OVERVIEW: A transient ischemic attack (TIA) is considered an acute episode of temporary neurologic dysfunction caused by a vascular occlusion.

. Symptoms typically last less than an hour. While the classical definition included symptoms lasting as long as 24 hours, advents in neuroimaging have suggested that many such cases represent minor strokes with resolved symptoms rather than true TIAs. Current guidelines recommend that a transient ischemic attack be defined as a transient episode of neurological dysfunction caused by focal brain, spinalcord, or retinal ischemia, without acute infarction.

FREQUENCY: United States Between 200,000-500,000 TIAs per year are diagnosed in the United States. ED visits for TIA occur at about 1.1 visits per 1,000 US population, and TIAs are diagnosed in 0.3% of ED visits.4 TIA carries a particularly high short-term risk of stroke, and approximately 15% of diagnosed strokes are preceded by TIAs.

International TIA occurs in about 150,000 patients per year in the United Kingdom.5 The population incidence likely mirrors that of stroke.

Sex The incidence of TIAs in men, at 101 cases per 100,000, is significantly higher than that in women, 70 cases per 100,000

Race The incidence of TIAs in blacks, at 98 cases per 100,000 population, is higher than that in whites, 81 cases per 100,000 population. Controversy exists regarding whether race influences emergent workup following TIA.

Age The incidence of TIAs appears to increase with age, from 1-3 cases per 100,000 in those younger than 35 years to up to 1500 cases per 100,000 in those older than 85.11 Fewer than 3% of all major cerebral infarcts occur in children. Pediatric strokes can often have quite different etiologies compared with adult strokes and are relatively more infrequent.

PATHOPHYSIOLOGY Temporary reduction or cessation of cerebral blood flow in a specific neurovascular distribution can be due to low flow through a partially occluded vessel or to an acute thromboembolic event.

CAUSES The transient ischemic attack (TIA) workup is focused on emergent/urgent risk stratification. A number of potential underlying causes can be rapidly identified.

Atherosclerosis of carotid and vertebral arteries Embolic sources - Valvular disease, ventricular thrombus, and thrombus formation due to atrial fibrillation Arterial dissection Arteritis - Inflammation of the arteries occurring primarily in elderly persons, especially women o Noninfectious necrotizing vasculitis (primary cause) o Drugs o Irradiation o Local trauma Sympathomimetic drugs (eg, cocaine) Mass lesions (eg, tumors, subdural hematomas) - Less frequently cause transient symptoms and more often result in progressive persistent symptoms TIA etiologies in children, which can be different than those in adults, include the following: o Congenital heart disease with cerebral thromboembolism (most common) o Drug abuse (eg, cocaine) o Clotting disorders o CNS infection o Neurofibromatosis o Vasculitis o Idiopathic progressive arteriopathy of childhood (moyamoya) o Fibromuscular dysplasia o Marfan disease o Tuberous sclerosis o Tumor

MORTALITY/MORBIDITY The most important short-term risk from a TIA is that of stroke.6 The early risk of stroke following TIA is approximately 4-5% at 2 days and as high as 11% at 7 days.5,7 Additionally, despite a public education program, many patients still do not seek medical attention after experiencing TIA symptoms. Public health professionals and physicians need to do more such as promoting and participating in medical screening fairs and public outreach program

CLINICAL HISTORY A transient ischemic attack (TIA) may last only minutes and has often resolved 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 may have perceived abnormalities that the patient could not, such as changes in behavior, speech, gait, memory, and movement. Significant medical history questions include the following: o Recent surgery (eg, carotid, cardiac) o Previous strokes o Known cardiovascular disease o Seizures o CNS infections o Use of illicit drugs o Complete medication regimen o Comorbidities related to metabolic disorders Carefully investigate 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 may have great insight into previous episodes and workup. o Attempt to clarify when symptoms first occurred, how long they lasted, if the patient recovered completely (returned to baseline status), and if a pattern of escalating symptoms is present. For those who woke up or are found with symptoms, the time last known to be normal should be documented. o History of associated trauma or cardiac symptoms widens the differential diagnosis. Pertinent negative items (eg, headache, chest pain, eye pain) in the review of systems also are important. o 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. Controversy exists regarding whether manipulation by a chiropractor or massage therapy increases the risk of arterial dissection.12 Elicit any risk factors for relevant underlying disease. o Known coagulopathy o History of arteritis o Noninfectious necrotizing vasculitis, drugs, irradiation, and local trauma are known to cause inflammatory arterial injury. o Thromboembolic risk factors such as carotid artery stenosis, venous or arterial thromboembolism, patent foramen ovale, atrial fibrillation, prior myocardial infarction, or left ventricular dysfunction.

PHYSICAL EXAMINATION: The goal of the physical examination is to carefully uncover any neurologic deficits, evaluate for underlying cardiovascular risk factors, and seek any potential thrombotic or embolic source of the event. 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). A stroke scale prompts the examiner to be thorough and allows different examiners to reliably repeat the examination during subsequent phases of the evaluation. Any neurologic abnormalities should suggest the diagnosis of stroke (or ongoing neurologic event) rather than TIA.

Initial vital signs should include the following: o Temperature o Blood pressure o Heart rate and rhythm o Respiratory rate and pattern o Oxygen saturation The examiner should assess the patient's overall health and appearance, making an assessment of the following: o Attentiveness o Ability to interact with the examiner o Language and memory skills o Overall hydration status o Development Identify signs of other active comorbidities including infections (eg, sinusitis, mastoiditis, meningitis) and vasculidities. Carotid arteries can be examined for pulse upstroke, bruit, and 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 or presence of a pacemaker/automatic implantable cardioverter defibrillator (AICD), or other clues that the patient may have a cardiac disorder and increased risk of a cardioembolic phenomenon. Cardioembolic events are significant causes of TIAs. Identify the rhythm for irregularity or other unusual rhythms and rates, murmurs, or rubs that might suggest valvular disease, atrioseptal defects, or ventricular aneurysm (a source of mural thrombi).

A neurologic examination is the foundation of the TIA evaluation and should particularly focus on the neurovascular distribution suggested by the patients symptoms. Subsets of the neurologic examination include the following: o Cranial nerve testing o Somatic motor strength o Somatic sensory testing o Cerebellar system (be sure to see the patient walk) - The cerebellar system can be tested by assessing ocular movement, gait, and finger-to-nose and heel-to-knee movements, looking for signs of past-pointing and dystaxia, hypotonia, overshooting, gait dystaxia, and nystagmus. Mental status can be assessed formally (Mini-Mental Status Examination, Quick Confusion Scale) or as part of the patient's overall response to questions and interactions with the examiner. The following signs may be present with cranial nerve dysfunction: o Ocular dysmotility o Forehead wrinkling asymmetry o Incomplete eyelid closure o Asymmetrical mouth retraction o Loss of the nasolabial crease o Swallowing difficulty o Lateral tongue movement o Weak shoulder shrugging o Visual field deficits Somatic motor testing o Test muscle stretch reflexes of biceps, triceps, and brachioradialis and patellar and Achilles reflexes. o Inspect posture and presence of tremors. Test shoulder girdle, upper extremity, abdominal muscle, and lower extremity strength. o Test passive movement of major joints to look for spasticity, clonus, and rigidity.

DIFFERENTIAL DIAGNOSIS: bell palsy headache, migraine hypoglycemia neoplasms, brain seizures in the emergency department stroke, hemorrhagic stroke, ischemic subarachnoid hemorrhage

LABORATORY STUDIES

Ruling out metabolic or drug-induced etiologies for symptoms consistent with a TIA is important. Most importantly, a fingerstick blood glucose should be checked for hypoglycemia. Serum electrolytes should be sent to investigate for electrolyte derangements. Emergency presentation o Serum chemistry profile including creatinine o Coagulation studies o Complete blood count Typically helpful and can often be performed urgently o Erythrocyte sedimentation rate (ESR) o Cardiac enzymes o Lipid profile o ECG: - 12-Lead electrocardiography should be performed as soon as possible after transient ischemic attack (TIA), and can evaluate for dysrhythmias such as atrial fibrillation. o Electroencephalography (EEG) may be indicated to evaluate for seizure activity. o Screening for hypercoagulable states (particularly in younger patients with no known vascular risk factors:1 Protein C, protein S, 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 As needed based upon history o Syphilis serology o Antiphospholipid antibodies o Toxicology screens o Hemoglobin electrophoresis o Serum protein electrophoresis o Cerebrospinal fluid examination

Imaging Studies National recommendations for urgent evaluation of the patient with a transient ischemic attack (TIA) include imaging of the brain within 24 hours of symptom onset; preferably MRI with DWI, but if this is not available, then a CT scan should be obtained.1,13 The cerebral vasculature should be imaged urgently, preferably at the same time as the brain. Brain imaging can identify an area of ischemia in up to 25% of patients, and TIA mimics may be identified as well. Vessel imaging can identify a stenosis or occlusion that requires early intervention.

Brain imaging o Noncontrast cranial CT scan: This test 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 o MRI MRI is more sensitive for acute ischemia, infarction, previous intracranial bleeding, and other underlying lesions than CT. The presence of ischemic lesions on MRI appears to increase the shortterm risk of stroke, highlighting its potential value in acute risk stratification.14,15 In addition, a negative DWI image in concert with low-risk clinical features can mark those at minimal short-term stroke risk.16 However, this study is less widely available on an acute basis than CT scan. Vascular imaging o Carotid Doppler ultrasonography of the neck can identify patients in need of urgent surgical or endovascular therapy. o Transcranial Doppler can be a complementary examination evaluating patency of cerebral vessels and collateral circulation. o Computed tomographic angiography (CTA) is of increasing value in identifying occlusive disease in the cerebrovascular circulation. o Magnetic resonance angiography (MRA) is another alternative for imaging vessels in both the brain and neck. o Conventional angiography can be performed when the above modalities are unavailable or yield discordant results. Cardiac imaging: Transthoracic or transesophageal echocardiography (TTE/TEE) can evaluate for a cardioembolic source or for risk factors such as patent foramen ovale.

TREATMENT AND MEDICATION:

Prehospital Care
Rapid transport is essential to evaluate the patient who may have fleeting or stuttering symptoms. Fingerstick glucose can quickly rule out hypoglycemia. Intravenous (IV) access can be established, although transport should not be delayed for this. Collect all the patients prescription bottles. The family or witnesses should be instructed to go to the ED, or contact information for these individuals should be obtained. Some communities may have EMS preferentially transfer patients with high-risk stroke symptoms to centers with specific stroke expertise.17

Emergency Department Care

Global CNS depression and airway or cardiac compromise are not typically features of a TIA. In fact, the level of consciousness and neurologic examination are expected to be at the patient's baseline. o Initial assessment is aimed at excluding emergent conditions that can mimic a TIA such as hypoglycemia, seizure, or intracranial hemorrhage. o Vital signs must be obtained promptly and addressed as indicated. o Cardiac monitoring can capture a relevant dysrhythmia. o Pulse oximetry can evaluate for hypoxia. o Intravenous access (if not already established by EMS) should be obtained. o Obtain a fingerstick glucose level and treat accordingly. o Laboratory studies, including CBC, coagulation studies, and electrolyte levels, should be obtained. o Obtain an ECG and evaluate for symptomatic rhythms or evidence of ischemia. o 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 American Heart Association recommends initiating antihypertensive therapy only if blood pressure is more than 220/120 mm Hg, or mean arterial pressure greater than 130 mm Hg. Unless there is a concerning comorbid cardiac or other condition requiring blood pressure lowering, allowing the patient's blood pressure to autoregulate at a higher level (during the acute phase) may help maximize cerebral perfusion pressure. 18 Brain imaging is recommended within 24 hours of symptom onset. While MRI with DWI is preferred, a noncontrast head CT as a widely accessible study, is a reasonable first choice when MRI is not readily available.1,19

Consultations
Neurologist: There is clear consensus on the need for rapid evaluation, and patients who undergo neurology evaluation and risk stratification within 24 hours versus within a few days appear to have a significantly decreased short-term risk of stroke. Therefore, decisions regarding ED evaluation, and inpatient versus rapid outpatient followup, are ideally made in concert with a neurologist. International recommendations also note that immediate consultation is more costeffective than outpatient follow-up.13 Primary care physician: This is the most important consultation that can occur, as the primary care physician will monitor the patient long term and ensure risk factor and lifestyle modification. In addition, rapid neurology consultation is not available in many communities, and the primary care doctor may well be primarily responsible for managing urgent risk stratification. Cardiologist: This consultation can be considered for those with clear findings that influence stroke risk, such as atrial fibrillation, patent foramen ovale, intracardiac thrombus, or valvular abnormalities. Vascular surgeon: This consultation should be considered for those with significant vessel stenosis or occlusion, with a goal of specialist assessment within 1 week and treatment within 2 weeks of symptom onset.13,20,21 In many centers, some vascular interventions can be performed by other specialists including interventional radiologists, neuroradiologists, and cardiologists.

MEDICATIONS Medical management is aimed at reducing both short- and long-term risk of stroke. Antithrombotic therapy should be initiated as soon as intracranial hemorrhage has been ruled out, given the high short-term risk of stroke following TIA. One set of guidelines from the American Stroke Association (and supported by the American Academy of Neurology) is summarized below:22 Noncardioembolic TIA (or for those in whom no source is determined)

Antiplatelet agents are recommended rather than oral anticoagulation as initial therapy. Aspirin (50-325 mg/d), combination aspirin/extended-release dipyridamole, and clopidogrel are all reasonable first-line options (class I recommendation). Combination aspirin/extended-release dipyridamole (Aggrenox) may be superior to aspirin alone (class IIa recommendation).23 Clopidogrel may be considered instead of aspirin alone (class IIb recommendation). Aspirin in combination with clopidogrel increases the risk of hemorrhage and is not routinely recommended for patients with TIA (class III recommendation).

For those with a known cardioembolic source

Atrial fibrillation: Long-term anticoagulation (goal INR 2-3) is typically recommended. Aspirin 325 mg/d is recommended for those unable to take oral anticoagulants. Acute MI with left ventricular thrombus o Oral anticoagulation (goal INR 2-3) is reasonable o Aspirin up to 162 mg/d should be used concurrently for ischemic coronary artery disease. Dilated cardiomyopathy: Either oral anticoagulation (goal INR 2-3) or antiplatelet therapy may be considered. Rheumatic mitral valve disease: Oral anticoagulation (goal INR 2-3) is reasonable. Antiplatelet agents would not normally be added to warfarin unless patients experience recurrent embolism despite a therapeutic INR. Mitral valve prolapse: Long-term antiplatelet therapy is reasonable. Mitral annular calcification: Antiplatelet therapy can be considered. Those with mitral regurgitation can be considered for warfarin or antiplatelet therapy. Aortic valve disease: Antiplatelet therapy may be considered. Prosthetic heart valves o For mechanical prosthetic valves, oral anticoagulants (goal INR 2.53.5) are recommended. For those with TIAs despite therapeutic INR, aspirin 75-100 mg/d can be added to the regimen. o For bioprosthetic valves, patients with TIA and no other source of thromboembolism can be considered for oral anticoagulation (INR 23).

FOLLOW-UP: Further Inpatient Care While controversy exists regarding the need for admission, there is no controversy regarding the need for urgent evaluation, risk stratification, and initiation of stroke prevention therapy.24,25,1 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%.26 Another initiated a program to admit patients to a "rapid evaluation unit," which dropped the 90-day stroke risk from 9.7% to 4.7%.27 Others have suggested similar benefits from rapid followup.28 The availability of local resources determines whether this urgent evaluation should occur as an inpatient, in an ED observation unit, or in rapid followup. In order to determine appropriate disposition, the emergency physician should determine necessary workup, then discuss with the neurologist or primary care doctor how best to ensure this occurs promptly.29 One randomized controlled trial of an emergency department diagnostic protocol found that they could reduce cost, 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.30 A number of patients present to the ED with a "transient neurological disturbance" that does not represent a true TIA, and these can be difficult to distinguish for the busy emergency practitioner. In addition, an emergent and comprehensive workup of all those with "possible TIA" may not be the most cost-effective or appropriate use of limited local resources. The emergency practitioner should use appropriate risk stratification to ensure that emergent 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.31,32,15 ABCD2 Score Open table in new window A: Age >60 B: Blood pressure >140/90 mm Hg C: Clinical features Unilateral weakness 2 points 1 point 1 point

Speech disturbance without weakness 1 point D: Duration >60 minutes 10-59 minutes D: Diabetes Total 2 points 1 point 1 point 0-7 points

Individuals with an ABCD2 score higher than 6 had an 8% risk of stroke within 2 days, while those with an ABCD2score less than 4 had a 1% risk of stroke within 2 days. Some of these patients with lower scores may well have non-TIA events rather than true TIAs.33 It has been proposed that this scoring system can be used to risk-stratify ED patients for emergent workup.31 Finally, abnormalities on brain imaging can highlight those at increased risk and should also be taken into consideration. Some groups have noted that the short-term stroke risk after TIA can be worrisome even in those with a low ABCD2 scores.34,35 The American Heart Association1 comments "It is reasonable to hospitalize patients with TIA if they present within 72 hours of the event and any of the following criteria are present:"

ABCD2 score of 3 (Class IIa, level of Evidence C) ABCD2 score of 0 to 2 and uncertainty that diagnostic workup can be completed within 2 days as an outpatient (Class IIa, level of Evidence C) ABCD2 score of 0 to 2 and other evidence that indicates the patient's event was caused by focal ischemia (Class IIa, level of Evidence C)

Further Outpatient Care

Patients selected for outpatient care should have a clear follow-up plan and stroke prevention initiated as above, including antiplatelet medication and risk factor modification. Patients with TIA and ipsilateral carotid artery stenosis may be candidates for urgent (<2 wk) carotid endarterectomy. In certain patients, carotid artery stenting is a reasonable alternative. This can be discussed acutely or rapid follow-up arranged. Patients with symptoms attributable to extracranial vertebral stenosis may be candidates for endovascular treatment, and again this should be arranged rapidly if available.

Inpatient & Outpatient Medications

Antiplatelet agents should typically be initiated as soon as intracranial bleeding is ruled out. As above, the agent to be used varies with the patient and the specific indication. Antihypertensive control for those with hypertension Lipid control, potentially including a statin agent Blood glucose control for those with diabetes A smoking cessation strategy, which may include medication, should be initiated. Heavy drinkers should eliminate or reduce alcohol consumption. Weight loss if overweight Exercise

Prognosis

With passive reporting, the early risk of stroke following TIA is approximately 4% at 2 days, 8% at 30 days, and 9% at 90 days.7 However, when patients with TIA are followed prospectively, the incidence of stroke is as high as 11% at 7 days.5 Patients with TIAs have an increased risk of stroke and death from coronary artery disease (depending on risk factors in the study group, approximately 6-10% per year). Probability of stroke in the 5 years following a TIA is reported to be 24-29%.

Patient Education

For patients to be discharged, make sure they understand the need for a complete and rapid workup through close follow-up care. Education regarding lifestyle modification and cardiovascular risk factors is essential. Education regarding stroke symptoms, the need to call emergency services immediately, and the contact number for emergency services (911 in the United States) is essential. For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education article Transient Ischemic Attack (Mini-stroke).