Although in the past most patients with TIA or minor stroke were hospitalized, not all patients with TIA or minor stroke require inpatient evaluation. For patients with TIA or MCI, hospitalization should be directed toward those who are at higher risk for early recurrent ischemic events. In general, the following patients usually are the best candidates for hospitalization: (1) those with more than four ischemic episodes within the 2 weeks preceding the initial presentation (particularly those without transient monocular blindness in isolation); (2) those with a probable cardiac source of emboli (Tables 12-1 and 12-2), including atrial fibrillation (AF), mechanical valve, dilated cardiomyopathy, known intracardiac thrombus, or recent myocardial infarction (MI); (3) symptomatic carotid artery stenosis or dissection; and (4) known hypercoagulable state. In patients with fewer than five TIAs, the most recent of which occurred within 2 weeks before presentation, and without a probable cardiac source of embolus, symptomatic carotid artery stenosis, or hypercoagulable state, the issue of hospitalization is less clear. However, in general, if the deficit that is associated with the event was marked; if the events are increasing in frequency, severity, or duration; or if there are other factors that suggest a high risk of further events, including a carotid bruit ipsilateral to probable carotid symptoms, then a patient is often hospitalized for assessment. For patients with TIA that occurred more than 2 weeks
before the current assessment or with symptoms involving only transient monocular blindness, an expedited outpatient workup may be indicated. Specific clinical syndromes, including stroke in the young, probable symptomatic carotid dissection, hypercoagulable state, inflammatory vasculopathies, stroke associated with illicit drug use, and cerebral venous thrombosis, usually lead to expedited inpatient evaluation and treatment that is appropriate for the specific clinical entity.

There are several scores used to predict the short-term risk of stroke after TIA that can inform the decision regarding hospitalization. A commonly used score that does not require brain imaging findings is the ABCD2 score (see Chapter 10 for details). The ABCD3-I (see Chapter 10) score may be more accurate in predicting those patients at highest risk of subsequent stroke, but requires MRI results as part of the scoring.

In patients who are selected for hospitalization, antithrombotic therapy should be instituted. Aspirin, 75 to 325 mg per day, should be initiated in most patients. For those who are allergic to aspirin, clopidogrel, 75 mg per day, may be used in its place. Some data suggest that at least short-term use of dual antiplatelet therapy (DAPT) with aspirin 81 mg in combination with clopidogrel 75 mg for the first 21 days followed by single antiplatelet therapy with either aspirin 81 to 325 mg per day or clopidogrel 75 mg per day alone may reduce the risk of recurrence, in those patients who do not require anticoagulation and do not have a carotid stenosis
for which a procedure would be indicated. The Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial showed a 32% reduction in stroke recurrence among Chinese patients treated with DAPT within 24 hours after TIA or minor ischemic stroke compared to those treated with aspirin alone and without an increase in hemorrhage. In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, within 12 hours of high-risk TIA or MCI (National Institutes of Health Stroke Scale < 3), patients were randomized to clopidogrel (75 mg per day after loading dose of 600 mg) in combination with aspirin (50-325 mg per day) compared to aspirin alone, for 90 days. The risk of major ischemic events was reduced from 6.5% to 5% during the first 90 days after study entry, with most events occurring early. Most of the prevented events were cerebral infarctions. The risk of major hemorrhage was increased (0.9% in those treated with DAPT, 0.4% with aspirin), but most of the hemorrhages were nonfatal and not intracranial in location. The benefit in stroke prevention for DAPT was noted for the first 7 to 30 days, and the risk of major hemorrhage became greater from 8 to 90 days after treatment. DAPT is reasonable for the first 21 days following TIA or MCI followed by single-agent antiplatelet therapy thereafter. Exceptions would be those patients who have a history of brain or systemic hemorrhage, or prior imaging studies showing cerebral microhemorrhages.

There are also some data to suggest that DAPT with cilostazol in combination with either aspirin or clopidogrel may be more effective in preventing recurrent ischemic stroke, compared to aspirin or clopidogrel alone, particularly among high-risk patients. In the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS) trial performed in Japan, in patients with recent noncardioembolic ischemic stroke and deemed to be at high risk, with 50% or more intracranial artery stenosis, 50% or more extracranial artery stenosis, or two or more vascular risk factors, over a median follow-up of 17 months, the combination therapy reduced the risk of recurrent ischemic stroke from 6.9% in those treated with monotherapy to 3.2% in those treated with dual therapy, without any difference in the risk of hemorrhage. It is unclear if these data are generalizable to other populations, and the medication remains under study.

There are no clear data supporting the use of short-term intravenous heparin following TIA or MCI. Pending further evidence from clinical trials, the use of heparin or low-molecular-weight heparin (LMWH) is still considered in selected patients with nonsurgical lesions, such as progressive or recurrent ischemic symptoms, crescendo TIAs, recurrent cardiac embolism, and acute cardioembolic stroke as a result of rheumatic AF, hypercoagulable states, and cerebral venous sinus thrombosis.

Heparin, a heterogeneous mixture of sulfate and mucopolysaccharides, activates antithrombin III and inhibits regulation factors II, IX, X, XI, and XII. It also blocks the conversion of fibrinogen to fibrin, exerts both proplatelet and antiplatelet aggregation action, and accelerates fibrinolysis and inactivates thrombin through heparin cofactor II. Intravenous infusion of heparin in very selected patients with TIA or MCI may be initiated with a bolus of 5,000 U followed by constant infusion of 800 to 1,000 U per hour. The anticoagulant effect of heparin is immediate and can be quantified from measurements of activated partial thromboplastin time. The therapeutic range is typically 1.5 to 2 times the normal control value. The patient’s activated partial thromboplastin time should be monitored every 6 hours until the therapeutic value has been documented and then daily during the time of infusion.

Hemorrhagic complications are the most frequent side effects of heparin therapy. These complications are related to the dose and the duration of heparin therapy. They may be more common in patients with high systemic blood pressure, but this association has not been well documented. The frequency of intracerebral hemorrhage in patients who have had ischemic stroke is between 1% and 7%, but the risk is higher in patients with large ischemic stroke than in patients with TIA or MCI.

Another complication that is associated with heparin involves heparin-induced thrombocytopenia. This complication is usually mild and transient (related to increased platelet aggregation), but it may be more serious in 1% to 2% of patients. The more serious form is related to an immunoglobulin G- and immunoglobulin M-induced immune response that can be associated with “paradoxic” arterial occlusions, typically after 4 to 6 days of heparin treatment. For this reason, platelet counts should be determined every 2 days during heparin treatment. If heparin-induced thrombocytopenia develops and continued short-term parenteral anticoagulation is required, then treatment sometimes includes LMWH, which has less propensity for inducing thrombocytopenia than the usual unfractionated heparin. LMWH exerts its anticoagulation effect in a more selective pattern, affecting almost exclusively the intrinsic clotting pathway and having little effect on platelets and thrombin.

The most recent American Stroke Association guidelines for the early treatment of patients with ischemic stroke recommend use of intermittent pneumatic compression devices for deep venous thrombosis (DVT) in immobilized patients. The benefit of subcutaneously administered heparin (unfractionated heparin 5,000 U twice daily or LMWH) in DVT prevention is less certain.

The initial evaluation in an inpatient setting is relatively similar to that in an expedited outpatient setting. CT of the head without contrast should be performed to quickly distinguish nonhemorrhagic from hemorrhagic cerebrovascular disease. MRI of the head (or CT of the head with contrast if there is a contraindication to MRI) may be required if the initial scan indicates a possible arteriovenous malformation, meningioma, or other mass lesion. Other baseline studies include complete blood cell count, activated partial thromboplastin time and international normalized ratio (INR)/prothrombin time, blood glucose, creatinine, liver function tests, electrolytes, erythrocyte sedimentation rate, and blood glucose. Lipid analyses, including high-density lipoprotein, low-density lipoprotein, and total cholesterol levels, should be performed but do not need to be performed acutely. Chest radiograph and electrocardiogram (EKG) should be obtained. Cardiac biomarkers such as troponin and creatine kinase also should be considered, particularly in circumstances that may clinically implicate cardiac ischemia. In patients who are selected for expedited outpatient evaluation and in patients who are hospitalized, unless there is a contraindication to the use of antiplatelet agents, DAPT with aspirin 75 to 325 mg per day in combination with clopidogrel 75 mg per day may be initiated during the evaluation as the mechanism is defined and such DAPT would be used for 21 days unless some other specific preventive antithrombotic approach is indicated.

The patient’s baseline medical history and neurologic history should already have been obtained and a neurologic examination performed (Chapters 1, 2, 3, 4, 5, 6). A minimal cardiac evaluation includes elicitation of cardiac history (with specific attention to both ischemic symptoms and previous arrhythmias) and cardiac
examination that includes careful auscultation for cardiac murmurs. Minimal laboratory investigations include electrocardiography, rhythm strip, and chest radiography. Cardiac biomarkers, including troponin and creatine kinase, should be obtained. If one of the proven cardiac risks is identified (Table 12-1), then anticoagulation may be needed for long-term prophylaxis even if another potential mechanism for the TIA or MCI is identified. The putative cardiac risks (Table 12-2) may also require antiplatelet or anticoagulant therapy, but an alternative mechanism must be considered.

The remainder of the evaluation should be guided by the number and the character of ischemic events. If a patient has stereotyped spells, which indicate recurrent events in the same vascular distribution, then cardioembolic events are relatively less likely, although they are still part of the differential diagnosis. Alternatively, nonstereotyped spells that implicate dissimilar symptoms during sequential spells and possible involvement of separate vascular territories lead to a different assessment.

In patients with multiple stereotyped spells or in those with only a single spell and no evidence of previous infarcts of large vessel distribution on CT or MRI, the evaluation should be tailored on the basis of the circulation implicated (Table 12-3).