Transient Ischemic Attack

Essentials of Diagnosis

• Acute, focal neurologic deficit

• Clinical deficit resolves completely within 24 hours

• Risk factors for vascular disease often present

General Considerations

• Focal, ischemic, cerebral neurologic deficits that last for < 24 h (usually < 1–2 h)

• Embolization is an important etiology and may explain why separate attacks may affect different parts of the territory supplied by the same vessel

• Cardiac embolic sources

  • Atrial fibrillation

  • Rheumatic mitral valve disease

  • Infective endocarditis

  • Atrial myxoma

  • Mural thrombi after myocardial infarction (MI)

  • Atrial septal defects and patent foramen ovale (PFO) may permit emboli from the veins to reach the brain ("paradoxical emboli")

• Cerebrovascular sources

  • An ulcerated plaque on a major artery to the brain may be a source of emboli

  • In the anterior circulation, atherosclerotic changes occur most commonly near the carotid bifurcation extracranially and may cause a bruit

  • Other (less common) abnormalities of blood vessels that may cause transient ischemic attacks (TIAs): fibromuscular dysplasia (particularly affects the cervical internal carotid artery); atherosclerosis of the aortic arch; inflammatory arterial disorders such as giant cell arteritis, systemic lupus erythematosus, polyarteritis, and granulomatous angiitis; and meningovascular syphilis

• Hypotension may reduce cerebral blood flow and rarely cause a TIA if a major extracranial artery to the brain is markedly stenosed

• The subclavian steal syndrome may lead to transient vertebrobasilar ischemia from stenosis or occlusion of one subclavian artery proximal to the source of the vertebral artery

• Hematologic causes

  • Polycythemia

  • Sickle cell disease

  • Hyperviscosity

Demographics

• Proper treatment of TIAs can help prevent strokes

• About 30% of patients with stroke have a history of TIAs

• Stroke develops within 90 days in 5–10% of patients with TIAs

• Incidence of stroke is not related to the number or duration of individual TIAs but is increased in patients with hypertension or diabetes mellitus

Symptoms and Signs

• Symptoms vary markedly among patients, but tend to be consistent in a given individual

• Onset is abrupt, and recovery often occurs within a few minutes

• TIA in the carotid territory may manifest with

  • Weakness and heaviness of the contralateral arm, leg, or face, singly or in combination

  • Numbness or paresthesias may occur either as sole manifestation or with motor deficits

  • Dysphagia

  • Transient monocular blindness (amaurosis fugax) may be the presenting feature when ophthalmic artery (the first branch of the internal carotid artery) is affected

  • During an attack, examination may reveal flaccid weakness with pyramidal distribution, sensory changes, hyperreflexia or an extensor plantar response on the affected side, dysphasia, or any combination of these

  • A carotid bruit or cardiac abnormality may be present

• Vertebrobasilar TIA may manifest with

  • Vertigo

  • Ataxia

  • Diplopia

  • Dysarthria

  • Dimness or blurring of vision

  • Perioral numbness and paresthesias

  • Weakness or sensory complaints on one, both, or alternating sides of the body

  • Drop attacks due to bilateral leg weakness, without headache or loss of consciousness, may occur, in relation to head movements

  • Attacks may occur intermittently and stop spontaneously

• Findings in the subclavian steal syndrome may include

  • A bruit in the supraclavicular fossa

  • Unequal radial pulses

  • A difference of 20 mm Hg or more between the systolic blood pressures in the arms

Differential Diagnosis

• Stroke

• Hypoglycemia

• Focal seizure (Todd paralysis)

• Syncope

• Migraine

• Peripheral causes of vertigo (eg, Ménière disease)

Laboratory Tests

• Complete blood count

• Fasting blood glucose and serum cholesterol

• Serologic test for syphilis

• Blood cultures if endocarditis is suspected

Imaging Studies

• CT or MRI scan

  • Indicated within 24 hours of symptom onset, in part to exclude the possibility of a small cerebral hemorrhage or a cerebral tumor masquerading as a TIA

  • MRI with diffusion-weighted sequences is particularly sensitive for revealing acute or subacute infarction

• Carotid duplex ultrasonography is useful for detecting significant stenosis of the internal carotid artery

• MR or CT angiography permits broader visualization of cervical and intracranial vasculature

Diagnostic Procedures

• ECG

• Ambulatory ECG (Holter) monitoring if a paroxysmal cardiac arrhythmia is suspected

• Assessment for

  • Hypertension

  • Heart disease

  • Hematologic disorders

  • Diabetes mellitus

  • Hyperlipidemia

  • Peripheral vascular disease

Medications

Anticoagulation

• Anticoagulants should be started immediately unless contraindicated

• Warfarin (target INR 2.0–3.0)

• Bridging warfarin with heparin is not necessary, but some experts advocate treatment with aspirin until the INR becomes therapeutic

• In patients with atrial fibrillation who require long-term anticoagulation, options include

  • Apixaban, 2.5–5 mg orally twice daily

  • Dabigatran, 150 mg orally twice daily

  • Edoxaban, 60 mg orally daily

  • Rivaroxaban, 20 mg orally daily

• Combination antiplatelet-anticoagulation therapy is only indicated in patients with

  • Mechanical heart valves

  • Separate indication for antiplatelet therapy, such as a cardiac stent

• In patients with cardiomyopathy and an ejection fraction under 35% without atrial fibrillation,

  • Warfarin (target INR 2.0–3.0) reduces ischemic stroke risk compared to aspirin

  • However, they each result in roughly equivalent increases in the risk of major hemorrhage

  • Treatment in this population should therefore be individualized

Antiplatelet therapy

• All patients in whom anticoagulation is not indicated should be treated with short-term dual antiplatelet therapy and long-term monotherapy to reduce the frequency of TIAs and the incidence of stroke

• Treatment should be initiated within 12 hours after the TIA or minor stroke (defined by an National Institutes of Health Stroke Scale of 3 or less) with an oral loading dose of clopidogrel (300–600 mg) followed by 75 mg/day orally plus aspirin (50–325 mg daily orally) for 21 days, followed by aspirin (81 mg daily orally monotherapy), by aspirin combined with extended-release dipyridamole (200 mg twice daily orally), or by clopidogrel (75 mg daily orally)

• Cilostazol (100 mg twice daily) had similar efficacy as aspirin at long-term stroke prevention in an Asian population with less risk of hemorrhage

• Combining clopidogrel with aspirin beyond 90 days increases the risk of hemorrhagic complications and is not recommended

Surgery

• Carotid endarterectomy or endovascular intervention (angioplasty or stenting)

  • Reduces the risk of ipsilateral carotid stroke, especially when TIAs are of recent onset (< 1 months)

  • Indicated when there is a surgically accessible high-grade stenosis (70–99% in luminal diameter) on the side appropriate to carotid ischemic attacks and there is relatively little atherosclerosis elsewhere in the cerebrovascular system

• Surgery is not indicated for mild stenosis (< 50%)

• Closure of PFO

  • Carefully selected patients with PFO and right-to-left shunt benefit from PFO closure along with antiplatelet therapy.

  • Potential candidates include patients who

    • Are age 18- to 60-years-old

    • Have a history of cryptogenic stroke or TIA

    • Do not have uncontrolled diabetes, hypertension, or a specific indication for long-term anticoagulation

  • Patients with moderate to large interatrial shunts or associated atrial septal aneurysms appear to benefit most from PFO closure

Therapeutic Procedures

• Cigarette smoking should be stopped

• Endovascular therapy is generally reserved for patients whose neck anatomy is unfavorable for surgery

• Treat cardiac sources of embolization appropriately

• Weight reduction and regular physical activity should be encouraged when appropriate

Prognosis

• In general, carotid TIAs are more likely than vertebrobasilar TIAs to be followed by stroke

• The stroke risk is greater

  • In patients older than 60 years

  • In diabetic persons

  • After TIAs that last longer than 10 minutes

  • With symptoms or signs of weakness, speech impairment, or gait disturbance

Prevention

• To prevent further attacks and stroke,

  • Treat diabetes, hematologic disorders, and hypertension (preferably with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medication)

  • Consider starting a statin medication regardless of the current LDL level; in addition to reducing stroke risk, antecedent statin use may improve the outcome if an ischemic stroke does occur

• Anticoagulation of atrial fibrillation (except lone atrial fibrillation)

• Control of hypertension

• Control of lipids

When to Refer

• All patients

When to Admit

• If seen within a week of a transient ischemic attack, patients should be considered for admission when

  • They have an ABCD² score (a 7-point score for identifying patients who have suffered a TIA and are at the highest risk of stroke in the following 2-day period) of 4 points or more

  • Outpatient evaluation is impractical

  • There are multiple TIAs

  • There is a carotid stenosis of > 70%

  • There is another concern for early recurrence or stroke