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    Embolic Stroke of Undetermined Source (ESUS) Criteria

    Diagnoses embolic stroke of undetermined source.
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    INSTRUCTIONS

    Use in patients with ischemic stroke only, not hemorrhagic stroke.

    When to Use
    Pearls/Pitfalls
    Why Use

    Patients with ischemic stroke of unclear etiology.

    • Diagnosis of ESUS can be established after sufficient evaluation, including long-term cardiac monitoring for ≥24 hours, for occlusive large vessel atherosclerosis and high-risk cardioembolic sources in nonlacunar infarcts.
    • Potential low-risk embolic sources are thought to comprise ESUS.
    • Transesophageal echocardiography (TEE) is not required in ESUS; thus, aortic arch atherosclerosis (shaggy aorta) evaluation is not included. 
    • Studies used to develop ESUS were in predominantly Caucasian populations.
    • An unknown proportion of ESUS patients may have non-embolic stroke mechanisms.
    • Defines cryptogenic stroke based on criteria, rather than from the absence of available test results.
    • Outlines sufficient diagnostic workup in ischemic strokes of unclear etiology not previously described.
    • The prior TOAST stroke classification, a diagnosis of exclusion, classifies a high proportion of strokes as cryptogenic.
    • Enables standardized diagnostic criteria for clinical trials.
    • Used in many ongoing randomized controlled trials studying secondary stroke prevention in patients with cryptogenic strokes.
    All 4 must be present:

    Diagnostic Result:

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    Next Steps
    Evidence
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    • Strokes that meet ESUS criteria are thought to be due to sources of uncertain risk, including:
      • Minor-risk potential cardioembolic sources.
      • Occult paroxysmal atrial fibrillation.
      • Undiagnosed malignancy.
      • Arteriogenic emboli such as aortic arch atherosclerotic plaques or non-stenotic cerebral arteries.
      • Paradoxical embolism through an atrial septal defect.

    Management

    • Depending on clinical suspicion, further evaluation may include any of the following:
      • Prolonged outpatient cardiac monitoring.
      • TEE.
      • Cardiac MRI.
      • Transcranial Doppler with monitoring for emboli.
      • Catheter angioplasty.
      • Workup for occult cancer.
      • Workup for non-embolic causes such as vasculitis.
    • Secondary prevention in all noncardioembolic ischemic strokes includes anti-platelet therapy, blood pressure control, anti-lipid therapy, and lifestyle modifications.
    • The benefit of anticoagulation therapy in ESUS without proven atrial tachyarrhythmia is unclear and the subject of ongoing clinical trials.
    • Certain patients aged ≤60 years with ESUS and patent foramen ovale (PFO) may benefit from percutaneous PFO closure in addition to antiplatelet therapy.
    • In patients with recurrent ESUS, switching antiplatelet agents or starting empiric anticoagulation therapy is reasonable.

    Critical Actions

    All ischemic strokes undergo the same acute therapy management regardless of etiology, including intravenous tPA or mechanical thrombectomy if indicated.

    Formula

    Selection of the appropriate criteria (all 4 must be present):

    1. Ischemic stroke detected by CT or MRI that is not lacunar*.
    2. Absence of extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischemia.
    3. No major risk cardioembolic source of embolism**.
    4. No other specific cause of stroke identified (e.g. arteritis, dissection, migraine/vasospasm, drug abuse).

    Note: diagnosis of ESUS requires a minimum diagnostic evaluation, including cardiac monitoring for >24 hours with automated rhythm detection, in addition to the above criteria.

    *Lacunar = subcortical infarct ≤1.5 cm (≤2.0 cm on MRI diffusion images) in largest dimension, including on MRI diffusion-weighted images, and in distribution of small, penetrating cerebral arteries of cerebral hemispheres and pons.

    **Permanent or paroxysmal atrial fibrillation, sustained atrial flutter, intracardiac thrombus, prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, recent (<4 weeks) MI, left ventricular ejection fraction <30%, valvular vegetations, or infective endocarditis.

    Evidence Appraisal

    • ESUS was developed by consensus in 2014 to outline diagnostic guidelines to ischemic strokes without clear etiology. An estimated 25% of all ischemic strokes are cryptogenic, with most appearing embolic (Lamy 2002).
    • Pooled studies revealed an average age of patients with ESUS was 65 years, and 42% were women. ESUS patients were younger, had less traditional stroke risk factors, and had less severe strokes based on NIH Stroke Scale than non-ESUS patients. (Hart 2017).
    • Larger systemic studies estimate 17% of ischemic strokes meet ESUS criteria, with an annualized recurrent stroke risk of 4.5% during mean follow-up of 2.7 years (Hart 2017).
    • Most studies used to develop ESUS criteria were done in predominantly white populations.
    • Duration of cardiac rhythm monitoring in studies affects incidence of ESUS. The optimal time for occult atrial fibrillation detection is uncertain. Long-term cardiac monitoring for at least 24 hours should be included in the workup. 
    Dr. Robert G. Hart

    About the Creator

    Robert G. Hart, MD, is a professor of medicine and neurology at McMaster University in Hamilton, Ontario, Canada. He also serves as co-director of the McMaster/Hamilton Health Sciences Stroke Fellowship Program and previously directed the stroke program at the University of Texas Health Sciences Center for 25 years. Dr. Hart's research interests include stroke prevention, stroke risk in atrial fibrillation, and novel stroke therapies.

    To view Dr. Robert G. Hart's publications, visit PubMed

    Content Contributors
    • Dixon Yang, MD
    Reviewed By
    • Cen Zhang, MD
    About the Creator
    Dr. Robert G. Hart
    Content Contributors
    • Dixon Yang, MD
    Reviewed By
    • Cen Zhang, MD