Top

Published in:

01-12-2013 | Stroke (C Sila, Section Editor)

Cryptogenic Stroke: How to Define It? How to Treat It?

Authors: Ava L. Liberman, Shyam Prabhakaran

Published in: Current Cardiology Reports | Issue 12/2013

Abstract

Stroke is a leading cause of disability worldwide. Cryptogenic strokes (CS) account for almost a quarter of ischemic strokes despite modern diagnostic evaluation. A working definition of CS based on stroke classification systems is essential for accurate conceptualization of this common entity. Mechanistic categories (potential paradoxical embolism; atherosclerotic disease of the aorta or supra-aortic vasculature; and occult arrhythmia) should aide in parsing the often heterogeneous mix of conditions included in the CS subtype. Despite efforts to unravel mechanisms of CS, specific or targeted recurrent stroke prevention strategies are lacking. For example, recent trials have shown no clear benefit of patent foramen ovale closure in stroke prevention after CS. There are promising ongoing clinical trials that will address appropriate diagnostic evaluations in CS as well as novel therapeutic interventions. Overall, a standardized approach must be framed to diagnose and manage patients with CS and guide clinical practice and future research.

Grau AJ, Weimar C, Buggle F, Heinrich A, Goertler M, Neumaier S, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke J Cerebral Circ. 2001;32(11):2559–66.

Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke J Cerebral Circ. 2001;32(12):2735–40.

Petty GW, Brown Jr RD, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke J Cerebral Circ. 1999;30(12):2513–6.

Sacco RL, Ellenberg JH, Mohr JP, Tatemichi TK, Hier DB, Price TR, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol. 1989;25(4):382–90. doi:10.1002/ana.410250410.PubMed

Adams Jr HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, 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 J Cerebral Circ. 1993;24(1):35–41.

Ay H. Advances in the diagnosis of etiologic subtypes of ischemic stroke. Curr Neurol Neurosci Rep. 2010;10(1):14–20. doi:10.1007/s11910-009-0074-x.PubMed

Ay H, Benner T, Arsava EM, Furie KL, Singhal AB, Jensen MB, et al. A computerized algorithm for etiologic classification of ischemic stroke: the Causative Classification of Stroke System. Stroke J Cerebral Circ. 2007;38(11):2979–84. doi:10.1161/STROKEAHA.107.490896.

Ay H, Furie KL, Singhal A, Smith WS, Sorensen AG, Koroshetz WJ. An evidence-based causative classification system for acute ischemic stroke. Ann Neurol. 2005;58(5):688–97. doi:10.1002/ana.20617.PubMed

• Marnane M, Duggan CA, Sheehan OC, Merwick A, Hannon N, Curtin D, 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 J Cereb Circ. 2010;41(8):1579–86. doi:10.1161/STROKEAHA.109.575373. Population-based prospective cohort study using single rater to classify ischemic strokes using the 3 major classification systems. Found that CCS assigned fewer patients to undetermined category than TOAST.

10.

Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG. New approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke. Cerebrovasc Dis. 2009;27(5):502–8. doi:10.1159/000210433.PubMed

11.

Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG. Classification of stroke subtypes. Cerebrovasc Dis. 2009;27(5):493–501. doi:10.1159/000210432.PubMed

12.

Lamy C, Giannesini C, Zuber M, Arquizan C, Meder JF, Trystram D, et al. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale: the PFO-ASA Study. Atrial Septal Aneurysm. Stroke J Cereb Circ. 2002;33(3):706–11.

13.

Roh JK, Kang DW, Lee SH, Yoon BW, Chang KH. Significance of acute multiple brain infarction on diffusion-weighted imaging. Stroke J Cereb Circ. 2000;31(3):688–94.

14.

Ueno Y, Kimura K, Iguchi Y, Shibazaki K, Inoue T, Hattori N, et al. Mobile aortic plaques are a cause of multiple brain infarcts seen on diffusion-weighted imaging. Stroke J Cereb Circ. 2007;38(9):2470–6. doi:10.1161/STROKEAHA.107.482497.

15.

Bhatt A, Majid A, Razak A, Kassab M, Hussain S, Safdar A. Predictors of occult paroxysmal atrial fibrillation in cryptogenic strokes detected by long-term noninvasive cardiac monitoring. Stroke Res Treat. 2011;2011:172074. doi:10.4061/2011/172074.PubMed

16.

Kim SJ, Ryoo S, Hwang J, Noh HJ, Park JH, Choe YH, et al. Characterization of the infarct pattern caused by vulnerable aortic arch atheroma: DWI and multidetector row CT study. Cerebrovasc Dis. 2012;33(6):549–57. doi:10.1159/000338018.PubMed

17.

Thaler DE, Ruthazer R, Di Angelantonio E, Di Tullio MR, Donovan JS, Elkind MS, et al. Neuroimaging findings in cryptogenic stroke patients with and without patent foramen ovale. Stroke J Cereb Circ. 2013;44(3):675–80. doi:10.1161/STROKEAHA.112.677039.

18.

Rolfs A, Bottcher T, Zschiesche M, Morris P, Winchester B, Bauer P, et al. Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet. 2005;366(9499):1794–6. doi:10.1016/S0140-6736(05)67635-0.PubMed

19.

Brouns R, Sheorajpanday R, Braxel E, Eyskens F, Baker R, Hughes D, et al. Middelheim Fabry Study (MiFaS): a retrospective Belgian study on the prevalence of Fabry disease in young patients with cryptogenic stroke. Clin Neurol Neurosurg. 2007;109(6):479–84. doi:10.1016/j.clineuro.2007.03.008.PubMed

20.

Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology. 2000;55(8):1172–9.PubMed

21.

Di Tullio MR, Sacco RL, Sciacca RR, Jin Z, Homma S. Patent foramen ovale and the risk of ischemic stroke in a multiethnic population. J Am College Cardiol. 2007;49(7):797–802. doi:10.1016/j.jacc.2006.08.063.

22.

Petty GW, Khandheria BK, Meissner I, Whisnant JP, Rocca WA, Christianson TJ, et al. Population-based study of the relationship between patent foramen ovale and cerebrovascular ischemic events. Mayo Clin Proc Mayo Clin. 2006;81(5):602–8. doi:10.4065/81.5.602.

23.

Cabanes L, Mas JL, Cohen A, Amarenco P, Cabanes PA, Oubary P, 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 J Cereb Circ. 1993;24(12):1865–73.

24.

Fisher DC, Fisher EA, Budd JH, Rosen SE, Goldman ME. The incidence of patent foramen ovale in 1,000 consecutive patients. A contrast transesophageal echocardiography study. Chest. 1995;107(6):1504–9.PubMed

25.

Mugge A, Daniel WG, Angermann C, Spes C, Khandheria BK, Kronzon I, et al. Atrial septal aneurysm in adult patients. A multicenter study using transthoracic and transesophageal echocardiography. Circulation. 1995;91(11):2785–92.PubMed

26.

Mas JL, Zuber M. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic attack. French Study Group on patent foramen ovale and atrial septal aneurysm. Am Heart J. 1995;130(5):1083–8.PubMed

27.

•• Thaler DE, Di Angelantonio E, Di Tullio MR, Donovan JS, Griffith J, Homma S, et al. The Risk of Paradoxical Embolism (RoPE) Study: initial description of the completed database. Int J Stroke J Int Stroke Soc. 2012. doi:10.1111/j.1747-4949.2012.00843.x. The RoPE database includes individual patient data for 3,674 subjects from 12 component databases This database will help determine who, if anyone, might benefit from PFO closure.

28.

•• Kent DM, Thaler DE. The Risk of Paradoxical Embolism (RoPE) Study: developing risk models for application to ongoing randomized trials of percutaneous patent foramen ovale closure for cryptogenic stroke. Trials. 2011;12:185. doi:10.1186/1745-6215-12-185. This paper presents details on the RoPE database and its plan to develop and test a set of predictive models to identify patients most likely to benefit from preventive treatment for PFO-related stroke recurrence.PubMed

29.

Albers GW, Comess KA, DeRook FA, Bracci P, Atwood JE, Bolger A, et al. Transesophageal echocardiographic findings in stroke subtypes. Stroke J Cereb Circ. 1994;25(1):23–8.

30.

Cujec B, Polasek P, Voll C, Shuaib A. Transesophageal echocardiography in the detection of potential cardiac source of embolism in stroke patients. Stroke J Cereb Circ. 1991;22(6):727–33.

31.

Pearson AC, Labovitz AJ, Tatineni S, Gomez CR. Superiority of transesophageal echocardiography in detecting cardiac source of embolism in patients with cerebral ischemia of uncertain etiology. J Am College Cardiol. 1991;17(1):66–72.

32.

Censori B, Colombo F, Valsecchi MG, Clivati L, Zonca A, Camerlingo M, et al. Early transoesophageal echocardiography in cryptogenic and lacunar stroke and transient ischaemic attack. J Neurol Neurosurg Psychiatry. 1998;64(5):624–7.PubMed

33.

Mohrs OK, Petersen SE, Erkapic D, Rubel C, Schrader R, Nowak B, et al. Diagnosis of patent foramen ovale using contrast-enhanced dynamic MRI: a pilot study. AJR Am J Roentgenol. 2005;184(1):234–40. doi:10.2214/ajr.184.1.01840234.PubMed

34.

Nusser T, Hoher M, Merkle N, Grebe OC, Spiess J, Kestler HA, et al. Cardiac magnetic resonance imaging and transesophageal echocardiography in patients with transcatheter closure of patent foramen ovale. J Am Coll Cardiol. 2006;48(2):322–9. doi:10.1016/j.jacc.2006.03.036.PubMed

35.

Zahuranec DB, Mueller GC, Bach DS, Stojanovska J, Brown DL, Lisabeth LD, et al. Pilot study of cardiac magnetic resonance imaging for detection of embolic source after ischemic stroke. J Stroke Cereb Dis J Nat Stroke Assoc. 2012;21(8):794–800. doi:10.1016/j.jstrokecerebrovasdis.2011.04.010.

36.

Kafka H, Mohiaddin RH. Cardiac MRI and pulmonary MR angiography of sinus venosus defect and partial anomalous pulmonary venous connection in cause of right undiagnosed ventricular enlargement. AJR Am J Roentgenol. 2009;192(1):259–66. doi:10.2214/AJR.07.3430.PubMed

37.

Ohyama H, Hosomi N, Takahashi T, Mizushige K, Osaka K, Kohno M, et al. Comparison of magnetic resonance imaging and transesophageal echocardiography in detection of thrombus in the left atrial appendage. Stroke J Cereb Circ. 2003;34(10):2436–9. doi:10.1161/01.STR.0000090350.73614.0F.

38.

O'Donnell DH, Abbara S, Chaithiraphan V, Yared K, Killeen RP, Cury RC, et al. Cardiac tumors: optimal cardiac MR sequences and spectrum of imaging appearances. AJR Am J Roentgenol. 2009;193(2):377–87. doi:10.2214/AJR.08.1895.PubMed

39.

Nellessen U, Daniel WG, Matheis G, Oelert H, Depping K, Lichtlen PR. Impending paradoxical embolism from atrial thrombus: correct diagnosis by transesophageal echocardiography and prevention by surgery. J Am Coll Cardiol. 1985;5(4):1002–4.PubMed

40.

Berthet K, Lavergne T, Cohen A, Guize L, Bousser MG, Le Heuzey JY, et al. Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause. Stroke J Cereb Circ. 2000;31(2):398–403.

41.

Schneider B, Hanrath P, Vogel P, Meinertz T. Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events. J Am Coll Cardiol. 1990;16(4):1000–9.PubMed

42.

Myers PO, Bounameaux H, Panos A, Lerch R, Kalangos A. Impending paradoxical embolism: systematic review of prognostic factors and treatment. Chest. 2010;137(1):164–70. doi:10.1378/chest.09-0961.PubMed

43.

Ozdemir AO, Tamayo A, Munoz C, Dias B, Spence JD. Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism. J Neurol Sci. 2008;275(1–2):121–7. doi:10.1016/j.jns.2008.08.018.PubMed

44.

Kitsios GD, Lasker A, Singh J, Thaler DE. Recurrent stroke on imaging and presumed paradoxical embolism: a cross-sectional analysis. Neurology. 2012;78(13):993–7. doi:10.1212/WNL.0b013e31824d58bc.PubMed

45.

Stollberger C, Slany J, Schuster I, Leitner H, Winkler WB, Karnik R. The prevalence of deep venous thrombosis in patients with suspected paradoxical embolism. Ann Intern Med. 1993;119(6):461–5.PubMed

46.

Cramer SC, Rordorf G, Maki JH, Kramer LA, Grotta JC, Burgin WS, et al. Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study. Stroke J Cereb Circ. 2004;35(1):46–50. doi:10.1161/01.STR.0000106137.42649.AB.

47.

Lethen H, Flachskampf FA, Schneider R, Sliwka U, Kohn G, Noth J, et al. Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack. Am J Cardiol. 1997;80(8):1066–9.PubMed

48.

Cushman M, Rosendaal FR, Psaty BM, Cook EF, Valliere J, Kuller LH, et al. Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: results from the Cardiovascular Health Study. Thromb Haemost. 1998;79(5):912–5.PubMed

49.

Hankey GJ, Eikelboom JW, van Bockxmeer FM, Lofthouse E, Staples N, Baker RI. Inherited thrombophilia in ischemic stroke and its pathogenic subtypes. Stroke J Cereb Circ. 2001;32(8):1793–9.

50.

Ridker PM, Hennekens CH, Miletich JP. G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation. 1999;99(8):999–1004.PubMed

51.

Hamedani AG, Cole JW, Mitchell BD, Kittner SJ. Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment. Stroke J Cereb Circ. 2010;41(8):1599–603. doi:10.1161/STROKEAHA.110.581256.

52.

Moster ML. Coagulopathies and arterial stroke. J Neuro-Ophthalmology J North American Neuro-Ophthalmology Soc. 2003;23(1):63–71.

53.

Calabro RS, La Spina P, Serra S, Lagana A, Postorino P, Savica R, et al. Prevalence of prothrombotic polymorphisms in a selected cohort of cryptogenic and noncryptogenic ischemic stroke patients. Neurol India. 2009;57(5):636–7.PubMed

54.

Austin H, Chimowitz MI, Hill HA, Chaturvedi S, Wechsler LR, Wityk RJ, et al. Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women. Stroke J Cereb Circ. 2002;33(12):2762–8.

55.

Janssen AW, de Leeuw FE, Janssen MC. Risk factors for ischemic stroke and transient ischemic attack in patients under age 50. J Thromb Thrombolysis. 2011;31(1):85–91. doi:10.1007/s11239-010-0491-3.PubMed

56.

Levine SR, Brey RL, Tilley BC, Thompson JL, Sacco RL, Sciacca RR, et al. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA. 2004;291(5):576–84. doi:10.1001/jama.291.5.576.PubMed

57.

Rajamani K, Chaturvedi S, Jin Z, Homma S, Brey RL, Tilley BC, et al. Patent foramen ovale, cardiac valve thickening, and antiphospholipid antibodies as risk factors for subsequent vascular events: the PICSS-APASS study. Stroke J Cereb Circ. 2009;40(7):2337–42. doi:10.1161/STROKEAHA.108.539171.

58.

Lichy C, Reuner KH, Buggle F, Litfin F, Rickmann H, Kunze A, et al. Prothrombin G20210A mutation, but not factor V Leiden, is a risk factor in patients with persistent foramen ovale and otherwise unexplained cerebral ischemia. Cerebrovasc Dis. 2003;16(1):83–7.PubMed

59.

Karttunen V, Hiltunen L, Rasi V, Vahtera E, Hillbom M. Factor V Leiden and prothrombin gene mutation may predispose to paradoxical embolism in subjects with patent foramen ovale. Blood Coagulation Fibrinolysis Int J Haemostasis and Thrombosis. 2003;14(3):261–8. doi:10.1097/01.mbc.0000061288.28953.c8.

60.

Offelli P, Zanchetta M, Pedon L, Marzot F, Cucchini U, Pegoraro C, et al. Thrombophilia in young patients with cryptogenic stroke and patent foramen ovale (PFO). Thromb Haemost. 2007;98(4):906–7.PubMed

61.

Palmieri V, Tufano A, Carmen Bonito M, Martino S, Sabatella M, Di Minno G, et al. Right-to-left shunt, atrial septal aneurysm and thrombophilia in patients with cryptogenic stroke or TIA vs. those with venous thrombo-embolism. Int J Cardiol. 2008;130(1):99–102.PubMed

62.

Belvis R, Santamaria A, Marti-Fabregas J, Leta RG, Cocho D, Borrell M, et al. Patent foramen ovale and prothrombotic markers in young stroke patients. Blood Coagulation Fibrinolysis Int J Haemostasis and Thrombosis. 2007;18(6):537–42. doi:10.1097/MBC.0b013e3281420398.

63.

Carod-Artal FJ, Vilela Nunes S, Portugal D. Thrombophilia and patent foramen ovale in young stroke patients. Neurologia. 2006;21(10):710–6.PubMed

64.

Pezzini A, Del Zotto E, Magoni M, Costa A, Archetti S, Grassi M, et al. Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke J Cereb Circ. 2003;34(1):28–33.

65.

Amarenco P, Duyckaerts C, Tzourio C, Henin D, Bousser MG, Hauw JJ. The prevalence of ulcerated plaques in the aortic arch in patients with stroke. The New Eng J Med. 1992;326(4):221–5. doi:10.1056/NEJM199201233260402.

66.

Fayad ZA, Fuster V. Characterization of atherosclerotic plaques by magnetic resonance imaging. Ann New York Acad Sci. 2000;902:173–86.

67.

Amarenco P, Cohen A, Tzourio C, Bertrand B, Hommel M, Besson G, et al. Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. The New England J Med. 1994;331(22):1474–9. doi:10.1056/NEJM199412013312202.

68.

Amarenco P, Heinzlef O, Lucas C, Touboul PJ, Gérard JL, Adraï V, et al. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. The French Study of Aortic Plaques in Stroke Group. N Engl J Med. 1996;334(19):1216–21. doi:10.1056/NEJM199605093341902.

69.

Cohen A, Tzourio C, Bertrand B, Chauvel C, Bousser MG, Amarenco P. Aortic plaque morphology and vascular events: a follow-up study in patients with ischemic stroke. FAPS Investigators. French Study of Aortic Plaques in Stroke. Circulation. 1997;96(11):3838–41.PubMed

70.

Mitusch R, Doherty C, Wucherpfennig H, Memmesheimer C, Tepe C, Stierle U, et al. Vascular events during follow-up in patients with aortic arch atherosclerosis. Stroke J Cereb Circ. 1997;28(1):36–9.

71.

Harloff A, Simon J, Brendecke S, Assefa D, Helbing T, Frydrychowicz A, et al. Complex plaques in the proximal descending aorta: an underestimated embolic source of stroke. Stroke J Cereb Circ. 2010;41(6):1145–50. doi:10.1161/STROKEAHA.109.577775.

72.

Russo C, Jin Z, Rundek T, Homma S, Sacco RL, Di Tullio MR. Atherosclerotic disease of the proximal aorta and the risk of vascular events in a population-based cohort: the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. Stroke J Cereb Circ. 2009;40(7):2313–8. doi:10.1161/STROKEAHA.109.548313.

73.

Meissner I, Khandheria BK, Sheps SG, Schwartz GL, Wiebers DO, Whisnant JP, et al. Atherosclerosis of the aorta: risk factor, risk marker, or innocent bystander? A prospective population-based transesophageal echocardiography study. J Am Coll Cardiol. 2004;44(5):1018–24. doi:10.1016/j.jacc.2004.05.075.PubMed

74.

Bang OY, Lee PH, Joo SY, Lee JS, Joo IS, Huh K. Frequency and mechanisms of stroke recurrence after cryptogenic stroke. Ann Neurol. 2003;54(2):227–34. doi:10.1002/ana.10644.PubMed

75.

Mazighi M, Labreuche J, Gongora-Rivera F, Duyckaerts C, Hauw JJ, Amarenco P. Autopsy prevalence of intracranial atherosclerosis in patients with fatal stroke. Stroke J Cereb Circ. 2008;39(4):1142–7. doi:10.1161/STROKEAHA.107.496513.

76.

Mazighi M, Labreuche J, Gongora-Rivera F, Duyckaerts C, Hauw JJ, Amarenco P. Autopsy prevalence of proximal extracranial atherosclerosis in patients with fatal stroke. Stroke J Cereb Circ. 2009;40(3):713–8. doi:10.1161/STROKEAHA.108.514349.

77.

Freilinger TM, Schindler A, Schmidt C, Grimm J, Cyran C, Schwarz F, et al. Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke. JACC Cardiovasc Imag. 2012;5(4):397–405. doi:10.1016/j.jcmg.2012.01.012.

78.

Takaya N, Yuan C, Chu B, Saam T, Underhill H, Cai J, et al. Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI–initial results. Stroke J Cereb Circ. 2006;37(3):818–23. doi:10.1161/01.STR.0000204638.91099.91.

79.

Singh N, Moody AR, Gladstone DJ, Leung G, Ravikumar R, Zhan J, et al. Moderate carotid artery stenosis: MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men. Radiology. 2009;252(2):502–8. doi:10.1148/radiol.2522080792.PubMed

80.

Schuchert A, Behrens G, Meinertz T. Impact of long-term ECG recording on the detection of paroxysmal atrial fibrillation in patients after an acute ischemic stroke. PACE. 1999;22(7):1082–4.PubMed

81.

Jabaudon D, Sztajzel J, Sievert K, Landis T, Sztajzel R. Usefulness of ambulatory 7-day ECG monitoring for the detection of atrial fibrillation and flutter after acute stroke and transient ischemic attack. Stroke J Cereb Circ. 2004;35(7):1647–51. doi:10.1161/01.STR.0000131269.69502.d9.

82.

Tayal AH, Tian M, Kelly KM, Jones SC, Wright DG, Singh D, et al. Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke. Neurology. 2008;71(21):1696–701. doi:10.1212/01.wnl.0000325059.86313.31.PubMed

83.

Sposato LA, Klein FR, Jauregui A, Ferrua M, Klin P, Zamora R, et al. Newly diagnosed atrial fibrillation after acute ischemic stroke and transient ischemic attack: importance of immediate and prolonged continuous cardiac monitoring. J Stroke Cereb Dis J Nat Stroke Assoc. 2012;21(3):210–6. doi:10.1016/j.jstrokecerebrovasdis.2010.06.010.

84.

Wallmann D, Tuller D, Wustmann K, Meier P, Isenegger J, Arnold M, et al. Frequent atrial premature beats predict paroxysmal atrial fibrillation in strok e patients: an opportunity for a new diagnostic strategy. Stroke J Cereb Circ. 2007;38(8):2292–4. doi:10.1161/STROKEAHA.107.485110.

85.

Miller DJ, Khan MA, Schultz LR, Simpson JR, Katramados AM, Russman AN, et al. Outpatient cardiac telemetry detects a high rate of atrial fibrillation in cryptogenic stroke. J Neurol Sci. 2013;324(1–2):57–61. doi:10.1016/j.jns.2012.10.001.PubMed

86.

•• Healey JS, Connolly SJ, Gold MR, Israel CW, Van Gelder IC, Capucci A, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120–9. doi:10.1056/NEJMoa1105575. The ASSERT trial showed that in patients > 65 years old who were monitored for 3 months who were found to have subclinical AT had an increased risk of ischemic stroke, systemic embolism, and clinical AF. This study suggests that subclinical AT is an important stroke risk factor and that there is a time-threshold effect of AT.PubMed

87.

Glotzer TV, Daoud EG, Wyse DG, Singer DE, Ezekowitz MD, Hilker C, et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythmia Electrophysiology. 2009;2(5):474–80. doi:10.1161/CIRCEP.109.849638.

88.

Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke J Cereb Circ. 2011;42(1):227–76. doi:10.1161/STR.0b013e3181f7d043.

89.

Easton JD, Saver JL, Albers GW, Alberts MJ, Chaturvedi S, Feldmann E, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke J Cereb Circ. 2009;40(6):2276–93.

90.

•• Furlan AJ, Reisman M, Massaro J, Mauri L, Adams H, Albers GW, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med. 2012;366(11):991–9. doi:10.1056/NEJMoa1009639. CLOSURE I is a prospective trial of PFO closure using STARFlex device compared with medical therapy in patients following CS, which showed no significance in primary and secondary endpoints between groups, but did show an increased incidence of clinical AF in closure group suggesting the STARFlex device is not as good as the Amplatzer PFO Occluder used in other closure trials.PubMed

91.

•• Meier B, Kalesan B, Mattle HP, Khattab AA, Hildick-Smith D, Dudek D, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368(12):1083–91. doi:10.1056/NEJMoa1211716. PC trial is a prospective trial of PFO closure to medical therapy in patients with PFO following CS that showed no significant difference in any endpoint.PubMed

92.

•• Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013;368(12):1092–100. doi:10.1056/NEJMoa1301440. RESPECT trial is the largest prospective trial of PFO closure compared with medical therapy that showed no benefit to closure in its primary analysis, but did show a trend towards benefit in patients with ASA or substantial shunt size in addition to showing benefit to closure in as-treated and per-protocol cohorts.PubMed

93.

Alsheikh-Ali AA, Thaler DE, Kent DM. Patent foramen ovale in cryptogenic stroke: incidental or pathogenic? Stroke J Cereb Circ. 2009;40(7):2349–55. doi:10.1161/STROKEAHA.109.547828.

94.

Hankey GJ. Warfarin-Aspirin Recurrent Stroke Study (WARSS) trial: is warfarin really a reasonable therapeutic alternative to aspirin for preventing recurrent noncardioembolic ischemic stroke? Stroke J Cereb Circ. 2002;33(6):1723–6.

95.

Sacco RL, Prabhakaran S, Thompson JL, Murphy A, Sciacca RR, Levin B, et al. 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:10.1159/000092331.PubMed

96.

Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP. Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation. 2002;105(22):2625–31.PubMed

97.

Ritter MA, Kochhauser S, Duning T, Reinke F, Pott C, Dechering DG, et al. Occult atrial fibrillation in cryptogenic stroke: detection by 7-day electrocardiogram versus implantable cardiac monitors. Stroke J Cereb Circ. 2013;44(5):1449–52. doi:10.1161/STROKEAHA.111.676189.

98.

Sinha AM, Diener HC, Morillo CA, Sanna T, Bernstein RA, Di Lazzaro V, et al. Cryptogenic Stroke and underlying Atrial Fibrillation (CRYSTAL AF): design and rationale. Am Heart J. 2010;160(1):36–41. doi:10.1016/j.ahj.2010.03.032.PubMed

99.

Corti R, Fuster V. Imaging of atherosclerosis: magnetic resonance imaging. Eur Heart J. 2011;32(14):1709–1719b. doi:10.1093/eurheartj/ehr068.PubMed

100.

Azarpazhooh MR, Chambers BR. Clinical application of transcranial Doppler monitoring for embolic signals. J Clin Neurosci J Neurosurg Soc Australia. 2006;13(8):799–810. doi:10.1016/j.jocn.2005.12.026.

101.

Grosset DG, Georgiadis D, Kelman AW, Lees KR. Quantification of ultrasound emboli signals in patients with cardiac and carotid disease. Stroke J Cerebral Circ. 1993;24(12):1922–4.

102.

Rothstein L, Jickling GC. Ischemic stroke biomarkers in blood. Biomark Med. 2013;7(1):37–47. doi:10.2217/bmm.12.104.PubMed

103.

Jickling GC, Stamova B, Ander BP, Zhan X, Liu D, Sison SM, et al. Prediction of cardioembolic, arterial, and lacunar causes of cryptogenic stroke by gene expression and infarct location. Stroke J Cereb Circ. 2012;43(8):2036–41. doi:10.1161/STROKEAHA.111.648725.

104.

Mitchell SA, Simon TA, Raza S, Jakouloff D, Orme ME, Lockhart I, et al. The Efficacy and Safety of Oral Anticoagulants in Warfarin-Suitable Patients With Nonvalvular Atrial Fibrillation: Systematic Review and Meta-Analysis. Clin Appl Thrombosis/Hemostasis J Int Acad Clin Appl Thrombosis/Hemostasis. 2013;00:1–13. doi:10.1177/1076029613486539.

Title: Cryptogenic Stroke: How to Define It? How to Treat It?
Authors: Ava L. Liberman
Shyam Prabhakaran
Publication date: 01-12-2013
Publisher: Springer US
Published in: Current Cardiology Reports / Issue 12/2013
Print ISSN: 1523-3782
Electronic ISSN: 1534-3170
DOI: https://doi.org/10.1007/s11886-013-0423-x

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

At a glance: The STEP trials

Springer Medicine

Cryptogenic Stroke: How to Define It? How to Treat It?

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 12/2013

The Challenge of Stroke Prevention with Intracranial Arterial Stenosis

Medical Treatment of Hypertension in Patients with Heart Failure with Preserved Ejection Fraction

Sudden Unexpected Death in Epilepsy or Voodoo Heart: Analysis of Heart/Brain Connections

Small Vessel Disease and Memory Loss: What the Clinician Needs to Know to Preserve Patients’ Brain Health

Acute Hypertensive Response Management in Patients with Acute Stroke

The Growing Problem of Stroke among Young Adults

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page