ARTICLE IN PRESS Case Studies Utility of Carotid Ultrasonography in Management of an Atypical High Vascular-Risk Patient with Recurrent Calcified Cerebral Embolic Stroke John W. Liang, MD,*,† Jesse Weinberger, MD,* and Aaron Tansy, MD* Objective: To describe a case of recurrent calcified cerebral emboli (CCE)-related acute ischemic stroke (AIS) and the diagnostic utility of plaque morphology characterization on carotid ultrasound. Background: CCE are a rare cause of AIS. CCErelated AIS has been previously reported only in high vascular-risk patients such as those with severe carotid stenosis, widespread atheromatous disease, or cardiac valvular disease. CCE-related AIS from a carotid origin has not been reported in patients without carotid stenosis. Case: A 69-year-old man with no known medical history presented with hemiparesis and aphasia was found to have a curvilinear calcification in the left sylvian fissure on brain imaging, consistent with CCE. Two months later, he developed a second episode of CCE-related AIS. Standard workup, as well as advanced imaging with digital subtraction angiography, revealed no carotid stenosis or valvular disease. Carotid ultrasound demonstrated normal flow velocities but a left carotid heterogeneous plaque with multiple ulcerative craters and lucencies, suggestive of an active thromboembolic source. Conclusion: To our knowledge, this is the first case reporting CCE-AIS from carotid origin in a patient with no carotid stenosis. Carotid ultrasound serves a diagnostic role in these patients. Key Words: Carotid—ultrasound—embolic—stroke—plaque. © 2017 Published by Elsevier Inc. on behalf of National Stroke Association. Introduction Calcified cerebral emboli (CCE) are a potential, but relatively little known cause of acute ischemic stroke (AIS).1-7 CCE-related AIS presumably results when thromboembolic material dislodges from a proximal, calcified, unstable From the *Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York; and †Department of Neurology, Divisions of Cerebrovascular Disease, Critical Care and Neurotrauma, Thomas Jefferson University, Philadelphia, Pennsylvania. Received July 15, 2016; revision received January 4, 2017; accepted April 29, 2017. Address correspondence to Aaron Tansy, MD, Mount Sinai Icahn School of Medicine, One Gustave L. Levy Place, Box 1052, New York, NY 10029. E-mail: aaron.tansy@mssm.edu. 1052-3057/$ - see front matter © 2017 Published by Elsevier Inc. on behalf of National Stroke Association. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.04.038 atherosclerotic lesion and travels distally to the cerebrovascular supply. Common arterial sources include the following: carotid stenosis,2,3 aortic valve,4 mitral valve,5,7 and the brachiocephalic trunk.6 CCE-related AIS has been reported to occur both spontaneously8 and via provoked causes.3,9 Because of its infrequency, clinical information on CCE-related AIS is overall sparse within the current literature. One single-center study utilizing noncontrast computed tomography (NCCT) estimated an approximate 3% prevalence rate in its stroke population; additionally, 27% of CCE on NCCT were misdiagnosed and 9% were overlooked on preliminary read by radiology residents.1 Furthermore, existing CCE-related literature has focused primarily only on high vascular-risk populations, the vast majority of which were due to high-grade arterial stenosis.2,8 We present a case of recurrent CCE-related, cryptogenic AIS in a patient who did not meet standard criteria for high vascular-risk status by routine and advanced Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2017: pp ■■–■■ 1 ARTICLE IN PRESS J.W. LIANG ET AL. 2 cerebrovascular imaging methods, but ultimately was considered so through and underwent endovascular treatment for nonstandard imaging criteria: lesion morphologic and qualitative findings on carotid ultrasound. This case highlights the potential importance of utilization of multimodal cerebrovascular imaging methods and integrative consideration of both standard and nonstandard imaging findings in management of CCE-related AIS. Case Report A 69-year-old man with no known medical history presented to our hospital network’s primary stroke center with acute onset aphasia, left gaze deviation, and right hemiparesis (NIH Stroke Scale 18). NCCT revealed a curvilinear calcification in the left sylvian fissure (Fig 1, A). Computed tomography angiogram revealed the calcification was nonocclusive and within a temporoparietal branch of the left middle cerebral artery, as well as bilateral carotid artery bifurcation atherosclerotic calcifications resulting in approximately 35% non–flow-limiting stenosis. There was no calcification at the aortic arch. The patient was treated with intravenous alteplase, and managed subsequently per routine protocol. At 24-hour post-treatment, NCCT demonstrated fragmentation of the calcification with evolving infarct (Fig 2, A-C). Further evaluation including echocardiography, cardiac telemetry monitoring, and outpatient long-term cardiac event monitoring revealed no definite thromboembolic source consistent with a cryptogenic event. Secondary stroke prevention optimal medical treatment including dual-agent antiplatelet therapy was initiated prior to discharge. The patient presented again to the same center approximately 2 months later with recurrent isolated aphasia (NIH Stroke Scale 2). NCCT accounted for all previously Figure 1. Noncontrast brain computed tomography with curvilinear calcification in the left sylvian fissure. seen calcified lesions and 1 newly seen calcified lesion within a previously unaffected vascular branch of the left middle cerebral artery (Fig 2, D). Treatment included intravenous alteplase, and managed again per routine protocol. Magnetic resonance imaging brain confirmed multiple small foci of acute infarction within the left middle cerebral arterial supply suggestive of an artery-to-artery thromboembolic phenomenon. The patient was subsequently transferred to our comprehensive stroke center for further care. He underwent digital subtraction angiography which revealed bilateral internal carotid artery calcified atheroma with nonsignificant <25% stenosis. Carotid ultrasound revealed normal flow patterns and velocities in both internal carotid arteries, a homogeneous appearing calcified plaque at the origin of the left ICA, as well as, slightly proximally, a heterogeneous plaque with multiple ulcerative craters and lucencies highly suggestive of an active, ruptured atherosclerotic lesion and thromboembolic source (Fig 3, A,B). Transesophageal echocardiography revealed no aortic arch plaques, left atrial appendage clots, or valvular calcifications (Fig 4). Given these radiographic findings and recurrent AIS despite maximal medical therapy, the patient underwent treatment with endovascular stent placement for plaque stabilization and protection from future events. Discussion We report a case of recurrent CCE-related, cryptogenic AIS in a patient who did not meet standard criteria for high vascular-risk status, but through nonstandard criteria found on multimodal cerebrovascular imaging was identified as such. Determination of an artery-to-artery thromboembolic source, initially not visualized with conventional and advanced imaging, was made ultimately through plaque morphology characterization uniquely appreciable with carotid ultrasound. Prior work in this laboratory has correlated ultrasound imaging of carotid plaque morphology with clinical events and pathological findings.10-12 This specialized diagnostic feature of carotid ultrasound highlights the potential utility and importance of integration and consideration of multimodal imaging techniques including ultrasound-aided plaque morphologic information when treating CCE-related AIS in patients with cryptogenic events and who may not meet standard criteria for high vascular-risk status. Importantly, although existing literature supports CCE-related AIS occurring in standard high vascular-risk patient populations,2,3,6,8,13 this case report supports that it may also occur in nonstandard high-risk ones. Furthermore, although the impact of plaque morphology and its characterization in clinical management already has been described in typical high-risk vascular populations,8,14,15 this report provides novel support that application of such nonroutine carotid ultrasound morphologic imaging techniques provides potential unique utility as well as in ARTICLE IN PRESS ATYPICAL CALCIFIED CEREBRAL EMBOLIC STROKE 3 Figure 2. (A-C) Noncontrast brain computed tomography 24 hours post intravenous alteplase with fragmentation of calcification (arrow) and development of parenchymal hypodensities. (D) New calcified lesion in a previously unaffected vascular branch (arrowhead). diagnosis and treatment for atypical high-risk vascular populations, particularly those with nonsignificant carotid stenosis like our patient had. In summary, we describe a case of recurrent ipsilateral CCE-related, cryptogenic AIS in a patient ultimately determined to meet high vascular-risk status through nonstandard criteria obtained by carotid ultrasound. This case highlights the potential importance of utilization of Figure 3. Ultrasound at origin of left internal and common carotid artery. Heterogenous low echodensity material (arrow) overlying plaque with underlying lucency (arrowhead) suggestive of an active, ruptured atherosclerotic lesion and thromboembolic source. multimodal cerebrovascular imaging methods and integrative consideration of both standard and nonstandard imaging findings especially ultrasound-aided plaque morphologic information in management of CCE-related AIS. Carotid ultrasound may play a role in the identification of the etiology of ischemic stroke in patients with cryptogenic stroke that does not have radiological findings of carotid stenosis by identifying large plaques with ARTICLE IN PRESS J.W. 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