Prevention of Recurrent Ischemic Stroke

Mechanisms of ischemic stroke are heterogeneous, and therapies to prevent recurrent stroke vary based on underlying mechanism. Determining the specific cause of stroke in the individual patient is therefore critical. Major mechanistic categories in the typical patient with stroke (i.e., older or with traditional vascular risk factors) include large vessel atherosclerotic stenosis, cardioembolism, small-vessel (lacunar) disease, and a host of infrequent other specific causes. Occasionally, hypercoagulable states, unusual infectious causes of stroke, and other less common causes will need to be considered. Note that these less common causes of stroke are more likely to be present in younger patients (< 60 years old), and thus evaluation is different in that group (see Chapter 45 , Ischemic Stroke in the Young).

A.

The location and pattern of infarction on brain imaging has mechanistic implications. Simultaneous acute infarctions in more than one vascular territory strongly implicates a proximal embolic source. When acute infarctions are present in all three vascular territories, consider hypercoagulability of malignancy. Carotid revascularization is an important intervention to prevent recurrent stroke, but it depends on the infarct being in the territory supplied by the carotid artery. For posterior circulation infarctions, there is little role for revascularization. Magnetic resonance imaging (MRI) of the brain is more sensitive than computed tomography (CT) at identifying and defining the infarction pattern; however, in a patient with an obvious mechanism (such as atrial fibrillation) it is not always necessary.
B.

CT and MR angiography of the head and neck provide a comprehensive assessment of the cerebral vasculature and are highly sensitive for identifying significant stenosis. As an alternative in older patients (> 60 years) with anterior circulation stroke, carotid ultrasound adequately evaluates the carotid bifurcation where the vast majority of carotid stenosis occurs, and transcranial Doppler can screen for intracranial stenosis. While less sensitive than CT or MR angiography, this strategy is also less expensive and resource intensive.
C.

In the older patient, atrial fibrillation is a major cause of stroke; electrocardiography and cardiac monitoring should be performed in all patients. Unless an obvious cause of stroke is apparent, transthoracic echocardiography (TTE) should generally also be performed. This can identify important cardioembolic sources, such as dilated cardiomyopathy, severe heart failure, apical akinesis, valvular disease, and intracardiac thrombus. Transesophageal echocardiography (TEE) is more sensitive than TTE for some of these findings, but is invasive and relatively low yield. It should be reserved for those with multiple unexplained infarcts or concern for infective endocarditis. It can also be considered in those with embolic-appearing stroke in which a complete evaluation has been unrevealing. Basic laboratory testing is indicated for all patients to screen for hematologic or coagulation abnormalities, kidney disease, diabetes, and hyperlipidemia. D-dimer is a useful test in many patients, as extreme elevations are strongly associated with hypercoagulability of malignancy. Be aware, however, that D-dimer is not useful when measured after thrombolysis.
D.

A number of uncommon causes of nonatherosclerotic vasculopathy exist. Arterial dissection should be treated with antiplatelet therapy; stenting or surgical revascularization should generally be avoided, as spontaneous healing of the vessel is common and early risk of recurrent stroke is low. Fibromuscular dysplasia (FMD), which can be associated with dissection, is also treated with antiplatelet therapy alone. In neither case is statin therapy necessary, as these conditions are not due to atherosclerosis. Syphilis, antiphospholipid antibody syndrome, Moyamoya disease, and vasculitis may also cause a nonatherosclerotic vasculopathy; all are quite rare.
E.

Large artery atherosclerosis can involve the cervical or intracranial arteries. When stroke is in the territory of > 50% cervical internal carotid artery stenosis, carotid endarterectomy (CEA) or carotid stenting (CAS) should be performed. Benefit is greatest when done within the first week after the stroke. CEA is preferred in most patients; CAS may be appropriate in younger patients and those with significant coronary disease. Vertebral artery and intracranial atherosclerosis are managed medically. With intracranial stenosis > 50%, a 90-day course of aspirin and clopidogrel is appropriate, followed by monotherapy thereafter.
F.

Long-term oral anticoagulation is imperative when atrial fibrillation is identified, reducing the risk of recurrent stroke by ~ 50%; it is also indicated if intracardiac thrombus is found. Severe cardiomyopathy with an ejection fraction < 35% and an embolic-appearing stroke warrants long-term oral anticoagulation. If the ejection fraction subsequently improves, anticoagulation may be changed to antiplatelet therapy. Valvular vegetations may indicate infectious endocarditis, in which case antibiotic therapy and surgical consultation should be pursued, or nonbacterial thrombotic endocarditis, in which case evaluation for underlying hypercoagulability and rheumatologic disease is indicated and anticoagulation typically started. Surgical resection should be considered in patients with a cardiac mass (fibroelastoma, myxoma). Complex aortic atherosclerosis (> 4 mm thickness or mobile) is generally treated with dual antiplatelet therapy for a period of at least 3–6 months.
G.

Lacunar (small-vessel) infarctions, by definition < 15 mm and located in deep, subcortical brain structures, are most often due to intrinsic disease in the small penetrating arteries, though embolism can mimic lacunar infarction. Classic lacunar syndromes include pure motor weakness, pure hemisensory loss, ataxia hemiparesis, and dysarthria–clumsy hand syndrome; the specificity of these clinical patterns for a small-vessel mechanism is poor, however.
H.

Specific clinical scenarios should prompt consideration of less common causes of stroke. Fever, particularly if present on hospital arrival, should prompt suspicion for infectious endocarditis, as should bacteremia. Blood cultures and TEE should be performed. Always consider the possibility of cancer causing hypercoagulability in older patients with stroke, particularly those with multiple recurrent unexplained strokes, prior recent venous thromboembolism, or markedly elevated D-dimer. When suspected, CT of the chest/abdomen/pelvis is appropriate.
I.

Vasculitis, either systemic or isolated to the central nervous system (CNS), is a rare cause of stroke. When suspected, a thorough diagnostic evaluation is critical, including serologic testing for systemic vasculitis, lumbar puncture to assess for cerebrospinal fluid inflammation and infectious processes, and catheter angiography to assess the smaller cerebral vessels. Brain/meningeal biopsy should be performed if isolated CNS vasculitis is strongly suspected, but a negative biopsy does not rule out the diagnosis. Treatment is usually steroids and cyclophosphamide. Rheumatology consultation is appropriate.
J.

Paroxysmal atrial fibrillation is found on prolonged outpatient cardiac rhythm monitoring in 5%–10% of stroke patients with no identified mechanism on initial evaluation. Patients with cortical embolic appearing stroke and stroke in multiple vascular territories are particularly likely to have occult atrial fibrillation.