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Feb.10.2022

Transient Ischemic Attack

Synopsis

Key Points

  • Transient ischemic attack is an episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction
  • Onset of transient ischemic attack symptoms is abrupt and focal, reflecting the anatomic location of the ischemic vessel; typically duration is less than 1 hour r1
  • Clinical diagnosis is based on thorough history (symptoms have usually resolved), as well as physical examination
  • Urgent diagnostic evaluation includes:
    • Brain imaging, preferably diffusion-weighted MRI, within 24 hours of symptom onset r2
    • Cervical vascular imaging (Doppler ultrasonography, CT or magnetic resonance angiography)
  • Disposition (inpatient or outpatient evaluation) varies based on risk assessment, local resources, clinical acumen, patient access to follow-up; choices include hospitalization, transient ischemic attack clinic, or observation bed
  • Focus of treatment is to prevent future stroke through medical treatment of risk factors, interventional procedures if indicated, and lifestyle modifications
    • Antithrombotic therapy for noncardioembolic transient ischemic attack or anticoagulation for cardioembolic transient ischemic attack
    • Interventional procedures (endarterectomy, angioplasty and stenting) for stenosis of extracranial vessels
    • Antihypertensive therapy and lipid modification; control of diabetes mellitus
    • Lifestyle modifications: smoking cessation, weight loss, increased physical activity, and improved diet
  • Prognosis varies depending on severity and cause of diseasek: increased risk of stroke, other major cardiovascular event, and death

Urgent Action

  • Diagnosis of transient ischemic attack is urgent (preferably within 24 hoursr3) to facilitate timely interventions and reduce risk of future stroke
    • Perform brain imaging, preferably diffusion-weighted MRI, to identify unsuspected infarction and exclude nonischemic causes; use head CT if MRI unavailable
    • Obtain noninvasive cervical vessel imaging (Doppler ultrasonography, CT or magnetic resonance angiography) to identify carotid stenosis
    • Obtain ECG to access for cardioembolic mechanism (atrial fibrillation)

Pitfalls

  • If symptoms have not resolved during evaluation, consider stroke and urgently evaluate in emergency department
  • Initiate timely evaluation to reduce risk of subsequent stroke
  • Do not rely on risk stratification tools alone, such as ABCD² scores, to safely discharge patients from emergency department
  • Fully educate patients about need to present immediately to emergency department if symptoms recur

Terminology

Clinical Clarification

  • Historically, transient ischemic attack has had a time-based definition: any focal cerebral ischemic event that resolved within 24 hours r4
    • Up to one-third of these patients were found to have infarction on imaging studies r5
    • Most transient ischemic attacks last less than 1 hour r1r6
  • Revised transient ischemic attack definition (based on tissue, not time): a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction r2
    • Requires brain imaging availability
    • If imaging is unavailable, older time-based definition may be used
      • Accepts the high probability of necrotic area in patients with symptoms lasting longer than 24 hours r5
  • Patients with transient ischemic attack have significantly increased risk for stroke (up to 5% of transient ischemic attacks are followed by stroke within 48 hours) r1d1
    • Same causes, pathophysiology, risks, and prevention strategies apply to both
    • Continuum of disease is analogous to angina and myocardial infarction

Classification

  • Subtypes r7
    • Lacunar
      • May have symptoms of a lacunar stroke
    • Non-lacunar
      • Cardioembolic
        • May have symptoms of a brainstem stroke or a stroke involving the cerebral cortex
      • Large vessel thrombotic or embolic
      • Cryptogenic

Diagnosis

Clinical Presentation

History

  • Focus on characteristics of the event; symptoms typically resolve before patient presentation
    • If symptoms have not resolved, assume that patient has had stroke or other stroke mimic and urgently treat accordingly
    • Ascertain onset abruptness and symptom duration
      • Transient ischemic attack onset is typically sudden and without prodrome c1
      • Most transient ischemic attacks are brief, often lasting less than 1 hour r6
    • Witnesses to event may provide useful information
  • Symptoms are usually focal, reflecting anatomic location of ischemic vessel (80% anterior and 20% posterior circulation) r8
    • Nonfocal signs and symptoms (eg, loss of consciousness, confusion, generalized weakness, lightheadedness, incontinence) are rarely caused by transient ischemic attacks r4c2c3c4c5c6
  • In general, negative symptoms (eg, loss of function) suggest ischemia and positive findings (eg, stimulated or increased function) suggest alternative diagnosis (eg, migraine, seizure)
    • Negative symptoms suggestive of ischemia (transient ischemic attack) include:
      • Motor: loss of movement (ie, hemiparesis, hemifacial weakness in upper motor neuron distribution) c7c8c9
      • Speech: altered or decreased (ie, aphasia) c10c11
      • Visual: loss of vision (ie, amaurosis fugax) c12c13
      • Sensation: anesthesia (ie, hemisensory loss) c14c15
    • Positive symptoms (eg, involuntary motions, dysesthesias, visual flashes) suggest alternative diagnosis
      • Exception: vertigo may be associated with posterior circulation ischemia c16
  • Pain is unlikely to be a symptom of transient ischemic attack, although unilateral neck pain with focal neurologic signs and symptoms may occur with cervical artery dissection c17c18

Physical examination

  • Physical examination findings at time of presentation may be entirely normal; treat presence of new neurologic deficits as stroke until proven otherwise
  • Focus of comprehensive examination is to detect any neurologic deficits, define the cause of the event, and assess for vascular risks
    • Complete neurologic assessment (eg, strength, sensation, coordination, balance, speech, language)
      • NIH stroke scale may be useful to document baseline neurologic findings r9
    • Neck and heart auscultation may find carotid bruits (stenosis), irregular heart rhythm (atrial fibrillation), or murmurs (valvular disease) c19c20c21
    • Ocular fundi may show evidence of emboli (Hollenhorst plaques), retinal artery occlusion, or chronic hypertensive vascular changes; vision testing may find loss or defects c22c23c24
    • Skin examination may demonstrate signs of trauma, coagulopathies, platelet disorders, or embolic lesions (Janeway lesions or Osler nodes) c25c26c27c28c29

Causes and Risk Factors

Causes

  • Transient ischemic attack and stroke share the same cause and pathophysiology: focal hypoperfusion with impaired cerebral oxygenation and metabolism
  • Causes (classification based on presumed mechanism and type and location of vascular lesion):
    • Cardioembolic (approximately 34% of casesr1), including: c30
      • Cardiac dysrhythmia (atrial fibrillation) c31c32
      • Valve disease and mechanical valve prosthesis c33c34
      • Patent foramen ovale; other atrial or ventricular septal defects c35c36c37
      • Dilated cardiomyopathies c38
      • Impaired left ventricular dysfunction (eg, recent myocardial infarction) c39c40
      • Infective endocarditis, septal aneurysms, and myxomas c41c42c43c44
    • Large artery atherosclerosis (9%-13% of casesr1) c45
      • May result in plaque emboli or stenosis with flow reduction or complete obstruction c46c47
      • Location may be intracranial or extracranial (eg, carotid or vertebral artery stenosis, aortic atherosclerosis) c48c49c50
    • Small artery occlusion/disease (lacunar; 10%-18% of casesr1) c51
      • Intracranial atherosclerosis c52
    • Other causes (3%-6% of casesr1), for example:
      • Dissection of vertebral or carotid artery c53c54
      • Hypercoagulable states c55
      • Vasculitis c56
      • Sympathomimetic drugs (eg, cocaine, amphetamines) c57c58c59
    • Undetermined causes (25%-50% of casesr1) c60

Risk factors and/or associations

Age
  • Incidence increases with age r10c61
Sex
  • Occurs more often in men than in women r10c62c63

Genetics

  • Parental family history of stroke is a risk factor; no specific genetic factor is clearly established r10c64
Ethnicity/race
  • In the United States, occurs more often in Black people and in Mexican Americans than in non-Hispanic White people r10c65c66c67
Other risk factors/associations
  • Risk factors for transient ischemic attack are the same as those for stroke
    • Previous transient ischemic attack or stroke c68c69
    • Hypertension c70
    • Dyslipidemia c71
    • Diabetes mellitus c72
    • Cigarette smoking c73
    • Obesity c74
    • Poor nutrition c75
    • Physical inactivity c76
    • Obstructive sleep apnea c77
    • Excessive alcohol intake c78

Diagnostic Procedures

Primary diagnostic tools

  • Accurate history and complete physical examination provide basis for clinical diagnosis c79
  • Conduct initial diagnostic evaluation promptly; complete thorough evaluation within 48 hours r11
    • Identify unsuspected infarction and exclude nonischemic causes
    • Identify high-risk, modifiable conditions that have effective therapeutic interventions (eg, carotid stenosis, atrial fibrillation)
  • Obtain fingerstick blood glucose measurement to exclude hypoglycemia, a mimic of transient ischemic attack and stroke
  • Perform brain and vasculature imaging in all patients with suspected transient ischemic attack r2
    • Obtain neuroimaging within 24 hours of symptom onset or as soon as possible after an event r2
      • Identify vascular origin and mechanism of event to prevent future stroke; may provide alternative diagnosis for patient symptoms
      • MRI, including diffusion-weighted imaging, is preferred brain imaging modality r2
        • Diffusion-weighted imaging is useful to predict short-term risk of stroke r12
      • Obtain head CT if MRI is not available
    • Noninvasive cervical vessel imaging
      • Predicts higher short-term risk for stroke (symptomatic carotid stenosis with narrowing more than 50%) r5r12
      • Doppler ultrasonography, magnetic resonance angiography, or CT angiography
        • Selection depends on local availability, provider expertise, and patient characteristics (eg, pacemaker presence, renal failure)
        • Use of supraaortic magnetic resonance and CT angiography can provide assessment of both carotid bifurcation and intracranial circulation r2
  • Noninvasive imaging (CT angiography or magnetic resonance angiography) of intracranial vasculature
    • Obtain when knowledge of intracranial vascular disease will alter management
    • Exclude presence of proximal intracranial stenosis and/or occlusion
      • Obtain catheter cerebral angiography (gold standardr13) to confirm reliable diagnosis of abnormalities (presence and degree of stenosis) when detected on noninvasive testing r2
  • Obtain laboratory tests
    • Order CBC, chemistry panel, and basic coagulation studies at time of initial presentation r2
      • Provides baseline and aids in identifying less common causes
    • Screening tests for vascular risk factors r7
      • Dyslipidemia: obtain fasting lipid profile
      • Diabetes: obtain fasting blood glucose level, hemoglobin A1C, or oral glucose tolerance tests (choice of test and timing are guided by clinical judgment)
    • Specialized coagulation studies may be useful in younger patients without vascular risk factors or known underlying cause r2
    • Obtain other laboratory tests on case-by-case basis (eg, pregnancy test, toxicologic screening) in relation to suspected cause and pretest risk assessment r1
    • Diagnostic and prognostic markers of transient ischemic attack are being studied, but none have been solidly identified as useful in clinical practice r1
  • Obtain ECG in all patients r2
    • Assess for cardioembolic mechanism (eg, atrial fibrillation, ventricular hypertrophy, cardiac ischemia) r2
      • Patients with atrial fibrillation are at high risk for stroke r14
    • Cardiac monitoring (inpatient telemetry or Holter monitor) is useful for patients in whom the origin of transient ischemic attack remains uncertain after brain imaging and ECG r2
  • Consider echocardiography when a cardiac cause is highly suspected or when no other cause has been identified in the work-up r2
    • Includes transthoracic echocardiography or transesophageal echocardiography
  • Consider prolonged cardiac rhythm monitoring (approximately 30 days)
    • May be useful to screen for atrial fibrillation when no other cause is apparent r7

Laboratory c80

  • Laboratory tests for all patients with suspected transient ischemic attack r1r2
    • Serum glucose and electrolyte levels (including renal function tests) c81c82
      • Provide baseline information of renal function and metabolic state
      • Hypoglycemia may mimic stroke
    • CBC with platelet count c83
      • Evaluates for inflammation, thrombocytosis, and myelodysplastic disease
      • Abnormal results may indicate cause of symptoms (eg, thrombocytosis, polycythemia, leukocytosis, thrombocytopenia)
    • Coagulation studies (eg, prothrombin time with INR, partial thromboplastin time) c84c85c86c87
      • Establish baseline for possible anticoagulation, patients on known anticoagulants, or patients with liver disease
  • Diabetes screening tests and fasting lipid profile r7c88c89c90c91c92
    • Aid in identifying diabetes and dyslipidemia, known risk factors for stroke
  • Optional coagulation screening tests (useful for younger patients with transient ischemic attack without vascular risk factor or known cause) r2
    • Protein C, protein S, and antithrombin III activities c93c94c95
    • Activated protein C resistance/factor V Leiden c96c97
    • Fibrinogen and D dimer c98c99
      • High D-dimer levels may be associated with the risk of stroke and adverse clinical outcomes in patients with transient ischemic attack r15
      • There is not an established dose-dependent relationship r15
    • Anticardiolipin antibody c100
    • Lupus anticoagulant c101
    • Anti–β₂-glycoprotein antibody r16c102
    • Homocysteine c103
    • F2 gene (prothrombin) mutation G20210A c104
    • Factor VIII activity c105
    • Von Willebrand factor c106
    • Plasminogen activator inhibitor c107
    • Endogenous tissue plasminogen activator c108
  • Toxicologic screening may detect sympathomimetic drug use in absence of typical stroke risk factors c109

Imaging

  • Neuroimaging
    • CT scan of head (without contrast material) c110
      • Useful for identifying intracranial hemorrhage and mass lesions r12
      • Not a reliable predictor of short-term risk for stroke r12
      • Early signs of cerebral ischemia include:
        • Loss of gray-white differentiation
        • Swelling of gyri, producing sulcal effacement
      • Relatively insensitive in detecting acute, small cortical or subcortical infarctions, especially in posterior fossa
      • Advantages over MRI
        • More widely available
        • Relatively easy to interpret
      • Limitations
        • Less sensitive than MRI in detecting ischemic lesions
        • Exposure to ionizing radiation
    • MRI of brain c111
      • Differentiates between temporary ischemia (transient ischemic attack) and infarction (stroke), especially in early hours after symptom onset; excludes other nonvascular causes r17
      • Diffusion-weighted MRI is preferred; very sensitive in detecting small areas of brain ischemia r2c112
        • Useful for predicting short-term stroke risk r12
          • Patients with diffusion-weighted lesions have higher risk of recurrent ischemic events r2
          • Presence of large-vessel occlusion is a predictor of new events r2
        • Increased sensitivity for ischemia over CT
          • Sensitivity to identify stroke using diffusion-weighted MRI within the first 12 hours of symptoms is 0.99, whereas sensitivity of CT is only 0.39 r1
      • Advantages over CT
        • Distinguishes acute and small cortical, deep, and posterior fossa infarcts
        • Distinguishes acute from chronic ischemia
        • Identifies subclinical satellite ischemic lesions, providing information on stroke mechanism
        • Improves spatial resolution
        • Avoids ionizing radiation
      • Limitations
        • More limited availability
        • Increased cost
        • Patient contraindications (eg, pacemakers, defibrillators, patient confusion or claustrophobia, extreme obesity)
  • Vessel imaging
    • Doppler ultrasonography c113
      • Carotid Doppler ultrasonography c114
        • Images carotid bifurcation and measures blood velocities
        • Useful initial screening tool to exclude severe carotid stenosis; accuracy is similar to that of magnetic resonance or CT angiography r12r13
          • More readily available, less expensive, avoids need for IV contrast material
        • Ultrasonography is slightly less sensitive than magnetic resonance angiography for detecting severe carotid stenosis; specificity appears to be similar r12
          • No studies directly compared ultrasonography and CT angiography
        • Insensitive in detecting arterial dissection and non–flow-limiting lesions; unable to evaluate intracranial portion of internal carotid artery
      • Transcranial Doppler ultrasonography c115
        • Use to evaluate intracranial vessel abnormalities, occlusions, and stenosis
        • Less accurate than CT and magnetic resonance angiography for steno-occlusive disease
    • Angiography c116
      • Magnetic resonance angiography c117
        • Noninvasive; can depict intracranial and extracranial circulation
        • Contrast-enhanced magnetic resonance angiography is more accurate, but use is restricted in patients with severe renal disease r2
        • Allows visualization of vertebrobasilar system
        • Limitations: patients with claustrophobia, extreme obesity, or incompatible implanted devices (eg, pacemakers, defibrillators)
      • CT angiography c118
        • Rapid, noninvasive visualization of both extracranial and intracranial vessels
        • Provides direct imaging of arterial lumen; high accuracy for determining severity of lumen stenosis r13
        • Supraaortic vessel CT (or magnetic resonance) angiography is recommended when other carotid imaging is inconclusive or when endarterectomy is planned
        • Requires administration of contrast material; avoid in patients with renal disease
      • Catheter angiography c119
        • Gold standard for diagnosis and grading of cerebrovascular lesions and disease r13
          • Confirms presence and degree of intracranial stenosis detected on noninvasive studies r2
          • May not be required if noninvasive imaging provides firm diagnostic findings
        • For extracranial vascular imaging (cervical carotid and vertebral arteries)
          • Gold standard for establishing degree of stenosis and determining patient eligibility for carotid endarterectomy, angioplasty, or stenting r13
            • Reserved for patients when noninvasive imaging is contraindicated, inconclusive, or yields discordant results
            • May use 2 concordant noninvasive studies (eg, ultrasonography, CT angiography, magnetic resonance angiography), avoiding catheterization risk
        • Invasive test; risks include contrast material use (eg, allergic reaction, kidney dysfunction), femoral artery injuries, injection site infection or hematoma, stroke, or death r13
          • Rate of serious complications is less than 1 in 1000 and less than 5% for minor events
  • Echocardiography c120
    • Useful for patients without clear cause for transient ischemic attack after initial evaluation and vessel imaging, or those with high suspicion of cardiac cause r3
      • Transthoracic echocardiography c121
        • Assess for cardiac hypertrophy, ventricular hypokinesis or thrombus, valve disease, and endocarditis r12
      • Transesophageal echocardiography c122
        • More sensitive than transthoracic echocardiography for aortic arch atheroma and interatrial septum abnormalities (eg, patent foramen ovale) r2

Functional testing

  • ECG c123
    • Assesses for cardioembolic mechanism (eg, atrial fibrillation, ventricular hypertrophy) or signs of cardiac ischemia r1
    • Approximately 2% of patients have new-onset atrial fibrillation r17
  • Prolonged cardiac monitoring/Holter monitoring c124
    • Identifies patients with suspected paroxysmal arrhythmias (eg, atrial fibrillation)
      • More likely to detect arrhythmias than continuous cardiac telemetry r18
      • Consider 24-hour telemetry to investigate for paroxysmal atrial fibrillation r1
      • Additional 4 days of Holter monitoring can detect paroxysmal atrial fibrillation in additional 14% of patients r17
      • Can extend up to 30 days for suspected embolic or cryptogenic cause r1

Other diagnostic tools

  • Risk stratification tools
    • Developed to help identify patients with high short-term risk for stroke and to assist in determining urgency of follow-up or need for hospitalization
    • No perfect scoring system has been developed, and clinical judgment, based on thorough history and physical examination, must be incorporated into clinical decision making r1
    • ABCD² score (age, blood pressure, clinical features, duration of transient ischemic attack, and presence of diabetes) r19c125
      • Most often used; provides framework for decision making
      • Score is determined by the following:
        • Age 60 or older: 1 point
        • Blood pressure 140/90 or higher: 1 point
        • Clinical features (choose 1)
          • Unilateral weakness: 2 points
          • Speech impairment without unilateral weakness: 1 point
        • Duration of transient ischemic attack
          • 60 minutes or longer: 2 points
          • 10 to 59 minutes: 1 point
        • Diabetes present: 1 point
      • Classification by score r19
        • Low risk: less than 4 points (stroke risk 1% at 2 days, 1.2% at 7 days, and 3.1% at 90 days)
        • Moderate risk: 4 to 5 points (stroke risk 4.1% at 2 days, 5.9% at 7 days, and 9.8% at 90 days)
        • High risk: greater than 5 points (stroke risk 8.1% at 2 days, 11.7% at 7 days, and 17.8% at 90 days)
      • Limitations r20
        • Does not reliably discriminate those at low and high risk for early recurrent stroke r20
          • Approximately one-third of patients with stroke mimic had score of 4 points or higher; approximately one-third of patients with true transient ischemic attack had score of less than 4 points r20
        • Does not identify patients with carotid stenosis or atrial fibrillation requiring urgent intervention r20
        • Should not be relied upon to identify patients that can safely be discharged from the emergency department r12
    • Other risk stratification tools (eg, ABCD, ABCD³, ABCD²-I, California score) have also been evaluated and not found useful alone as risk stratification instruments r12c126c127c128c129

Differential Diagnosis

Most common

  • Migraine with aura (complicated) c130d2
    • Reflects cortical spreading depression; spreading onset corresponds to adjacent cortical regions over minutes r21
      • Usually resolves within 30 minutes (rarely over 1 hour)
    • Visual disturbances are most commonly reported; positive symptoms include teichopsia (zigzag) and geometric patterns
    • Can include sensory, motor, or speech disturbances
      • Often occurs sequentially with migraine; simultaneously with transient ischemic attack
    • Typically associated with headache, either immediate or delayed; frequently accompanied by nausea, vomiting, and/or photophobia
    • Differentiation suggested by history of migraines; more common in younger people
      • MRI findings are usually normal
      • Headache may accompany transient ischemic attack; first episode or worst headache warrants brain imaging
  • Seizure disorder c131
    • Nonepileptic or epileptic seizures d3
    • Paroxysmal transient disturbances of brain function
      • Partial seizures can cause episodic neurologic deficits
    • Positive symptoms: limb movements, lip smacking, head turning, dystonic posturing, and/or painful sensory disturbance
      • Symptoms often spread sequentially (jacksonian march); transient ischemic attack symptoms typically have sudden onset without progression
    • Associated symptoms: tongue biting, incontinence, muscle pains, and/or postictal disorientation
      • Altered consciousness is more likely with seizure than with transient ischemic attack
    • Suggestive history and physical examination findings are diagnostic; obtain EEG to confirm
  • Hypoglycemia c132
    • Serum glucose level less than 70 mg/dL; most common in type 1 diabetes d4
    • Symptoms can include anxiety, tremors, weakness, sweating, nausea, convulsions, and confusion
      • Blurred vision and focal neurologic signs may occur
    • Diagnosed by low serum glucose level and resolution of symptoms with administration of glucose
  • Mass lesions (eg, tumor, subdural hematoma, abscess) c133c134c135
    • Symptoms are based on location and may not follow vascular distribution
      • Onset is typically gradual
    • Focal disturbances of cerebral function (eg, weakness, ataxia, cranial nerve deficits, aphasia) may occur abruptly and are likely to persist
    • Consider in patients with primary cancer, fever, immunosuppression, or recent trauma
    • Diagnosed using cerebral imaging studies (CT or MRI)
  • Functional anxiety c136c137c138
    • Psychogenic conditions (eg, anxiety, panic disorder, conversion reaction) may mimic transient ischemic attack d5
    • Diagnosed by history and physical examination; MRI findings are usually normal
      • Symptoms are often stereotypical and recurrent; findings are nonanatomic or inconsistent

Treatment

Goals

  • Prevent future stroke
    • Identify cause and treat underlying predisposing conditions
    • Modify risk factors

Disposition

Admission criteria

Patients with transient ischemic attack require urgent evaluation (preferably within 24 hoursr3); no clear guidelines exist on hospitalization

Disposition (inpatient or outpatient) varies based on local resources, risk assessment, clinical acumen, and patient access to follow-up

  • Inpatient hospitalization
    • Provides decreased time to thrombolysis if stroke occurs; permits cardiac monitoring and timely diagnostic work-up
    • Recommended for high-risk patients, as determined by any of the following: r12
      • Abnormal initial head CT scan
      • Suspected embolic source (presence of atrial fibrillation, cardiomyopathy, or valvuloplasty)
      • Known carotid stenosis
      • Previous large stroke
      • Crescendo transient ischemic attacks (multiple, recurrent, increasing frequency)
  • Observation unit
    • Useful for adult patients with suspected transient ischemic attack without high-risk conditions r12
    • An emergency department diagnostic protocol can rapidly stratify patients with high short-term risk for stroke r12
      • Provide cardiac monitoring, serial clinical examinations, access to brain and vascular imaging, and consultation as needed
      • May require rapid access to emergent therapy and hospital admission, when indicated
      • Advantage: reduced costs and shortened length of stay (compared with inpatient hospitalization)
  • Outpatient transient ischemic attack clinic
    • Exclusion criteria and risk stratification differ among various studies r12
    • Referred patients receive comprehensive testing and evaluation by stroke expert within 24 to 48 hours r3
    • Advantage: decreased cost (compared with inpatient hospitalization)

Transient ischemic attack clinics and observation units are noninferior to inpatient hospitalization in reducing stroke risk after transient ischemic attack in medium- and low-risk patients r1

  • Timing of work-up (preferably within 24 hours of symptom onset) is more important than location
  • Patients not admitted must be fully educated about the need to return immediately if symptoms recur

American Heart Association/American Stroke Association transient ischemic attack guidelines state the following: r2

  • It is reasonable to hospitalize patients with transient ischemic attack who present within 72 hours of symptoms with:
    • ABCD² score of 3 points or higher
    • ABCD² score of 0 to 2 points with evidence of focal ischemia
    • ABCD² score of 0 to 2 points if uncertain that patient can obtain outpatient work-up within 2 days
  • The ABCD² score does not sufficiently identify short-term risk for stroke to use alone as a risk stratification tool r4r12

2006 National Stroke Association guidelines state the following: r11

  • Consider hospitalization for patients with first transient ischemic attack within the past 24 to 48 hours to provide:
    • Early intervention with lytic therapy if symptoms recur and progress to stroke
    • Completion of appropriate diagnostic testing
    • Initiation of definitive secondary prevention therapy
  • Crescendo transient ischemic attacks may also justify hospitalization
  • In patients with recent (within 1 week) transient ischemic attack, timely hospital referral with hospitalization is reasonable for:
    • Symptoms duration longer than 1 hour
    • Crescendo or stuttering pattern of transient ischemic attacks
    • Symptomatic internal carotid stenosis with narrowing more than 50%
    • Known cardiac source of embolus (eg, atrial fibrillation)
    • Known hypercoagulable state
    • ABCD² score greater than 3 points r19
Criteria for ICU admission
  • Not specifically recommended unless necessitated by comorbidities

Recommendations for specialist referral

  • All patients with suspected transient ischemic attack should be promptly assessed by a neurologist or stroke expert r3
  • Consider cardiologist consultation for patients with cardiac findings influencing stroke risk (eg, atrial fibrillation, cardiac thrombus, valvular abnormalities)
  • Consider consulting vascular surgeon or neurosurgeon for patients with significant vessel stenosis or occlusion

Treatment Options

There is no specific acute intervention for patients with transient ischemic attack, as findings have usually resolved; goal is to reduce potential for future strokes

Fully educate patients about need to present immediately to emergency department if symptoms recur

General recommendations r1

  • Maintain adequate cerebral perfusion and oxygenation
    • Position patient in supine position with head flat unless contraindicated
    • Obtain IV access and maintain euvolemic state
    • Administer supplemental oxygen only in cases of hypoxia (oxygen saturation less than 94% on room air alone)
  • Specific recommendations for strategies aimed at prevention of future stroke often depend on the transient ischemic attack subtype r7

Urgently begin stroke prevention therapy to reduce short- and long-term risk of stroke

  • Antihypertensive treatment
    • Lower blood pressure gradually, after first several days, to below 130/80 according to current evidence-based guidelines r7r22
      • Permissive hypertension may be allowed for first few days; abrupt lowering of blood pressure reduces cerebral blood flow and can potentially precipitate stroke in patients at risk
      • Maintain long-term blood pressure at recommended levels r23
  • Lipid modification
    • Begin statin therapy for patients with: r7
      • LDL-C level of 100 mg/dL or higher and transient ischemic attack presumed to be of atherosclerotic origin
      • LDL-C level less than 100 mg/dL and transient ischemic attack presumed not to be of atherosclerotic origin (lower level evidence)
    • Consult 2018 American College of Cardiology/American Heart Association cholesterol guidelines for expanded management of patients with transient ischemic attack and comorbid atherosclerotic cardiovascular disease r24

Direct treatment to the cause, based on patient evaluation and risk factors for stroke:

  • Noncardioembolic transient ischemic attack
    • Start antiplatelet therapy in all cases, if not contraindicated r7
      • Reduces rate of recurrence of stroke, myocardial infarction, or death r7
    • Base agent selection on relative effectiveness, safety, cost, tolerance, patient characteristics, risk factors, and patient preference r7
    • American Heart Association/American Stroke Association guidelines recommend the following: r7
      • Aspirin monotherapy or aspirin plus extended-release dipyridamole as initial therapy
        • Aspirin monotherapy r1
          • First line for initial therapy
          • Best studied and most widely prescribed; inexpensive
          • Increased risk for gastrointestinal bleeding; small absolute increase in hemorrhagic stroke risk
        • Aspirin plus dipyridamole
          • More effective than aspirin alone
          • Less well tolerated (primarily owing to headache)
      • Clopidogrel monotherapy: reasonable option; useful for patients allergic to or intolerant of aspirin
      • Ticlopidine: high adverse effect profile; rarely used in clinical practice r7
      • Dual antiplatelet therapy with aspirin and clopidogrel r25r26
        • Consider starting within 24 hours of transient ischemic attack and continuing for 21 days r7
          • May be effective in preventing recurrent stroke within the first 90 days r7
          • Not recommended for routine long-term stroke prevention
    • 2018 clinical practice guideline by an expert panel recommends dual antiplatelet therapy with clopidogrel and aspirinr28 to be started within 24 hours in patients with high risk of transient ischemic attack or minor stroke; it is to be continued for 10 to 21 days, at which time patients should continue with monotherapy r27
  • Nonvalvular atrial fibrillation (paroxysmal or permanent) r7
    • Anticoagulation therapy is indicated for prevention of recurrent stroke r7
    • Base agent selection on risk factors, cost, tolerability, potential for drug interaction, renal function, and patient preference r7
      • Vitamin K antagonist therapy
        • Target INR of 2.5 is recommended (range, 2-3) r7
        • Anticoagulant effects may be reversed with prothrombin complex concentrates or vitamin K if needed
        • Limitations
          • Requires frequent INR testing and dose adjustments; narrow therapeutic margins
          • Multiple food and drug interactions
          • Increased hemorrhage risk (reversible)
      • Non–vitamin K antagonist oral anticoagulants
        • Better safety profile (especially for intracranial bleeding); lacks specific antidotes
        • Options include the following:
          • Apixaban (factor Xa inhibitor)
          • Dabigatran (direct thrombin inhibitor)
          • Rivaroxaban (factor Xa inhibitor)
          • Edoxaban (factor Xa inhibitor); newer, not included in American Stroke Association guidelines r1
    • Patients unable to take oral anticoagulants should receive aspirin monotherapy; consider addition of clopidogrel r7
  • Valvular disease and transient ischemic attack r7
    • Anticoagulation
      • Treat with long-term vitamin K antagonist with INR target of 2.5 (range, 2-3) for rheumatic mitral valve disease with atrial fibrillation r7
        • Consider for rheumatic mitral valve disease without atrial fibrillation or other likely cause for symptoms (eg, carotid stenosis) instead of antiplatelet therapy
    • Antiplatelet therapy r7
      • For patient without atrial fibrillation or other indication for anticoagulation and:
        • Native aortic disease
        • Nonrheumatic mitral valve disease, mitral valve prolapse, and mitral annular calcification
  • Prosthetic heart valves r7
    • Mechanical heart valves
      • In patients with mechanical heart valves and history of transient ischemic attack before valve insertion, treat with vitamin K antagonist therapy r7
        • Target INR varies by valve location r7
          • Mechanical aortic valve: target INR of 2.5 (range, 2-3)
          • Mechanical mitral valve: target INR of 3 (range, 2.5-3.5)
        • Add aspirin (75-100 mg/day) if patient has low risk for bleeding r7
      • In patients with mechanical heart valves and systemic embolization despite adequate antithrombotic therapy, consider intensifying therapy by increasing aspirin dose to 325 mg/day or increasing target INR (depending on bleeding risk) r7
    • Bioprosthetic heart valves r7
      • In patients with bioprosthetic aortic or mitral valves, history of transient ischemic attack before valve insertion, and no other indication for anticoagulation therapy (beyond 3-6 months from the valve placement), treat with long-term aspirin (75-100 mg/day). Preferred over long-term anticoagulation r7
      • In patients with bioprosthetic aortic or mitral valves and transient ischemic attack or systemic embolization despite antiplatelet therapy, consider addition of vitamin K antagonist therapy with target INR of 2.5 (range, 2-3) r7
  • Cardiomyopathy
    • Treat with either oral vitamin K antagonist anticoagulation or antiplatelet therapy
    • With evidence of left atrial or ventricular thrombus, vitamin K antagonist therapy is recommended for at least 3 months r7
  • Acute myocardial infarction and left ventricular thrombus formation with transient ischemic attack
    • Treat with vitamin K antagonist; target INR is 2.5 (range, 2-3) for 3 months r7
  • Unstable angina or coronary artery stenting with transient ischemic attack r7
    • Consider combination anticoagulant with antiplatelet therapy
  • Other conditions
    • Aortic arch atheroma with transient ischemic attack: antiplatelet therapy is recommended r7
    • Arterial dissections (extracranial carotid or vertebral) with transient ischemic attack: antiplatelet or anticoagulant therapy is reasonable for 3 to 6 months or longer r7
    • Patent foramen ovale: It is considered reasonable to percutaneously close patent foramen ovale in patients who meet each of the following criteria: age 18–60 years, nonlacunar stroke, no other identified cause, and high risk patent foramen ovale features. May consider closing after transient ischemic attack. r7
  • Interventional treatments for extracranial carotid disease
    • Consider in addition to optimal medical therapy (eg, antiplatelet therapy, statin therapy, risk factor modification)
    • Perform within 6 months of index event; early intervention (within 2 weeks) is reasonable if no contraindications exist r13
    • Not recommended for carotid artery stenosis with narrowing less than 50% r7
    • Procedural choices:
      • Carotid endarterectomy
        • Older procedure; more existing data regarding safety and outcomes
      • Carotid angioplasty and stenting
        • Alternative to carotid endarterectomy; useful in patients with severe carotid stenosis and high risk for surgical complications r7
        • Consider angioplasty and stenting in patients with extracranial vertebral artery stenosis and symptoms despite optimal medical treatment r7
        • Advantages: less invasive, decreased patient discomfort, and shorter recuperation time
    • Consider patient age r7
      • In older patients (approximately 70 years or older), carotid endarterectomy may be associated with improved outcome compared with carotid angioplasty and stenting
      • For younger patients, carotid angioplasty and stenting and carotid endarterectomy are equivalent in risk for periprocedural complications

Drug therapy c139c140

Nondrug and supportive care c260

Procedures
Carotid endarterectomy r7c261
General explanation
  • Involves surgical exposure and clamping of the common carotid artery, internal carotid artery, and external carotid artery
  • Arteries are opened under direct visualization and atherosclerotic plaque is manually removed until the lumen is widely patent
  • Arteries are then sutured closed; no stents are left in the arteries
  • Carotid endarterectomy and carotid angioplasty with stenting are similar procedures with the same indications
    • Carotid endarterectomy is older and more data exist regarding safety and outcomes
    • Choice of procedure is made by the treating vascular surgeon
  • Results
    • Increased diameter of internal carotid artery with improved cerebral blood flow as demonstrated by CT or MRI perfusion protocol
    • Reduced symptoms of transient ischemic attack and cerebrovascular accident
Indication
  • Indicated for transient ischemic attack, ipsilateral carotid stenosis, and perioperative morbidity and mortality risk less than 6% for: r7
    • Severe (70%-90%) ipsilateral stenosis documented by noninvasive imaging and transient ischemic attack within past 6 months
    • Moderate (50%-69%) ipsilateral stenosis documented by catheter-based imaging or noninvasive imaging with corroboration (eg, magnetic resonance angiography, CT angiography) and recent transient ischemic attack
      • Consider patient-specific factors (eg, age, sex, comorbidities)
Contraindications
  • Absolute r30
    • Asymptomatic complete carotid occlusion
  • Relative (high-risk features) r13
    • Previous radiation therapy or surgery on neck
    • Presence of tracheostomy
    • Contralateral carotid occlusion or laryngeal nerve palsy
    • Surgically inaccessible lesion
    • Recurrent carotid stenosis
    • Unacceptably high medical risk (eg, severe lung or coronary artery disease, renal insufficiency, congestive heart failure)
Complications
  • Cranial nerve palsy r13
  • Stroke r13
  • Venous thromboembolism r13
  • Acute arterial occlusion r13
  • Arterial restenosis r13
  • Myocardial infarction r13
Carotid angioplasty with stenting r7c262c263
General explanation
  • Deflated balloon catheter is placed percutaneously in peripheral blood vessel and advanced under fluoroscopy into central circulation through aortic arch and into internal carotid artery
  • Balloon is inflated to press open atherosclerotic plaque and wire stent is inserted to increase diameter of stenotic vessel
  • Results
    • Increased diameter of internal carotid artery with improved cerebral blood flow as demonstrated by CT or MRI perfusion protocol
    • Reduced symptoms of transient ischemic attack and cerebrovascular accident
Indication
  • Alternative to carotid endarterectomy for symptomatic patients when: r31
    • Patient has average or low risk of complications associated with endovascular intervention
    • Diameter of internal carotid artery lumen reduced by more than 70% (by noninvasive imaging) or more than 50% (by catheter-based imaging or noninvasive imaging with corroboration) r32
    • Rate of periprocedural stroke or death is less than 6% r33
  • Consider in patients with symptomatic severe stenosis (greater than 70%) with: r31r32
    • Anatomic or medical conditions present that greatly increase the risk for surgery
    • Specific circumstances such as radiation-induced stenosis or restenosis after carotid endarterectomy
  • In younger patients, carotid angioplasty with stenting is equivalent to carotid endarterectomy in risk for periprocedural complications (eg, stroke, myocardial infarction, death) and long-term risk for ipsilateral stroke r31
  • In patients aged 70 years or older, carotid endarterectomy is associated with improved outcome compared with carotid angioplasty with stenting, particularly when arterial anatomy is unfavorable for endovascular intervention r31
Contraindications
  • Absolute
    • Visible thrombus within the lesion r34
    • Inability to achieve vascular access r34
    • Presence of infection r34
  • Relative
    • Severely calcified or circumferential carotid plaque
    • Unsuitable or severely tortuous carotid artery
    • IV contrast material allergy
    • Unsuitable or heavily calcified aortic arch anatomy
    • Near occlusion of carotid artery
    • Peripheral artery occlusive disease
    • Severe aortic valvular stenosis
Complications
  • Perioperative cerebrovascular accident
  • Hyperperfusion syndrome
  • Carotid restenosis

Comorbidities c264

Complications and Prognosis

Complications c265

Prognosis

  • Prognosis varies by severity and by cause of disease
  • Short-term risk of stroke or other adverse vascular events is high
    • Stroke
      • Substantial short-term risk of stroke after transient ischemic attack; approximately 3% to 10% at 2 days and 9% to 17% at 90 days r10
      • Approximately 12% of all strokes are heralded by transient ischemic attack r10
    • All major cardiovascular events: annual risk of major cardiovascular events is increased after transient ischemic attack r10
    • Death: in one study, the 1-year mortality rate after a transient ischemic attack was 12% r35
  • Transient ischemic attack survivors of high-risk period have 10-year stroke risk of approximately 19% and combined stroke, myocardial infarction, or vascular death risk of 43% (4% per year) r10

Screening and Prevention

Screening c266

Prevention

  • Lifestyle modification r7c267
    • Smoking cessation c268
    • Eliminate or reduce alcohol consumption c269
    • Weight loss: beneficial for cardiovascular risk; effect on risk of transient ischemic attack specifically is uncertain c270
    • Regular aerobic physical activity: moderate to vigorous-intensity aerobic exercise is suggested (3-4 sessions per week) if patient is able r7c271
    • Nutrition: conduct nutrition assessment c272
      • Diet rich in fruits, vegetables, whole grains, and low-fat dairy products (eg, Mediterranean-type diet) is recommended c273
      • Advise salt restriction to less than approximately 2.4 g/day (less than 1.5 g/day is associated with greater blood pressure reduction) r7c274
      • Routine vitamin supplementation is not recommended
  • Control treatable conditions r7
    • Hypertension: maintain blood pressure at reference range levels c275
    • Hyperlipidemia: initiate statin therapy to normalize cholesterol levels c276
    • Diabetes: maintain good control of blood sugar c277
    • Sleep apnea: treat with CPAP c278
  • Low-dose rivaroxaban plus aspirin is a new option to consider for efficacious antithrombotic therapy for primary as well as secondary prevention of stroke in patients with atherosclerosis r36
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