Transient Ischemic Attack

A transient ischemic attack (TIA) is an acute episode of temporary neurologic dysfunction that results from focal cerebral, spinal cord, or retinal ischemia, and is not associated with acute tissue infarction.[7] The clinical symptoms of TIA typically last less than 1 hour and often last for less than 30 minutes, but prolonged episodes can occur.

Whereas the classical definition of TIA included symptoms lasting as long as 24 hours, advances in neuroimaging have suggested that many such cases represent minor strokes with resolved symptoms rather than true TIAs. Thus, in 2009 the American Heart Association (AHA) and the American Stroke Association (ASA) endorse a tissue-based definition of TIA (ie, as an episode of focal ischemia rather than acute infarction) rather than a time-based definition.[1]

Clinical assessment of possible TIA involves careful investigation of the onset, duration, fluctuation, location, and intensity of symptoms. Reviewing the patient’s medical record is extremely important for identifying deficits from previous strokes, seizures, or cardiac events. The primary care physician can be a reliable resource for insights into previous episodes and workup.

A neurologic examination is the foundation of the TIA evaluation and should focus in particular on the neurovascular distribution suggested by the patient’s symptoms. (See Presentation.)

Initial assessment is aimed at excluding emergency conditions that can mimic a TIA, which include the following:

• Hypoglycemia

• Seizure

• Tumor or mass lesion

• Migraine with aura

• Peripheral nerve/root disorder

• Demyelinating disease

• Vestibular dysfunction

• Intracranial hemorrhage

• Electrolyte derangements

Thus, a fingerstick blood glucose test should be performed to check for hypoglycemia, and blood should be drawn for laboratory studies. The following tests are considered on an emergency basis: serum chemistry profile, including creatinine; coagulation studies; and complete blood count (CBC).[1, 8] (See Workup.)

Antithrombotic therapy should be initiated as soon as intracranial hemorrhage has been ruled out. (See Treatment and Medication .)

For more information, see Ischemic Stroke in Emergency Medicine.

TIAs are characterized by a temporary reduction or cessation of cerebral blood flow in a specific neurovascular distribution as a result of partial or total occlusion—typically, from an acute thromboembolic event—or stenosis of a small penetrating vessel. Clinical manifestations will vary, depending on the vessel involved and the cerebral territory it supplies (see Ischemic Stroke in Emergency Medicine).

The TIA workup should focus on emergency/urgent risk stratification and management. Numerous potential underlying causes can be readily identified, including the following:

• Atherosclerosis of extracranial carotid and vertebral or intracranial arteries

• Embolic sources - Valvular disease, ventricular thrombus, or thrombus formation from atrial fibrillation, aortic arch disease, paradoxical embolism via a patent foramen ovale (PFO) or atrial-septal defect (ASD)

• Arterial dissection

• Arteritis - Inflammation of the arteries occurring primarily in elderly persons, especially women; noninfectious necrotizing vasculitis (primary cause); drugs; irradiation; local trauma; connective tissue diseases

• Sympathomimetic drugs (eg, cocaine)

• Mass lesions (eg, tumors or subdural hematomas) – These less frequently cause transient symptoms and more often result in progressive persistent symptoms

• Hypercoagulable states (eg, genetic or associated with cancer or infection)

Causes in children

TIA etiologies in children, which can differ from those in adults, include the following:

• Congenital heart disease with cerebral thromboembolism (most common)

• Drug abuse (eg, cocaine)

• Clotting disorders

• Central nervous system infection

• Neurofibromatosis

• Vasculitis

• Idiopathic progressive arteriopathy of childhood (moyamoya)

• Fibromuscular dysplasia

• Marfan disease

• Tuberous sclerosis

• Tumor

• Sickle cell disease

• Focal arteriopathies

Between 200,000 and 500,000 TIAs are diagnosed annually in the United States.[9, 10] Emergency department (ED) visits for TIAs occur at an approximate rate of 1.1 per 1000 US population, and TIAs are diagnosed in 0.3% of ED visits.[11] TIA carries a particularly high short-term risk of stroke, and approximately 15% of diagnosed strokes are preceded by TIAs.

Internationally, the probability of a first TIA is around 0.42 per 1000 population in developed countries.[12] TIAs occur in about 150,000 patients per year in the United Kingdom.[3] The incidence likely mirrors that of stroke.

The incidence of TIAs increases with age, from 1-3 cases per 100,000 in those younger than 35 years to as many as 1500 cases per 100,000 in those older than 85 years.[9] Fewer than 3% of all major cerebral infarcts occur in children. Pediatric strokes often can have quite different etiologies from those of adult strokes and tend to occur with less frequency.

The incidence of TIAs in men (101 cases per 100,000 population) is significantly higher than that in women (70 per 100,000).[13]

The incidence of TIAs in blacks (98 cases per 100,000 population) is higher than that in whites (81 per 100,000 population). Controversy exists regarding whether race influences emergency workup after TIA.[7, 6]

With passive reporting, the early risk of stroke after TIA is approximately 4% at 2 days, 8% at 30 days, and 9% at 90 days.[14] When patients with TIA are followed prospectively, however, the incidence of stroke is as high as 11% at 7 days.[3] The probability of stroke in the 5 years following a TIA is reported to be 24-29%. In addition, patients with TIAs or stroke have an increased risk of coronary artery disease.[15]

Before being discharged from the hospital, patients who have been diagnosed with TIA must receive clear instruction to ensure that they understand the need for a complete and rapid workup through close follow-up care. Also essential for patients is education on stroke symptoms, the need to call emergency services immediately if any of these symptoms occur, and the contact number for emergency services (911 in the United States and Canada).

Despite program efforts in public education, many patients still do not seek medical attention after experiencing TIA symptoms. A 2010 population-based study found that 31% of all patients who experienced a recurrent stroke within 90 days of their first TIA or minor stroke had not sought medical attention after the initial event.[16]

Public health professionals and physicians need to do more, such as promoting and participating in medical screening fairs and public outreach programs. In addition, patients need to be educated about lifestyle modification and cardiovascular risk factors.

For patient education information, see the Stroke Center, as well as Transient Ischemic Attack (Mini-stroke).

A transient ischemic attack (TIA) may last only minutes, and symptoms often resolve before the patient presents to a clinician. Thus, historical questions should be addressed not just to the patient but also to family members, witnesses, and emergency medical services (EMS) personnel. Witnesses often perceive abnormalities that the patient cannot, such as changes in behavior, speech, gait, memory, and movement.

Significant medical history questions to elicit any risk factors for relevant underlying disease include questions about the following:

• Recent surgery (eg, carotid or cardiac)

• Previous strokes or TIAs

• Seizures

• Systemic or central nervous system (CNS) infections

• Use of illicit drugs

• Complete medication regimen, including all over-the-counter medications

• Comorbidities related to metabolic disorders, especially diabetes

• Known coagulopathy or family history of early clotting or thrombotic events

• History of arteritis

• Noninfectious necrotizing vasculitis, irradiation, and local trauma

• Thromboembolic risk factors (eg, carotid artery stenosis, venous or arterial thromboembolism, patent foramen ovale or atrial septal defect, atrial fibrillation, prior myocardial infarction, and left ventricular dysfunction)

• Other known cardiovascular disease

• History of migraine

Carefully investigate the onset, duration, fluctuation, and intensity of symptoms. Reviewing the patient's medical record is extremely important for identifying deficits from previous strokes, seizures, or cardiac events. The primary care physician can be a reliable resource for insights into previous episodes and workup.

Use these various resources to attempt to clarify when symptoms first occurred, how long they lasted, whether the patient recovered completely (ie, returned to baseline status), and if a pattern of escalating symptoms is present. For patients who woke up or are found with symptoms, the time they were last known to be normal should be documented.

If a patient has a history of associated trauma or cardiac symptoms, the differential diagnosis widens. Pertinent negative items (eg, lack of headache, lack of chest pain, and lack of eye pain) in the review of systems are also important.

Carotid or vertebral dissection can occur in association with both major and minor trauma. The patient may provide a history of blunt or torsion injury to the neck. An apparent association between cervical manipulation (as in chiropractic neck adjustment or massage therapy) and arterial dissections has been frequently reported.[17, 18]

The goals of the physical examination are to uncover any neurologic deficits, to evaluate for underlying cardiovascular risk factors, and to seek any potential thrombotic or embolic source of the event. Global CNS depression and airway or cardiac compromise are not typically features of a TIA. In fact, the level of consciousness and neurologic examination findings are expected to be at the patient’s baseline.

Ideally, any neurologic deficits should be recorded with the aid of a formal and reproducible stroke scale, such as the National Institutes of Health Stroke Scale (NIHSS) (For additional information on this systematic assessment tool, see Stroke Scale). A stroke scale prompts the examiner to be thorough and allows different examiners to repeat the examination reliably during subsequent phases of the evaluation. Any neurologic abnormalities should suggest the diagnosis of stroke (or ongoing neurologic event) rather than TIA.

Identify signs of other active comorbidities, including infections (eg, sinusitis, mastoiditis, and meningitis) and vasculitides. The carotid arteries can be examined for pulse upstroke or bruit, and the neck can be examined for the presence of carotid endarterectomy scars.

Funduscopy can identify retinal plaques, retinal pigmentation, and optic disc margins. Pupil reaction to direct and consensual light exposure can be assessed.

In addition to performing standard auscultation, examine the chest for the presence of surgical scars, for the presence of a pacemaker or automatic implantable cardioverter-defibrillator (ICD), or for other clues that the patient may have a cardiac disorder and may be increased risk for a cardioembolic phenomenon.

Cardioembolic events are significant causes of TIAs. Assess for irregular rhythm or other unusual rhythms and rates, murmurs, or rubs that might suggest valvular disease, atrial-septal defects, or ventricular aneurysm (a source of mural thrombi). Check for splinter hemorrhages in the nail beds.

The following signs may be present in patients with cranial nerve dysfunction:

• Ocular dysmotility

• Forehead wrinkling asymmetry

• Incomplete eyelid closure

• Asymmetrical mouth retraction

• Loss of the nasolabial crease

• Swallowing difficulty

• Lateral tongue movement

• Weak shoulder shrugging

• Visual field deficits

The cerebellar system can be tested by assessing ocular movement, gait, and finger-to-nose and heel-to-knee movements, with an eye to signs of past-pointing and dystaxia, hypotonia, overshooting, gait dystaxia, and nystagmus. The speech and language system can be tested to assess for both aphasia and dysarthria. Mental status can be assessed formally (eg, with the Mini-Mental Status Examination or Quick Confusion Scale) or as part of the patient’s overall response to questions and interactions with the examiner.

A neurologic examination is the foundation of the TIA evaluation and should focus in particular on the neurovascular distribution suggested by the patient’s symptoms. Subsets of the neurologic examination include the following:

• Cranial nerve testing

• Determination of somatic motor strength

• Somatic sensory testing

• Speech and language testing

• Assessment of the cerebellar system (be sure to watch the patient walk)

For somatic motor testing, test muscle stretch reflexes of the biceps, triceps, brachioradialis, patellar, and Achilles. In addition, inspect posture and look for tremors. Test the strength of the shoulder girdle, upper extremities, abdominal muscles, and lower extremities. Test passive movement of major joints to look for spasticity, clonus, and rigidity.

The National Institutes of Health Stroke Scale (NIHSS) (see Table 1 below) is used mostly by stroke teams for quantifying neurologic impairment. It enables rapid determination of the severity and possible location of the stroke. A patient’s score on the NIHSS is strongly associated with outcome, and it can help identify those patients who are likely to benefit from thrombolytic therapy and those who are at higher risk for developing hemorrhagic complications of thrombolytic use.

Table 1. National Institutes of Health Stroke Scale (Open Table in a new window)

The NIHSS is easily used and focuses on the following 6 major areas of the neurologic examination:

• level of consciousness

• Visual function

• Motor function

• Sensation and neglect

• Cerebellar function

• Language

The NIHSS is a 42-point scale, with minor strokes usually being considered to result in a score lower than 5. An NIHSS score higher than 10 correlates with an 80% likelihood of visual flow deficits on angiography. Yet, discretion must be used in assessing the magnitude of the clinical deficit; for instance, if a patient’s only deficit is being mute, the NIHSS score will be 3. Additionally, the scale does not measure some deficits associated with posterior circulation strokes (eg, vertigo and ataxia).

Initial vital signs should include the following:

• Temperature

• Blood pressure

• Heart rate and rhythm

• Respiratory rate and pattern

• Oxygen saturation

The examiner should assess the patient’s overall health and appearance, making an assessment of the following:

• Attentiveness

• Ability to interact with the examiner

• Language and memory skills

• Overall hydration status

• Development

Ruling out metabolic or drug-induced causes of symptoms consistent with a transient ischemic attack (TIA) is important. Initial assessment is aimed at excluding emergency conditions that can mimic a TIA (eg, hypoglycemia, seizure, or intracranial hemorrhage). A fingerstick blood glucose test should be performed and blood drawn for a complete blood count (CBC), coagulation studies, and serum electrolyte levels. Obtain a 12-lead electrocardiogram (ECG) with rhythm strip, and evaluate for symptomatic arrhythmias or evidence of ischemia.

Brain imaging is recommended within 24 hours of symptom onset. Although magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) is preferred, noncontrast computed tomography (CT) of the head is a reasonable first choice when MRI is not readily available.[1, 8, 4]

The cerebral vasculature should be imaged on an urgent basis, preferably at the same time as the brain. Brain imaging can identify an area of ischemia in as many as 25% of patients, and TIA mimics may be identified as well. Vessel imaging can identify a stenosis or occlusion that may warrant early intervention.

Electroencephalography (EEG) may be indicated to evaluate for seizure activity. Lumbar puncture (LP) may be indicated if subarachnoid hemorrhage, central nervous system (CNS) infection, or demyelinating disease is to be excluded.

The following tests are considered on an emergency basis:

• Serum chemistry profile, including creatinine

• Screening coagulation studies

• CBC

The following tests may be helpful and often can be performed on an urgent basis:

• Erythrocyte sedimentation rate (ESR)

• Cardiac enzymes

• Lipid profile

Screening for hypercoagulable states (particularly in younger patients with no known vascular risk factors) may be performed, though this practice is not evidence-based. Tests include the following[1] :

• Protein C, protein S, and antithrombin III activities

• Activated protein C resistance/factor V Leiden

• Fibrinogen

• D-dimer

• Anticardiolipin antibody

• Lupus anticoagulant

• Homocysteine

• Prothrombin gene G20210A mutation

• Factor VIII

• Von Willebrand factor

• Plasminogen activator inhibitor-1

• Endogenous tissue plasminogen activator activity

Additional laboratory tests, ordered as needed and on the basis of the history and examination, include the following:

• Syphilis serology

• Antiphospholipid antibodies

• Toxicology screens

• Hemoglobin electrophoresis

• Serum protein electrophoresis

• Cerebrospinal fluid examination

Noncontrast cranial CT is widely and rapidly available and often serves as the initial imaging evaluation. It can aid in diagnosing the following:

• A new area of ischemia or infarction

• Old areas of ischemia

• Intracranial mass, such as tumor

• Intracranial bleeding, such as subdural hematoma or intracerebral hemorrhage

MRI is more sensitive than CT for acute ischemia, infarction, previous intracranial bleeding, and other underlying lesions; however, it is less widely available on an acute basis than CT is.

The presence of ischemic lesions on MRI appears to increase the short-term risk of stroke, a finding that highlights the value of this modality in acute risk stratification.[20, 21, 22] In addition, negative DWI in concert with low-risk clinical features can identify patients at minimal short-term stroke risk.[23] Patients with DWI abnormalities, despite low ABCD2 scores (see Risk Stratification Scores), may be at just as high a risk for stroke as patients with high ABCD2 scores but no DWI abnormalities.[24]

Vascular imaging for TIA includes Doppler ultrasonography, CT angiography (CTA), and magnetic resonance angiography (MRA). CTA is of increasing value in identifying occlusive disease in the cerebrovascular circulation. MRA is another alternative for imaging vessels in both the brain and the neck. Conventional catheter angiography can be performed when the other modalities are unavailable or yield discordant results.

Carotid Doppler ultrasonography of the neck can be used to identify patients in need of urgent surgical or endovascular therapy. Transcranial Doppler can be a complementary examination evaluating the patency of cerebral vessels and collateral circulation.

Transthoracic (TTE) or transesophageal echocardiography (TEE) can evaluate for a cardioembolic source or for risk factors such as patent foramen ovale. A 12-lead ECG should be performed as soon as possible after TIA to evaluate for dysrhythmias such as atrial fibrillation. Cardiac monitoring (inpatient telemetry or Holter monitoring) may be useful in patients without a clear diagnosis after initial brain imaging and ECG.

Some patients present to the emergency department (ED) with a transient neurologic disturbance that does not represent a true TIA, and distinguishing between such disturbances and TIAs can be difficult for the busy practitioner. In addition, an emergency comprehensive workup of all patients with “possible TIA” may not be the most cost-effective or appropriate use of limited local resources. Appropriate risk stratification must be employed to ensure that diagnostic and therapeutic interventions are targeted to the highest-risk patients.

A number of risk stratification scores are available to assist in this task, but the most widely validated is the ABCD2 score.[21, 25, 26] (See Table 2 below.)

Table 2. ABCD² Score (Open Table in a new window)

Individuals with an ABCD2 score of 6 or 7 have an 8% risk of stroke within 2 days, whereas those with an ABCD2 score lower than 4 have a 1% risk of stroke within 2 days.[8] Some of these patients with lower scores may well have non-TIA events rather than true TIAs.[27]

It has been proposed that this scoring system can be used to risk-stratify ED patients for emergency workup and to predict the severity of recurrent stroke after TIA.[25, 28, 29, 30] Others have suggested that when a comprehensive workup can be obtained routinely in the ED, the value of the ABCD2 score diminishes significantly.[31] Some groups have noted, however, that short-term stroke risk after TIA can be worrisome even in those with low ABCD2 scores.[32, 33]

ABCD3 score

One group has developed 2 variations of the ABCD2 score that may improve risk stratification after TIA in secondary settings. The ABCD3 score assigns 2 points for dual TIA (an earlier TIA within 7 days of the index event), and the ABCD3 imaging score adds stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points). However, further validation and study are needed before use of the ABCD3 score can be recommended.[34]

Rapid transport to hospital is essential to evaluate the patient who may have fleeting or stuttering symptoms. Fingerstick glucose testing can quickly rule out hypoglycemia. Intravenous (IV) access can be established, though transport should not be delayed for this. Collect all the patient’s prescription bottles.

The family or witnesses should be instructed to go to the emergency department (ED), or contact information for these individuals should be obtained. In some communities, emergency medical services (EMS) may preferentially transfer patients with high-risk stroke symptoms to centers with specific stroke expertise.[35]

Vital signs must be obtained promptly and addressed as indicated. Cardiac monitoring can capture a relevant dysrhythmia. Pulse oximetry can evaluate for hypoxia. IV access (if not already established by EMS) should be obtained. Obtain a fingerstick glucose level, and treat the patient accordingly.

Patients with possible transient ischemic attack (TIA) require urgent evaluation and risk stratification. Local resources and practice patterns will determine whether this is done on an inpatient or an outpatient basis.

Initiation of stroke prevention therapy must be provided urgently. Medical management is aimed at reducing both short-term and long-term risk of stroke and varies according to the underlying cause of the episode.

Although controversy exists regarding the need for hospital admission, there is no controversy regarding the need for urgent evaluation, risk stratification, and initiation of stroke prevention therapy.[1, 36, 37, 26] When one community implemented a strategy to ensure patients were seen within an average of 1 day, compared with an average of 3 days, the 90-day stroke risk fell from 10% to 2%.[38]

Similarly, programs to admit patients to a "rapid evaluation unit" or "observation unit" have reduced the 90-day stroke risk from approximately 10% to 4–5%.[39, 40] Other authors have suggested similar benefits from rapid follow-up.[41]

The availability of local resources determines whether this urgent evaluation should occur on an inpatient basis, in an ED observation unit, or in rapid follow-up. To determine appropriate disposition, the emergency physician should decide on the necessary workup, then discuss with the neurologist or primary care physician how best to ensure that this occurs promptly.[42]

One randomized controlled trial of an ED diagnostic protocol found that it was possible to reduce cost, shorten length of stay, and provide appropriate risk stratification by performing this workup in an ED observation unit (with neurology consultation) rather than in an inpatient unit.[43] On the other hand, admission offers the potential benefit of decreased time to thrombolysis in hospitalized patients diagnosed with TIA who develop a new ischemic stroke in the first 24–48 hours after diagnosis.

The American Heart Association (AHA) suggests hospital admission as a reasonable choice for patients with TIA if they present within 72 hours of the event and meet any of the following criteria:[1]

• ABCD2 score of 3 (class IIa recommendation; evidence level C)

• ABCD2 score of 0–2 and uncertainty that diagnostic workup can be completed within 2 days as an outpatient (class IIa recommendation; evidence level C)

• ABCD2 score of 0–2 and other evidence that indicates the patient's event was caused by focal ischemia (class IIa recommendation; evidence level C)

The National Stroke Association consensus guidelines for the management of TIAs recommend considering patient hospitalization if it is the first TIA within the previous 24–48 hours. This would facilitate possible early treatment with tissue plasminogen activator (tPA) and other medical management for recurrent symptoms, and it would expedite risk stratification and implementation of secondary prevention.

For patients with a recent (≤1 week) TIA, the guidelines recommend a timely hospital referral with hospitalization for the following:[26]

• Crescendo TIAs

• Symptoms lasting longer than 1 hour

• Symptomatic internal carotid stenosis greater than 50%

• Known cardiac source of embolus (eg, atrial fibrillation)

• Known hypercoagulable state

• Appropriate combination of the California score or ABCD score

Patients may be significantly hypertensive. Unless there is specific concern for end-organ damage from a hypertensive emergency, blood pressure should be managed conservatively while ischemic stroke is being ruled out.

For acute ischemic stroke, the AHA recommends initiating antihypertensive therapy only if blood pressure is higher than 220/120 mm Hg or if mean arterial pressure exceeds 130 mm Hg. Unless there is a comorbid cardiac or other condition that necessitates reduction of blood pressure, allowing the patient’s blood pressure to autoregulate at a higher level (during the acute phase) may help maximize cerebral perfusion pressure.[44]

In view of the high short-term risk of stroke after TIA, antithrombotic therapy should be initiated as soon as intracranial hemorrhage has been ruled out. The guidelines developed by the AHA and the American Stroke Association (ASA) for the prevention of stroke in patients with stroke or TIA, issued in 2006[45] and updated in 2014,[46] are summarized below.

Noncardioembolic transient ischemic attack

Antiplatelet agents, rather than oral anticoagulants, are recommended as initial therapy. Aspirin 50–325 mg/day, a combination of aspirin and extended-release dipyridamole, and clopidogrel are all reasonable first-line options (class I recommendation).[46]

The AHA/ASA guidelines state that the combination of aspirin and clopidogrel might be considered for initiation within 24 hours of a minor ischemic stroke or TIA and for continuation for 21 days. However, the combination of aspirin and clopidogrel, when initiated days to years after a minor stroke or TIA and continued 2 to 3 years, increases the risk of hemorrhage relative to either agent alone and is not recommended for routine long-term secondary prevention after ischemic stroke or TIA.[46]

Cardioembolic transient ischemic attack

In patients who have atrial fibrillation in association with a TIA, long-term anticoagulation with warfarin to a target international normalized ratio (INR) of 2–3 is typically recommended. Aspirin 325 mg/day is recommended for patients unable to take oral anticoagulants. However, the addition of clopidogrel to aspirin therapy, compared with aspirin therapy alone, might be reasonable. For most patients with a stroke or TIA in the setting of AF, it is reasonable to initiate oral anticoagulation within 14 days after the onset of neurological symptoms. Anticoagulation can be delayed beyond 14 days in the presence of high risk for hemorrhagic conversion.[46]

The 2014 AHA/ASA guidelines also state that bridging therapy with subcutaneous low-molecular-weight heparin (LMWH) is reasonable for patients with atrial fibrillation who require temporary interruption of oral anticoagulation but are at high risk for stroke.[46]

In acute myocardial infarction (MI) with left ventricular thrombus, oral anticoagulation with warfarin (target INR, 2–3) is reasonable.[46]

In dilated cardiomyopathy, either oral anticoagulation with warfarin (target INR, 2–3) or antiplatelet therapy may be considered. In rheumatic mitral valve disease, oral anticoagulation with warfarin (target INR, 2–3) is reasonable. Antiplatelet agents would not normally be added to warfarin unless patients experience recurrent embolism despite a therapeutic INR. The benefit of warfarin after stroke or TIA in patients with sinus rhythm and cardiomyopathy characterized by systolic dysfunction has not been established.[46]

In mitral valve prolapse, long-term antiplatelet therapy is reasonable. In mitral annular calcification, antiplatelet therapy can be considered. Patients with mitral regurgitation can be considered for warfarin or antiplatelet therapy.

In aortic valve disease, antiplatelet therapy may be considered. For patients with mechanical prosthetic valves, oral anticoagulation with warfarin (target INR, 2.5–3.5) is recommended. For those who experience TIAs despite therapeutic INR, aspirin 75–100 mg/day can be added to the regimen. Patients with bioprosthetic valves and no other source of thromboembolism who experience TIAs can be considered for oral anticoagulation with warfarin (target INR, 2–3).

Patients who have experienced a transient ischemic attack (TIA) may undergo closure of a patent foramen ovale (PFO). Findings from an observational study suggest PFO closure results in a low rate of long-term recurrent stroke (1%). The study included 201 consecutive patients (mean age, 47 years) from two Canadian hospitals who underwent PFO closure because of a cryptogenic embolism (stroke, 76%; transient ischemic attack, 32%; systemic embolism, 1%). Previous studies had shown benefit in closing a PFO for patients who have had a stroke for which there was no other suspected cause, but follow-up was limited. This new study, however, had an average follow-up of 12 years.[47, 48]  

Intracranial atherosclerosis

The 2014 AHA/ASA guidelines state the following for patients with stroke or TIA due to 50–99% stenosis of a major intracranial artery:[46]

• Aspirin 50–325 mg/day, rather than warfarin, is recommended

• Maintenance of blood pressure below 140/90 mm Hg and total cholesterol below 200 mg/dL is recommended

• Extracranial or intracranial bypass surgery is not recommended

• Angioplasty and stent placement are investigational and of unknown utility

A randomized trial has shown that aggressive medical management (antiplatelet therapy combined with intensive management of vascular risk factors) is safer than percutaneous transluminal angioplasty and stenting (PTAS) in patient with 70–99% stenosis of a major intracranial artery. Enrollment in this trial was stopped after 451 patients underwent randomization because the 30-day rate of stroke or death was 14.7% in the PTAS group and 5.8% in the medical-management group.[49]

Ipsilateral carotid artery stenosis

Patients with TIA and ipsilateral carotid artery stenosis may be candidates for urgent (performed within 2 weeks) carotid endarterectomy. In certain patients, carotid artery angioplasty and stenting is a reasonable alternative. This can be discussed acutely, or rapid follow-up can be arranged.

Extracranial vertebral stenosis

Patients with symptoms attributable to extracranial vertebral stenosis may be candidates for endovascular treatment. Again, this should be arranged expeditiously if available.

According to the AHA/ASA 2014 guidelines, optimal medical treatment for these patients includes antiplatelet and statin therapies, as well as risk factor modification. This is also optimal medical treatment for patients with symptomatic extracranial carotid disease.[46]

Ideally, decisions regarding ED evaluation and inpatient versus rapid outpatient follow-up are made in concert with a neurologist. There is clear consensus on the importance of rapid evaluation.[4] For example, in the EXPRESS (Early use of eXisting PREventive Strategies for Stroke) study, the 90-day risk of recurrent stroke in patients with TIA or minor stroke was 10.3% in those patients who underwent assessment after a median of 3 days, compared with 2.1% in those assessed in a median of 1 day, who then received prompt treatment.[50]

In some settings, the only way to access expedited evaluation and workup may be through interfacility transfer to a hospital with the appropriate resources. The National Stroke Association consensus guidelines recommend that “[h]ospitals and general practitioners should agree on a local admissions policy and a local protocol for referral to specialist assessment clinics for patients with TIA who do not require hospital admission.”[26]

For ED physicians, consultation with the patient’s primary care physician is the most important consultation because the primary care physician will monitor the patient over the long term and ensure risk-factor and lifestyle modification. In addition, a rapid neurology consultation is not available in many communities, and the primary care doctor may be primarily responsible for managing urgent risk stratification. However, when a neurologist is rapidly available, this consultation should be obtained on an urgent basis as well.

Consultation with a cardiologist can be considered for patients with clear cardiac findings that influence stroke risk, such as atrial fibrillation, patent foramen ovale, intracardiac thrombus, or valvular abnormalities.

Consultation with a neurosurgeon or vascular surgeon should be considered for patients with significant vessel stenosis or occlusion, with a goal of specialist assessment within 1 week and treatment within 2 weeks of symptom onset.[4, 51, 52] In many centers, some endovascular interventions can be performed by other specialists, including interventional neurologists, radiologists, and neuroradiologists.

Patients selected for outpatient care should have a clear follow-up plan and stroke prevention initiated as described, including antiplatelet medication and risk-factor modification. Antiplatelet agents typically should be initiated as soon as intracranial bleeding is ruled out. As noted (see above), the agent to be used varies with the patient and the specific indication.

The following measures should be included in any long-term monitoring of TIA patients:

• Antihypertensive control should be optimized for patients with hypertension

• Lipid control should be initiated, potentially including a statin agent

• Blood glucose control should be optimized for patients with diabetes

• A smoking-cessation strategy, which may include medication, should be initiated

• Heavy drinkers should eliminate or reduce alcohol consumption

• Overweight patients should be encouraged to lose weight

• All patients should be encouraged to exercise

Pharmacologic management for transient ischemic attacks (TIAs) is aimed at reducing both short-term and long-term risk of stroke. In view of the high short-term risk of stroke after TIA, antithrombotic therapy should be initiated as soon as intracranial hemorrhage has been ruled out.

Class Summary

Antiplatelet agents inhibit platelet function by blocking cyclooxygenase and subsequent aggregation.

Aspirin (Anacin, Ascriptin, Ecotrin, Bufferin, Bayer Aspirin)

Aspirin blocks prostaglandin synthetase action, and this, in turn, inhibits prostaglandin synthesis and prevents formation of platelet-aggregating thromboxane A2.

Aspirin 25 mg/dipyridamole 200 mg (Aggrenox)

Combination aspirin-dipyridamole therapy has been shown to prevent cardiovascular events following TIAs. Each capsule contains 25 mg of aspirin and 200 mg of dipyridamole, for a daily total dose of 50 mg of aspirin and 400 mg of dipyridamole.

Aspirin irreversibly inhibits formation of cyclooxygenase, thus preventing formation of thromboxane A2, a platelet aggregator and vasoconstrictor. Platelet inhibition lasts for the life of a cell (approximately 10 days).

Dipyridamole is a platelet adhesion inhibitor that possibly inhibits red blood cell (RBC) uptake of adenosine, itself an inhibitor of platelet reactivity. In addition, it may inhibit phosphodiesterase activity, leading to increased cyclic 3′,5′-adenosine monophosphate within platelets and formation of the potent platelet activator thromboxane A2.

Clopidogrel (Plavix)

Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.

Dipyridamole (Persantine)

Dipyridamole is administered to complement usual warfarin therapy. It inhibits platelet adhesion, which may inhibit adenosine uptake by RBCs. It may increase cyclic 3′,5′-adenosine monophosphate (cAMP) within platelets and formation of the potent platelet activator thromboxane A2. In addition, it may reduce the risk of stroke when used as monotherapy instead of aspirin.

Ticlopidine (Ticlid)

Ticlopidine is a second-line antiplatelet therapy for patients who cannot tolerate or do not respond to aspirin therapy. In some circumstances, it can be an alternative to clopidogrel.

Class Summary

Controlled therapeutic inhibition of blood clotting by means of appropriate drugs (ie, anticoagulants) is indicated for prevention of ischemic stroke in patients with risk factors for thromboembolism, such as atrial fibrillation.

Warfarin (Coumadin)

Warfarin interferes with hepatic synthesis of vitamin K−dependent coagulation factors. It is used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders.