume in milliliters. We created mirror ROIs by reflecting the ischemic ROI across the midline in the unaffected hemisphere (fig. 1a).
Ozkul-Wermester et al.
Downloaded by: UCSF Library & CKM 169.230.243.252 - 2/16/2015 12:58:57 PM
Multimodal CT, including NCT, perfusion CT (PCT) and CT angiography (CTA), contributes to the evaluation of acute stroke patients with an accuracy similar to that of DWI [3, 4]. Large-vessel occlusions and poor collateral vessels on CTA have been demonstrated to be associated with an increased rate of HT and poor clinical outcomes [5–7]. PCT can distinguish between the infarct core and the penumbra using quantitative assessments of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT). Ischemic lesion volume derived from MTT maps and admission values for CBV have been reported to be strongly associated with HT [3, 8, 9]. Recently, several authors have described methods of quantifying blood-brain barrier (BBB) integrity with PCT to predict HT risk [10–14]. Loss of BBB integrity is believed to be a precursor of HT [15, 16]. Using the Johnson-Wilson model, PCT enables radiologists to calculate the permeability surface area product (PS), which assesses the rate of contrast material extravasation from the intravascular to the extravascular space through a disrupted BBB [17]. Aviv et al. [10] and Hom et al. [11] reported that patients with an increased PS have a higher risk of developing HT after acute ischemic stroke. Predicting HT in ischemic stroke patients could have essential implications for acute management, especially for recombinant tissue plasminogen activator (rtPA) administration [18]. The aim of this prospective study was to determine whether admission PCT-derived PS can predict HT after ischemic stroke.
Color version available online
a
b
c
d
with sudden onset of right hemiplegia and aphasia. a MTT map showing hypoperfusion with left middle cerebral artery acute ischemic stroke (arrow). b PS map showing abnormally high infarct PS with a mean value of 1 ml/100 g/min (arrow). c CTA with a collateral filling score of 1 (arrow). d Follow-up DWI showing PH-2 HT (arrow).
The hypoperfused areas on CBV maps with a threshold at 50% but
