cryptogenic stroke; embolic stroke of undetermined source
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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
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[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]
More general terms
References
- ↑ Jump up to: 1.0 1.1 1.2 1.3 1.4 1.5 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26227434 <Internet> http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2815%2900132-5/fulltext
- ↑ Jump up to: 2.0 2.1 2.2 2.3 Medical Knowledge Self Assessment Program (MKSAP) 17, 19 American College of Physicians, Philadelphia 2015, 2021
- ↑ Jump up to: 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/24300230
- ↑ Jump up to: 4.0 4.1 4.2 4.3 4.4 4.5 Saver JL. CLINICAL PRACTICE. Cryptogenic Stroke. N Engl J Med. 2016 May 26;374(21):2065-74. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27223148 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcp1503946
- ↑ Jump up to: 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/27412144
- ↑ Jump up to: 6.0 6.1 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
- ↑ Jump up to: 7.0 7.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29694824 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMclde1715853 - ↑ Jump up to: 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/29766772 https://www.nejm.org/doi/10.1056/NEJMoa1802686
- ↑ Jump up to: 9.0 9.1 9.2 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: https://www.ncbi.nlm.nih.gov/pubmed/30045912 https://www.bmj.com/content/362/bmj.k2515
- ↑ Jump up to: 10.0 10.1 Emery G Pradaxa Fails to Prevent Recurrence After Cryptogenic Stroke, Medscape - May 15, 2019. https://www.medscape.com/viewarticle/913077
- ↑ Jump up to: 11.0 11.1 Triantafyllou S et al. Implantable cardiac monitoring in the secondary prevention of cryptogenic stroke. Ann Neurol 2020 Aug 22; PMID: https://www.ncbi.nlm.nih.gov/pubmed/32827232 https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25886
- ↑ Jump up to: 12.0 12.1 12.2 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: https://www.ncbi.nlm.nih.gov/pubmed/35285869 PMCID: PMC8922202 (available on 2023-03-14) https://jamanetwork.com/journals/jamaneurology/fullarticle/2790077
- ↑ Jump up to: 13.0 13.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/38324415 PMCID: PMC10851142 (available on 2024-08-07) https://jamanetwork.com/journals/jama/fullarticle/2814933 - ↑ Jump up to: 14.0 14.1 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: https://www.ncbi.nlm.nih.gov/pubmed/39365971 https://www.neurology.org/doi/10.1212/WNL.0000000000209949