378
Views
0
CrossRef citations to date
0
Altmetric
Review

Current perspectives on the clinical management of cryptogenic stroke

&
Pages 213-226 | Received 29 Jan 2023, Accepted 14 Mar 2023, Published online: 19 Mar 2023

References

  • Saver J, Solomon CG. Clinical practice. Cryptogenic stroke. N Engl J Med. 2016;374(21):2065–2074.
  • Kunitz SC, Gross CR, Heyman A, et al. The pilot stroke data bank: definition, design, and data. Stroke. 1984;15(4):740–746.
  • Adams JHP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke. 1993;24(1):35–41.
  • Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and white. Stroke. 2004;35(7):1552.
  • Lee BI, Nam HS, Heo JH, et al. Yonsei stroke registry: analysis of 1000 patients with acute cerebral infarctions. Cerebrovasc Dis. 2001;12(3):145.
  • Ornello R, Degan D, Tiseo C, et al. Distribution and temporal trends from 1993 to 2015 of ischemic stroke subtype: a systemic review and meta-analysis. Stroke. 2018;49(4):814.
  • Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: the NINCDS stroke data bank. Ann Neurol. 1989;25(4):382–390.
  • Boeckh-Behrens T, Kleine JF, Zimmer C, et al. Thrombus histology suggests cardioembolic cause in cryptogenic stroke. Stroke. 2016;47(7):1864.
  • Ay H, Furie KL, Singhal A, et al. An evidence-based causative classification system for acute ischemic stroke. Ann Neurol. 2005;58(5):688.
  • Ay H, Benner T, Arsava EM, et al. A computerized algorithm for etiologic classification of ischemic stroke: the causative classification of stroke system. Stroke. 2007;38(11):2979.
  • Amarenco P, Bogousslavsky J, Caplan LR, et al. A new approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke. Cerebrovasc Dis. 2009;27(5):502–508.
  • Gordon DL, Bendixen BH, Adams JHP, et al. Interphysician agreement in the diagnosis of subtypes of acute ischemic stroke: implications for clinical trials. The TOAST investigators. Neurology 1993;43(5):1021–1027.
  • Amarenco P, Bogousslavsky J, Caplan LR, et al. The ASCOD phenotyping of ischemic stroke (updated ASCO phenotyping). Cerebrovasc Dis. 2013;36(1):1–5.
  • Marnane M, Duggan CA, Sheehan OC, et al. Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-S-C-O, and causative classification system: direct comparison in the North Dublin population stroke study. Stroke. 2010;41(8):1579–1586.
  • Hart RG, Diener HC, Coutts SB, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13(4):429–438.
  • Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191–2201.
  • Diener HC, Sacco RL, Easton JD, et al. Dabigatran for prevention of stroke after embolic stroke of undetermined source. N Engl J Med. 2019;380(20):1906–1917.
  • Kamel H, Longstreth WT Jr, Tirschwell DL, et al. The atrial cardiopathy and antithrombotic drugs in prevention after cryptogenic stroke randomized trial: rationale and methods. Int J Stroke. 2019;14(2):207–214.
  • Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 guideline for the prevention of stroke in patients with stroke and transient attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364–e467.
  • Chalela JA, Kidwell CS, Nentwich LM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet. 2007;369(9558):293–298.
  • Koelemay MJ, Nederkoorn PJ, Reitsma JB, et al. Systematic review of computed tomographic angiography for assessment of carotid artery disease. Stroke. 2004;35(10):2306–2312.
  • Debrey SM, Yu H, Lynch JK, et al. Diagnostic accuracy of magnetic resonance angiography for internal carotid artery disease: a systematic review and meta-analysis. Stroke. 2008;39(8):2237–2248.
  • Wardlaw JM, Chappell FM, Best JJK, et al. Non-invasive imaging compared with intra-arterial angiography in the diagnosis of symptomatic carotid stenosis: a meta-analysis. Lancet. 2006;367(9521):1503–1512.
  • McGrath ER, Paikin JS, Motlagh B, et al. Transesophageal echocardiography in patients with cryptogenic ischemic stroke: a systematic review. Am Heart J. 2014;168(5):706–712.
  • Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001;345(20):1444–1451.
  • Sacco RL, Prabhakaran S, Thompson JL, 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.
  • Healey JS, Gladstone DJ, Swaminathan B, et al. Recurrent stroke with rivaroxaban compared with aspirin according to predictors of atrial fibrillation: secondary analysis of the NAVIGATE ESUS randomized clinical trial. JAMA Neurol. 2019;76(7):764–773.
  • Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11–19.
  • Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med. 2018;379(3):215–225.
  • Sposato LA, Cipriano LE, Saposnik G, et al. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol. 2015;14(4):377–387.
  • Boriani G, Vitolo M, Imberti JF, et al. What do we do about atrial high rate episodes? Eur Heart J Suppl. 2020;22(SupplO):O42–O52.
  • Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120.
  • Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370:2467–2477.
  • Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370:2478–2486.
  • Favilla CG, Ingala E, Jara J, et al. Predictors of finding occult atrial fibrillation after cryptogenic stroke. Stroke. 2015;46(5):1210–1215.
  • Suzuki S, Sagara K, Otsuka T, et al. Usefulness of frequent supraventricular extrasystoles and a high CHADS2 score to predict first-time appearance of atrial fibrillation. Am J Cardiol. 2013;111(11):1602–1607.
  • Diederichsen SZ, Haugan KJ, Brandes A, et al. Incidence and predictors of atrial fibrillation episodes as detected by implantable loop recorder in patients at risk: from the LOOP study. Am Heart J. 2020;219:117–127.
  • Svendsen JH, Diederichsen SZ, Hojberg S, et al. Implantable loop recorder detection of atrial fibrillation to prevent stroke (the LOOP Study): a randomized control trial. Lancet. 2021;398(10310):1507–1516.
  • Lu Z, Scherlag BJ, Lin J, et al. Atrial fibrillation begets atrial fibrillation: autonomic mechanism for atrial electrical remodeling induced by short-term rapid atrial pacing. Circ Arrhythm Electrophysiol. 2008;1(13):184–192.
  • Culebras A, Messé SR. Summary of evidence-based guideline update: prevention of stroke in nonvalvular atrial fibrillation: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014;83(13):1220.
  • Lopes RD, Alings M, Connolly SJ, et al. Rationale and design of the apixaban for the reduction of thrombo-embolism in patients with device-detected sub-clinical Atrial Fibrillation (ARTESiA) trial. Am Heart J. 2017;189:137–145.
  • Kirchhof P, Blank BF, Calvert M, et al. Probing oral anticoagulation in patients with atrial high rate episodes: rationale and design of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6) trial. Am Heart J. 2017;190:12–18.
  • Elkind MSV. Atrial cardiopathy and stroke prevention. Curr Cardiol Rep. 2018;20(11):103.
  • Al-Khatib SM, Allen Lapointe NM, Chatterjee R, et al. Rate- and rhythm-control therapies in patients with atrial fibrillation: a systematic review. Ann Intern Med. 2014;160(11):760–773.
  • Benjamin EJ, D’Agostino RB, Belanger AJ, et al. Left atrial size and the risk of stroke and death. The Framingham Heart Study. Circulation 1995;92(4):835–841.
  • Yaghi S, Moon YP, Mora-McLaughlin C, et al. Left atrial enlargement and stroke recurrence: the Northern manhattan stroke study. Stroke. 2015;46(6):1488–1493.
  • Kamel H, Hunter M, Moon YP, et al. Electrocardiographic left atrial abnormality and risk of stroke: Northern Manhattan Study. Stroke. 2015;46(11):3208–3212.
  • Binici Z, Intzilakis T, Nielsen OW, et al. Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke. Circulation. 2010;121(17):1904–1911.
  • Kamel H, Elkind MS, Bhave PD, et al. Paroxysmal supraventricular tachycardia and the risk of ischemic stroke. Stroke. 2013;44(6):1550–1554.
  • Folsom AR, Nambi V, Bell EJ, et al. Troponin T, N-terminal pro-B-type natriuretic peptide, and incidence of stroke: the atherosclerosis risk in communities study. Stroke. 2013;44(4):961–967.
  • Kamel H, Okin PM, Elkind MSV, et al. Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke. 2016;47(3):895–900.
  • Di Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol. 2012;60(6):531–538.
  • Yaghi S, Boehme AK, Hazan R, et al. Atrial cardiopathy and cryptogenic stroke: a cross-sectional pilot study. J Stroke Cerebrovasc Dis. 2016;25(1):110–114.
  • Kamel H, Bartz TM, Elkind MSV, et al. Atrial cardiopathy and the risk of ischemic stroke in the CHS (Cardiovascular Health Study). Stroke. 2018;49(4):980–986.
  • Prior IA, Trial CS. ESOC 2022 – Late breaking science, ongoing trials & young stroke physicians and researchers. Eur Stroke J. 2022;7(1 Suppl):546–588.
  • Mas JL. Patent foramen ovale, atrial septal aneurysm and ischaemic stroke in young adults. Eur Heart J. 1994 Apr;15(4):446–449.
  • Meer I, Whisnant JP, Khandheria BK, et al. Prevalence of potential risk factors for stroke assessed by transesophageal echocardiography and carotid ultrasonography: the SPARC study. Stroke prevention: assessment of risk in a community. Mayo Clin Proc. 1999;74(9):862–869.
  • Pearson AC, Nagelhout D, Castello R, et al. Atrial septal aneurysm and stroke: a transesophageal echocardiographic study. J Am Coll Cardiol. 1991;18(5):1223–1229.
  • Cabanes L, Mas JL, Cohen A, et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography. Stroke. 1993;24(12):1865–1873.
  • Kent DM, Ruthazer R, Weimar C, et al. An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke. Neurology. 2013;81(7):619–625.
  • Elgendy AY, Saver JL, Amin Z, et al. Proposal for updated nomenclature and classification of potential causative mechanism in patent foramen ovale-associated stroke. JAMA Neurol. 2020;77(7):878–886.
  • Abushora MY, Bhatia N, Alnabki Z, et al. Intrapulmonary shunt is a potentially unrecognized cause of ischemic stroke and transient ischemic attack. J Am Soc Echocardiogr. 2013;26(7):683–690.
  • Caputi L, Carriero MR, Falcone C, et al. Transcranial Doppler and transesophageal echocardiography: comparison of both techniques and prospective clinical relevance of transcranial Doppler in patent foramen ovale detection. J Stroke Cerebrovasc Dis. 2009;18(5):343–348.
  • Schneider B, Zienkiewicz T, Jansen V, et al. Diagnosis of patent foramen ovale by transesophageal echocardiography and correlation with autopsy findings. Am J Cardiol. 1996;77(14):1202–1209.
  • Homma S, Sacco RL, Di Tullio MR, et al. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in cryptogenic stroke study. Circulation. 2002;105(22):2625–2631.
  • Furlan AJ, Reisman M, Massaro J, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012;366(11):991–999.
  • Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368(12):1083–1091.
  • Carroll JD, Saver JL, Thaler DE, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013;368(12):1092–1100.
  • Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022–1032.
  • Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033–1042.
  • Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011–1021.
  • Kent DM, Saver JL, Kasner SE, et al. Heterogeneity of treatment effects in an analysis of pooled individual patient data from randomized trials of device closure of patent foramen ovale after stroke. JAMA. 2021;326(22):2277–2286.
  • Messe SR, Gronseth GS, Kent DM, et al. Practice advisory update summary: patent foramen ovale and secondary stroke prevention: report of the guideline subcommittee of the American Academy of Neurology. Neurology. 2020;94(20):876–885.
  • Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2022 update: a report from the american heart association. Circulation. 2022;146(10):e141.
  • Hays AG, Sacco RL, Rundek T, et al. Left ventricular systolic dysfunction and the risk of ischemic stroke in a multiethnic population. Stroke. 2006;37:1715–1719.
  • Lip GY, Ponikowski P, Andreotti F, et al. Thrombo-embolism and antithrombotic therapy for heart failure in sinus rhythm. A joint consensus document from the ESC Heart Failure Association and the ESC working group on thrombosis. Eur J Heart Fail. 2012;14(7):681–695.
  • Kannel WB, Wolf PA, Verter J. Manifestations of coronary disease predisposing to stroke. The framingham study. JAMA. 1983;250(21):2942–2946.
  • Abdul-Rahim AH, Perez AC, Fulton R, et al. Risk of stroke in chronic heart failure patients without atrial fibrillation: analysis of the controlled rosuvastatin in multinational trial heart failure (corona) and the Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials. Circulation. discussion 1494. 2015;131(17):1486–1494.
  • Sandhu RK, Hohnloser SH, Pfeffer MA, et al. Relationship between degree of left ventricular dysfunction, symptom status, and risk of embolic events in patients with atrial fibrillation and heart failure. Stroke. 2015;46(3):667–672.
  • Lip GY, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow’s triad revisited. J Am Coll Cardiol. 1999;33(5):1424–1426.
  • Lam CS, Brutsaert DL. Endothelial dysfunction: a pathophysiologic factor in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2012;60(18):1787–1789.
  • Massie BM, Collins JF, Ammon SE, et al. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation. 2009;119(12):1616.
  • Homma S, Thompson JL, Pullicino PM, et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366(20):1859.
  • Zannad F, Anker SD, Byra WM, et al. Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. N Engl J Med. 2018;379(14):1332.
  • Mehra MR, Vaduganathan M, Fu M, et al. A comprehensive analysis of the effects of rivaroxaban on stroke or transient ischaemic attack in patients with heart failure, coronary artery disease, and sinus rhythm: the COMMANDER HF trial. Eur Heart J. 2019;40(44):3593–3602.
  • Ospel JM, Singh N, Marko M, et al. Prevalence of nonstenotic carotid plaques on computed tomography angiography in embolic stroke of undetermined source. Stroke. 2020;51(6):1743.
  • Kamel H, Navi BB, Merkler AE, et al. Reclassification of ischemic stroke etiological subtypes on the basis of high-risk nonstenosing carotid plaque. Stroke. 2020;51(2):504–510.
  • Kamel H, Gialdini G, Baradaran H, et al. Cryptogenic stroke and nonstenosing intracranial calcified atherosclerosis. J Stroke Cerebrovasc Dis. 2017;26(4):863–870.
  • Goyal M, Singh N, Marko M, et al. Embolic stroke of undetermined source and symptomatic nonstenotic carotid disease. Stroke. 2020;51(4):1321.
  • Zhao X, Hippe DS, Rui L, et al. Prevalence and characteristics of carotid artery high-risk atherosclerotic plaques in Chinese patients with cerebrovascular symptoms: a Chinese atherosclerosis evaluation II study. J Am Heart Assoc. 2017;6(8):e005831.
  • Gutierrez J, Khasiyev F, Liu M, et al. Determinants and outcomes of asymptomatic intracranial atherosclerotic stenosis. J Am Coll Cardiol. 2021;78(6):562–571.
  • Suri MF, Qiao Y, Ma X, et al. Prevalence of intracranial atherosclerotic stenosis using high-resolution magnetic resonance angiography in the general population: the atherosclerosis risk in communities study. Stroke. 2016;47(5):1187–1193.
  • Von Sarnowski B, Schminke U, Tatisumak T, et al. Prevalence of stenoses and occlusions of brain-supplying arteries in young stroke patients. Neurology. 2013;80(14):1287–1294.
  • Uchiyama S, Toyoda K, Kitagawa K, et al. Branch atheromatous disease diagnosed as embolic stroke of undetermined source: a sub-analysis of NAVIGATE ESUS. Int J Stroke. 2019;14(9):915–922.
  • Song JW, Pavlou A, Xiao J, et al. Vessel wall magnetic resonance imaging biomarkers of symptomatic intracranial atherosclerosis: a meta-analysis. Stroke. 2021;52(1):193–202.
  • Rerkasem A, Orrapin S, Howard DP, et al. Carotid endarterectomy for symptomatic carotid stenosis. Cochrane Database Syst Rev. 2020;9(9):CD001081.
  • Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352(13):1305–1316.
  • Agmon Y, Khandheria BK, Meer I, et al. Relation of coronary artery disease and cerebrovascular disease with atherosclerosis of the thoracic aorta in the general population. Am J Cardiol. 2002;89(3):262–267.
  • Davies MJ, Richardson PD, Woolf N, et al. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993;69(5):377.
  • Macleod MR, Amarenco P, Davis SM, et al. Atheroma of the aortic arch: an important and poorly recognised factor in the aetiology of stroke. Lancet Neurol. 2004;3(7):408–414.
  • Petty GW, Khandheria BK, Meer I, et al. Population-based study of the relationship between atherosclerotic aortic debris and cerebrovascular ischemic events. Mayo Clin Proc. 2006;81(5):609–614.
  • Amarenco P, Cohen A, Tzourio C, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med. 1994;331(22):1474–1479.
  • Tunick PA, Perez JL, Kronzon I. Protruding atheromas in the thoracic aorta and systemic embolization. Ann Intern Med. 1991;115:423–427.
  • Di Tullio MR, Sacco RL, Savoia MT, et al. Aortic atheroma morphology and the risk of ischemic stroke in a multiethnic population. Am Heart J. 2000;139(2 Pt 1):329–336.
  • Chan KL. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The stroke prevention in atrial fibrillation investigators committee on echocardiography. Ann Intern Med. 1998;128(8):639–647.
  • Amarenco P, Davis S, Jones EF, et al. Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke. 2014;45(5):1248–1257.
  • Stern A, Tunick PA, Culliford AT, et al. Protruding aortic arch atheromas: risk of stroke during heart surgery with and without aortic arch endarterectomy. Am Heart J. 1999t;138(4 Pt 1):746–752.
  • Navi BB, Reiner AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol. 2017;70(8):926–938.
  • Navi BB, Howard G, Howard VJ, et al. New diagnosis of cancer and the risk of subsequent cerebrovascular events. Neurology. 2018;90(23):e2025–e2033.
  • Navi BB, Kasner SE, Elkind MSV, et al. Cancer and embolic stroke of undetermined source. Stroke. 2021;52(3):1121–1130.
  • Navi BB, Reiner AS, Kamel H, et al. Arterial thromboembolic events preceding the diagnosis of cancer in older persons. Blood. 2019;133(8):781–789.
  • Cocho D, Gendre J, Boltes A, et al. Predictors of occult cancer in acute ischemic stroke patients. J Stroke Cerebrovasc Dis. 2015;24(6):1324–1328.
  • Nouh AM, Staff I, Finelli PF. Three Territory Sign: an MRI marker of malignancy-related ischemic stroke (Trousseau syndrome). Neurol Clin Pract. 2019;9(2):124–128.
  • Navi BB, Sherman CP, Genova R, et al. Mechanisms of ischemic stroke in patients with cancer: a prospective study. Ann Neurol. 2021;90(1):159–169.
  • Carrier M, Lazo-Langner A, Shivakumar S, et al. Screening for occult cancer in unprovoked venous thromboembolism. N Engl J Med. 2015;373(8):697–704.
  • Merkler AE, Navi BB, Singer S, et al. Diagnostic yield of echocardiography in cancer patients with ischemic stroke. J Neurooncol. 2015;123(1):115–121.
  • Chen ST, Hellkamp AS, Becker RC, et al. Efficacy and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and a history of cancer: observations from ROCKET AF. Eur Heart J Qual Care Clin Outcomes. 2019;5(2):145–152.
  • Melloni C, Dunning A, Granger CB, et al. Efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation and a history of cancer: insights from the ARISTOTLE Trial. Am J Med. 2017;130(12):1440–1448.e1.
  • Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496–520.
  • Agnelli G, Becattini C, Meyer G, et al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020;382(17):1599–1607.
  • Navi BB, Marshall RS, Bobrow D, et al. Enoxaparin vs aspirin in patients with cancer and ischemic stroke: the TEACH pilot randomized clinical trial. JAMA Neurol. 2018;75(3):379–381.
  • Arsava EM, Helenius J, Avery R, et al. Assessment of the predictive validity of etiologic stroke classification. JAMA Neurol. 2017;74(4):419–426.
  • Kolominsky-Rabas PL, Weber M, Gefeller O, et al. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. 2001;32(12):2735–2740.
  • Bang OY, Lee PH, Joo SY, et al. Frequency and mechanisms of stroke recurrence after cryptogenic stroke. Ann Neurol. 2003;54(2):227–234.
  • Boyd LA, Hayward KS, Ward NS, et al. Biomarkers of stroke recovery: consensus-based core recommendations from the stroke recovery and rehabilitation roundtable. Int J Stroke. 2017;12(5):480–493.
  • Frazin L, Talano JV, Stephanides L, et al. Esophageal echocardiography. Circulation. 1976;54(1):102–108.
  • Nouh A, Mehta T, Hussain M, et al. Clot composition of embolic strokes of undetermined source: a feasibility study. BMC Neurol. 2020;20(1):383.
  • Jickling GC, Xu H, Stamova B, et al. Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol. 2010;68(5):681–692.
  • Jickling GC, Stamova B, Ander BP, et al. Profiles of lacunar and nonlacunar stroke. Ann Neurol. 2011;70(3):477–485.
  • García-Berrocoso T, Palà E, Consegal M, et al. Cardioembolic ischemic stroke gene expression fingerprint in blood: a systematic review and verification analysis. Transl Stroke Res. 2020;11(3):326–336.
  • Jickling GC, Stamova B, Ander BP, et al. Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location. Stroke. 2012;43(8):2036–2041.
  • Mandell DM, Mossa-Basha M, Qiao Y, et al. Intracranial vessel wall MRI: principles and expert consensus recommendations of the american society of neuroradiology. AJNR Am J Neuroradiol. 2017;38(2):218–229.
  • Roy Cardinal MH, Heusinkveld MHG, Qin Z, et al. Carotid artery plaque vulnerability assessment using noninvasive ultrasound elastography: validation with MRI. AJR Am J Roentgenol. 2017;209(1):142–151.
  • Ropper AH. Tipping point for patent foramen ovale closure. N Engl J Med. 2017;377(11):1093–1095.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.