The definition and appropriate evaluation of transient ischemic attack

Review of Key Journal Article
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By Douglas J Lanska MD MS MSPH

Article under review: Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke 2009;40(6):2276-93.

Background: Beginning in the 1960s, transient ischemic attack (TIA) was operationally defined as a focal cerebral ischemic event with symptoms lasting less than 24 hours; a reversible ischemic neurologic event (RIND) was defined as a focal cerebral ischemic event with symptoms lasting 24 hours to 7 days; and only symptoms lasting more than 7 days were thought to reliably indicate a stroke. However, during the 1970s it became evident that most events with symptoms lasting 24 hours to 7 days were associated with cerebral infarction and, hence, were strokes. More recently, studies in the 1980s utilizing high-resolution CT and later studies utilizing diffusion-weighted MRI have demonstrated that about one third of individuals with traditionally defined transient ischemic attacks (ie, with symptoms lasting less than 24 hours) have evidence of new cerebral infarction (Shah et al 2007). As a result, in 2002 a new tissue-based definition of transient ischemic attack was proposed: "a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, and without evidence of acute infarction" (Albers et al 2002).

Purpose: To promulgate a new American Heart Association/American Stroke Association Stroke Council practice guideline concerning the definition and evaluation of transient ischemic attacks.

Methods: The authors developed practice guidelines based on evidence-based literature review and consensus of subject-matter experts.

Results:

Definition of transient ischemic attack:

Because the previous 24-hour criterion for transient ischemic attack does not adequately distinguish between patients with and without infarction and because defining transient ischemic attack with a maximum 24-hour duration has the potential of delaying the initiation of effective therapies, the authors propose a revised definition of transient ischemic attack based on the earlier one proposed by Albers and colleagues in 2002 (Albers et al 2002). Notably, the phrase "typically less than 1 hour" in the definition proposed by Albers and colleagues was not helpful, because a 1-hour time point also did not accurately distinguish between patients with and without cerebral infarction.

The revised definition of transient ischemic attack endorsed by the American Heart Association is "a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without cerebral infarction" (Easton et al 2009).

Evaluation of patients with transient ischemic attack:

  • Patients with transient ischemic attack should have neuroimaging within 24 hours of symptom onset. MRI with diffusion-weighted imaging is the preferred neuroimaging modality, but head CT is acceptable if MRI/diffusion-weighted imaging is not available.
     
  • Noninvasive imaging of the extracranial cervicocephalic vessels should be performed. Initial assessment of the extracranial cervicocephalic vessels may involve carotid ultrasound, magnetic resonance angiography (MRA), or CT angiography (CTA), depending on patient characteristics (eg, presence of pacemaker, contrast allergy, etc.) and on local availability and expertise. Patients with significant abnormalities on one form of noninvasive vascular imaging should have confirmatory testing with a second form of noninvasive vascular imaging. If the 2 non-invasive tests are discordant, catheter angiography should be considered before consideration of carotid endarterectomy.
     
  • Noninvasive imaging of the intracranial vasculature with transcranial Doppler ultrasonography, MRA, or CTA can reliably exclude significant intracranial stenosis and is reasonable to obtain if knowledge of intracranial steno-occlusive disease will alter management (eg, consideration of stenting). However, catheter angiography remains the gold standard for diagnostic evaluation of intracranial vascular diseases and may be required in selected patients based on clinical circumstances and the results of noninvasive imaging.
     
  • EKG should be obtained as soon as possible after a transient ischemic attack. Prolonged cardiac monitoring with inpatient telemetry or Holter monitor is useful in patients without a clear explanation for their transient ischemic attack after initial brain imaging and EKG.
     
  • Echocardiography (at least transthoracic and preferably transesophageal echocardiography) is recommended if no cause for the transient ischemic attack has been identified by neuroimaging and cardiac monitoring. Transesophageal echocardiography is useful for identifying patent foramen ovale, aortic arch atherosclerosis, and cardiac valvular disease. Transesophageal echocardiography is reasonable to obtain if knowledge of these conditions will alter management.
     
  • Routine blood tests should include a complete blood count, chemistry panel, prothrombin time and partial thromboplastin time, and fasting lipid panel. Although not mentioned in the article, it would seem reasonable to obtain an international normalized ratio if that does not come routinely with the prothrombin time test results and a hemoglobin A1c level as well. Additional specialized coagulation screening tests can be considered in younger patients with transient ischemic attacks, especially when no underlying cause has been identified: protein C, protein S, antithrombin III activities; activated protein C resistance/Factor V Leiden mutation; fibrinogen; D-dimer; anticardiolipin antibody; lupus anticoagulant; fasting homocysteine; prothrombin gene G20210A mutation; factor VIII; von Willebrand factor; plasminogen activator inhibitor-1; and endogenous tissue plasminogen activator activity.
     
  • Hospitalization can be used for close monitoring to ensure rapid administration of tissue plasminogen activator in the event that a stroke occurs soon after the onset of a transient ischemic attack and is cost-effective if the 24-hour risk of stroke is greater than 4% (Nguyen-Huynh and Johnston 2005); this corresponds to an ABCD2 risk-stratification score of higher than 3 (Johnston et al 2007). Although no randomized trial has evaluated the benefit of hospitalizing transient ischemic attack patients or the utility of the ABCD2 risk-stratification score in triaging patients for hospitalization, the authors concluded that hospitalization was "reasonable" if patients with transient ischemic attack present within 72 hours of onset and any of the following are present:
  • ABCD2 risk-stratification score of 3 or higher
  • ABCD2 risk-stratification score lower than 3 and either of the following:
    - workup cannot be completed within 2 days as an outpatient
    - other evidence that the event was caused by focal ischemia

Conclusions and commentary: The revised definition of transient ischemic attack does not use an arbitrary time-based criterion, recognizing that the typical duration of a transient ischemic attack is less than 2 hours but that occasionally prolonged symptomatic episodes may occur without infarction. Because the revised definition of transient ischemic attack uses a tissue-based criterion rather than a time-based criterion, stroke and transient ischemic attack rates with the new definition will not be directly comparable to such rates under the prior definition. Diagnostic certainty under the new definition will also depend on the extensiveness of the diagnostic evaluation and the availability of advanced neuroimaging, so estimates of stroke and transient ischemic attack incidence will vary by whether and when advanced neuroimaging studies are performed. Because some infarcts will not be visualized even with state-of-the-art imaging techniques, patients should still be diagnosed as having a stroke if they have persistent symptoms lasting several days that are consistent with a small deep infarct, even in the absence of neuroimaging confirmation of a new ischemic lesion.

In some patients it will be difficult to know whether to label the problem as a transient ischemic attack or a stroke. For example, in patients with symptoms of relatively brief duration (ie, lasting 2 to 24 hours), it may be difficult to determine the correct diagnosis in the absence of a detailed diagnostic evaluation. Similarly, in patients with acute cerebrovascular symptoms who have not had neurodiagnostic testing, it is not yet known whether the symptoms will resolve or persist. Although the authors of the present report stopped short of proposing a specific terminology for such situations, they did suggest that it would be "reasonable" to refer to such situations as "acute neurovascular syndromes" analogous to terminology used in cardiology, pending clarification with further observation and/or advanced neuroimaging.