Emilio A. Russo, MD
G. Daud Noaz, MD, MSBME
image BASICS
  • A transient episode of neurologic dysfunction due to focal brain, retinal, or spinal cord ischemia without acute infarction
  • No longer diagnosed based on timeframe of symptoms
  • Most important predictor of stroke: 7-40% of patients with stroke report previous TIA.
  • Synonym(s): ministroke
  • Incidence of TIA underestimated because some patients do not report symptoms.
  • 200,000 to 500,000 new TIA cases reported each year
    • 83 cases/100,000 people/year in the United States
    • 400 to 800 cases/100,000 persons aged 50 to 59 years
  • Prevalence of TIA in general population: ˜ 2.3%
  • Predominant age: risk increases >60 years; highest in 7th and 8th decades
  • Predominant sex: male > female (3:1)
  • Predominant race/ethnicity: African Americans > Hispanics > Caucasians. The difference in African Americans is exaggerated at younger ages.
Temporary reduction/cessation of cerebral blood flow adversely affecting neuronal function
  • Carotid/vertebral atherosclerotic disease
    • Artery-to-artery thromboembolism
    • Low-flow ischemia
  • Small, deep vessel disease associated with HTN
    • Lacunar infarcts
  • Cardiac diseases
    • 1-6% of patients with MI develop stroke.
  • Embolism secondary to the following:
    • Valvular (mitral valve) pathology
    • Mural hypokinesias/akinesias with thrombosis (acute anterior MI/congestive cardiomyopathies)
    • Cardiac arrhythmia (atrial fibrillation accounts for 5-20% incidence)
  • Hypercoagulable states
    • Antiphospholipid antibodies
    • Deficiency of protein S, protein C
    • Presence of antithrombin III
    • Oral contraceptives
    • Pregnancy and parturition
  • Arteritis
    • Noninfectious necrotizing vasculitis
    • Drugs
    • Irradiation
    • Local trauma
  • Sympathomimetic drugs (e.g., cocaine)
  • Other causes: spontaneous and posttraumatic (e.g., chiropractic manipulation) arterial dissection
  • Fibromuscular dysplasia
Inheritance is polygenic, with tendency to clustering of risk factors within families.
  • Hypertension (HTN)
  • Cardiac diseases (A-fib, MI, valvular disease)
  • Diabetes
  • Hyperlipidemia
  • Atherosclerotic disease (carotid/vertebral stenosis)
  • Cigarette smoking
  • Thrombophilias
  • Lifestyle changes: smoking cessation, diet modification, weight loss, regular aerobic exercise, and limited alcohol intake
  • Use of ASA and statins as primary prevention may be considered in certain populations.
  • Strict control of medical risk factors: diabetes (glycemic control), HTN (thiazide and/or ACE/ARB), hyperlipidemia (statins), anticoagulation when high risk of cardioembolism (e.g., atrial fibrillation, mechanical valves)
Geriatric Considerations
  • Older patients have a higher mortality rate than younger patients—highest in 7th and 8th decades.
  • Atrial fibrillation is a frequent cause among the elderly.
Pediatric Considerations
  • Congenital heart disease is a common cause among pediatric patients.
  • Other causes include the following:
    • Metabolic: homocystinuria, Fabry disease
    • Central nervous system (CNS) infection
    • Clotting disorders
    • Marfan syndrome
    • Moyamoya disease
Pregnancy Considerations
  • Preeclampsia, eclampsia, and HELLP
  • TTP and hemolytic uremic syndrome
  • Postpartum angiopathy
  • Cerebral venous thrombosis
  • Hypercoagulable states related to pregnancy
  • Atrial fibrillation
  • Uncontrolled HTN
  • Carotid stenosis
  • Vital signs, oxygen saturation
  • Thorough neurologic and cardiac exams
  • ABCD2 score:
  • Evolving stroke
  • Migraine (hemiplegic)
  • Focal seizure (Todd paralysis)
  • Hypoglycemia
  • Bell palsy
  • Neoplasm of brain
  • Subarachnoid hemorrhage
  • Intoxication
  • Electrolyte abnormalities
Initial Tests (lab, imaging)
  • Patients with TIA should undergo neuroimaging evaluation within 24 hours of symptom onset.
  • MRI, including diffusion-weighted imaging, is the preferred brain diagnostic modality; if not available then noncontrast head CT (2)[B].
  • Noninvasive imaging of the cervicocephalic vessels should be performed routinely as part of the evaluation of suspected TIA (2)[A].
  • Initial assessment of the extracranial vasculature may involve carotid US/TCD, MRA, or CTA depending on the availability and expertise and characteristics of the patient (2)[B].
  • Routine blood tests (CBC, chemistry, PT/PTT, UPT, and fasting lipid panel) are reasonable in evaluation of patient with TIA (2)[B].
Follow-Up Tests & Special Considerations
  • If only noninvasive testing is performed prior to CEA, it is reasonable to pursue two concordant noninvasive findings; otherwise, catheter angiography should be considered (2)[B].
  • Echo is reasonable in evaluation of patients with suspected TIA especially when no other cause is noted (2)[B].
  • TEE is useful in identifying PFO, aortic arch atherosclerosis, and valvular disease and is reasonable when this will alter management (2)[B].
  • Prolonged cardiac monitoring is useful in patients with an unclear etiology after initial brain imaging and ECG (2)[B].
  • EEG: if seizure suspected
  • After TIA, all patients should be screened for DM with either fasting plasma glucose or hemoglobin A1C.
  • Consider a sleep study due to the high prevalence of sleep apnea among TIA patients; treatment with CPAP has shown to improve patient outcomes (3)[B].
  • TIA is a neurologic emergency. Immediate medical attention should be sought within 24 hours of symptom onset.
  • Current evidence suggests that patients with high-risk TIAs require rapid referral and 24-hour admission (see ABCD2 scoring).
  • Acute phase
    • Inpatient for surgery and high-risk groups
    • Outpatient investigations may be considered based on patient's stroke risk, arrangement of follow-up, and social circumstances.
  • Antiplatelet therapy to prevent recurrence or future CVA
  • Treatment/control of underlying associated conditions

  • For patients with TIA, the use of antiplatelet agents rather than oral anticoagulation is recommended to reduce risk of recurrent stroke and other cardiovascular events, with the exception of cardioembolic etiologies (2)[A].
  • Uncertain if switching agent in patients who have additional ischemic attacks while on antiplatelet therapy is beneficial (4)[C].
First Line
  • Enteric-coated aspirin: 160 to 325 mg/day in the acute phase (5)[A] followed by long-term antiplatelet therapy for noncardioembolic TIA and anticoagulation for cardioembolic etiology
  • Antiplatelet therapy
    • ER dipyridamole-ASA (Aggrenox): 25/200 mg BID (4,6)[B]
    • Combined therapy with dipyridamole and ASA is better than ASA alone (5,7)[A].
    • More expensive than ASA alone and may have more side effects
    • Aspirin 50 to 325 mg/day (4)[A]
      • Contraindications: active PUD and hypersensitivity to ASA or NSAIDs
      • Precautions: may aggravate preexisting peptic ulcer disease; may worsen symptoms of asthma
      • Significant possible interactions: may potentiate effects of anticoagulants and sulfonylurea analogues
    • Clopidogrel 75 mg/day (4)[B]
      • Can be used in patients who are allergic to ASA (4)[B]
      • Precautions: Thrombotic thrombocytopenic purpura (TTP) can occur and increases risk of bleeding when combined with aspirin.
      • May be very slightly more effective than aspirin alone (5)[B]; more expensive and more side effects than aspirin
  • Combined aspirin and clopidogrel therapy has been demonstrated to reduce the incidence of subsequent stroke by 21% without increased risk of bleeding when used for a duration of 1 month or less immediately following TIA or CVA (6)[A].
  • Anticoagulation therapy
    • Factor Xa inhibitors (rivaroxaban, apixaban), direct thrombin inhibitor (dabigatran)
      • Noninferior to warfarin in nonvalvular A-fib
      • Precautions: avoid in CKD (CrCl <30 mL/min)
      • Expensive
    • Warfarin (INR-adjusted dose) (4)[A]
      • Contraindications: intolerance/allergy, active liver disease, active bleeding, pregnancy
      • Significant possible interactions: antibiotics, antiepileptics, antifungals, and many others
    • ASA 325 mg/day or ASA 81 mg/day and clopidogrel 75 mg/day (4)[A]
      • Patients who cannot take anticoagulation for reasons other than bleeding risk
Second Line
Ticlopidine (Ticlid): 250 mg PO BID
  • For patients who cannot tolerate other agents
  • Contraindications: hypersensitivity, presence of hematopoietic/hemostatic disorders, conditions associated with bleeding, severe liver dysfunction
  • Precautions: neutropenia (0.8% severe), which is reversible with cessation of the drug. Monitor blood counts every 2 weeks for first 3 months. TTP can occur.
  • Significant possible interactions: Digoxin plasma levels decreased 15%; theophylline half-life increased from 8.6 to 12.2 hours.
  • Neurology for ongoing workup and treatment
  • Cardiology if cardiac cause suspected
  • Vascular surgery if carotid endarterectomy appropriate
  • Secondary prevention of TIA should be initiated; venous thromboembolism (VTE) prophylaxis
  • Patients with TIA or ischemic stroke should be started on a statin.
  • BP should be reduced when appropriate after 24 hours. ACE inhibitors/thiazide have shown to be of benefit.
  • Patients with DM or pre-DM should be advised to follow ADA guidelines to maintain tight glycemic control (3)[A].
  • Consider carotid endarterectomy in patients with a high degree of carotid artery stenosis.
  • When carotid endarterectomy is indicated for patients with TIA, surgery within 2 weeks is reasonable if there are no contraindications to early revascularization.
Admission Criteria/Initial Stabilization
  • Symptoms <72 hours and the following:
    • ABCD2 score of ≥3
    • ABCD2 score of 0 to 2 and uncertainty that dx workup can be completed within 2 days as outpatient.
    • ABCD2 score of 0 to 2 and evidence that indicates the patient's event was caused by focal ischemia.
  • Correct fluid and electrolyte imbalances.
Discharge Criteria
Consider safety at home if another incident occurs.
Patient Monitoring
  • Follow-up every 3 months for 1st year then annually
  • Close attention to recurrent or subsequent CVA
  • As appropriate for underlying medical problems
  • The risk of stroke on the ipsilateral side within 90 days and cumulative thereafter is 10-20%.
  • Frequency increases with the addition of multiple risk factors and severity of carotid stenosis.
  • Patients with larger artery occlusion or cardioembolic etiology are at increased risk of recurrence.
  • The major cause of death in the first 5 years is cardiac disease.
1. Tsivgoulis G, Stamboulis E, Sharma VK, et al. Multicenter external validation of the ABCD2 score in triaging TIA patients. Neurology. 2010;74(17):1351-1357.
2. Adams RJ, Albers G, Alberts MJ, et al. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2008;39(5):1647-1652.
3. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-2236.
4. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e601S-e636S.
5. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;133(6 Suppl):630S-669S.
6. Chen S, Shen Q, Tang Y, et al. Efficacy and safety of adding clopidogrel to aspirin on stroke prevention among high vascular risk patients: a meta-analysis of randomized controlled trials. PLoS One. 2014;9(8):e104402. doi:10.1371/journal. pone.0104402.
7. De Schryver EL, Algra A, van Gijn J. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. Cochrane Database Syst Rev. 2007;(3):CD001820.
Additional Reading
Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.. Circulation. 2007;115(20):e478-e534.
See Also
Algorithms: Stroke; Transient Ischemic Attack and Transient Neurologic Defects
  • G45.9 Transient cerebral ischemic attack, unspecified
  • G45.1 Carotid artery syndrome (hemispheric)
  • G45.0 Vertebro-basilar artery syndrome
Clinical Pearls
  • Primary/secondary prevention is important, stressing smoking cessation, exercise, weight loss, limited ETOH intake, and control of HTN, hyperlipidemia, and diabetes.
  • Antiplatelet therapy (e.g., aspirin or clopidogrel or aspirin-dipyridamole) should be initiated.
  • Warfarin should be initiated in patients with atrial fibrillation or cardioembolic risk factors.
  • A 30% risk of stroke exists within 5 years of a TIA.