cryptogenic stroke; embolic stroke of undetermined source

Etiology

• embolic stroke arising from proximal arterial sources, heart, or venous system (with right-to-left shunt)
  • paroxysmal atrial fibrillation in older patients
  • association with patent foramen ovale is unclear
    • patent foramen ovale in 1/2 of young adults with cryptogenic stroke but is also found in 1/4 of healthy persons
  • large, nonstenotic carotid plaques associated with embolic-like strokes of unknown source
• idiopathic 25%

* cryptogenic cases were less likely to have hypertension, diabetes, hypercholesterolemia, or a smoking history than ischemic strokes where the cause is identifiable

Epidemiology

• 10-40% of all ischemic strokes

Laboratory

• investigation for coagulopathy

Diagnostic procedures

• investigation for cardiovascular disease
  • carotid ultrasound
  • transthoracic echocardiography bubble study (diagnostic)
    • agitated saline is injected into a peripheral intravenous catheter to demonstrate right-to-left intracardiac shunt (patent foramen ovale) often enhanced by the Valsalva maneuver in patients < 50 years of age
  • electrocardiogram & HOLTER monitoring for a week of longer for paroxysmal atrial fibrillation
  • benefit of implantable cardiac monitor is uncertain

Complications

• similar risk of death or dependency at 6 months & similar 10-year risk for recurrence, compared with ischemic stroke where the cause is identifiable
• no 12-year increase risk for acute coronary syndrome, MI or carotid disease compared with cases due to small-vessel disease or cardioembolic events
• recurrent ischemic stroke (mean age 41 years) 1.9/100 patient-years
• new-onset atrial fibrillation 15/535 (mean age 41 years)

Management

• anti-platelet therapy*
• randomized trials of novel oral anticoagulants suggested
  • rivaroxaban is not superior to aspirin for prevention of recurrent embolic stroke of undetermined origin & is associated with a higher risk of bleeding
  • dabigatran is not superior to aspirin for prevention of cryptogenic stroke
• patent foramen ovale
  • anticoagulation superior to antiplatelet therapy
  • patent foramen ovale closure might reduce risk of recurrent stroke more than medical therapy (anticoagulation)
    • patent foramen ovale occlusion device FDA approved (10/16) for prevention of recurrent cryptogenic stroke*
    • endovascular device closure of patent foramen ovale reduces stroke risk for patients with prior cryptogenic stroke (RR=0.03 in CLOSE trial - 0.23 in REDUCE trial)
  • for patients in whom anticoagulation is not appropriate, patent foramen ovale closure plus antiplatelet therapy
• optimal antithrombotic strategy for cancer-associated cryptogenic stroke
  • no difference between aspirin & apixaban after cryptogenic ischemic stroke

* presence of patent foramen ovale does not alter therapy

* incidence of recurrent cryptogenic stroke in patients with patent forament ovale is low, but reportedly diminished 50% with Amplatzer PFO occlusion device

More general terms

• embolic stroke