Small Carotid Thrombus and Minimal Stenosis CausingRepeated Embolic Strokes

Hoan Tran, MD, Howard Yonas, MDFrom the Department of Neurosurgery, University of New Mexico, Albuquerque, NM.

Keywords: Computed tomographic an-giography, endothelial hyperplasia, orga-nizing thrombus.

Acceptance: Received March 29, 2009,and in revised form January 30, 2010. Ac-cepted for publication February 9, 2010.

Correspondence: Address correspon-dence to Hoan Tran, MD, Department ofNeurosurgery, MSC10 5615 1 Universityof New Mexico, Albuquerque, NM, 87123.E-mail: htran@salud.unm.edu.

J Neuroimaging 2011;21:266-268.DOI: 10.1111/j.1552-6569.2010.00493.x

A B S T R A C TDespite current developments in neuroradiology, the sources of infarctions go undiag-nosed in 28% of cases. An embolic source in the setting of minimal stenosis at thecarotid bifurcation has rarely been reported. The authors report a previously healthy48-year-old woman, without any risk factors for cerebrovascular events, sustained mul-tiple cerebral infarctions in the right anterior and middle cerebral artery territory.Repeated imaging of the heart and cerebral vessels missed a very small abnormal-ity arising from the posterior wall of the internal carotid artery, until it was diag-nosed by computed tomographic angiography. This is problematic because by NorthAmerican Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, minimal steno-sis essentially excludes the carotid artery as an embolic source. Despite maximum an-tiplatelet and anticoagulation therapy, she continued to have neurological deteriortationby progression of her strokes. She underwent standard carotid endarterectomy and sus-tained no new embolic phenomena. Histopathological examination showed an endothe-lial hyperplasia with organizing thrombus, which on the posterior wall of the internalcarotid artery, is likely a hemodynamically induced on top of preexisting atheroscleroticplaque.

IntroductionCarotid artery disease as a cause of embolic stroke has beenextensively studied; however, the mechanism of infarction re-mains elusive in as many as 28% of cases.1 This case reportillustrates a very small organizing thrombus arising from a min-imal atherosclerotic plaque on the posterior wall of the internalcarotid artery (ICA) that was missed by magnetic resonance an-giography (MRA) and conventional angiogram but diagnosedonly by computed tomographic angiography (CTA). After fail-ure to respond to medical therapy, the patient was successfullytreated with standard carotid endarterectomy.

Case ReportThe patient is a previously healthy 48-year-old woman, whoexperienced intermittent left hand numbness followed by fa-cial weakness and dysarthria. The past medical history andfamily history was negative except for a second-degree rela-tive who was treated for a cerebral aneurysm. A brain MRIdisclosed a right subinsular and subcortical frontal lobe infarc-tion on restricted diffusion. Conventional cerebral angiogramand MRA revealed no abnormality of the extra or intracra-nial vessels and the patient was started on aspirin and plavixtherapy. The transesophageal echocardiogram was negative forany thrombogenic phenomenon. CT angiogram of the headand neck revealed no narrowing of the extra- or intracranialvessels or any aneurysmal dilatation. Three-dimensional ren-dering of the CTA study demonstrated a small finger-like ab-normality extending a few millimeters into the lumen of theICA arising from its posterior wall just distal to the carotid

bifurcation (Fig 1). IV heparin was initiated, however, de-spite full anticoagulation and continued antiplatelet therapy,the patient experienced additional embolic events over the next24 hours.

ResultsA standard endarterectomy approach was used to explore thecarotid bulb. A very thin plaque covered about one-third ofthe circumference of the bulb easily separated from the un-derlying muscularis was found at surgery. In the center ofthe thin plaque was a broad base thrombus formation (Fig 2).The specimen measured .2 cm by .7 cm with a plaque thick-ness of .2-.3 cm. On histological examination, an organizedfibrin thrombus was identified interwoven with layers of inti-mal hyperplasia. The thrombus was fibrin and platelets, dis-cretely separated from the smooth base. The base consists ofatherosclerotic plaque with intimal proliferation (Fig 3). Anelastin stain was negative for dissection. The postoperative CTAshowed no ICA irregularity and the patient sustained no newstrokes.

DiscussionIt is well accepted that plaque formation is caused by endothe-lial cell dysfunction resulting in intimal hyperplasia, followedby lipid accumulation, cellular recruitment, and inflammation.It has been shown that biomechanical forces can account forthe preferential location of plaque formation. These forces can

266 Copyright ◦C 2011 by the American Society of Neuroimaging

Fig 1. (A) Head CT angiogram confirms a small defect on the posterior wall of the right internal carotid, just after the bifurcation (arrowhead).(B) Sagittal reconstruction of the CT angiogram shows a small defect measuring about 2 mm, pointing rostrally, initially read as a carotiddissection (arrowhead).

cause endothelial dysfunction by increasing permeability be-cause of low shear stress and high spatial shear stress gradi-ents.2 Temporal gradients of shear stress by itself can stimulateendothelial proliferation.3 Biomechanical studies have repeat-edly shown that areas of low wall shear stress are most likely todevelop atherosclerosis, while areas of high wall stress are moreatheroprotective, particularly in the human carotid artery.4 Us-ing MRI/MRA, Gelfand et al. found that there is circumfer-ential heterogeneity of flow within the internal carotid sinusjust distal to the bifurcation, and the area of lowest wall shearstress is again opposite to the bifurcation.5 Our patient had anabnormality on the posterior wall of the ICA directly oppositethe bifurcation, the most likely location for biomechanicallyinduced endothelial dysfunction and atherosclerotic plaque ini-tiation. Histopathology of the surgical specimen confirmed thepresence of endothelial proliferation on top of a preexistingsmooth plaque.

In our case, conventional angiography and MRA was unableto detect the finding on CTA: a very small abnormality arisingfrom the posterior wall of the ICA. In this setting, NASCETis problematic because NASCET advocates for medical treat-ment for stenosis less than 50%. After aspirin, plavix, and IVheparin, the patient remained resistant to medical therapy andcontinued to have strokes. Only after medical therapy did weconsider surgical therapy, which proved successful for the fail-ing patient.

ConclusionAn embolic source in the setting of minimal stenosis hasbeen rarely reported. We believe this lesion, which in-volves endothelial hyperplasia with an organizing throm-bus, is hemodynamically induced on top of an existingatherosclerotic plaque of the ICA. The same mechanical forcesthat damage the endothelium are likely to have provided

Fig 2. (A) Finger-like projection of surface organizing thrombus (white arrowheads), dissected with the smooth early atheroscleroticplaque. (B) Longitudinal microsection of the thrombus. Notice the thin atherosclerotic plaque underneath, separate and discrete from thethrombus with hemorrhagic ill-defined margins. (C) Longitudinal section of the specimen shows layers of platelets and fibrin clot (blackarrowheads).

Tran and Yonas: Small Carotid Thrombus and Minimal Stenosis 267

Fig 3. Between the layer of intimal proliferation on top and thesmooth atherosclerotic plaque on the bottom, is an organized fibrinthrombus capable of embolizing. Immunohistochemical staining ruledout atrial myxoma, and elastin staining was negative for dissection.

a site for early thrombus formation, ultimately leading to em-bolic phenomena. Finding a symptomatic embolic source froma nonstenotic ICA is rare, but it suggests that our method fordetection and our criteria for surgical intervention should bemodified to include such presumably rare phenomena. Thisalso illustrates the ability of CTA to detect such rare and verysmall pathology. Because this type of lesion is often easily over-looked, its true incidence remains to be determined.

References1. Fieschi C, Argentino C, Lenzi GL, et al. Clinical and instrumental

evaluation of patients with ischemic strokes within the first 6 hours.J Neurol Sci 1989;91:311-321.

2. Himburg HA, Grzybowski DM, Hazel AL, et al. Spatial comparisonbetween wall shear stress measures and porcine arterial endothelialpermeability. Am J Physiol 2004;286:H1916.

3. White CR, Haidekker M, Bao X, et al. Temporal gradients in shear,but not spatial, gradients stimulate endothelial cell proliferation. Cir-culation 2001;103:2508.

4. Ku DN, Giddens DP, Zarins CK, et al. Pulsatile flow and atheroscle-rosis in the human carotid bifurcation. Positive correlation be-tween plaque location and low oscillating shear stress. Artheriosclerosis1985;5:293-302.

5. Gelfand BD, Epstein FH, Blackman BR. Spatial and Spectral hetero-geneity of time varying shear stress profiles in the carotid bifurcationby Phase contrast MRI. J Magn Reson Imaging 2006;24:1386-1392.

268 Journal of Neuroimaging Vol 21 No 3 July 2011