nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2014-2S-42-49nnp-423Research ArticleREVIEWSОБЗОРЫCryptogenic strokeКриптогенный инсультШамаловН.А.ShamalovN.A.

117997, Москва, ул. Островитянова, д. 1

shamalovn@gmail.comКустоваМ.А.KustovaM.A.

117997, Москва, ул. Островитянова, д. 1

НИИ цереброваскулярной патологии и инсульта ГБОУ ВПО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, МоскваРоссияResearch Institute of Cerebrovascular Disease and Stroke, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia, 1, Ostrovityanov St., Moscow 117997Russian Federation20140410201462SSpecial issue "Stroke"4249Copyright © Shamalov N., Kustova M., 20142014Шамалов Н., Кустова М.Shamalov N., Kustova M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/423

This review analyzes the pathogenetic factors of cryptogenic stroke, the results of investigations into secondary prevention, and current approaches to diagnostic criteria for this condition. The rate of cryptogenic stroke (stroke with no unspecified or identifiable cause) is 20 to 40%. A great deal of etiological factors leading to the development of cryptogenic stroke determine the extraordinary heterogeneity of this patient cohort; at the same time there is no universally accepted opinion as to the identification of cryptogenic stroke, its risk factors, and medical treatment. The conception of ischemic stroke with no identifiable cause of embolism and with clearer diagnostic criteria will be able to perform special studies in this group of patients, which will contribute to more differentiated and effective therapy and secondary prevention.

В настоящем обзоре проанализированы патогенетические факторы криптогенного инсульта, результаты исследований, посвященных вторичной профилактике, а также современные подходы к диагностическим критериям данного состояния. Частота криптогенного инсульта (инсульта неуточненной, или неустановленной, этиологии) составляет от 20 до 40%. Значительное количество возможных причин инсульта, обусловливает чрезвычайную гетерогенность данной когорты пациентов, при этом отсутствует общепринятая точка зрения в отношении определения криптогенного инсульта, факторов риска его развития и медикаментозной терапии. Концепция ишемического инсульта с неустановленным источником эмболии и более четкими диагностическими критериями позволит проводить специальные исследования у больных данной группы, что будет способствовать более дифференцированной и эффективной терапии и вторичной профилактике.

криптогенный инсультинсульт с неустановленным источником эмболииcryptogenic strokestroke with no identifiable cause of embolismReferencesAdams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. Stroke. 1993;24(1):35–41. DOI:http://dx.doi.org/10.1161/01.STR.24.1.35.Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. Stroke. 1993;24(1):35–41. DOI:http://dx.doi.org/10.1161/01.STR.24.1.35.Bogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke. 1988;19(():1083–92.Bogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke. 1988;19(():1083–92.Touboul PJ, Elbaz A, Koller C, et al. Common carotid artery intima-media thickness and ischemic stroke subtypes: the GENIC casecontrol study. The GENIC Investigators. Circulation. 2000;102(3):313–8. DOI: http://dx.doi.org/10.1161/01.CIR.102.3.313.Touboul PJ, Elbaz A, Koller C, et al. Common carotid artery intima-media thickness and ischemic stroke subtypes: the GENIC casecontrol study. The GENIC Investigators. Circulation. 2000;102(3):313–8. DOI: http://dx.doi.org/10.1161/01.CIR.102.3.313.Amarenco P, Bogousslavsky J, Caplan LR, et al. Classification of stroke subtypes. Cerebrovascular Dis. 2009;27(5):493–501. DOI: 10.1159/000210432. Epub 2009 Apr 3.Amarenco P, Bogousslavsky J, Caplan LR, et al. Classification of stroke subtypes. Cerebrovascular Dis. 2009;27(5):493–501. DOI: 10.1159/000210432. Epub 2009 Apr 3.Amarenco P, Bogousslavsky J, Caplan LR, et al. New Approach to Stroke Subtyping: The A-S-C-O (Phenotypic) Classification of Stroke. Cerebrovascular Dis. 2009;27(5):502–8. DOI: 10.1159/000210433. Epub 2009 Apr 3.Amarenco P, Bogousslavsky J, Caplan LR, et al. New Approach to Stroke Subtyping: The A-S-C-O (Phenotypic) Classification of Stroke. Cerebrovascular Dis. 2009;27(5):502–8. DOI: 10.1159/000210433. Epub 2009 Apr 3.Суслина ЗА, Верещагин НВ, Пирадов МА. Подтипы ишемических нарушений мозгового кровообращения: диагностика и лечение. Consilium Medicum. 2001;3(5):218–21. [Suslina ZA, Vereshchagin NV, Piradov MA. Subtypes of ischemic violations of brain blood circulation: diagnostics and treatment. Consilium Medicum. 2001;3(5):218–21. (In Russ.)].Суслина ЗА, Верещагин НВ, Пирадов МА. Подтипы ишемических нарушений мозгового кровообращения: диагностика и лечение. Consilium Medicum. 2001;3(5):218–21. [Suslina ZA, Vereshchagin NV, Piradov MA. Subtypes of ischemic violations of brain blood circulation: diagnostics and treatment. Consilium Medicum. 2001;3(5):218–21. (In Russ.)].Guercini F, Acciarresi M, Agnelli G, Paciaroni M. Cryptogenic stroke: time to determine aetiology. J Thromb Haemost. 2008;6(4):549–54. DOI: 10.1111/j.1538-7836.2008.02903.x. Epub 2008 Jan 15.Guercini F, Acciarresi M, Agnelli G, Paciaroni M. Cryptogenic stroke: time to determine aetiology. J Thromb Haemost. 2008;6(4):549–54. DOI: 10.1111/j.1538-7836.2008.02903.x. Epub 2008 Jan 15.Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol. 1989;25(4):382–90. DOI:http://dx.doi.org/10.1002/ana.410250410.Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol. 1989;25(4):382–90. DOI:http://dx.doi.org/10.1002/ana.410250410.Palomeras SE, Fossas FP, Cano OAT, Sanz CP. Cryptogenic infarct. A follow-up period of 1Palomeras SE, Fossas FP, Cano OAT, Sanz CP. Cryptogenic infarct. A follow-up period of 1year study. Neurologia. 2009;24(5):304–8.10. Kistler JP. The risk of embolic stroke. Another piece of the puzzle. N Engl J Med. 1994;331(22):1517–9. DOI: http://dx.doi.org/10.1056/NEJM199412013312211.year study. Neurologia. 2009;24(5):304–8.10. Kistler JP. The risk of embolic stroke. Another piece of the puzzle. N Engl J Med. 1994;331(22):1517–9. DOI: http://dx.doi.org/10.1056/NEJM199412013312211.Liebeskind A, Chinichian A, Schechter MM. The moving embolus seed during serial cerebral angiography. Stroke.1971;2(5):440–3. DOI: http://dx.doi.org/10.1161/01.STR.2.5.440.Liebeskind A, Chinichian A, Schechter MM. The moving embolus seed during serial cerebral angiography. Stroke.1971;2(5):440–3. DOI: http://dx.doi.org/10.1161/01.STR.2.5.440.Santamarina E, Penalba A, Garcia-Berrocoso T, et al. Biomarker level improves the diagnosis of embolic source in ischemic stroke of unknown origin. J Neurol. 2012;259(12):2538–45. DOI: 10.1007/s00415-012-6532-4. Epub 2012 May 17.Santamarina E, Penalba A, Garcia-Berrocoso T, et al. Biomarker level improves the diagnosis of embolic source in ischemic stroke of unknown origin. J Neurol. 2012;259(12):2538–45. DOI: 10.1007/s00415-012-6532-4. Epub 2012 May 17.Sharifkazemi MB, Aslani A, Zamirian M, Moaref AR. Signifi cance of aortic atheroma in elderly patients with ischemic stroke. A hospital-based study and literature review. Clin Neurol Neurosurg. 2007;109(4):311–6. DOI:http://dx.doi.org/10.1016/j.clineuro.2006.12.003.Sharifkazemi MB, Aslani A, Zamirian M, Moaref AR. Signifi cance of aortic atheroma in elderly patients with ischemic stroke. A hospital-based study and literature review. Clin Neurol Neurosurg. 2007;109(4):311–6. DOI:http://dx.doi.org/10.1016/j.clineuro.2006.12.003.Grotta JC. Clinical practice. Carotid stenosis. N Engl J Med. 2013;(369):1143–50.Grotta JC. Clinical practice. Carotid stenosis. N Engl J Med. 2013;(369):1143–50.Hart RG. Cardiogenic embolism to the brain. Lancet. 1992;339(8797):589–94. DOI: http://dx.doi.org/10.1016/0140-6736(92)90873-2.Hart RG. Cardiogenic embolism to the brain. Lancet. 1992;339(8797):589–94. DOI: http://dx.doi.org/10.1016/0140-6736(92)90873-2.Hart RG, Diener HC, Coutts SB. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13(4):429–38. DOI: 10.1016/S1474-4422(13)70310-7.Hart RG, Diener HC, Coutts SB. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13(4):429–38. DOI: 10.1016/S1474-4422(13)70310-7.Finsterer J. Management of cryptogenic stroke. Acta Neurol Belg. 2010;110(2):135–47.Finsterer J. Management of cryptogenic stroke. Acta Neurol Belg. 2010;110(2):135–47.Mas J-L, Arquizan C, Lamy C, et al.; Patent Foramen Ovale and Atrial Septal Aneurysm Study Group. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med. 2001;(345):1740–6. DOI:http://dx.doi.org/10.1056/NEJMoa011503.Mas J-L, Arquizan C, Lamy C, et al.; Patent Foramen Ovale and Atrial Septal Aneurysm Study Group. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med. 2001;(345):1740–6. DOI:http://dx.doi.org/10.1056/NEJMoa011503.Homma S, DiTullio MR, Sacco RL, et al.; PICSS Investigators. Age as a determinant of adverse events in medically treated cryptogenic stroke patients with patent foramen ovale.Stroke. 2004;35(9):2145–9. DOI: http://dx.doi.org/10.1161/01.STR.0000135773.24116.18. Epub 2004 Jul 1.Homma S, DiTullio MR, Sacco RL, et al.; PICSS Investigators. Age as a determinant of adverse events in medically treated cryptogenic stroke patients with patent foramen ovale.Stroke. 2004;35(9):2145–9. DOI: http://dx.doi.org/10.1161/01.STR.0000135773.24116.18. Epub 2004 Jul 1.Arauz A, Murillo L, Marquez JM, et al. Long-term risk of recurrent stroke in young cryptogenic stroke patients with and without patent foramen ovale. Int J Stroke. 2012;7(8):631–4. DOI: 10.1111/j.1747-4949.2011.00641.x. Epub 2011 Oct 6.Arauz A, Murillo L, Marquez JM, et al. Long-term risk of recurrent stroke in young cryptogenic stroke patients with and without patent foramen ovale. Int J Stroke. 2012;7(8):631–4. DOI: 10.1111/j.1747-4949.2011.00641.x. Epub 2011 Oct 6.Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke (8th editionn). Chest. 2008;133(6 Suppl):630S–669S. DOI:10.1378/chest.08-0720.Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke (8th editionn). Chest. 2008;133(6 Suppl):630S–669S. DOI:10.1378/chest.08-0720.Adams RJ, Albers G, Alberts MJ, et al.; American Heart Association; American Stroke Association. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2008;39(5):1647–52.DOI: 10.1161/STROKEAHA.107.189063. Epub 2008 Mar 5.Adams RJ, Albers G, Alberts MJ, et al.; American Heart Association; American Stroke Association. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2008;39(5):1647–52.DOI: 10.1161/STROKEAHA.107.189063. Epub 2008 Mar 5.European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25(5):457–507. DOI: 10.1159/000131083. Epub 2008 May 6.European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25(5):457–507. DOI: 10.1159/000131083. Epub 2008 May 6.Furie KL, Kasner SE, Adams RJ, et al.; American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/americanFurie KL, Kasner SE, Adams RJ, et al.; American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/americanstroke ssociation. Stroke. 2011;42(1):227–76. DOI: 10.1161/STR.0b013e3181f7d043. Epub 2010 Oct 21.stroke ssociation. Stroke. 2011;42(1):227–76. DOI: 10.1161/STR.0b013e3181f7d043. Epub 2010 Oct 21.Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141 (2 Suppl):e601S–36S.Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141 (2 Suppl):e601S–36S.DOI: 10.1378/chest.11-2302.DOI: 10.1378/chest.11-2302.Lindsay P, Bayley M, Hellings C, et al.; Canadian Stroke Strategy Best Practices; Standards Writing Group on behalf of the Canadian Stroke Strategy. Canadian Best Practice Recommendations for stroke care (update 2008). Can Med Assoc J. 2008;179 (suppl):1–25. DOI: http://dx.doi.org/10.Lindsay P, Bayley M, Hellings C, et al.; Canadian Stroke Strategy Best Practices; Standards Writing Group on behalf of the Canadian Stroke Strategy. Canadian Best Practice Recommendations for stroke care (update 2008). Can Med Assoc J. 2008;179 (suppl):1–25. DOI: http://dx.doi.org/10./cmaj.081148.R2./cmaj.081148.R2.Jauch EC, Saver JL, Adams HP Jr, et al.; American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology.Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:870–947. DOI: http://dx.doi.org/10.1161/STR.0b013e318284056a.Jauch EC, Saver JL, Adams HP Jr, et al.; American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council on Clinical Cardiology.Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44:870–947. DOI: http://dx.doi.org/10.1161/STR.0b013e318284056a.Kernan WN, Ovbiagele B, Black HR, et al.; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Peripheral Vascular Disease. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. A Guideline for Healthcare Professionals From the American Heart Association/American StrokeKernan WN, Ovbiagele B, Black HR, et al.; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, Council on Peripheral Vascular Disease. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. A Guideline for Healthcare Professionals From the American Heart Association/American StrokeAssociation. Stroke. 2014;45(7):2160–236. DOI: 10.1161/STR.0000000000000024. Epub 2014 May 1.Association. Stroke. 2014;45(7):2160–236. DOI: 10.1161/STR.0000000000000024. Epub 2014 May 1.Mohr JP, Thompson JLP, Lazar RM, et al.; Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345(20):1444–51. DOI:http://dx.doi.org/10.1056/NEJMoa011258.Mohr JP, Thompson JLP, Lazar RM, et al.; Warfarin-Aspirin Recurrent Stroke Study Group. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345(20):1444–51. DOI:http://dx.doi.org/10.1056/NEJMoa011258.Sacco RL, Prabhakaran S, Thompson JLP, et al.; WARSS Investigators. Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study. Cerebrovasc Dis. 2006;22(1):4–12. DOI: http://dx.doi.org/10.1159/000092331. Epub 2006 Mar 27.Sacco RL, Prabhakaran S, Thompson JLP, et al.; WARSS Investigators. Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study. Cerebrovasc Dis. 2006;22(1):4–12. DOI: http://dx.doi.org/10.1159/000092331. Epub 2006 Mar 27.Homma S, Sacco RL, Di Tullio MR, et al.; PFO in Cryptogenic Stroke Study (PICSS) Investigators. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation. 2002;105(22):2625–31. DOI: http://dx.doi.org/10.1161/01.CIR.0000017498.88393.44.Homma S, Sacco RL, Di Tullio MR, et al.; PFO in Cryptogenic Stroke Study (PICSS) Investigators. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation. 2002;105(22):2625–31. DOI: http://dx.doi.org/10.1161/01.CIR.0000017498.88393.44.Longstreth WT Jr, Kronmal RA, Thompson JLP, et al. Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy. Stroke. 2013;44(3):714–9. DOI: 10.1161/STROKEAHA.112.675942. Epub 2013 Jan 22.Longstreth WT Jr, Kronmal RA, Thompson JLP, et al. Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy. Stroke. 2013;44(3):714–9. DOI: 10.1161/STROKEAHA.112.675942. Epub 2013 Jan 22.Connolly S, Pogue J, Hart R, et al.; ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fi brillation in the Atrial fi brillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903–12. DOI: http://dx.doi.org/10.1016/S0140-6736(06)68845-4.Connolly S, Pogue J, Hart R, et al.; ACTIVE Writing Group of the ACTIVE Investigators. Clopidogrel plus aspirin versus oral anticoagulation for atrial fi brillation in the Atrial fi brillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903–12. DOI: http://dx.doi.org/10.1016/S0140-6736(06)68845-4.Connolly SJ, Eikelboom J, Joyner C, et al.; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806–17. DOI: 10.1056/NEJMoa1007432. Epub 2011 Feb 10.Connolly SJ, Eikelboom J, Joyner C, et al.; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806–17. DOI: 10.1056/NEJMoa1007432. Epub 2011 Feb 10.Homma S, Thompson JLP, Pullicino PM, et al.; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366(20):1859–69. DOI: 10.1056/NEJMoa1202299. Epub 2012 May 2.Homma S, Thompson JLP, Pullicino PM, et al.; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366(20):1859–69. DOI: 10.1056/NEJMoa1202299. Epub 2012 May 2.Chatterjee S, Sardar P, Biondi-Zoccai G, Kumbhani DJ. New oral anticoagulants and the risk of intracranial hemorrhage. Traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol. 2013;70(12):1486–90. DOI: 10.1001/jamaneurol.2013.4021.Chatterjee S, Sardar P, Biondi-Zoccai G, Kumbhani DJ. New oral anticoagulants and the risk of intracranial hemorrhage. Traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation. JAMA Neurol. 2013;70(12):1486–90. DOI: 10.1001/jamaneurol.2013.4021.Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8th edn). Chest. 2008;133(suppl 6):454S–545S. DOI: 10.1378/chest.08-0658.Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-based Clinical Practice Guidelines (8th edn). Chest. 2008;133(suppl 6):454S–545S. DOI: 10.1378/chest.08-0658.Brighton TA, Eikelboom JW, Mann K, et al.; ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367(21):1979–87. DOI: 10.1056/NEJMoa1210384. Epub 2012 Nov 4.Brighton TA, Eikelboom JW, Mann K, et al.; ASPIRE Investigators. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med. 2012;367(21):1979–87. DOI: 10.1056/NEJMoa1210384. Epub 2012 Nov 4.Halkes PH, van Gijn J, Kappelle LJ, et al.; ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007;6(2):115–24. DOI:http://dx.doi.org/10.1016/S1474-4422(06)70685-8.Halkes PH, van Gijn J, Kappelle LJ, et al.; ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007;6(2):115–24. DOI:http://dx.doi.org/10.1016/S1474-4422(06)70685-8.Ferrari E, Vidal R, Chevallier T,Baudouy M. Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor prognosis: benefit of oral anticoagulants. J Am Coll Cardiol. 1999;33(5):1317–22. DOI: http://dx.doi.org/10.1016/S0735-1097(99)00003-0.Ferrari E, Vidal R, Chevallier T,Baudouy M. Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor prognosis: benefit of oral anticoagulants. J Am Coll Cardiol. 1999;33(5):1317–22. DOI: http://dx.doi.org/10.1016/S0735-1097(99)00003-0.Dressler FA, Craig WR, Castello R, Labovitz AJ. Mobile aortic atheroma and systemic emboli: efficacy of anticoagulation and influence of plaque morphology on recurrent stroke. J Am Coll Cardiol. 1998;31(1):134–8. DOI: http://dx.doi.org/10.1016/S0735-1097(97)00449-X.Dressler FA, Craig WR, Castello R, Labovitz AJ. Mobile aortic atheroma and systemic emboli: efficacy of anticoagulation and influence of plaque morphology on recurrent stroke. J Am Coll Cardiol. 1998;31(1):134–8. DOI: http://dx.doi.org/10.1016/S0735-1097(97)00449-X.Di Tullio MR, Russo C, Jin Z, et al.; Patent Foramen Ovale in Cryptogenic Stroke Study Investigators. Aortic arch plaques and risk of recurrent stroke and death. Circulation. 2009;119(7):2376–82. DOI: 10.1161/CIRCULATIONAHA.108.811935. Epub 2009 Apr 20.Di Tullio MR, Russo C, Jin Z, et al.; Patent Foramen Ovale in Cryptogenic Stroke Study Investigators. Aortic arch plaques and risk of recurrent stroke and death. Circulation. 2009;119(7):2376–82. DOI: 10.1161/CIRCULATIONAHA.108.811935. Epub 2009 Apr 20.Halkes PH, van Gijn J, Kappelle LJ, et al.; ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007;6(2):115–24. DOI:http://dx.doi.org/10.1016/S1474-4422(06)70685-8.Halkes PH, van Gijn J, Kappelle LJ, et al.; ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol. 2007;6(2):115–24. DOI:http://dx.doi.org/10.1016/S1474-4422(06)70685-8.The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. Ann Neurol 1997; 42: 857–65. DOI: http://dx.doi.org/10.1002/ana.410420606.The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. Ann Neurol 1997; 42: 857–65. DOI: http://dx.doi.org/10.1002/ana.410420606.Granger CB, Alexander JH, McMurray JJV, et al, and the ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. DOI:Granger CB, Alexander JH, McMurray JJV, et al, and the ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. DOI:1056/NEJMoa1107039. Epub 2011 Aug 27.1056/NEJMoa1107039. Epub 2011 Aug 27.Connolly SJ, Ezekowitz MD, Yusuf S, et al.; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–5. DOI:10.1056/NEJMoa0905561. Epub 2009 Aug 30.Connolly SJ, Ezekowitz MD, Yusuf S, et al.; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–5. DOI:10.1056/NEJMoa0905561. Epub 2009 Aug 30.Diener H-C. Rationale, objectives and design of a secondary stroke prevention study of dabigatran etexilate versus acetylsalicylic acid in patients with embolic stroke of undetermined source (RE-SPECT-ESUS). Abstracts of the European Stroke Conference. Cerebrovasc Dis. 2014;37(suppl 1):1–2.Diener H-C. Rationale, objectives and design of a secondary stroke prevention study of dabigatran etexilate versus acetylsalicylic acid in patients with embolic stroke of undetermined source (RE-SPECT-ESUS). Abstracts of the European Stroke Conference. Cerebrovasc Dis. 2014;37(suppl 1):1–2.Meissner I, Khandheria BK, Heit JA, et al. Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study. J Am Coll Cardiol. 2006;47(2):440–5. DOI: http://dx.doi.org/10.1016/j.jacc.2005.10.044. Epub 2005 Dec 6.Meissner I, Khandheria BK, Heit JA, et al. Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study. J Am Coll Cardiol. 2006;47(2):440–5. DOI: http://dx.doi.org/10.1016/j.jacc.2005.10.044. Epub 2005 Dec 6.Srivastava TN, Payment MF. Images in clinical medicine. Paradoxical embolism-thrombus in transit through a patent foramen ovale. N Engl J Med. 1997;337(10):681. DOI: http://dx.doi.org/10.1056/NEJMSrivastava TN, Payment MF. Images in clinical medicine. Paradoxical embolism-thrombus in transit through a patent foramen ovale. N Engl J Med. 1997;337(10):681. DOI: http://dx.doi.org/10.1056/NEJMOverell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology. 2000;55(8):1172–9. DOI: http://dx.doi.org/10.1212/WNL.55.8.1172.Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology. 2000;55(8):1172–9. DOI: http://dx.doi.org/10.1212/WNL.55.8.1172.Olsen TS, Skriver EB, Herning M. Cause of cerebral infarction in the carotid territory. Its relation to the size and the location of the infarct and to the underlying vascular lesion. Stroke. 1985;16(3):459–66. DOI: http://dx.doi.org/10.1161/01.STR.16.3.459.Olsen TS, Skriver EB, Herning M. Cause of cerebral infarction in the carotid territory. Its relation to the size and the location of the infarct and to the underlying vascular lesion. Stroke. 1985;16(3):459–66. DOI: http://dx.doi.org/10.1161/01.STR.16.3.459.Freilinger TM, Schindler A, Schmidt C, et al. Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke. JACC Cardiovasc Imaging. 2012;5(4):397–405. DOI: 10.1016/j.jcmg.2012.01.012.Freilinger TM, Schindler A, Schmidt C, et al. Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke. JACC Cardiovasc Imaging. 2012;5(4):397–405. DOI: 10.1016/j.jcmg.2012.01.012.Schwarz F, Bayer-Karpinska A, Poppert H, et al. Serial carotid MRI identifies rupture of a vulnerable plaque resulting in amaurosis fugax. Neurology. 2013;80(12):1171–2. DOI: 10.1212/WNL.0b013e31828869ad.Schwarz F, Bayer-Karpinska A, Poppert H, et al. Serial carotid MRI identifies rupture of a vulnerable plaque resulting in amaurosis fugax. Neurology. 2013;80(12):1171–2. DOI: 10.1212/WNL.0b013e31828869ad.

The authors declare that there are no conflicts of interest present.