Extracranial Large Artery Atherothrombosis

Chapter 5 Extracranial Large Artery Atherothrombosis

Extracranial atherothrombotic disease is an important cause of stroke, and the management of asymptomatic occlusive disease poses additional challenges and opportunities for stroke prevention. Depending on the population studied, approximately 20% of strokes are attributed to large vessel extracranial disease.¹ The prevalence of asymptomatic carotid stenosis greater than 50% stenosis is approximately 3% in the general population.²^–⁴ There is a higher prevalence of extracranial atherosclerotic disease in whites compared with African Americans and other ethnic groups.^5,⁶

The workup of stroke patients requires a careful examination of the extravascular tree to determine vessel pathology and stroke etiology. This investigation must include the carotid bifurcation and vertebral artery origin, which are sites characteristically affected by atherosclerosis. Other forms of extracranial vasculopathy such as arterial dissections typically spare these regions but tend to occur in the distal cervical segments of the carotid and vertebral arteries. Inflammatory extracranial vasculopathies are rare; the most common, Takayasu arteritis, typically affects the origins of the large extracranial vessels as they exit the aortic arch. Understanding how various arterial segments are preferentially affected by different vascular pathologies is often helpful in making an accurate diagnosis of stroke etiology.

Diagnostic imaging of the extracranial cerebrovasculature includes ultrasonography, magnetic resonance (MR), computed tomography (CT), and catheter cerebral angiography. In patients with stroke or transient ischemic attacks (TIA), it is essential to determine the degree of internal carotid artery (ICA) stenosis because this is the most important predictor of stroke recurrence. Symptomatic patients with 50% to 69% and greater than 70% stenosis and asymptomatic patients with stenosis exceeding 60% must be reliably identified because arterial revascularization is typically considered at these cutoff points.

ULTRASONOGRAPHY

Ultrasound remains a powerful screening and diagnostic tool in the examination of extracranial carotid and vertebral vessels. It has excellent diagnostic accuracy for carotid stenosis and correlation with the gold standard cerebral catheter angiography. The advantages of ultrasonography include its ease of performance and direct visualization of plaque composition and contour.

Determining the exact degree of stenosis remains the single most important goal of extracranial ultrasonography. However, plaque composition is an additional determinant of future stroke risk, particularly in the setting of symptomatic stenosis. Carotid plaques that are hypoechoic (i.e., have a dark intraplaque area), or ulcerated are of particular concern.⁷^–¹¹ These hypoechoic areas are likely to represent intraplaque hemorrhage, and these plaques should be considered unstable, thus having an increased thromboembolic potential. The presence of calcifications, in contrast, imparts relative plaque stability, and such plaques are less likely to be symptomatic¹² (Figure 5-1).

Figure 5-1 (A) Heavily calcified plaque at the internal carotid artery (ICA) origin. The arrows outline an acoustic shadow created by the plaque on the near wall of the artery (top wall on the image shown). The shadow prevents further morphological characterization of the plaque as well as velocity determination within the plaque. This may potentially interfere with determining the true degree of stenosis with ultrasonography and should be recognized as a potential limitation of the study. (B) Hypoechoic plaque. The arrows point to the dark outlines of a circumferential echolucent plaque. Echolucencies are associated with plaque instability. (C) Ulcerated plaque: power Doppler of an ulcerated plaque. The image on the left shows the depth of the ulcer measured at 2.5 mm.

Ultrasonography is technician-dependent and requires considerable skill and expertise. It is typically used as an initial screening tool, and thereby sensitivity is optimized at the expense of specificity-that is, it will tend to overestimate the degree of stenosis resulting in some false-positive results. Therefore a confirmatory test is necessary to improve the overall accuracy of the diagnostic approach.¹³ Ultrasound is less reliable in identifying carotid stenosis in moderate ranges (between 50% and 69%)^14,¹⁵ and carotid occlusion.¹³

Because ultrasonography uses an increase in flow velocities as the main diagnostic criterion, the findings of ultrasonography in the setting of abnormal collateral flow patterns must be carefully interpreted. This situation often arises during insonation of a moderately stenotic plaque in patients with contralateral occlusion or high-grade stenosis. In these cases, ultrasound may overestimate the degree of stenosis of the moderately stenotic plaque,^16,¹⁷ and the findings on ultrasonography must be cautiously reviewed and confirmed with other imaging modalities.

It is also important to realize that ultrasonography only visualizes the proximal portion of the carotid artery, and pathology involving the distal cervical segment may be unrecognized.

MR AND CT ANGIOGRAPHY

In general clinical practice, the findings on ultrasonography are often confirmed with an alternate imaging technique. MR and CT angiography have essentially replaced catheter angiography as the confirmatory test. The advantages MR and CT angiography are that they are noninvasive and readily available. The sensitivity and specificity for both techniques exceeds 80% to 90%.^13,^15,^18,¹⁹ For the majority of patients, this approach (i.e., ultrasonography and CT/MR angiography combined) will correctly identify the true degree of stenosis. However, it continues to be controversial if noninvasive techniques are reliable enough to make decisions about surgical intervention, particularly if the degree of stenosis is in the moderate (50%–69%) range.¹⁵

CT angiography has recently experienced a revival with the advent of multislice detectors and development of sophisticated postimaging software. Advantages of CT over MR angiography lie in its acquisition speed. Even though few data are available with these newer techniques, they are likely to improve further the diagnostic accuracy of CT angiography.¹⁹

MR angiography is widely used at present but has some inherent limitations. There is a tendency for overestimation of the degree of stenosis because of sampling error. Therefore MR angiography may be more valuable as a screening tool rather than to confirm that stenosis is actually present.²⁰ The specificity and sensitivity can be improved with gadolinium administration.^20,²¹

Diagnostic accuracy of noninvasive imaging is generally improved if results of ultrasonography and MR or CT angiography are concordant.¹³

CATHETER CEREBRAL ANGIOGRAPHY

Catheter cerebral angiography remains the gold standard in determining the degree of stenosis and identifying surgical candidates. However, even in recent clinical trials, there has been a trend in favor of noninvasive testing, particularly in asymptomatic patients, given the risks of catheter angiography.²² The risk of stroke may be as high as 1.2% in asymptomatic patients; however, other reports have shown a reduced risk of serious complications in general practice.^23,²⁴

Less well recognized are subclinical infarcts detected by diffusion-weighted MR imaging after diagnostic cerebral angiography. Such lesions are present in up to 20% of patients and are the result of silent microembolism,²⁵ but might produce subtle neuropsychiatric manifestations that go undetected.

A 75-year-old hypertensive diabetic woman developed right-sided weakness. Extracranial ultrasonography showed a right ICA occlusion and left ICA high-grade stenosis meeting diagnostic criteria for stenosis exceeding 70% of the luminal diameter. MR angiography of the neck showed a high-grade left internal stenosis and confirmed the right internal carotid occlusion. On cerebral angiography, the left carotid stenosis was carefully measured to be 60% (Figure 5-2). The external carotid artery was occluded.

Figure 5-2 (A) Ultrasound shows elevation of flow velocities across the plaque with a peak systolic velocity of 279.9 cm/sec. This is suggestive of a high-grade stenosis exceeding 70%. Peak systolic flow velocities are the most reliable and reproducible diagnostic criteria in the determination of the degree of stenosis. (B) A high-grade stenosis is also apparent on magnetic resonance angiography. (C) Cerebral angiography measures the degree of stenosis at 60%.

♦ The results of ultrasonography must be carefully interpreted in situations in which increased blood flow from collateralization is expected, for example, in this case because of occlusion of the contralateral ICA and possibly the ipsilateral external carotid artery.

♦ Noninvasive tests may overestimate the degree of stenosis in cases of moderate (50%–69%) narrowing.

CLINICAL FEATURES OF CAROTID ATHEROTHROMBOSIS

A 76-year-old man with a prior history of hypertension developed three episodes of sudden transient left hand and forearm numbness lasting 10 to 15 minutes over the previous week. His neurological examination showed no abnormalities. A harsh right carotid bruit was heard on neck auscultation. He underwent an emergent carotid ultrasound, which revealed a hypoechoic plaque at the right internal carotid origin causing high-grade stenosis of the lumen. MR angiography of the neck performed later confirmed these findings (Figure 5-3). He was admitted to a local hospital and placed on antithrombotic therapy. The following morning, he developed left-sided facial droop, dysarthria, and left-arm paralysis. He underwent an emergent endarterectomy and recovered without residual deficits.

Figure 5-3 (A and B) Longitudinal and axial ultrasound images of a hypoechoic plaque indicated by arrows. ICA, internal carotid artery. (C) Magnetic resonance angiography image confirms a high-grade stenosis.

This case illustrates the clinical hallmarks of large arterial atherothrombosis:

♦ High association with TIA compared with other stroke mechanisms

♦ Repetitive stereotypical symptoms within the same vascular distribution that are unlikely to occur with cardiac embolism

♦ Presence of a bruit, even though the sensitivity and specificity of a carotid bruit for high-grade stenosis is only approximately 60%²⁶

♦ High risk of stroke and hyperacute stroke recurrence after initial presentation. Large arterial disease is the stroke subtype associated with the highest incidence of early stroke recurrence ²⁷

♦ Failure of medical therapy to prevent recurrent symptoms and need for early surgical intervention (In fact the benefit of endarterectomy diminishes greatly if performed more than 2 weeks after symptom onset.²⁸)

A 55-year-old smoker underwent a routine ocular examination and was found to have a Hollenhorst plaque in her right eye. She denied any visual symptoms. Carotid ultrasound revealed an ulcerated plaque at the origin of the right ICA causing no more than 30% to 40% stenosis (Figure 5-4). She was placed on aspirin, and her vascular risk factors were treated intensively.

Figure 5-4 Ultrasound image of a low-grade bifurcation stenosis. ICA, internal carotid artery.

MECHANISMS OF INFARCTION

In extracranial large vessel disease the brain is affected by important pathophysiological events taking place at significant distances. These processes include thromboembolism and the downstream effects of decreased perfusion with increasing degrees of stenosis. These two mechanisms are embolic and hemodynamic.

Atherothrombotic Embolism

Artery-to-artery embolism is the most common mechanism of symptoms in large-artery disease. Emboli generated from an unstable carotid plaque may lead to a wide spectrum of symptoms from benign to disabling. These include asymptomatic retinal emboli, transient monocular blindness, retinal arterial infarction, hemispheric TIA, and small or large territorial strokes. Emboli are likely to consist of varying combinations of platelets, cholesterol particles and fibrin.

♦ Cholesterol emboli are often asymptomatic.

♦ Asymptomatic retinal emboli are surprisingly common and have a prevalence of approximately 1% in a general population aged 50 and older.²⁹

♦ Retinal emboli identify a subgroup of patients with asymptomatic atherosclerotic disease who will require aggressive management of vascular risk factors.

A 68 year-old man with history of hypertension, dyslipidemia, and diabetes developed sudden onset of left arm and leg numbness. On examination, he had diminished left-arm sensation and sensory extinction. Brain MRI showed an acute infarct in the right parietal lobe on diffusion-weighted imaging sequence. Fluid-attenuated inversion recovery (FLAIR) showed a prior infarct in right middle cerebral territory (Figure 5-5). Carotid ultrasound and MR angiography revealed high-grade stenosis of the right ICA artery at its origin.

Figure 5-5 (A) Diffusion-weighted imaging (DWI) showing an acute right parietal infarction. (B) Review of fluid-attenuated inversion recovery images show prior ischemic insult; DW imaging does not demonstrate this infarction to be acute.

♦ Carotid atherosclerotic disease frequently causes partial territorial infarctions as a consequence of artery-to-artery embolism.

♦ Subclinical infarction may be seen in the vascular distribution of the stenotic vessel, suggesting prior asymptomatic embolism.

♦ Infarcts related to atherothrombosis are generally smaller than those associated with cardiac embolism, which tend to generate large emboli and complete territorial infarctions.

Even though the degree of carotid stenosis remains the single most important factor in predicting stroke risk in symptomatic patients, certain situations warrant a more careful assessment of carotid disease, as illustrated in the next case vignette.

A 56-year-old man with hypertension and dyslipidemia had a history of two previous strokes in the territory of the left middle cerebral artery. He presented with new onset of right-arm weakness and mild speech difficulties. Brain MRI showed a small acute ischemic stroke in the left frontal lobe. He underwent a careful investigation of his vascular tree and cardiac evaluations including MR angiography of the brain, transthoracic and transesophageal echocardiograms, and Holter monitoring of the cardiac rhythm. All tests failed to reveal the mechanism of his infarction.

A carotid ultrasound showed plaque formation in the left carotid bulb, which produced no alteration of Doppler flow pattern and was estimated to cause no more than 50% stenosis of the luminal diameter (Figure 5-6). Subsequently, he underwent a catheter cerebral angiogram, which confirmed the presence of an ulcerated left carotid bulb plaque, causing no significant stenosis. Given the repetitive nature of his symptoms restricted to a single vascular distribution, it was felt that his symptoms were most likely explained by repeated thromboembolism from the proximal ICA plaque. Consequently, he was treated with left carotid endarterectomy. A hemorrhagic ulcerated plaque was found at the time of the operation. He recovered well from surgery and has been symptom-free for the following 2 years.

Figure 5-6 (A) Ultrasound of proximal internal carotid artery shows plaque formation in the carotid bulb. The arrows outline the wall of the artery. Velocity measurements do not suggest a high-grade stenosis. (B) Cerebral angiography shows an ulcerated plaque. The arterial wall of the bulb filled with a sizable atheroma is outlined by the arrows, not causing significant luminal stenosis.

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Tags: Practical Neuroimaging in Stroke A Case-Based Approach

Jul 23, 2016 | Posted by admin in NEUROLOGICAL IMAGING | Comments Off

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