Spontaneous Echo-Contrast in the Internal Jugular Veins of Patients with Ischemic Stroke Jay Chol Choi, MD, PhD,1 Yun-Hee Oh, RN,1 Joong Goo Kim, MD,1 Hyeon-Ju Kim, MD, PhD,2 Mi-Hee Kong, MD, PhD,2 Dong-Guk Paeng, PhD,3 Nerissa U. Ko, MD, MAS,4 J. Donald Easton, MD4 1

Department of Neurology, Jeju National University, Jeju, Korea Department of Family Medicine, Jeju National University, Jeju, Korea 3 Department of Ocean System Engineering, Jeju National University, Jeju, Korea 4 Department of Neurology, University of California–San Francisco, San Francisco, California 2

Received 3 April 2014; accepted 7 October 2014

ABSTRACT: Purpose. Spontaneous echo-contrast (SEC) appears on B-mode images as moving curls of smoke in the lumen of veins. The aims of this study were to investigate the prevalence and characteristics of internal jugular vein SEC among patients with stroke, in comparison with control subjects. Methods. We enrolled 97 Korean patients with acute ischemic stroke and 50 controls. Both internal jugular veins were examined for the presence and severity of SEC and measurement of flow velocity. Venous samples were obtained for laboratory evaluation of hematologic factors. Results. In 294 internal jugular veins, the prevalence of SEC was 81% in stroke patients and 68% in controls (odds ratio, 2.0; 95% confidence interval, 1.1– 3.6; p 5 0.013). Stroke patients were more likely to have SEC on the left (p 5 0.025) than on the right (p 5 0.184) internal jugular vein. Overall, the association between stroke and SEC remained significant after adjustment for other variables (odds ratio, 4.3; 95% confidence interval, 1.7–10.8; p 5 0.002). Conclusions. Internal jugular vein SEC was found more frequently in stroke patients than in controls. However, local as well as systemic factors must be C 2014 considered in the interpretation of this finding. V Wiley Periodicals, Inc. J Clin Ultrasound 43:431–437,

Additional Supporting Information may be found in the online version of this article. This work was supported by a research grant from Jeju National University Hospital. The authors report no conflicts of interest. Correspondence to: J. C. Choi C 2014 Wiley Periodicals, Inc. V

VOL. 43, NO. 7, SEPTEMBER 2015

2015; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.22249 Keywords: spontaneous echo-contrast; internal jugular vein; ischemic stroke

INTRODUCTION

S

pontaneous echo-contrast (SEC) appears on B-mode images as moving curls of smoke and can be frequently observed in the left atrium on transesophageal echocardiography of patients with mitral stenosis or nonvalvular atrial fibrillation.1–3 This phenomenon is caused by increased ultrasonic backscattering from red blood cells and macromolecules, usually fibrinogen.4–6 Clinically, SEC found in the left atrium is closely correlated with increased risk of subsequent thromboembolism.3,7 SEC has been also observed in internal jugular veins (IJVs),8,9 more frequently in patients with carotid atherosclerosis than in patients with normal carotid sonographic findings.9 Recently, a history of ischemic stroke was found to be associated with severe grades of SEC in IJVs.8 Unfortunately, the study enrolled only a small number of patients with a history of ischemic stroke and did not report detailed characteristics of their strokes.8 Therefore, the clinical significance of IJV SEC in ischemic stroke patients is still unclear. In the present study, we investigated the prevalence and characteristics of IJV SEC in patients with ischemic stroke in comparison 431

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with controls, and we searched for correlations with any particular stroke pathologic mechanism in stroke patients. METHODS

Study Participants Participants in this study were Korean patients with acute ischemic stroke aged more than 18 years. We enrolled the patients who received carotid sonographic examination at admission to Jeju National University Hospital within 7 days of symptom onset. They were diagnosed as acute ischemic stroke on the basis of neurologic examination, cranial CT, or MRI. The controls were subjects who visited the hospital for a regular checkup and had no history of stroke. To verify their stroke-free status, the interviewer asked each control if he or she had been advised as having had a stroke by a physician or had ever experienced hemiparesis, hemi-sensory loss, or speech difficulty.10 We received written informed consent from all participants, and this study was approved by the local ethics committee. Clinical and Laboratory Assessment Fasting venous blood was drawn for laboratory evaluation of hemoglobin, hematocrit, glucose, total cholesterol, and serum fibrinogen in control subjects on the same day as their sonographic examination. For the patients with strokes, blood samples for measurement of glucose, hemoglobin, hematocrit, and fibrinogen were obtained on the day of admission; venous blood for the measurement of low-density lipoprotein (LDL) cholesterol and total cholesterol was obtained on the day after admission when the patients had been fasting for at least 8 hours. Before the sonographic examination, we measured body height, weight, and systolic and diastolic blood pressure of all participants. Body mass index was calculated as body weight (in kilograms) divided by height (in meters) squared. Hypertension was defined as a blood pressure of at least 140/90 mmHg or the use of an antihypertensive agent. Diabetes mellitus was defined as a fasting blood glucose level of at least 126 mg/dl or the use of antidiabetic medication. Hypercholesterolemia was defined as total cholesterol over 240 mg/dl. Smoking status was determined by self-reporting as a smoker (current or ex-smoker) or nonsmoker. Atrial fibrillation was defined as electrocardiographic evidence including Holter monitoring in stroke patients or documented history of atrial fibrillation. In patients with ischemic 432

stroke, the location of their infarct was identified on brain CT or MRI and were categorized as cortex, subcortex (basal ganglia, internal capsule, thalamus, or corona radiata), brainstem or cerebellum (midbrain, pons, medulla, or cerebellum), or multiple. Symptomatic arterial stenosis was defined as greater than 50% diameter reduction of the artery supplying the acute infarct.11 Ischemic stroke was classified as large-artery atherosclerosis, small-vessel occlusion, cardio-embolism, ischemic stroke of undetermined etiology, or ischemic stroke of other determined etiology according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.12 The severity of stroke was measured using the initial National Institutes of Health stroke scale (NIHSS) score on the day of admission. Sonographic Examination Sonography was performed in the supine position using a HD15 ultrasound system (Philips, Andover, MA, USA) equipped with an 8–12MHz linear transducer, by an experienced sonographer. The dynamic range was set at 50 dB and the initial gain was set at 70 dB to acquire B-mode images. We tried to minimize changes of settings during insonation, although depth was adjusted according to subjects’ condition. For insonation of carotid arteries and IJVs, the head of the participant was turned away from the insonated side by 10–20 . The examination of carotid arteries included longitudinal and axial sections of the common carotid artery, the internal carotid artery, and the external carotid artery. The angle-adjusted peak-systolic, end-diastolic, and time-averaged mean flow velocities were obtained in all carotid arteries. Flow velocities were also measured within the area of greatest stenosis along the carotid artery, and the degree of carotid artery diameter reduction was stratified into normal (no stenosis),