Chapter 89

Cerebrovascular Disease

Martyn Knowles and Carlos H. Timaran

Key Points

1 Worldwide stroke has become the second leading cause of death

2 Atherosclerotic occlusive disease of the extracranial carotid artery accounts for a major cause of

ischemic stroke

3 Duplex ultrasonography is of great use in the identification of cerebrovascular disease

4 Risk factor modification is imperative in patients with atherosclerotic cerebrovascular disease

5 Surgical treatment for occlusive carotid artery disease is preferred over medical management for

symptomatic disease and severe asymptomatic disease

6 Carotid artery stenting continues to be evaluated for efficacy

7 The diagnosis of vertebrobasilar insufficiency is often difficult due to subtle symptoms shared by

many organ systems

8 Endovascular management of vertebral artery disease has not been sufficiently investigated for

efficacy

9 Open repair of brachiocephalic disease should be based on patient comorbidities, and high-risk

patients should undergo extra-anatomic revascularization

INTRODUCTION

Stroke continues to be a common cause of death and disability. The morbidity caused by a stroke can be

debilitating, worse than that of a myocardial infarction (MI). Stroke can cause permanent disability that

includes aphasia, paralysis, blindness, numbness, or weakness. If transient, <24 hours, it is termed a

transient ischemic attack (TIA) and manifests similarly. Long-term sequelae from stroke can have longlasting financial and social burdens on a patient, family, and the healthcare system in general.

Atherosclerotic plaque at the bifurcation of the carotid artery extending into the internal carotid

artery continues to be a common cause of CVA, accounting for approximately 40% to 60% of all

ischemic strokes. Since the introduction of the carotid endarterectomy (CEA) in 1954, operative

treatment of carotid artery occlusive lesions has been shown in multiple randomized trials to decrease

the risk of subsequent ipsilateral ischemic strokes. More recently, endovascular carotid artery stenting

(CAS) techniques have seen a surge in popularity; however, controversy still exists regarding the

appropriate use of endovascular intervention, and the evaluation of surgical, endovascular, and medical

management of carotid occlusive disease continues to be investigated.

Vertebral artery occlusive disease typically occurs at the origin of the vertebral arteries – due to

atherosclerosis – and can cause posterior circulation symptoms, such as diplopia, drop attacks, and

vertigo. The diagnosis of vertebrobasilar disease is usually more difficult than carotid occlusive disease

as the symptoms are often vague and can be confused easily with other diagnoses. Treatment has

traditionally been open surgical repair; however, endovascular repair is feasible although outcomes

have not been evaluated extensively.

Brachiocephalic occlusive disease is most often caused by atherosclerosis and involves the origin of

the great vessels. Symptoms can include stroke, TIA, and arm fatigue and weakness. Diagnosis often

requires imaging and a keen physical examination. Treatment involves either extra-anatomic or

transthoracic surgical repair or more recently the introduction of endovascular management with

angioplasty and stenting.

This chapter provides a comprehensive review of epidemiology, pathophysiology, diagnosis,

treatment, and controversy in the management of carotid artery occlusive disease, as well as vertebral

artery and brachiocephalic occlusive disease.

2544

CAROTID ARTERY OCCLUSIVE DISEASE

Epidemiology

1 Worldwide, stroke is the second most common cause of mortality and third of disability.1 The

incidence appears to be decreasing in the United States; however, is increasing in low-income

countries.2,3 In the United States, the annual incidence of a new or recurrent stroke is 795,000, of which

610,000 are first-ever strokes.4 There appear to be a higher number of strokes in the Southeast United

States as compared to other regions. Men have a higher risk of stroke at younger ages, but women have

a higher risk over the age of 75 years.4 The risk of stroke appears to be affected by race, with whites

having a lower incidence than blacks and Hispanics in the United States.5,6 The risk of first-ever strokes

in blacks is twice that in whites.7 Recently, stroke has been decreased from the third leading cause of

death in the United States to the fourth. This decrease is related to a decrease in the incidence of strokes

over the last few decades, up to a 40% decrease since the 1980s.8,9 This decrease in mortality has been

fueled by improvements in acute stroke care over the years. The incidence of TIA is approximately 2.3%

and has a higher risk of subsequent stroke. TIAs can herald a stroke 15% of the time, usually within the

first 90 days.7 The risk factors for stroke include age over 55, male sex, hypertension, family history,

atrial fibrillation, smoking, hypercholesterolemia, diabetes, obesity, renal insufficiency, and alcohol.

Overall, five factors cause a significant number of strokes: hypertension, smoking, obesity, diet, and

physical inactivity.10

PATHOGENESIS OF STROKE

The etiology of CVA in the United States is most commonly related to ischemia (87%), intracerebral

hemorrhage (10%), and subarachnoid hemorrhage (3%).4 Ischemia can be broken down into

thrombosis, embolism, and hypoperfusion. Thrombosis refers to in situ obstruction of an artery,

typically from atherosclerosis, dissection, or fibromuscular dysplasia (FMD). A stroke occurs from

reduced flow distal to the thrombosis, and can be either large or small vessel. Large vessels include the

extracranial carotid and proximal intracranial arteries. Small vessel disease is branch vessels from the

intracranial vessels. Embolism refers to debris from a source, such as the heart or arterial segment, that

becomes free and flows downstream until lodging in a small vessel. Hypoperfusion refers to a more

global circulatory problem. Often there is a combination of etiologies that leads to a stroke such as a

pre-existing lesion that becomes a source of emboli.

2 Atherosclerosis is the most common cause of disease in the extra- and intracranial carotid arteries.

This etiology remains a major preventative cause of ischemic stroke. The incidence of carotid artery

disease is 3.8% to 10.5% in men and 2.7% to 5.5% in women.11,12 Although, a definitive cause of stroke

is often not identified, large vessel cervical disease is a major cause in about 15% of cases (Fig. 89-1).

Stroke from carotid vessel etiology also has the highest rate of recurrence at 30 days.13

The carotid bifurcation is an area of low flow and shear stress, due to a separation of flow between

the high-resistance external carotid artery and the low-resistance internal carotid artery (Fig. 89-2).

Plaque usually forms in this area due to the shear stress, and forms on the walls opposite from the flow

divider. As per typical atherosclerosis formation, the inciting event is intimal injury. There is then

platelet deposition, smooth muscle proliferation, fibroplasia, and loss of the luminal diameter. As the

lumen diameter gets smaller, the flow velocities and turbulence increase which can lead to

hypoperfusion or atheroembolization (Fig. 89-3). Furthermore, a large number of carotid plaques have a

necrotic core of lipid rich debris and cholesterol. There is a fibrous cap that separates this from the

lumen, which is typically a thin rim of cellular components and extracellular matrix. This thin cap can

rupture and cause plaque disruption which can have severe clinical consequences. Hemorrhage within

the plaque can also occur and is an important risk factor for rupture of the cap. Additionally, dense

plaque inflammation with macrophage infiltration is strongly associated with cap rupture. Conversely,

the presence of a thick plaque is associated with a more stable plaque.

2545

Figure 89-1. Stroke due to carotid bifurcation occlusive disease is usually caused by atheroemboli arising from the internal carotid

artery, which provides the majority of blood flow to the cerebral hemisphere. With increasing degrees of stenosis in the carotid

artery, flow becomes more turbulent, and the risk of atheroembolization escalates.

Figure 89-2. A: The carotid bifurcation is an area of low flow velocity and low shear stress. As the blood circulates through the

carotid bifurcation, there is separation of flow into the low-resistance internal carotid artery and the high-resistance external

carotid artery. B: The carotid atherosclerotic plaque typically forms in the outer wall opposite to the flow divider due in part to

the effect of the low shear stress region, which also creates a transient reversal of flow during the cardiac cycle.

2546

Figure 89-3. Duplex ultrasonography showing a carotid plaque with narrowing of the vessel lumen that can either embolize or

cause low flow causing hypoperfusion. B-mode imaging shows a heterogeneous plaque with severe narrowing.

CLINICAL MANIFESTATIONS OF STROKE

Symptomatic carotid artery disease is classically thought of as a corresponding TIA, stroke, or amaurosis

fugax. A TIA is a neurologic event that manifests stroke-like symptoms for <24 hours. These are

considered a precursor of a more serious event and a large number will progress to a stroke. Symptoms

correspond with a focal defect that can be related to carotid artery atherosclerosis. These symptoms

typically include the anterior or middle cerebral artery circulations. Motor symptoms can include

hemiparesis contralateral to the affected hemisphere. Sensory deficits can also occur in a similar fashion,

such as numbness or paresthesia. Aphasia, dysphagia, or dysarthria can also occur. Amaurosis fugax is

the temporary monocular blindness from cholesterol embolization to the retinal artery via the

ophthalmic artery. Dizziness, syncope, vertigo, seizures, bowel or bladder incontinence, or migraines

are not typically related to carotid disease and other causes must be sought. Once the symptoms

progress past 24 hours, the TIA has become a full stroke. The full severity of a stroke can often take

weeks to manifest as the penumbra either recovers or does not. Global ischemia is generally uncommon

with carotid artery disease.

DIAGNOSTIC EVALUATION

3 Carotid artery duplex ultrasonography (DUS) is the primary diagnostic tool for the evaluation of

carotid artery disease. Although the role in screening is controversial, those with concerning symptoms

should undergo DUS. The benefits of DUS include excellent sensitivity for the diagnosis of occlusive

carotid artery disease, but also the avoidance of radiation and the rapid availability and ease of

evaluation. The decision for carotid intervention is often taken solely on the information provided by

the DUS. A complete examination includes evaluation of the common, external, and internal carotid

arteries, as well as the vertebral arteries, and often the subclavian arteries. The peak systolic velocity

(PSV), end-diastolic velocity (EDV), and the ratio of the common carotid artery to internal carotid

artery (CCA/ICA) are used to determine the severity of stenosis (Fig. 89-4). Although labs differ in their

ranges, patients are typically classified into: normal, 1% to 49%, 50% to 69%, 70% to 99% or occluded

(Table 89-1). Additionally, the DUS can provide important information regarding the plaque

morphology. The identification of high-risk echolucent plaques can aid the practitioner in estimating the

risk of neurologic symptoms. The diagnostic accuracy of DUS does, however, depend on having a skilled

sonographer. Magnetic resonance angiography (MRA) and computerized tomographic angiography

(CTA) are becoming more popular for diagnosis with improvements in the technology. These imaging

modalities can provide important information regarding the aortic arch, tortuosity, brachiocephalic

disease, carotid bifurcation location, and intracerebral collateral circulation. They can, however,

overestimate the amount of stenosis and often require correlation with DUS. Angiography remains the

gold standard for diagnosis; however, the procedure itself carries approximately 1% risk of neurologic

complications (Fig. 89-5). Transcranial Doppler (TCD) can provide information related to the

significance of a stenosis and how it alters intracerebral hemodynamics.

2547

Figure 89-4. A: Color power Doppler shows a severe stenosis at the origin of the internal carotid artery. B: The peak systolic

velocity is 497 cm/s, correlating to a >70% stenosis.

Table 89-1 Duplex Ultrasound Criteria for Carotid Artery Stenosis

TREATMENT OF CAROTID ARTERY OCCLUSIVE DISEASE

Patients with carotid artery occlusive disease are placed into two main categories: asymptomatic or

symptomatic. A recent (<6 months) TIA, stroke, and amaurosis fugax are considered symptoms of

occlusive carotid disease. These patients have the highest risk of recurrence of symptoms or possible

ipsilateral stroke. In patients who have a TIA, 15% will go on to a CVA, 10% within 90 days.7 Several

studies have examined the risk reduction of stroke with medical and surgical management.

SYMPTOMATIC

Patients with symptomatic lesions are at the highest risk of ipsilateral stroke, and the degree of stenosis

corresponds with the risk. Validated in multiple trials – most prominently in the North American

Symptomatic Carotid Endarterectomy Trial (NASCET) study – the degree of stenosis was correlated with

Stroke risk. A stenosis <50% was unlikely to cause neurologic manifestations. In patients with >50%

stenosis, those treated with medical therapy were more likely to progress to ipsilateral stroke than

those that underwent surgical management. This benefit to surgical intervention was highest in the 70%

to 99% stenosis range. In the NASCET study, symptomatic patients were assigned to medical therapy or

endarterectomy with symptomatic disease and a stenosis >50%. After 2 years, there was a significant

reduction in ipsilateral stroke in those who underwent a CEA ([50% to 69% stenosis: 22.2% in medical

patients and 16.7% in surgical patients over 5 years] and [70% to 99% stenosis: 26% in medical patients

and 9% in surgical patients over a 2-year period]).14 The European Carotid Surgery Trial (ECST) showed

similar findings for severe stenosis, however, no benefit was found to surgery over medical

management with mild stenosis.15 Medical therapy has advanced since the NASCET trial with the

introduction of improved antiplatelet medications such as clopidogrel, and HMG-CoA reductase

inhibitors. In the NASCET trial, aspirin was the medical therapy that surgery was compared against.

Aspirin is an important medication in secondary stroke prevention. It can be used alone or in

combination with dipyridamole or clopidogrel. Most neurologists recommend aspirin and clopidogrel in

symptomatic patients for prevention of stroke until surgical intervention is performed. Statins lower

stroke risk by 30% by plaque stabilization and are important for the reduction of stroke.16

2548