Management of Transient Ischemic Attack and Asymptomatic Carotid Bruit

Amy A. Pruitt

Stroke is the leading cause of disability among adults in the United States. Although medical and surgical therapies for stroke are improving, prevention is still the most effective strategy and a major responsibility of the primary care physician. Stroke prevention through risk factor management may be a major contributor to the rapid decline during the last two decades in death rates from stroke. The cornerstone of the preventive effort is the early identification and vigorous treatment of stroke risk factors (e.g., hypertension, hypercholesterolemia, diabetes, coronary artery disease, smoking; see Chapters 26, 27, 30, 54, and 102). Atrial fibrillation (AF), a major risk factor for embolic stroke, also requires serious attention (see Chapters 28 and 83).

Patients who present with a transient ischemic attack (TIA) or an asymptomatic carotid bruit pose the problem of stroke prevention at a more advanced stage of cerebrovascular disease. It is difficult to state precise incidence and prevalence rates for TIAs due to differences in definitions and difficulty recognizing them, but a rough estimate has been over 200,000 per year. Among patients who present with stroke, the reported prevalence of prior TIA ranges between 7% and 40%. The primary physician is well positioned to detect TIA by history and recognize carotid bruit (whether symptomatic or asymptomatic) on physical examination. Tasks include risk stratification, cost-effective ordering of brain imaging and noninvasive flow studies, and knowing when to initiate more-aggressive measures, such as anticoagulant therapy and referral for consideration of interventional therapy.

PATHOPHYSIOLOGY, CLINICAL PRESENTATION, AND COURSE (1, 2, 3, 4, 5, 6, 7, 8 and 9)

Transient Ischemic Attack

Definition

The concept of TIA has undergone refinement with the advent of new neuroimaging techniques, which have clarified the pathophysiologic basis of older clinical distinctions between TIA, cerebral infarction with transient signs, and stroke. Until recently, TIAs were defined in time-based fashion as episodes of temporary (<24 hours) focal cerebral dysfunction resulting from vascular disease. However, the majority of TIAs actually resolve within 1 hour, and most resolve within 30 minutes. Among patients who present with an ischemic focal deficit that lasts more than 1 hour, only 2% have resolution in 24 hours. Approximately one third of patients with traditionally defined TIA show brain injury on diffusion-weighted magnetic resonance imaging (MRI).

Subsequently, a tissue-based rather than time-based definition was proposed specifying clinically symptoms of less than 1 hour and negative diffusion-weighted imaging (DWI). Recent joint recommendations from the American Heart Association (AHA) and American Stroke Association recognize that it is impossible to define a specific time cutoff that can distinguish whether a symptomatic ischemic event will result in brain injury. Consequently, the current consensus definition defines TIA as transient episode of neurologic deficit caused by focal brain, spinal cord, or retinal ischemia, without acute infarction.

Pathogenesis

TIAs can develop through any of several mechanisms. In the majority of cases, emboli of platelets and fibrin or of atheromatous material that breaks off from a vessel wall (usually the carotid but also the aortic arch) transiently occlude a cerebral or ophthalmic artery or one of its branches. Thrombus formation distal to an atherosclerotic plaque is common in tightly stenosed arteries (>75% stenosis, residual lumen <2 mm) or even in totally occluded carotid arteries, and the thrombus often serves as a source of emboli. Occasionally, the intracranial arteries are the source of emboli.

The heart is the other important source of emboli. AF greatly increases stroke risk, estimated to be on the order of 3% per year (see Chapter 28). Other cardiac lesions predisposing to cerebral embolism include mitral valve stenosis, mitral valve prolapse, calcified mitral annulus, ventricular aneurysm or dyskinesia, atrial or ventricular clot, valvular vegetation, and interatrial shunt. The combination of patent foramen ovale and atrial septal aneurysm confers significantly increased risk of recurrent stroke in persons with a prior stroke of unknown origin, but a patent foramen ovale alone does not appear to pose as much of a risk, especially if it is small (<2 mm).

TIAs may also develop when transient hypotension occurs in conjunction with a hemodynamically significant carotid stenosis (>75% occlusion). The resulting reduction in collateral flow to the ipsilateral carotid territory can lead to transient neurologic symptoms. The reduced blood pressure rarely results in focal symptoms unless a severely stenotic lesion is already present.

Small-vessel thrombotic or lacunar stroke may be preceded by transient, focal neurologic deficits in as many as one third of patients who go on to have a completed stroke. The clinician must be aware that the distinction between stroke mechanisms, particularly distal emboli or large-vessel origin and small-vessel thrombotic disease, may be difficult. Because management of the two types of conditions differs considerably, it is important to be aware of syndromes that commonly are associated with small-vessel disease (pure motor hemiparesis, ataxic hemiparesis, clumsy hand dysarthria syndrome).

In certain rare instances, TIAs may be attributable to one of the following: steal phenomena (e.g., subclavian steal), hyperviscosity states (e.g., polycythemia), vasculitis, coagulopathies (e.g., antiphospholipid antibody syndrome, deficiency of factor V Leiden, protein C, protein S, or antithrombin III), and dissection of the carotid or vertebral artery. These underlying causes of stroke and TIA are more common in younger patients (younger than age 45 years).

Clinical Presentation

TIAs from large-vessel stenosis can be divided into those caused by disease in the carotid circulation and those that are a consequence of disease in the vertebrobasilar territory.

Carotid TIAs.

Symptoms of TIA associated with carotid disease include transient monocular blindness (amaurosis fugax), clumsiness, weakness or numbness of the hand, and disturbed speech. Transient monocular blindness is caused by occlusion of the ophthalmic artery or branches ipsilateral to the carotid stenosis and classically is described by the patient as a “shade” or “curtain” that descends over the affected eye. In patients with symptoms suggestive of carotid disease, the detection of a carotid bruit on the same side
as the symptomatic eye or cerebral hemisphere is suggestive but not diagnostic of high-grade carotid stenosis. The nonsimultaneous occurrence of transient hemispheric episodes and transient monocular blindness correlated with an 80% incidence of carotid disease.

Vertebrobasilar TIAs.

Symptoms of vertebrobasilar disease include binocular visual disturbance, vertigo, paresthesias, diplopia, ataxia, dysarthria, light-headedness, generalized weakness, loss of consciousness, and transient global amnesia. Each of these may be an isolated symptom of disease of the posterior circulation, although isolated vertigo without other brainstem symptoms is rarely caused by vertebrobasilar occlusive disease (see Chapter 166).

Clinical Course and Risk Stratification for Stroke

The interval since the most recent TIA appears to be the most important factor in predicting the risk for stroke. The short-term stroke risk following a TIA is substantial: In one study of prognosis following a TIA, the stroke risk was 11%, with half of the strokes occurring within 2 days of the TIA. The short-term risks of cardiovascular events, death, and recurrent TIA were 25% in the 3 months after a TIA. The risk for stroke cannot be predicted by the number of TIAs, duration of symptoms, or clinical phenomena.

One validated prognostic score, the age, blood pressure, clinical features, duration, and diabetes status (ABCD)² score, considers these major risk factors for rapid progression to stroke. A low score (<4) means a 2-day stroke risk of 1% versus a high score (>5) of 8.1% (see Table 171-1). Nonetheless, even those with a high ABCD² score have a low risk of stroke if they have negative diffusion-weighted MRI imaging (DWI) (see Table 171-2). Pooled data from over 2,000 patients with TIA showed that early stroke risk increased substantially with carotid stenosis ≥50% even after adjustment for ABCD² score and MRI DWI results. While it remains in widespread use, the ABCD² score has been felt by some to add little incremental value beyond an emergency room evaluation that is able to perform expeditious DWI scans and carotid artery imaging.

Asymptomatic Carotid Bruits

Incidental discovery on physical examination of an asymptomatic carotid bruit suggests the presence of an atherosclerotic lesion that has narrowed the lumen by at least 50% to less than 3 mm. The pitch of the bruit increases with the severity of stenosis. Prolonged, very-high-pitched bruits suggest a residual lumen of less than 1.5 mm (>75% stenosis). Most atherosclerotic lesions causing bruits tend to be located on the posterior wall of the common carotid artery at the bifurcation, compromising flow at the origin of the internal carotid. When stenosis is tight and flow is reduced, a mural thrombus may form distally in the proximal internal carotid artery, worsening occlusion and serving as a source of emboli. Plaque ulceration may also provide a nidus for mural thrombus formation.

TABLE 171-1 The ABCD² Score*

Age
	≥60 y	1 point
Blood Pressure
	SBP ≥140 mm Hg and/or DBP ≥90 mm Hg	1 point
Clinical Features
	Unilateral weakness	2 points
	Speech disturbance without weakness	1 point
	Other symptoms	0 points
Duration of Symptoms
	≥60 min	2 points
	10-59 min	1 point
	<10 min	0 points
Diabetes
	Yes	1 point
*Adapted from Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischemic attack. Lancet 2007;369:283.

TABLE 171-2 Stroke Risk After Transient Ischemic Attack

ABCD² Score	Patients (%)	% Stroke Risk 2 d	DWI + Risk 7 d	DWI — Risk 7 d
0-3	1,628 (34%)	1.0%	4/223 (1.8%)	1/1,023 (0.1%)
4-5	2,168 (45%)	4.1%	35/469 (7.5%)	7/1,032 (0.7%)
6-7	1,012 (21%)	8.1%	24/192 (12.5%)	1/268 (0.4%)
Adapted from Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischemic attack. Lancet 2007;369:283; and Giles MF, Albers GW, Amarenco P, et al. Early stroke risk and the ABCD² score performance in tissue-vs time-defined TIA. Neurology 2011;77:1222.

Stroke Risk

Epidemiologic studies indicate that asymptomatic bruits are associated with an increased risk for stroke, coronary disease, and death but not necessarily with an increased risk for stroke on the side of the bruit. In observational study, the overall risk for stroke in patients who remain asymptomatic is 1% at 1 year and 1.7% when those in whom TIAs develop are included. A major predictor of stroke is the severity of carotid stenosis, as is progression to high-grade stenosis (>75% stenosis, residual lumen <2 mm). Other risk factors include hypertension, preexisting heart disease, male gender, and a positive family history.

Cardioembolic Stroke with Transient Symptoms

In patients with cardioembolic stroke who have transient symptoms, the symptoms tend to last several hours. The neurologic event is maximal at onset in 80% of patients, and about 75% of emboli lodge in one of the middle cerebral arteries and cause symptoms similar to those of carotid occlusive disease. A hemispheric attack lasting longer than 60 minutes, whether single or multiple, is predictive of cardiac embolization.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of a TIA-like episode includes any condition that causes transient symptoms in a focal distribution and is not limited to those of vascular origin. Vascular mechanisms include carotid or vertebrobasilar occlusive disease, small-vessel ischemic stroke, and occlusion by emboli originating in the heart or aortic arch. Focal seizures (see Chapter 170) can produce symptoms similar to those of a TIA, as can the focal aura of migraine, which is not always followed by headache (see Chapter 165). Hyperventilation can produce distal tingling and numbness. Carpal tunnel syndrome may present with intermittent (often nocturnal) paresthesias in a median nerve distribution. Even a protruding cervical disk or osteophyte may produce transient focal motor or sensory symptoms (as during manipulation of the head or neck; see Chapter 167).

WORKUP (9, 10, 11, 12 and 13)

The goals in evaluating a TIA or an asymptomatic bruit are the detection of significant vascular disease and the assessment of stroke risk. One needs to identify those patients who
require aggressive intervention. In addition, if cerebrovascular disease can be ruled out as the cause, a search for other causes is required. The patient with a new onset of TIAs has an increased risk for stroke and should be evaluated promptly. However, a recent U.S. Preventive Services Task Force guideline recommends against screening for asymptomatic carotid artery stenosis in the general adult population.

To assess stroke risk, the clinician should have rapid access to three sets of information: (a) clinical history and physical examination for the ABCD² score, (b) computed tomography (CT) or MRI imaging, and (c) vascular imaging.

History

For the patient with a suspected TIA, questioning should first confirm that the transient episode was indeed a TIA, based on onset and duration. Symptoms lasting longer than 24 hours exclude TIA; cessation within 10 minutes increases the probability. The onset of headache during resolution of the neurologic deficit is more suggestive of a migrainous episode (see Chapter 165). In addition, the frequency of episodes, date of first onset, and presence of underlying heart disease and cardiovascular risk factors are important to ascertain because they can help to predict the clinical course. If the patient has hypertension or cardiac disease or is older (>65 years), the risk for subsequent stroke is increased. A disabling stroke is more likely to develop in patients with carotid symptoms than in those with vertebrobasilar dysfunction. The patient is at greatest risk for stroke in the first few months after the onset of TIAs.

When an apparently asymptomatic carotid bruit is found on physical examination, it is worthwhile to go back to the patient’s history and check carefully for overlooked transient neurologic events. Their presence would greatly increase the significance of the physical examination finding and indicate a heightened risk for stroke.

Inquiry into a history of hypertension or heart disease and any family history of stroke further helps to determine stroke risk. Risk factors for stroke include advanced age, elevated systolic blood pressure, current smoking, and the presence of diabetes, AF, or coronary heart disease.

Physical Examination

Physical examination should be directed to the cardiovascular and nervous systems. One checks for hypertension, AF, and heart murmurs (see Chapters 21 and 33). Fundoscopic examination at the time visual symptoms occur may reveal an embolus in a retinal artery branch. Neurologic examination findings are likely to be normal if the examination is conducted after the TIA has passed.

Gentle palpation and auscultation of the carotid arteries should be performed to note upstroke, volume, and the presence of a bruit. As stated earlier, the presence of a bruit does not invariably herald significant stenosis (a bruit can be present with hemodynamically insignificant lesions), but in as many as 70% to 80% of cases, the bruit does indicate important ipsilateral carotid disease. Some suggest taking note of the bruit’s pitch and duration, believing these features tend to correlate with severity of stenosis (higher pitch and greater duration suggesting a greater degree of stenosis).

Laboratory Studies

Initial laboratory studies should include a complete blood cell count and an erythrocyte sedimentation rate and a determination of glucose, lipid profile, and creatinine. Homocysteine has been independently associated with stroke risk and should be measured, along with serum folate and vitamin B₁₂ if it is elevated.

Carotid Imaging and Flow Determinations

In the last two decades, great strides have been made in the noninvasive evaluation of the carotid arteries and vessels of the posterior circulation. For the assessment of suspected carotid lesions, the combination of Doppler and B-mode ultrasonography allows a determination of lumen size and visualization of the carotid arterial lesion. In studies comparing arteriography with duplex carotid ultrasonography, a reduction in the diameter of the carotid artery of more than 60% was associated with a residual lumen at arteriography of less than 2 mm. However, in some instances, one cannot tell whether the carotid artery is completely occluded or only tightly stenosed. The degree of media and intima thickening correlates well with risk of stroke and myocardial infarction and can be used as a predictor of prognosis and guide to management. Echolucent plaque (unstable due to lipid-rich core) carries a particular ominous prognosis.

Magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) are being used increasingly in lieu of standard arteriography in the preoperative assessment of symptomatic carotid disease, also providing visualization of the intracranial vasculature. The use of transcranial Doppler techniques helps to measure flow in the ophthalmic system, assess the hemodynamic significance of the carotid stenosis, and detect any major stenosis of the intracranial vessels.

Vertebrobasilar Imaging and Flow

For the study of the posterior circulation, transcranial Doppler ultrasonography provides a relatively inexpensive means of noninvasively surveying large intracranial vessels. The test measures the velocity of flow, which increases in the setting of stenosis. However, it does not provide direct anatomic information. MRA and CTA provide noninvasive visualization of the vertebrobasilar system.

Brain and Cerebrovascular Imaging

To detect silent or prior infarction, unsuspected hemorrhage, or nonvascular disease such as tumor, noninvasive neuroimaging by means of CT or MRI with diffusion-weighted sequences should be performed. CT scan is unable to distinguish reliably between new and old infarction; moreover, a negative CT does not have the same negative predictive value as an MRI, but presence of any infarction on CT indicates a higher risk of future stroke in TIA patients. MRI DWI shows acute infarction within minutes of the ischemic event and normalizes by about 1 to 2 weeks after the event. Image acquisition requires greater cooperation on the part of the patient. As note, MRA and CTA provide cerebral vascular imaging noninvasively and often obviate need for invasive angiography.

Arteriography with the use of selective transfemoral catheterization remains the gold standard for evaluating intracranial and extracranial vessels. Because it is an invasive study with attendant risks, it is largely limited to persons who cannot undergo MRA or CTA or who require it for interventional procedures or diagnosis of giant cell arteritis.

Cardiac Imaging and Monitoring

Transthoracic echocardiography makes it possible to identify cardiac lesions that predispose to embolization, but the yield is low in patients older than the age of 50 years without evidence of cardiac disease on physical examination (see Chapter 33). Transesophageal echocardiography is more sensitive and specific for detecting intracardiac and aortic sources of embolization,
such as left atrial thrombus and atherosclerosis of the ascending aortic arch. It should be considered when standard echocardiography is unrevealing but clinical suspicion of embolization is strong. Ambulatory Holter monitoring is useful when AF as a precipitant of embolization is a concern and results of the resting electrocardiogram are normal (see Chapters 25 and 29).

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