Carotid stenosis

I. What every physician needs to know.

The proximal internal carotid artery and the carotid bifurcation are the locations most frequently affected by carotid atherosclerosis. Atheromatous plaque at the carotid bifurcation results in luminal narrowing, also known as carotid stenosis. This process can lead to ischemic stroke or transient ischemic attack (TIA) in the carotid system from hemodynamic compromise, embolization or thrombosis.

The definition of asymptomatic or symptomatic carotid artery stenosis is based upon the history and physical examination, depending upon whether or not there are symptoms or signs of carotid territory ischemia.

II. Diagnostic Confirmation: Are you sure your patient has carotid stenosis?

Symptomatic carotid disease is defined as focal neurologic symptoms that are sudden in onset and referable to the stenotic carotid artery distribution.

Patients that developed one or more transient ischemic attacks characterized by focal neurologic findings or transient monocular blindness or minor ischemic strokes within the previous 6 months and have documented carotid stenosis on imaging studies meet the criteria for symptomatic carotid artery stenosis. Vertigo and syncope are not generally caused by carotid stenosis.

Carotid stenosis may also be identified in asymptomatic patients by performing carotid duplex ultrasound screening (CDUS), magnetic resonance angiography (MRA) or computed tomography angiography (CTA).

A. History Part I: Pattern Recognition:

Carotid stenosis is associated with an increased risk of stroke in the internal carotid artery territory and the mechanism of stroke may be embolic from an ulcerated plaque or low flow due to the stenosis with inadequate collateral compensation.

Embolic events

Transient ischemic attacks may be due to low flow in which case they are repetitive and cause symptoms in the territory of the internal carotid artery, or embolic and in that case symptoms are related to the vascular territories involved.

Most often, an embolic event related to carotid artery stenosis will produce symptoms referable to the middle cerebral artery territory, although the anterior cerebral artery can also be involved (please see the chapter on stroke for more details on the cerebral artery territories).

Amaurosis fugax refers to transient monocular blindness caused by a small embolus to the opthalmic artery.

Thrombosis and low flow events

Total carotid artery occlusion can also cause low flow or embolic events depending on collateral flow through the orbit and across the circle of Willis.

B. History Part 2: Prevalence:

The risk factors for carotid stenosis are the same as those for ischemic stroke and include the following:

Old age
Diabetes mellitus
Hypertension
Tobacco smoking
Elevated cholesterol levels

Identification of modifiable risk factors and prophylactic intervention to lower risk is extremely important in patients with carotid stenosis as the number of strokes could be reduced substantially by these means.

The natural history of asymptomatic stenosis is an approximate 2% per year stroke rate, while symptomatic patients experience a 13% per year risk of stroke.

Prospective studies of asymptomatic carotid artery stenosis suggest that the rate of ipsilateral stroke increases dramatically when the residual lumen diameter narrows to greater than 70% stenosis. In one study the incidence of stroke was 1.7% per year overall but 5.5% per year in those with more than a 75% carotid artery stenosis.

A risk model for patients with recently symptomatic carotid stenosis has been derived from the European Carotid Surgery Trial (ESCT) data and validated by showing that the predicted stroke risk for patients assigned to medical treatment in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) was close to the observed risk. While the model does not account for the risk and benefit of surgery, it may be useful for assessment of baseline stroke risk and patient selection for carotid endarterectomy (CEA).

The baseline ipsilateral stroke risk for patients with recently symptomatic carotid disease is calculated based on the following factors: age, sex, degree of carotid stenosis, type of presenting symptomatic event (ocular TIA, hemispheric TIA, minor, or major stroke), time since last symptomatic event, and carotid plaque morphology (smooth versus ulcerated or irregular). A version of the ECST stroke risk model calculator is available online.

C. History Part 3: Competing diagnoses that can mimic carotid stenosis.

Since asymptomatic carotid stenosis is usually an incidental finding, there is no need to discuss differential diagnosis.

For patients with symptomatic carotid stenosis the differential diagnosis discussion is similar to that for thromboembolic stroke (see appropriate chapter).

If ocular symptoms occur, special consideration should be given to exclude giant cell arteritis and other large vessel vasculitides, non-arteritic anterior ischemic optic neuropathy (NAAION) and embolic occlusion (cardioembolic or artery to artery stroke). Dissection of the internal carotid artery is a common source of embolic stroke in young patients, is usually painful and precedes strokes by several hours or days.

For patients with hemispheric signs of cerebral infarction please see the section on differential diagnosis of stroke.

D. Physical Examination Findings.

The clinical manifestations of carotid artery disease are a carotid bruit and symptoms of ischemia, but none of the below symptoms and signs is specific to carotid stenosis. Carotid stenosis may also exist in the absence of any clinical signs or symptoms and in that case it is called asymptomatic carotid stenosis. The symptomatic status of the artery is important to the neurologist in making diagnostic and treatment decisions.

A carotid bruit heard over the site of the stenosis is an important sign of carotid stenosis. However, a carotid bruit in asymptomatic patients is a poor predictor for the presence of an underlying carotid stenosis and for subsequent development of stroke. The yield is higher in patients with symptomatic carotid disease and 75% of patients with a bruit had a moderate to severe stenosis (more than 60% stenosis), but as a conclusion a carotid bruit is a poor predictor of carotid stenosis or stroke risk, but is an indicator of ischemic cardiac disease.

Ischemic symptoms may be transient, representing TIAs or permanent, resulting in cerebral infarction. Features of ocular ischemia include partial or complete blindness in one eye and an absent pupillary response. Fundoscopic exam may demonstrate arterial occlusion or ischemic damage to the retina.

Hemispheric signs of cerebral infarction from carotid disease include contralateral homonymous hemianopsia, hemiparesis and hemisensory loss. Specific signs of left hemisphere ischemia include aphasia, while right hemisphere ischemia may be manifest by left visuospatial neglect, constructional apraxia (inability to perform purposeful movements) and dysprosody (please see stroke chapter).

E. What diagnostic tests should be performed?

Patients suspected of having carotid atherosclerosis typically undergo CDUS. Other useful non-invasive methods for assessing stenosis of the internal carotid artery include CTA, MRA and contrast enhanced magnetic resonance angiography (CEMRA).

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The major treatable risk factors for carotid artery atherosclerosis are similar to those for coronary atherosclerosis. Therefore patients with carotid stenosis should be screened for diabetes mellitus, dyslipidemia and hypertension.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Asymptomatic carotid stenosis

In asymptomatic patients with suspected carotid stenosis, duplex ultrasonography is recommended as the initial diagnostic test to detect hemodynamically significant carotid stenosis.

In patients with a hemodynamically significant atherosclerotic lesion identified on CDUS, it remains controversial if further imaging is needed prior to endarterectomy to verify the degree of stenosis or further evaluate arterial anatomy.

It is reasonable to perform duplex ultrasound to detect hemodynamically significant stenosis in asymptomatic patients with carotid bruit.

Symptomatic carotid disease

In the symptomatic patient, the preoperative evaluation should also include computed tomography (CT) or magnetic resonance imaging (MRI) of the brain to assess the degree of cerebral infarction, if any, and exclude other disorders that might be responsible for the symptoms (malignancy, subdural hematoma etc.).

The combination of CDUS and MRA is sufficient in the presurgical evaluation of carotid stenosis, particularly when the results agree.

CDUS is a non-invasive, safe and relatively inexpensive technique for evaluation of the carotid arteries, that is, 81 to 98% sensitive and 82 to 89% specific in detecting a significant stenosis of the internal carotid artery. CDUS tends to overestimate the degree of stenosis and can miss hairline residual lumens.

Transcranial Doppler (TCD) can evaluate the intracranial hemodynamic consequences of high-grade carotid lesions, such as development of collateral flow patterns in the circle of Willis, reversal of flow in the opthalmic and anterior cerebral arteries and reduced MCA flow velocity. This test has a limited contribution for carotid stenosis and should not be routinely used.

The magnetic resonance techniques for evaluation of extracranial carotid arteries utilize either MRA or gadolinium enhanced MRA (contrast enhanced MRA). MRA produces a reproducible three-dimensional image of the carotid bifurcation with good sensitivity (91 to 99%) and specificity (88 to 99%) for detecting high grade carotid stenosis. Compared with CDUS, MRA is less operator dependent, but more expensive and time consuming.

CTA is an accurate method for the detection of carotid stenosis particularly when CDUS is not reliable (severe kinking, severe calcification, short neck, or high bifurcation). CTA requires a contrast bolus comparable to that administered during a conventional angiogram. Impaired renal function is a relative contraindication for its use.

Conventional cerebral angiography has been considered the gold standard for the evaluation of carotid stenosis, but it is associated with a small risk of stroke and therefore non-invasive tests have replaced cerebral angiography in presurgical assessment of patients with carotid stenosis.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

The American Academy of Neurology (AAN) noted that the clinical utility of TCD to assist with stroke risk assessment in patients with carotid stenosis requires evaluation and confirmation in randomized clinical trials, but in general carotid duplex and MRA are the tests of choice.

III. Default Management.

Symptomatic carotid stenosis

Step I – Carotid ultrasound. The general approach to patients with suspected carotid stenosis is to first perform carotid ultrasound.
Patients with stenosis under 50% are followed with serial examinations, usually on an annual basis to see if there is progression.
Step II – MRA. Those with stenosis greater than 50% are evaluated with MRA.
Step III – CTA is performed instead of MRA if there is a contraindication to MRI and in cases where duplex ultrasound and MRA do not agree.
Step IV – Conventional cerebral angiography is performed in patients that cannot tolerate MRA and in whom non-atherosclerotic disease is suspected (dissection, vasculitis).

A. Immediate management.

Medical management should be initiated upon admission in patients with symptomatic carotid stenosis and may include the following:

Antiplatelet drugs
Statins
Drugs to reduce risk factors for atherosclerosis (diabetes mellitus, hypertension, smoking, dyslipidemia)

Antiplatelet therapy

Antiplatelet therapy with aspirin is beneficial in the acute phase of ischemic stroke and in patients at high risk of stroke because of carotid disease, however it has not been proven to be effective in the prevention of stroke in asymptomatic patients. Lower dose aspirin (81 or 325mg) seems to be more effective than a higher dose. For patients with aspirin allergy, either clopidogrel (75mg daily) or ticlopidine (250mg twice daily) is a reasonable alternative.

In patients with symptomatic carotid artery disease, aspirin alone, clopidogrel alone, or a combination of aspirin plus dipyridamole is preferred over the combination of aspirin with clopidogrel.

Antiplatelet agents are recommended rather than oral anticoagulation for the prevention of stroke in patients with carotid artery stenosis, with the exception of patients that have an indication for anticoagulation, such as atrial fibrillation or a mechanical prosthetic valve.

Statins

Statins are recommended for all patients with extracranial carotid disease to reduce low-density lipoprotein (LDL) cholesterol below 100mg/dl.

Treatment of hypertension

The recommendation is to maintain blood pressure below 140/90mmHg. This target is different than the usual goal for hypertensive patients because of concerns related to poststenosis relative hypoperfusion. It is not clear for how long this goal should be achieved postrevascularization.

Cessation of tobacco smoking

Patients with extracranial carotid disease should be advised to quit smoking and offered smoking cessation interventions.

Diabetes mellitus

Glucose lowering drugs and diet should be used for patients with diabetes mellitus and carotid artery stenosis, however intense glucose control to a hemoglobin A1c level less than 7% has not been correlated with better neurologic outcomes. Administration of a statin to reduce LDL cholesterol to a level near or below 70mg/dl is reasonable in patients with diabetes and carotid stenosis.

B. Physical Examination Tips to Guide Management.

All patients have to be monitored for new neurological symptoms once a diagnosis of carotid stenosis is made.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

N/A

D. Long-term management.

Management options for symptomatic carotid stenosis include CEA, carotid artery stenting (CAS) and medical therapy.

SYMPTOMATIC CAROTID ARTERY STENOSIS

Carotid endarterectomy

For patients with recently (within the previous 4 to 6 months) symptomatic carotid stenosis of 70 to 99% stenosis on non-invasive imaging or more than 50% stenosis on catheter angiography, who have a life expectancy of at least 5 years, CEA is recommended in conjunction with medical management, if all of the following conditions apply:

A surgically accessible carotid lesion
Absence of clinically significant cardiac, pulmonary or other disease that would greatly increase the risk of anesthesia or surgery
No prior ipsilateral endarterectomy

These recommendations apply only when the perioperative risk of stroke and death with CEA for the surgeon or center is less than 6%. In studies, no significant benefit of CEA was noted with near occlusion of the internal carotid artery and in symptomatic carotid stenosis of 30 to 49%. There was some benefit noted for patients with 50 to 69% symptomatic stenosis, but not enough to warrant a clear recommendation for CEA.

Timing of surgery has been the subject of considerable debate, but two retrospective studies found that CEA within 2 weeks of a non-disabling stroke or TIA significantly improved outcomes compared with later surgery. The benefit of CEA for patients with moderate to severe stroke has not been evaluated in randomized controlled trials and patients with persistent disabling neurologic deficits are unlikely to benefit from revascularization. Emergent CEA for progressive stroke or crescendo TIA is also not recommended, since it appears to have a high operative risk.

Carotid artery stenting

With CAS the perioperative risk of stroke or death for patients age 70 or older is two fold higher in symptomatic carotid disease, compared to CEA.

CAS is suggested rather than CEA, for a group of patients with recently symptomatic carotid disease of 70 to 99% on non-invasive imaging or 50 to 99% stenosis on catheter angiography, who have any of the following conditions:

A carotid lesion that is not suitable for surgical access
Radiation-induced stenosis
Restenosis after endarterectomy
Clinically significant cardiac, pulmonary or other disease that greatly increases the risk of surgery

The benefit to risk ratio of CAS for patients 70 and older with these characteristics is unknown. These recommendations apply only when the perioperative risk of stroke and death with CAS for the operator or center is less than 6%.

The benefit of CEA may be greater for men than for women. Therefore men with recently symptomatic carotid stenosis of 50 to 69% who have a life expectancy of at least 5 years benefit from CEA rather than medical management. For women with recently symptomatic carotid stenosis of 50 to 69%, medical management is suggested instead of CEA.

Medical management

Medical management rather than CEA or CAS is recommended for patients with symptomatic carotid stenosis that is less than 50%. Low dose aspirin (81 to 325mg/day) should be prescribed, as well as a statin. Aspirin treatment is also recommended for all patients who are having CEA and should be continued for at least 3 months after surgery.

ASYMPTOMATIC CAROTID ARTERY STENOSIS

Medical management

Patients with asymptomatic carotid stenosis benefit from risk factor intervention, antiplatelet drugs and statins.

Carotid endarterectomy

CEA may be indicated for selected patients with asymptomatic carotid stenosis of 60 to 99% who have a life expectancy of at least 5 years, if the perioperative risk of stroke and death is less than 3%.

Carotid revascularization is not recommended for patients with chronic total occlusion of the targeted carotid artery.

E. Common Pitfalls and Side-Effects of Management

Critical pathways can improve results after CEA. A five step protocol has been found to be safe and cost-effective and includes the following:

Duplex ultrasound performed in an accredited vascular laboratory
Admission on the day of surgery
Cervical block anesthesia to eliminate electroencephalography (EEG) monitoring and other costly intraoperative monitoring tests
Transfer from the recovery room after short observation to the vascular ward
Discharge on the first postoperative day

Periprocedural management of patients undergoing carotid endarterectomy

Aspirin (81 to 325mg daily) is recommended before CEA and may be continued indefinitely postoperatively.
Antihypertensive medication is recommended to control blood pressure before and after CEA.
The findings on clinical neurological examination should be documented within 24 hours before and after CEA.
Statin use is reasonable for patients who have undergone CEA, irrespective of serum lipid levels, to prevent restenosis.

Acute complications after CEA or stenting include the following:

Postoperative cardiac events

It is important to do the appropriate preoperative work-up in these patients.

Postoperative stroke

This can be caused by plaque emboli, thrombosis, improper flushing, or relative hypotension. Evaluation of CEA patients with new neurologic deficits varies among surgeons (intraoperative ultrasound versus opening the endarterectomy site). Carotid stenting is used if the cause is a flow limiting dissection and intra-arterial thrombolytics are used for distal emboli.

Hyperperfusion syndrome

This is probably the cause of most postoperative intracerebral hemorrhages and seizures in the first 2 weeks after CEA. Strict control of postoperative hypertension in the first 2 weeks postprocedure is paramount to prevent cerebral hyperperfusion. Seizures related to hyperperfusion are usually successfully treated with standard anticonvulsants (e.g. phenytoin).

Bleeding

This is usually self-limiting.

Hypotension

Hypotension compared to a patient’s baseline value will likely result in cerebral ischemia in patients with intracerebral small vessel disease.

IV. Management with Co-Morbidities

Bilateral CEA should be approached as a staged procedure, with a delay of at least 2 weeks between surgeries.

Intracranial aneurysms that are distal to the carotid stenosis could rupture with CEA. Unfortunately, data for this situation are too sparse to allow firm recommendation as to which problem should be treated first.

A. Renal Insufficiency.

Creatinine clearance should be taken into consideration when selecting preoperative imaging studies.