AUTHOR INFORMATION

Section 1 of 11

Authored by Jerome FX Naradzay, MD, FACEP, Emergency Services Medical Director, Department of Emergency Medicine, Maria Parham Medical Center

Jerome FX Naradzay, MD, FACEP, is a member of the following medical societies: American College of Emergency Physicians, and Society for Academic Emergency Medicine

Edited by Peter MC DeBlieux, MD, Professor of Clinical Medicine and Pediatrics, Section of Pulmonary and Critical Care Medicine, Program Director, Department of Emergency Medicine, Louisiana State University Health Sciences Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; J Stephen Huff, MD, Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health System; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital

Author's Email:	Jerome FX Naradzay, MD, FACEP
Editor's Email:	Peter MC DeBlieux, MD

eMedicine Journal, November 15 2006, VOLUME 7, Number 11

INTRODUCTION

Section 2 of 11

Background: A transient ischemic attack (TIA) is an acute episode of temporary and focal loss of cerebral function of vascular (occlusive) origin. TIAs are rapid in onset; symptoms reach their maximal manifestation in fewer than 5 minutes (usually <1 min). Manifestations are of variable duration and typically last 2-15 minutes (rarely as long as 24 h). Most TIA durations are less than 1 hour; median duration is 14 minutes in the carotid distribution and 8 minutes in vertebrobasilar ischemia.

Pathophysiology: Temporary reduction or cessation of cerebral blood flow adversely affects neuronal function in cortical, subcortical, and nuclear regions of the CNS.

Frequency:

• In the US: Previous estimates state that TIAs conservatively affect 50,000 Americans every year. Updated incidence rates that include blacks, whites, Hispanics, and out-of-hospital events suggest that approximately 240,000 TIAs occurred in 2002 in the United States. For many of these Americans, a TIA is not an isolated insult. In approximately one third of these patients, a TIA signals an impending stroke.

  Race, age, and gender-adjusted incidence rates for TIA are specific based on race, gender, and age. Overall, incident rates for TIA have ranged from 83 cases per 100,000 up to more than 200 cases per 100,000.

  The annual age-adjusted incidence of first ischemic stroke per 100,000 was 88 (75 to 101) in whites, 149 (132 to 165) in Hispanics, and 191 (160 to 221) in blacks.

  More details about race and gender differences in incidence rates reflect a growing concern that more people are affected by TIA than previously appreciated. It is increasingly clear that blacks are more likely to have TIA than other races. This heightened awareness prompts an increased vigilance for TIA symptoms in the emergency patient.

Mortality/Morbidity: Death does not occur directly from a single episode of TIA. A TIA may be considered a sign of generalized atherosclerotic disease. In fact, the primary cause of death following a TIA is coronary artery disease. The patient with a TIA should undergo cardiac evaluation to help stratify risk and management of potential coronary artery disease.

• Despite a public education program, too many patients are still not seeking medical attention after experiencing TIA symptoms. Physicians need to do more such as promoting and participating in medical screening fairs and public outreach programs.

• The early risk of stroke following TIA could be as high as of 5-10% at 1 week and 10-20% at 3 months following a TIA.

Race: Blacks and men had significantly higher rates of TIA than whites and women.

• Several studies report that African American patients with signs or symptoms of ischemic stroke or TIA are less likely to undergo a CT scan expeditiously (within 25 min), cardiac monitoring, or receive smoking cessation counseling (odds ratio [OR], 0.27; confidence interval [CI], 0.17-0.42). However, according to one study, the quality of hospital care for African American and white patients with acute ischemic stroke and TIA was similar in many respects.

Age: TIAs are uncommon in persons younger than 60 years. Incidence of TIA is 4-8 cases per 1000 persons per year aged 50-59 years. The Rochester study included cases of individuals aged 45-54 years and reported incidence to be 16 cases per 100,000 people per year.

The emergency provider must be aware of the overall incidence rate in their population.

• Fewer than 3% of all major cerebral infarcts occur in children. Pediatric strokes have different etiologies than adult strokes.

CLINICAL

Section 3 of 11

History: A TIA may last only several minutes. Thus, historical questions should be addressed not just to the patient but also to family members, witnesses, and emergency medical services (EMS) personnel. Of concern is the careful detection of changes in behavior, speech, gait, memory, movement, and vision.

• Significant medical history questions include the following:

• Recent surgery (eg, carotid, cardiac)

• Previous strokes

• Seizures

• CNS infections

• Use of illicit drugs

• Complete medication regimen

• Carefully investigate onset, duration, fluctuation, and intensity of symptoms.

• Reviewing the patient's medical record is extremely important for identifying deficits from previous strokes, TIAs, seizures, or cardiac events. Use the results of previous diagnostic tests or therapeutic interventions to guide the next phase of testing and therapy. Contacting the patient's primary physician is important.

• In a patient with a history of multiple TIAs, imaging studies and diagnostic tests are managed much differently than in the patient experiencing a first TIA episode.

• Family members are an invaluable source of information concerning symptoms of a TIA.

• Fleeting symptoms may be more noticeable to a family member or coworker.

• By talking to the family, the examiner not only can discuss symptoms but also can begin an assessment of the home environment.

• Discharge may depend on the presence of reliable and safe home support.

• These discussions should provide answers to the following questions:
  • Are family members at home who can notify EMS if symptoms return?

  • Can someone support the patient physically if falls occur during another TIA?

  • Can medications be administered reliably?

  • Can the patient be trusted to follow up with outpatient testing and repeat examination by the primary physician?

• A patient with a TIA may present to the ED with very subtle complaints. If the ED physician can tabulate the chief complaint (CC) and ascertain exact onset and duration of the CC, then the examiner can better localize the cause of the TIA or CNS location of the deficit. For example, patients may complain vaguely of feeling short of breath and, sometime later, feel they cannot speak properly. Careful questioning will elucidate complaints of shortness of breath preceded by palpitations or a little chest pain, which was followed by inability to articulate and facial droop.

• Attempt to isolate the CC into symptoms that are clues to a neurologic disorder.

• As a TIA has a duration of fewer than 24 hours, question the presence of symptoms within the preceding 24 hours, 48 hours, or week.

• Attempt to clarify when symptoms first occurred, how long they lasted, if the patient recovered completely (returned to baseline status), if a pattern of escalating symptoms is present, and if associated cardiac symptoms are present.

• History of associated trauma or cardiac symptoms widens the differential diagnosis. Pertinent negative items in the review of systems also are important (eg, headache, chest pain, eye pain).

• Carotid or vertebral dissection can occur from seemingly trivial trauma or injury. The patient may provide a history of blunt or torsion injury to the neck with subsequent mild neck pain and have an associated TIA symptom.

• Determine the state of overall health of the patient and risk factors for various relevant diseases.

• History of arteritis is very important.

• Noninfectious necrotizing vasculitis, drugs, irradiation, and local trauma are known to cause inflammatory arterial injury.

• Patients may complain of nonspecific symptoms, such as a low-grade fever or weight loss.

• Elicit any history of substance abuse. Use of sympathomimetic drugs (eg, cocaine) is associated with the following risk factors for TIAs:

• Hypercoagulable states

• Platelet aggregation

• Vasospasm

• Dysrhythmia

• Transient hypertension

• Hyperdynamic states

• Vasculitis

Physical: A patient with a suspected TIA requires a complete physical examination with attention to a detailed neurologic examination. Approach the patient who has had an apparent TIA with the goals of accurately diagnosing conditions that resemble a TIA, correctly describing a true TIA, and identifying a patient with a stroke-in-evolution. The importance of a detailed neurologic examination is paramount, but the importance of a thorough physical examination cannot be overstated.

Ideally, severity of neurologic deficits should be recorded with the aid of stroke scales (eg, 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.

• Initial vital signs should include the following:

• Rectal temperature

• Blood pressure recorded in each arm

• Peripheral pulses compared to the apical pulse

• Respiratory rate and pattern

• 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

• Further assessment will contribute to the eventual discharge plan. Taking note of the following may be helpful:

• Does the patient appear to be able to care for self in the event of another incident?

• Is evidence of general deterioration in health and failure to thrive present?

• Is indication of an injury or trauma that occurred during the TIA present?

• If family members are present, are they supportive?

• Identify signs of vasculitis, sinusitis, mastoiditis, and meningitis. Carotid arteries are examined for pulse upstroke, bruit, and presence of carotid endarterectomy scars.

• Perform funduscopy to identify retinal plaques, retinal pigmentation, and pupil reaction to direct and consensual light exposure.

• In addition to performing standard auscultation, identify the presence of surgical scars or pacemaker 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 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. Subsets of the neurologic examination include the following:

• Cranial nerve testing

• Somatic motor strength

• Somatic sensory testing

• Cerebellar system

• Mental status can be assessed formally (eg, Mini-mental Status Examination) 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:

• 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

• Somatic motor testing

• Test muscle stretch reflexes of biceps, triceps, and brachioradialis and patellar and Achilles reflexes using the standard grading system 0-4.

• Inspect posture and presence of tremors. Formally test shoulder girdle, upper extremity, abdominal muscle, and lower extremity strength.

• Test passive movement of major joints to look for spasticity, clonus, or rigidity.

• The cerebellar system is 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.

• The following symptoms should raise the suspicion that the patient may have cranial arteritis:

• Fever

• Visual disturbance (eg, blindness, diplopia)

• Nodular or tender cranial arteries

Causes: The majority of TIAs are caused by carotid and vertebral artery atherosclerotic disease. However, nonvascular causes occasionally produce TIA symptoms. Proper diagnosis is essential for choosing appropriate therapy.

• Atherosclerosis of carotid and vertebral arteries: Large vessel stenosis of the carotid or vertebral arteries is the single largest cause of TIAs.

• Cerebral embolism

• Embolic sources - Valvular disease, ventricular thrombus, and thrombus formation due to atrial fibrillation

• Arterial dissection

• Arteritis - Inflammation of the arteries occurring primarily in the elderly, especially women

• Noninfectious necrotizing vasculitis (primary cause)

• Drugs

• Irradiation

• Local trauma

• Sympathomimetic drugs (eg, cocaine)

• Mass lesions (eg, tumors, subdural hematomas) - Rarely cause transient symptoms

• TIA etiologies in children, which are different than those in adults, include the following:

• Congenital heart disease with cerebral thromboembolism (most common)

• Drug abuse (eg, cocaine)

• Clotting disorders

• CNS infection

• Neurofibromatosis

• Vasculitis

• Idiopathic progressive arteriopathy of childhood (moyamoya)

• Fibromuscular dysplasia

• Marfan disease

• Tuberous sclerosis

• Tumor

DIFFERENTIALS

Section 4 of 11

Bell Palsy
Headache, Migraine
Hypoglycemia
Neoplasms, Brain
Stroke, Hemorrhagic
Stroke, Ischemic
Subarachnoid Hemorrhage

WORKUP

Section 5 of 11

Lab Studies:

• Serum chemistry profile

• Coagulation studies

• Erythrocyte sedimentation rate (ESR)

• Syphilis serology

• Complete blood count

• Platelet count

• Antiphospholipid antibodies

• Glucose level

• Drug screens

• Cardiac index markers (may be considered)

• Optional studies

• Screening for hypercoagulable states (particularly in patients younger than 50 years)

• Levels of protein C and protein S

• Antithrombin III level

• Thrombin time

• Hemoglobin electrophoresis

• Serum protein electrophoresis

• Cerebrospinal fluid examination

• Testing for silent myocardial ischemia

• Anemia and elevated ESR (>100 mm/h) - Hallmarks of temporal artery arteritis

Imaging Studies:

• Location of the disease is very important for treatment and prognosis. Evaluation of the patient with a TIA includes diagnostic tests for the following:

• Carotid or vertebral artery plaques that produce arteriogenic emboli

• Flow-limiting stenosis

• Penetrating cerebral artery disease

• Noncontrast cranial CT scan of the head: An area of infarction appropriate for the TIA symptoms has been identified in 29-34% of patients with TIA. Support for obtaining a cranial CT scan includes the following:

• Locating the new area of ischemia or infarction

• Locating a silent infarction from a previous undocumented stroke (may predict prognosis for further TIA/stroke)

• Excluding other lesions that simulate TIA (eg, subdural hematoma, brain tumor, arteriovenous malformation, cerebral aneurysm)

• MRI of the brain

• Acute infarcts are located more accurately using MRI than CT scan.

• Abnormal vascular flow can be detected within minutes of onset of symptoms.

• Limited availability and cost of MRI scanners restrict the immediate requirement for a stat MRI. MRI can be obtained on a less urgent or outpatient basis if less-costly tests do not identify the cause of TIA symptoms.

• Magnetic resonance angiography: MRA provides noninvasive images of carotid and vertebral arteries.

• Cerebral arteriography: Selective catheterization of the cerebral vessels is necessary to evaluate the carotid arteries prior to carotid endarterectomy, identify the vertebral and basilar arteries, and define intracranial stenosis or occlusion.

• Cerebral arterial imaging: Carotid and vertebral artery ultrasound is required to identify the surgical candidate with high-grade carotid stenosis.

Other Tests:

• 12-lead electrocardiogram

• 12-lead ECG is indicated to assess the rhythm and guide case management.

• Rhythms such as atrial fibrillation are associated with cardioembolic events.

• Lumbar puncture (LP) is indicated if the diagnosis is in doubt and subarachnoid hemorrhage, infectious etiology, or demyelinating disease is to be excluded.

TREATMENT

Section 6 of 11

Prehospital Care:

• Rapid transport is essential to evaluate the patient who may have fleeting symptoms.

• The following can facilitate immediate intervention and reduce delay in evaluation once the patient has arrived in the ED:

• Cardiac monitoring

• Rapid glucose assessment

• Pulse oximetry

• Establishing intravenous (IV) access

• Administer supplemental oxygen.

• EMS personnel should collect prescription bottles and instruct family members or witnesses to go to the ED.

Emergency Department Care: Global CNS depression and airway or cardiac compromise are not features of a TIA. Therefore, ED intervention is relatively minimal.

• Supporting the airway and restoring perfusion or a stable rhythm are tenets of emergency care. By definition, patients with TIA are hemodynamically stable and able to support their own airways. Rapid assessment excludes those conditions that mimic a TIA such as hypoglycemia or an intracranial hemorrhage.

• Vital signs must be obtained promptly and addressed as indicated. Place the patient on a cardiac monitor and a pulse oximeter and establish an IV line (if one has not already been established by EMS).

• Obtain a fingerstick glucose level and treat accordingly.

• Obtain an ECG and initiate treatment for symptomatic rhythms or evidence of ischemia.

• A significant area of controversy is whether to treat hypotension or hypertension during a stroke. For patients with TIA who are diabetic, recent evidence indicates that blood pressure (BP) treatment targets should be lower than previously recommended to less than 130/85 mm Hg.

• While BP and perfusion should be supported, cerebral perfusion pressure may respond inconsistently to antihypertensive therapy.

• Even a modest reduction in BP can extend a fragile ischemic penumbra.

• If an antihypertensive agent is administered, closely monitor the patient's response by repeating the physical examination.

• Consensus suggests not treating hypertension during an acute stroke unless the mean arterial peripheral pressure exceeds 130 mm Hg. Mean pressure is calculated as (systolic BP + [2 x diastolic BP]) /3.

• When a TIA is caused by large or small vessel arteritis, distinguishing between pure arteritis and arteritis that produces penetrating arterial disease is important. The former is treated with dexamethasone, often on an outpatient basis, but the latter is better treated with IV steroids and observation.

Consultations:

• Contact the patient's primary care physician. Any further specialist consultation needed (eg, neurologist, vascular surgeon, cardiologist) should occur after consulting the patient's primary care provider. The decision to admit after a TIA appears to vary regionally; all patients require additional workup on an inpatient or outpatient basis.

• Neurologist (particularly if questioning whether the presentation is consistent with TIA)

• Vascular surgeon (not typically performed in the ED)

• Cardiologist: Although not typically performed in the ED, cardiology consultation is useful, in particular when a cardiac etiology is suspected (eg, atrial fibrillation, valvular disease).

MEDICATION

Section 7 of 11

Rapid pharmacologic intervention in patients with TIAs caused by atherosclerosis is limited to antiplatelet or anticoagulation therapy. Treatment for TIA caused by dysrhythmias, extracranial embolisms, or metabolic disorders can require a specific treatment dictated by the cause.

Emergency physicians may be in the unique position to limit the progression of the TIA. Emergency physicians must know when to initiate single-agent antiplatelet therapy, adjust existing antiplatelet therapy, initiate anticoagulant therapy, or advance other pharmacologic treatment. Recent therapeutic intervention and outcome studies have advanced the understanding of TIA. Patient outcomes are no longer clumped with "all stroke patients." We appreciate unique TIA therapy is available. Emergency physicians must closely examine the therapeutic options for patients who experience a TIA.

If the patient is already taking aspirin, he or she may be a candidate to take aspirin plus extended-release dipyridamole. Recent reports suggest that this combination is more effective than aspirin alone at preventing stroke, particularly in patients at high risk for stroke. Although dual therapy carries the increased risk of GI bleeding.

A possible benefit may exist by administering antiplatelet therapy with aspirin and clopidogrel to patients who are showering the cerebral circulation with microemboli.

Several new oral anticoagulant medications, including ximelagatran, are in the final stages of clinical trials for use in the prophylaxis of ischemic thromboembolic stroke. Once approved for use, the potential of such drugs in the arena of stroke treatment is significant.

Emergency physicians interested in keeping abreast of the challenging field of post-TIA therapy must closely follow the results of the PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study. This is a randomized, double blind interventional study designed to compare 25 mg aspirin/200 mg extended-release dipyridamole with clopidogrel monotherapy and to compare telmisartan with placebo in the prevention of recurrent stroke.

Drug Category: Antiplatelet agents -- These agents inhibit platelet function by blocking cyclooxygenase and subsequent aggregation. Antiplatelet therapy is demonstrated to be superior to placebo in reducing rates of subsequent infarction and death in patients who have experienced multiple TIAs. Compared to control groups, patients with a history of TIAs who take antiplatelet therapy have significant reductions in rates of fatal stroke, fatal myocardial infarction, and vascular death. Patients presenting with thromboembolic complications are to be anticoagulated promptly if they do not have a therapeutic international normalized ratio (INR) of 2.5-3.5.

Drug Name	Aspirin (Anacin, Ascriptin, Ecotrin, Bufferin, Bayer Aspirin) -- Blocks prostaglandin synthetase action, which in turn inhibits prostaglandin synthesis and prevents formation of platelet-aggregating thromboxane A2. Recent studies show 350 mg/d as effective as larger doses and may be associated with fewer adverse effects.
Adult Dose	50-325 mg/d PO (current FDA recommendation)
Pediatric Dose	10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d
Contraindications	Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma Because of association with Reye syndrome, do not use in children ( <16 y) with flu
Interactions	Antacids and urinary alkalinizers may decrease effects; corticosteroids decrease serum levels; anticoagulants may cause additive hypoprothrombinemic effects and increase bleeding times; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Pregnancy	D - Unsafe in pregnancy
Precautions	May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants

Drug Name	Dipyridamole (Persantine) -- Administer to complement usual warfarin therapy. Inhibits platelet adhesion, which may inhibit adenosine uptake by RBCs. May increase cyclic-3', 5'-AMP within platelets and formation of potent platelet activator thromboxane A2. When compared to placebo in several studies, neither patients receiving dipyridamole and aspirin in combination or dipyridamole therapy alone have shown benefit.
Adult Dose	75-100 mg PO qid
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Theophylline may decrease hypotensive effects; because of antiplatelet effects, may increase heparin toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution with hypotension; has peripheral vasodilating effects

Drug Name	Ticlopidine (Ticlid) -- Second-line antiplatelet therapy for patients who cannot tolerate or do not respond to aspirin therapy. Also administered to patients already taking aspirin who have continued TIA symptoms.
Adult Dose	250 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; neutropenia or thrombocytopenia; liver damage; active bleeding disorders
Interactions	Corticosteroids and antacids may decrease effects; theophylline, cimetidine, aspirin, and NSAIDs increase toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Discontinue if absolute neutrophil count falls to <1200/mm3 or if platelet count falls to <80,000/mm3

Drug Name	Warfarin (Coumadin) -- Interferes with hepatic synthesis of vitamin K-dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to desired INR.
Adult Dose	5-15 mg/d PO for 2-5 d
Pediatric Dose	0.05-0.34 mg/kg/d PO (infants may require doses at, or near, high end of this range)
Contraindications	Documented hypersensitivity; severe liver or kidney disease; open wounds; GI ulcers
Interactions	Many medications may impact warfarin activity Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate Medications that may increase anticoagulant effects of warfarin include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac
Pregnancy	D - Unsafe in pregnancy
Precautions	Do not switch brand after achieving therapeutic response; caution with active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis

Drug Name	Heparin -- Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.
Adult Dose	Initial dose: 40-170 U/kg IV Maintenance infusion: 18 U/kg/h IV Alternatively, 50 U/kg/h IV initially, followed by continuous infusion of 15-25 U/kg/h and increase dose by 5 U/kg/h IV q4h prn using aPTT results
Pediatric Dose	Initial dose: 50 U/kg IV Maintenance infusion: 15-25 U/kg/h IV Increase dose by 2-4 U/kg/h IV q6-8h prn using aPTT results
Contraindications	Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia
Interactions	Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Some preparations contain benzyl alcohol as preservative and, when used in large amounts, may be associated with fetal toxicity (ie, gasping syndrome); use of preservative-free heparin recommended in neonates; use with caution in shock or severe hypotension

Drug Name	Clopidogrel (Plavix) -- Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.
Adult Dose	75 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active pathological bleeding, such as peptic ulcer or intracranial hemorrhage
Interactions	Naproxen associated with increased occult GI blood loss; prolongs bleeding time; safety of coadministration with warfarin not established
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in patients at increased risk of bleeding from trauma, surgery, or other pathological conditions; caution in patients with lesions with propensity to bleed (such as ulcers)

FOLLOW-UP

Section 8 of 11

Further Inpatient Care:

• The following are suggested admission criteria for the patient with TIA; these vary considerably in the medical community:

• New or first TIA

• If serial neurologic examinations are needed or outpatient setting does not ensure easy and reliable patient access for follow-up care

• If the clinical picture is complicated (eg, cardiac etiology, labile hypertension) and/or the diagnosis is in doubt (eg, when signs and symptoms have not resolved fully)

• When active therapeutic intervention will lower risk of stroke or is required for an active, unstable medical condition (eg, dysrhythmia, embolic source)

• Posterior circulation symptoms or signs

• TIA associated with trauma

• Patients with more than 4 spells within 2 weeks or multiple events within a few hours

• Patients found to have high-grade carotid stenosis (>70%) or symptomatic high-grade stenosis who are suitable candidates for carotid endarterectomy

• When home support or nursing care is not available on an outpatient basis

Further Outpatient Care:

• Formally establish disposition plans if the patient is a candidate for discharge. Patients who are of older age, have diabetes, have TIA with long duration of symptoms, or have a speech disturbance may be at the highest risk for progressing to a stroke, as are patients with large artery atherosclerosis.

• Having the patient call the office for an appointment is not an optimal discharge plan.

• Clearly prescribe medications (eg, aspirin dose, ticlopidine) if the patient is going to be discharged.

• Establish a firm follow-up appointment.

• Contact the patient's primary care physician or neurologist and discuss the need for continued outpatient (or inpatient) care.

• Forward ED records to the private practitioner in order to complete the patient's records for all health care providers. By doing so, a better picture (eg, a crescendo pattern of TIAs) of the patient's symptomatology can be developed.

• TIA can be considered a sign of generalized atherosclerotic disease, particularly coronary atherosclerosis.

• The primary cause of death following TIA is coronary artery disease.

• Consider cardiac evaluation for patient with a TIA to help stratify risk and management of potential coronary artery disease.

• For patients with TIAs occurring in the vascular distribution of a carotid stenosis in the 50-69% range, evidence from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) suggests a potential benefit from carotid endarterectomy.

In/Out Patient Meds:

• Prescribe aspirin 325 mg orally per day.

• For crescendo TIA symptoms, eliminate aspirin and substitute clopidogrel 75 mg orally once a day OR ticlopidine 250 mg orally twice a day.

• For patients with TIA who are diabetic, recent evidence indicates that BP treatment targets should be lower than previously recommended to less than 130/85 mm Hg.

• Target levels for fasting blood glucose of less than 126 mg/dL are recommended for patients with TIA.

Deterrence/Prevention:

• For patients with TIAs occurring in the vascular distribution of a carotid stenosis in the 50-69% range, evidence from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) suggests a potential benefit from carotid endarterectomy.

Complications:

• Major stroke (subsequently experienced by one third of patients with TIAs over time)

• Seizure

• Injury to self

Prognosis:

• 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%/y).

• Probability of stroke in the 5 years following a TIA is reported to be 24-29%.

• For patients with a first-time (index) TIA, the risk of stroke is 8% in the first 30 days, 10.5% in the first 90 days, 5% per year for the next 3 years, and approximately 3% per year thereafter. The majority of these events occur within the first few days following the index event.

• For patients with a hemispheric TIA and more than 70% carotid stenosis, stroke rate is more than 40% in 2 years. Five factors are independently associated with stroke in these patients: age greater than 60 years, diabetes mellitus, symptom duration longer than 10 minutes, weakness, and speech impairment.

• Stroke, death, or recurrent TIA occurs in more than 25% of patients within the first 90 days following index TIA.

Patient Education:

• Instruct patient to return to the ED if symptoms return.

• Make sure patient understands the need for a complete workup through close follow-up care.

• For excellent patient education resources, visit eMedicine’s Stroke Center. Also, see eMedicine’s patient education article Transient Ischemic Attack (Mini-stroke).

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• The emergency physician must be aware that a TIA can be a harbinger of an impending stroke. It has been reported that a quarter of the patients with a TIA will have a stroke within 24 hours. In one study, 17% of patients with an acute ischemic stroke had a TIA on the day of the stroke. The take home message is: TIA is a warning for an impending stroke.

Special Concerns:

• The following are possible discharge criteria for the patient with a TIA:

• Institutionalized individual with severe preexisting irreversible disability such as untreatable dementia, terminal illness, or profound irreversible neurologic deficits

• Noninstitutionalized individual with preexisting disability or terminal illness who has adequate home support

• Mild neurologic deficits not due to unruptured aneurysm, infection, trauma, or cerebrovascular shunt malfunction, which are identified more than 48 hours after symptom onset and can receive expeditious outpatient evaluation

• Mild neurologic deficit due to lacunar stroke syndrome and normal cranial CT scan (excluding previous documented CT scan findings), no risk for embolic event, uncontrolled diabetes, or cardiac event (eg, uncontrolled hypertension)

• Transient neurologic symptoms limited to monocular blindness or amnesia

TEST QUESTIONS

Section 10 of 11

CME Question 1: A 65-year-old man presents with right hand weakness and garbled speech. His symptoms resolve within 2 hours of onset. These transient ischemic attack (TIA) symptoms most likely are caused by which of the following?

A: Hypoglycemia
B: Sympathomimetic drugs
C: Atrial fibrillation
D: Cardioembolic event
E: Atherosclerosis of the carotid arteries

The correct answer is E: By far the most common cause of a TIA is atherosclerosis of the carotid arteries. All the other causes of TIA symptoms, such as cardioembolic events, atrial fibrillation, and hypoglycemia, together constitute fewer than one third of all TIAs.

CME Question 2: Transient ischemic attack (TIA) etiologies in children include all of following except:

A: Congenital heart disease with cerebral thromboembolism
B: Drug abuse
C: Neurofibromatosis
D: Marfan disease
E: All of the above

The correct answer is E: All of these choices are correct. Although typically different in adults, TIA etiologies in children include the following: congenital heart disease with cerebral thromboembolism (most common), drug abuse (eg, cocaine), clotting disorders, CNS infection, neurofibromatosis, vasculitis, idiopathic progressive arteriopathy of childhood (moyamoya), fibromuscular dysplasia, Marfan disease, and tuberous sclerosis.

Pearl Question 1 (T/F): All patients with a first-time transient ischemic attack (TIA) require admission to a hospital.

The correct answer is False: Discharge is appropriate for institutionalized individuals who have severe, preexisting, irreversible disability (eg, untreatable dementia, terminal illness, or profound irreversible neurologic deficits). Noninstitutionalized individuals with preexisting disability or terminal illness may be discharged appropriately if they have adequate home support. Patients with mild neurologic deficits not due to unruptured aneurysm, infection, trauma, or cerebrovascular shunt malfunction may be discharged appropriately if their TIA is identified more than 48 hours after symptom onset and they can receive expeditious outpatient evaluation. Patients with mild neurologic deficit due to lacunar stroke syndrome who have normal cranial CT scan and no previous documented abnormal CT scan findings and no risk for embolic event, uncontrolled diabetes, or cardiac risk (eg, uncontrolled hypertension), may be discharged appropriately. Neurologic symptoms in these patients are limited to monocular blindness or amnesia.

Pearl Question 2 (T/F): The imaging study of choice when evaluating a patient with a transient ischemic attack (TIA) is noncontrast cerebral CT scan.

The correct answer is True: Patients with a suspected TIA should undergo a noncontrast cranial CT scan with contiguous slice thickness 5-10 mm. CT scan has identified the area of infarction appropriate for the TIA symptoms in 29-34% of patients. Reasons for getting a CT scan of the head include (1) locating the anatomic location of the lesion, (2) locating an infarct (either silent from previous undocumented stroke or the cause of the current symptoms), and (3) exclusion of other lesions that may simulate a stroke (eg, subdural hematoma, brain tumor, arteriovenous malformation, aneurysm).

Pearl Question 3 (T/F): Excluding contraindications, an antiplatelet agent is recommended for first-line therapy in the patient with a transient ischemic attack (TIA).

The correct answer is True: Aspirin is the standard therapy for prevention in patients at risk of stroke. Many authors recommend 325 mg/d as the initial dose.

Pearl Question 4 (T/F): Assuming the patient is taking aspirin, additional antiplatelet therapy is indicated for patients who have had more than 4 transient ischemic attack (TIA) episodes in the preceding 2 weeks.

The correct answer is True: Clopidogrel 75 mg once a day or ticlopidine therapy 250 mg twice a day taken orally or heparin is recommended for patients with crescendo TIAs. Heparin is indicated if a cardiac source of embolism is identified.

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