Contents

Search

cryptogenic stroke; embolic stroke of undetermined source

Etiology: - embolic stroke arising from proximal arterial sources, heart, or venous system (with right-to-left shunt) [4] - paroxysmal atrial fibrillation in older patients [4] - 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 [4] - large, nonstenotic carotid plaques associated with embolic-like strokes of unknown source [5] - idiopathic 25% [1,4] * cryptogenic cases were less likely to have hypertension, diabetes, hypercholesterolemia, or a smoking history than ischemic strokes where the cause is identifiable [1] Epidemiology: - 10-40% of all ischemic strokes [4] Laboratory: - investigation for coagulopathy Special laboratory: - 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 [2] - electrocardiogram & HOLTER monitoring for a week of longer for paroxysmal atrial fibrillation - benefit of implantable cardiac monitor is uncertain [11] 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 [1] - no 12-year increase risk for acute coronary syndrome, MI or carotid disease compared with cases due to small-vessel disease or cardioembolic events [1] - recurrent ischemic stroke (mean age 41 years) 1.9/100 patient-years [12] - new-onset atrial fibrillation 15/535 (mean age 41 years) [12] Management: - anti-platelet therapy [2,3]* - randomized trials of novel oral anticoagulants suggested [1] - rivaroxaban is not superior to aspirin for prevention of recurrent embolic stroke of undetermined origin & is associated with a higher risk of bleeding [8] - dabigatran is not superior to aspirin for prevention of cryptogenic stroke [10] - patent foramen ovale - anticoagulation superior to antiplatelet therapy [14] - patent foramen ovale closure might reduce risk of recurrent stroke more than medical therapy (anticoagulation) [9] - 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) [7] - for patients in whom anticoagulation is not appropriate, patent foramen ovale closure plus antiplatelet therapy [9] - optimal antithrombotic strategy for cancer-associated cryptogenic stroke - no difference between aspirin & apixaban after cryptogenic ischemic stroke [13] * presence of patent foramen ovale does not alter therapy [2] * incidence of recurrent cryptogenic stroke in patients with patent forament ovale is low, but reportedly diminished 50% with Amplatzer PFO occlusion device [6]

General

embolic stroke

References

  1. Li L, Yiin GS, Geraghty OC et al Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-based study. Lancet Neurology. July 27, 2015 PMID: 26227434 http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2815%2900132-5/fulltext
  2. Medical Knowledge Self Assessment Program (MKSAP) 17, 19 American College of Physicians, Philadelphia 2015, 2021
  3. Chen L, Luo S, Yan L, Zhao W A systematic review of closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and cryptogenic stroke or transient ischemic attack. J Neurol Sci. 2014 Feb 15;337(1-2):3-7 PMID: 24300230
  4. Saver JL. CLINICAL PRACTICE. Cryptogenic Stroke. N Engl J Med. 2016 May 26;374(21):2065-74. PMID: 27223148 http://www.nejm.org/doi/full/10.1056/NEJMcp1503946
  5. Coutinho JM, Derkatch S, Potvin AR et al Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke. Neurology. 2016 Aug 16;87(7):665-72. PMID: 27412144
  6. FDA News Release. October 28, 2016 FDA approves new device for prevention of recurrent strokes in certain patients. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm527096.htm
  7. Phend C PFO Closure for Cryptogenic Stroke Prevents Recurrences - First overall stroke reduction with closure reported in two trials. MedPage Today. May 16, 2017 https://www.medpagetoday.com/Cardiology/Strokes/65348 - Mi MY, Block PC, Broderick JP PFO Closure for Cryptogenic Stroke N Engl J Med 2018; 378:1639-1642 PMID: 29694824 http://www.nejm.org/doi/full/10.1056/NEJMclde1715853
  8. Hart RG, Sharma M, Mundl H et al Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. N Engl J Med 2018; 378:2191-2201 PMID: 29766772 https://www.nejm.org/doi/10.1056/NEJMoa1802686
  9. Kuijpers T, Spencer FA, Siemieniuk RAC et al Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline. BMJ 2018;362:k2515 PMID: 30045912 https://www.bmj.com/content/362/bmj.k2515
  10. Emery G Pradaxa Fails to Prevent Recurrence After Cryptogenic Stroke, Medscape - May 15, 2019. https://www.medscape.com/viewarticle/913077
  11. Triantafyllou S et al. Implantable cardiac monitoring in the secondary prevention of cryptogenic stroke. Ann Neurol 2020 Aug 22; PMID: 32827232 https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25886
  12. Perera KS et al. Evaluating rates of recurrent ischemic stroke among young adults with embolic stroke of undetermined source: The Young ESUS longitudinal cohort study. JAMA Neurol 2022 May; 79:450-458 PMID: 35285869 PMCID: PMC8922202 (available on 2023-03-14) https://jamanetwork.com/journals/jamaneurology/fullarticle/2790077
  13. Navi BB et al. Apixaban vs aspirin in patients with cancer and cryptogenic stroke: A post hoc analysis of the ARCADIA randomized clinical trial. JAMA Neurol 2024 Aug 12; PMID: 39133474 PMCID: PMC11320331 (available on 2025-08-12) https://jamanetwork.com/journals/jamaneurology/fullarticle/2822378 - Kamel H et al. Apixaban to prevent recurrence after cryptogenic stroke in patients with atrial cardiopathy: The ARCADIA randomized clinical trial. JAMA 2024 Feb 20; 331:573. PMID: 38324415 PMCID: PMC10851142 (available on 2024-08-07) https://jamanetwork.com/journals/jama/fullarticle/2814933
  14. Ghannam M et al. Anticoagulation vs antiplatelets across subgroups of embolic stroke of undetermined source: A meta-analysis of randomized controlled trials. Neurology 2024 Nov 12; 103:e209949 PMID: 39365971 https://www.neurology.org/doi/10.1212/WNL.0000000000209949