Transient Ischemic Attack (TIA)

Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. A “tissue-based” definition is currently used rather than the former time-based limit of symptoms lasting less than 24 hours. The causes of TIA may be small clots or thromboemboli imposed on a blood vessel compromised by atherosclerosis, inflammation, or amyloid; inadequate cerebral blood flow from vasoconstriction; or severe hypotension. The clinical presentation includes transient neurologic deficits that resolve spontaneously. Management includes the reduction of risk factors to decrease the risk of a future stroke.

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Overview

Definition

A transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored.

Epidemiology

  • Difficult to determine due to other mimicking disorders
  • Incidence: approximately 500,000 cases per year in the US
  • The estimated overall prevalence of TIA in the US is 2%.

Etiology

  • Thrombosis with rupture of atherosclerotic plaques
  • Emboli from cardiac sources:
    • Left atrial thrombi/atrial fibrillation
    • Left ventricular thrombi
    • Rheumatic mitral or aortic valve disease
    • Bioprosthetic and mechanical heart valve emboli
    • Carotid atherosclerosis
    • Bacterial endocarditis (septic emboli)
    • Patent foramen ovale
    • Arterial dissection (rupture of an arterial wall followed by thrombus formation and embolization)
  • Atherosclerosis may also be embolic (in addition to thrombotic):
    • Iatrogenic embolization after an angiogram or other vascular procedures
    • Emboli released during carotid artery surgery

Risk factors

  • Hypertension (most important)
  • Previous history of TIA
  • Diabetes mellitus
  • Smoking
  • Hyperlipidemia
  • Atrial fibrillation
  • Carotid stenosis or other arterial stenoses
  • Patent foramen ovale

Pathophysiology and Clinical Presentation

The presentation depends on the pathophysiologic mechanism: embolic, lacunar (small penetrating vessel) TIA, or large artery TIA.

Pathophysiology

  • Temporary occlusion of a blood vessel (due to a small thrombus, embolus, vasoconstriction, or systemic hypoperfusion) to the brain, spinal cord, or retina →
  • Reduction in blood flow to the region supplied by the vessels →
  • Cerebral or other tissues undergo ischemia →
  • Neurons are deprived of glucose and oxygen → failure of mitochondria to produce ATP
  • Minutes to hours later, before infarction occurs, blood flow is restored and all neurologic dysfunction resolves.

Clinical presentation

The affected individual may not recall the time of onset of neurological symptoms. Establish a precise account of the event, if possible, from family members or caregivers, and include the time of onset and resolution, if the symptoms have already improved.

Symptoms of TIA relate to the vascular territory that is being compromised:

  • Internal carotid artery and middle cerebral artery (MCA) symptoms:
    • Transient monocular blindness (amaurosis fugax) or hemianopia
    • Motor weakness in the arm/hand > leg > face
    • Milder sensory loss in the same areas
    • Aphasia and alexia (inability to interpret written language)
  • Vertebral artery/basilar artery symptoms:
    • Quadriparesis
    • Crossed motor weakness and sensory abnormalities (1 side of the cranial nerve distribution with the opposite side limbs and the trunk)
    • Gait ataxia
    • Brainstem and cranial nerve symptoms: dizziness, diplopia, tinnitus
  • Posterior cerebral artery (PCA):
    • Hemianopia/blindness
    • Hemisensory loss in the arm/hand > leg or face
    • Amnesia
    • Alexia
  • Lacunar infarcts:
    • Hemiparesis
    • Hemisensory loss in the face > arm or leg
    • Limb ataxia/weakness
    • Mild dysarthria and dysphagia
  • Atypical TIA symptoms:
    • Gradual increase in symptoms over > 5 minutes
    • Progression of symptoms from 1 body part to another
    • Isolated visual disturbances (e.g., flashing lights)
    • Isolated sensory symptoms (e.g., in a finger or the tongue)
    • Isolated brainstem symptoms (e.g., dysarthria, diplopia, or hearing loss)

Diagnosis

Since the etiologies for stroke and TIA are very similar, the diagnostic evaluation for TIA resembles that for ischemic stroke.

  • History as above; always ask about:
    • Past episodes of TIA
    • Medications
    • Cardiovascular risk factors
    • Prior carotid or heart surgeries
  • Physical examination:
    • Neurologic symptoms may have been resolved by the time the affected individual arrives at the ED.
    • Vital signs and simultaneous point-of-care glucose
    • General exam including cardiac exam
    • Detailed neurological exam as much as feasible:
      • Signs and symptoms depend on the vascular territory affected.
      • Affected individuals may exhibit some degree of memory loss or amnesia of the events.
  • Labs:
    • CBC including platelet count
    • Chemistry: electrolytes, glucose, BUN, and creatinine
    • Serum lipid profile provides a baseline but may not be accurate in an acute emergency situation.
    • PT and PTT
    • Cardiac enzymes
    • Direct factor Xa activity assay: if the affected individual is taking a direct thrombin inhibitor or direct factor Xa inhibitor and is a candidate for thrombolytic therapy
    • Urinalysis
  • Other tests: ECG for arrhythmia or ischemic changes
  • Imaging:
    • Noncontrast head CT:
      • Only for differentiation between ischemic and hemorrhagic strokes
      • Acute ischemic zones are NOT visualized (can be mistaken for a normal scan).
      • Preferred emergency imaging modality
    • MRI brain:
      • Allows visualization of acute ischemia and ischemic penumbra = greater sensitivity
      • Better resolution but longer time for imaging
      • Less availability
    • Carotid ultrasonography or transcranial Doppler ultrasonography: to evaluate for atherosclerotic stenosis or aneurysms
    • Echocardiogram/transesophageal echocardiogram: to detect structural abnormalities that could facilitate embolization
      • Patent foramen ovale
      • Atrial septal defect
      • Clots in the atria or ventricles
Axial cut of a CT scan of a patient with acute ischemic stroke

Axial cut of a CT scan of an individual with acute ischemic stroke performed at the time of admission:
Note the lack of discernible changes.

Image: “Pseudoradial Nerve Palsy Caused by Acute Ischemic Stroke” by Tahir H, Daruwalla V, Meisel J, Kodsi SE. License: CC BY 3.0

Management

Initial management

  • Assess the individual’s airway, breathing, and circulation (ABC).
  • Treat hypoglycemia or hyperglycemia accordingly (may mimic TIA or stroke).
  • IV fluids
  • ABCD2 score = stroke risk stratification
    • Predicts stroke risk in the next 2 days, 7 days, and 90 days
    • Consider hospitalization if the score is ≥ 4.
    • Age ≥ 60 years
    • Blood pressure (initial): higher risk of stroke if systolic blood pressure ≥ 140 or diastolic blood pressure ≥ 90
    • Clinical features of TIA:
      • Unilateral weakness
      • Speech disturbance without weakness
    • Duration of symptoms
    • Diabetes history
  • Consider thrombolytic therapy if TIA evolves to a diagnosis of stroke.

Prevention of future TIAs and stroke

  • Lifestyle changes:
    • Healthy diet (e.g., Mediterranean diet)
    • Exercise as tolerated, consider weight loss if obese
    • Smoking cessation counseling, if applicable
  • Risk-factor management with improved control of:
    • Diabetes
    • Hypertension
    • Hyperlipidemia
  • Medications:
    • Antiplatelet therapy unless contraindicated:
      • Aspirin
      • Clopidogrel or extended-release dipyridamole if unable to take aspirin
    • Statins (e.g., atorvastatin) in clinically important atherosclerotic disease
    • Anticoagulants, if indicated for atrial fibrillation or coagulation disorder
  • Treat the underlying causes.
  • Surgery (carotid endarterectomy):
    • If workup reveals symptomatic internal carotid artery stenosis > 70%
    • Benefits of surgery must outweigh the risks, which also include stroke.
  • Family and patient education:
    • Continuation of preventive measures at home 
    • The “FAST” mnemonic is helpful for lay individuals to identify the recurrence of TIAs:
      • Facial droop
      • Arm weakness
      • Speech abnormality
      • Time

Prognosis

  • TIA is a prognostic indicator of stroke.
  • 50% risk of stroke within the 1st 2 days after symptom onset
  • 10%–15% risk of stroke in the 1st 3 months
  • 5%–6% annual mortality rate after TIA

Differential Diagnosis

  • Ischemic (or hemorrhagic) stroke (cerebrovascular accident): an acute neurologic injury resulting from brain ischemia, which may be due to cerebral blood vessel occlusion by thrombosis or embolism. The clinical presentation includes neurologic symptoms with varying degrees of motor and sensory loss. Diagnosis is made by physical examination and imaging. Management is ideally with thrombolytic therapy. Long-term rehabilitation with PT is important after the acute event.
  • Migraine: a common primary headache disorder characterized by episodic, moderate-to-severe headaches that may be associated with increased sensitivity to light and sound, and nausea and/or vomiting. Migraines with aura may be indistinguishable from TIA due to vasoconstriction, which causes ischemia and neurologic deficits similar to an ischemic stroke, including hemiplegia. Diagnosis is based on clinical history, physical exam, and imaging findings. Management includes medications to treat migraines and the avoidance of triggers.
  • Intracranial tumor: can be a primary neoplasm derived from intracranial tissues (astrocytoma, oligodendroglioma, meningioma) or a metastatic process from another malignancy such as lung or breast cancer. As the mass grows, it can give rise to neurological symptoms similar to those seen in an ischemic stroke. Diagnosis is based on imaging studies and management is based on addressing the underlying cause.
  • Brain abscess: a life-threatening condition involving the collection of pus in the brain parenchyma due to an infection. Brain abscesses may also result from trauma or a surgical complication. The most common presentations include headache, fever with chills, seizures, and neurologic deficits. Diagnosis is by MRI and/or CT-guided aspiration of the contents for culture. Management requires surgical drainage and antibiotics.
  • Carotid artery aneurysm or dissection: a condition that may occur when the integrity of the arterial walls fails, usually abruptly, resulting in intramural hematoma formation and a false lumen leading to the formation of an aneurysm and, later, dissection. Affected individuals typically present with unilateral head or neck pain and/or stroke-like symptoms. Dissections are confirmed based on imaging studies and are treated by medical management and, sometimes, surgical management. Complications can include cerebrovascular stroke and death in severe cases.
  • Hypoglycemia: an emergency condition characterized by a drop in glucose levels to < 55 mg/dL (3 mmol/L), although the specific values vary among and within individuals over time. The clinical presentations of hypoglycemia include neuroglycopenic symptoms such as dizziness, confusion, lethargy, and loss of consciousness, and can mimic a TIA or stroke. Diagnosis is based on lab testing. Management is with oral glucose or IV dextrose and depends on the severity of symptoms.

References

  1. Panuganti, K.K., Tadi, P., Lui, F. (2021). Transient ischemic attack. StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved August 5, 2021, from http://www.ncbi.nlm.nih.gov/books/NBK459143/ 
  2. Smith, W.S., Johnston, S.C., Hemphill, J., Claude, I. I. I. (2018). Ischemic Stroke. In J.L. Jameson, et al. (Eds.), pp. 3079–3091, Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill Education.
  3. Powers, W.J., et al. (2019). Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke, 50(12), e344–e418. https://doi.org/10.1161/STR.0000000000000211 
  4. Kasner, S. (2021). Stroke and other cerebrovascular diseases. DeckerMed Medicine. Retrieved July 31, 2021, from doi:10.2310/.1027.
  5. Furie, K.L., Rost, N.S. (2021). Definition, etiology, and clinical manifestations of transient ischemic attack. UpToDate. Retrieved August 5, 2021, from https://www.uptodate.com/contents/definition-etiology-and-clinical-manifestations-of-transient-ischemic-attack
  6. Caplan, L.R. (2019). Differential diagnosis of transient ischemic attack and acute stroke. UpToDate. Retrieved August 6, 2021, from https://www.uptodate.com/contents/differential-diagnosis-of-transient-ischemic-attack-and-acute-stroke

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