Skip to main content

Advertisement

SpringerLink
Log in

Patent Foramen Ovale and Stroke: Prognosis and Treatment in Young Adults

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

A patent foramen ovale (PFO) is found with increased frequency in patients with stroke of undetermined origin but the significance and therapeutic implications of this observation remain unclear. Several lines of evidence suggest a role for the PFO in stroke pathophysiology for some cryptogenic stroke patients, such as those whose PFO is accompanied by a prothrombotic state, atrial septal aneurysm, or lower extremity/pelvic DVT. Diagnostic evaluation of the patient with cryptogenic stroke and PFO is directed at identifying these subgroups. Appropriate therapy for primary and secondary stroke prevention in a subject with a PFO remains unclear given current uncertainties as to the pathophysiological significance of PFO. Additional studies are needed, such as those focused on lower extremity veins or the cardiac interatrial septum, to guide therapy in specific stroke subpopulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gresham G, Duncan P, Stason W, et al. Post-Stroke Rehabilitation. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service, Agency for Health Care Policy and Research, 1995.

  2. Broderick J, Brott T, Kothari R, et al. The greater Cincinnati/northern Kentucky stroke study: Preliminary first-ever and total incidence rates of stroke among blacks. Stroke 1998;29:415–421.

    PubMed  Google Scholar 

  3. Jacobs B, Boden-Albala B, Lin I, Sacco R. Stroke in the young in the northern Manhattan stroke study. Stroke 2002;33:2789–2793.

    Google Scholar 

  4. Yonemura K, Kimura K, Hasegawa Y, Yokota C, Minematsu K, Yamaguchi T. Analysis of ischemic stroke in patients aged up to 50 years. Rinsho Shinkeigaku 2000;40:881–886.

    PubMed  Google Scholar 

  5. Gandolfo C, Conti M. Stroke in young adults: Epidemiology. Neurol Sci 2003;24(Suppl 1):S1–3.

    Article  PubMed  Google Scholar 

  6. Bendixen B, Posner J, Lango R. Stroke in young adults and children. Curr Neurol Neurosci Rep 2001;1:54–66.

    PubMed  Google Scholar 

  7. Sacco R, Ellenberg J, Mohr J, Tatemichi T, Hier D, Price T, Wolf P. Infarcts of undetermined cause: The NINCDS stroke data bank. Ann Neurol 1989;25:382–390.

    Article  PubMed  Google Scholar 

  8. Mohr J, Caplan L, Melski J, et al. The Harvard cooperative stroke registry: A prospective registry of patients hospitalized with stroke. Neurology 1978;28:754–762.

    PubMed  Google Scholar 

  9. Mohr J, Thompson J, Lazar R, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. New England Journal of Medicine 2001;345:1444–1451.

    Article  PubMed  Google Scholar 

  10. The Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, org 10172 (danaparoid), and outcome after acute ischemic stroke. JAMA 1998;279:1265–1272.

    Article  PubMed  Google Scholar 

  11. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–1587.

    Article  PubMed  Google Scholar 

  12. Albers G, Amarenco P, Easton J, Sacco R, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001;119:300S–320S.

    Article  PubMed  Google Scholar 

  13. Cabanes L, Mas J, 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;24:1865–1873

    PubMed  Google Scholar 

  14. Overell J, Bone I, Lees K. Interatrial septal abnormalities and stroke: A meta-analysis of case- control studies. Neurology 2000;55:1172–1179.

    PubMed  Google Scholar 

  15. Thompson T, Evans W. Paradoxical embolism. QJ Med 1930;23:135–152.

    Google Scholar 

  16. Hagen P, Scholz D, Edwards W. Incidence and size of patent foramen ovale during the first 10 decades of life: An autopsy study of 965 normal hearts. Mayo Clin Proc 1984;59:17–20.

    PubMed  Google Scholar 

  17. Lechat P, Mas J, Lascault G. Prevalence of patent foramen ovale in patients with stroke. N Engl J Med 1988;318:1148–1152.

    PubMed  Google Scholar 

  18. Hausmann D, Mugge A, Becht I, Daniel W. Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events. Am J Cardiol 1992;70:668–672.

    Article  PubMed  Google Scholar 

  19. Jeanrenaud X, Bogousslavsky J, Payot M, Regli F, Kappenberger L. Patent foramen ovale and cerebral infarct in young patients. Schweiz Med Wochenschr 1990;120:823–829.

    PubMed  Google Scholar 

  20. Di Tullio M, Sacco R, Gopal A, Mohr J, Homma S. Patent foramen ovale as a risk factor for cryptogenic stroke. Ann Intern Med 1992;117:461–465.

    PubMed  Google Scholar 

  21. Job F, Ringelstein E, Grafen Y, et al. Comparison of transcranial contrast doppler sonography and transesophageal contrast echocardiography for the detection of patent foramen ovale in young stroke patients. Am J Cardiol 1994;74:381–384.

    Article  PubMed  Google Scholar 

  22. Klotzsch C, Janssen G, Berlit P. Transesophageal echocardiography and contrast-TCD in the detection of a patent foramen ovale. Neurology 1994;44:1603–1606.

    PubMed  Google Scholar 

  23. Petty G, Khandheria B, Chu C-P, Sicks J, Whisnant J. Patent foramen ovale in patients with cerebral infarction. Arch Neurol 1997;54:819–822.

    PubMed  Google Scholar 

  24. Homma S, Di Tullio M, Sacco R, Mihalatos D, Li Mandri G, Mohr J. Characteristics of patent foramen ovale associated with cryptogenic stroke. A biplane transesophageal echocardiographic study. Stroke 1994;25:582–586.

    PubMed  Google Scholar 

  25. Ranoux D, Cohen A, Cabanes L, Amarenco P, Bousser M, Mas J. Patent foramen ovale: Is stroke due to paradoxical embolism? Stroke 1993;24:31–34.

    PubMed  Google Scholar 

  26. Steiner M, Di Tullio M, Rundek T, et al. Patent foramen ovale size and embolic brain imaging findings among patients with ischemic stroke. Stroke 1998;29:944–948.

    PubMed  Google Scholar 

  27. Homma S, Sacco R, Di Tullio M, Sciacca R, Mohr J, for the 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;105:2625–2631.

    Article  PubMed  Google Scholar 

  28. Webster M, Chancellor A, Smith H, et al. Patent foramen ovale in young stroke patients. Lancet 1988;1988:11–12.

    Article  Google Scholar 

  29. de Belder M, Tourikis L, Leech G, Camm A. Risk of patent foramen ovale for thromboembolic events in all age groups. Am J Cardiol 1992;69:1316–1320.

    Article  PubMed  Google Scholar 

  30. De Castro S, Cartoni D, Fiorelli M, Rasura M, Anzini A, Zanette E, Beccia M, Colonnese C, Fedele F, Fieschi C, Pandian N. Morphological and functional characteristics of patent foramen ovale and their embolic implications. Stroke 2000;31:2407–2413.

    PubMed  Google Scholar 

  31. Mas J-L, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, Coste J, the 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;345:1740–1746.

    Article  PubMed  Google Scholar 

  32. Messe S, Silverman I, Kizer J, et al. Practice parameter: Recurrent stroke with patent foramen ovale and atrial septal aneurysm. Neurology 2004;62:1042–1050.

    PubMed  Google Scholar 

  33. Schuchlenz H, Saurer G, Weihs W. Patent foramen ovale, atrial septal aneurysm, and recurrent stroke. N Engl J Med 2002;346:1331–1332; author reply 1331–1332.

    Article  Google Scholar 

  34. Lethen H, Flachskampf F, Schneider R, et al. Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack. Am J Cardiol 1997;80:1066–1069.

    Article  PubMed  Google Scholar 

  35. Ha J, Shin M, Kang S, Pyun W, et al. Enhanced detection of right-to-left shunt through patent foramen ovale by transthoracic contrast echocardiography using harmonic imaging. Am J Cardiol 2001;87:669–671, A611.

    Article  PubMed  Google Scholar 

  36. Stendel R, Gramm H, Schroder K, Lober C, Brock M. Transcranial doppler ultrasonography as a screening technique for detection of a patent foramen ovale before surgery in the sitting position. Anesthesiology 2000;93:971–975.

    Article  PubMed  Google Scholar 

  37. Droste D, Lakemeier S, Wichter T, et al. Optimizing the technique of contrast transcranial Doppler ultrasound in the detection of right-to-left shunts. Stroke 2002;33:2211–2216.

    Article  PubMed  Google Scholar 

  38. Gin K, Huckell V, Pollick C. Femoral vein delivery of contrast medium enhances transthoracic echocardiographic detection of patent foramen ovale. J Am Coll Cardiol 1993;22:1994–2000.

    PubMed  Google Scholar 

  39. Hamann G, Schatzer-Klotz D, Frohlig G, et al. Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale. Neurology 1998;50:1423–1428.

    PubMed  Google Scholar 

  40. Schuchlenz H, Weihs W, Horner S, Quehenberger F. The association between the diameter of a patent foramen ovale and the risk of embolic cerebrovascular events. Am J Med 2000;109:456–462.

    Article  PubMed  Google Scholar 

  41. Hausmann D, Mugge A, Daniel W. Identification of patent foramen ovale permitting paradoxic embolism. J Am Coll Cardiol 1995;26:1030–1038.

    Article  PubMed  Google Scholar 

  42. Kerut E, Norfleet W, Plotnick G, Giles T. Patent foramen ovale: A review of associated conditions and the impact of physiological size. J Am Coll Cardiol 2001;38:613–623.

    Article  PubMed  Google Scholar 

  43. Gautier J, Durr A, Koussa S, Lasault G, Grosgogeat T. Paradoxical cerebral embolism with a patent foramen ovale. Cerebrovasc Dis 1991;1:193–202.

    Google Scholar 

  44. Stollberger C, Slany J, Schuster I, Leitner H, Winkler W, Karnik R. The prevalence of deep vein thrombosis in patients with suspected paradoxical embolism. Ann Intern Med 1993;119:461–465.

    PubMed  Google Scholar 

  45. Cramer S, Rordorf G, Maki J, et al. Increased pelvic vein thrombi in cryptogenic stroke: Results of the paradoxical emboli from large veins in ischemic stroke (PELVIS) study. Stroke 2004;35:46–50

    Article  PubMed  Google Scholar 

  46. Warlow C, Ogston D, Douglas A. Deep venous thrombosis of the legs after strokes. British Medical Journal 1976;1:1178–1183.

    PubMed  Google Scholar 

  47. Kelly J, Rudd A, Lewis R, Hunt B. Venous thromboembolism after acute stroke. Stroke 2001;32:262–267.

    PubMed  Google Scholar 

  48. Pezzini A, Del Zotto E, Magoni M, et al. Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale. Stroke 2003;34:28–33.

    Article  PubMed  Google Scholar 

  49. Landi G, D'Angelo A, Boccardi E, Candelise L, Mannuci P AM, Orazio E. Venous thromboembolism in acute stroke: Prognostic importance of hypercoagulability. Arch Neurol 1992;49:279–283.

    PubMed  Google Scholar 

  50. Havig O. Deep vein thrombosis. Acta Chirurgica Scandinavica 1977;(Suppl 478):4–11.

    Google Scholar 

  51. Philbrick J, Becker D. Calf deep venous thrombosis. A wolf in sheep's clothing? Arch Intern Med 1988;148:2131–2138.

    Article  PubMed  Google Scholar 

  52. Lohr J, James K, Deshmukh R, Hasselfeld K. Allastair B. Karmody award. Calf vein thrombi are not a benign finding. Am J Surg 1995;170:86–90.

    Article  PubMed  Google Scholar 

  53. Havig O. Source of pulmonary emboli. Acta Chirurgica Scandinavica 1977;(478 Suppl):42–47.

    Google Scholar 

  54. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. A statement for healthcare professionals. Council on thrombosis (in consultation with the council on cardiovascular radiology), American Heart Association. Circulation 1996;93:2212–2245.

    PubMed  Google Scholar 

  55. Salzman E. Venous thrombosis made easy. N Engl J Med 1986;314:847–848.

    PubMed  Google Scholar 

  56. Kearon C, Ginsberg J, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med 1998;129:1044–1049.

    PubMed  Google Scholar 

  57. Mohr J. Cryptogenic stroke. New Engl J Med 1988;318:1197–1198.

    PubMed  Google Scholar 

  58. Loscalzo J. Paradoxical embolism: Clinical presentation, diagnostic strategies, and therapeutic options. Am Heart J 1986;112:141–145.

    Article  PubMed  Google Scholar 

  59. Cramer S, Maki J, Waitches G, et al. Paradoxical emboli from calf and pelvic veins in cryptogenic stroke. J Neuroimaging 2003;13:218–223.

    Article  PubMed  Google Scholar 

  60. Corrin B. Paradoxical embolism. Br Heart J 1964;26:549–553.

    PubMed  Google Scholar 

  61. Johnson B. Paradoxical emboli. J Clin Pathol 1951;4:316–332.

    PubMed  Google Scholar 

  62. Spritzer C, Arata M, Freed K. Isolated pelvic deep venous thrombosis: Relative frequency as detected with mr imaging. Radiology 2001;219:521–525.

    PubMed  Google Scholar 

  63. Au V, Walsh G, Fon G. Computed tomography pulmonary angiography with pelvic venography in the evaluation of thrombo-embolic disease. Australas Radiol 2001;45:141–145.

    Article  PubMed  Google Scholar 

  64. Loud P, Katz D, Bruce D, Klippenstein D, Grossman Z. Deep venous thrombosis with suspected pulmonary embolism: Detection with combined CT venography and pulmonary angiography. Radiology 2001;219:498–502.

    PubMed  Google Scholar 

  65. Stern J, Abehsera M, Grenet D, et al. Detection of pelvic vein thrombosis by magnetic resonance angiography in patients with acute pulmonary embolism and normal lower limb compression ultrasonography. Chest 2002;122:115–121.

    Article  PubMed  Google Scholar 

  66. Cramer S, Rordorf G, Kaufman J, Buonanno F, Koroshetz W, Schwamm L. Clinically occult pelvic-vein thrombosis in cryptogenic stroke. Lancet 1998;351:1927–1928.

    Article  Google Scholar 

  67. Greer D, Buonanno F. Cerebral infarction in conjunction with patent foramen ovale and May-Thurner syndrome. J Neuroimaging 2001;11:432–434.

    PubMed  Google Scholar 

  68. Noser E, Felberg R, Alexandrov A. Thrombolytic therapy in an adolescent ischemic stroke. J Child Neurol 2001;16:286–288.

    PubMed  Google Scholar 

  69. Bergqvist D, Bergentz S-E. Diagnosis of deep vein thrombosis. World J Surg 1990;14:679–687.

    Article  PubMed  Google Scholar 

  70. Wheeler H, Anderson F. Diagnostic methods for deep vein thrombosis. Haemostasis 1995;25:6–26.

    PubMed  Google Scholar 

  71. Obernosterer A, Aschauer M, Schnedl W, Lipp R. Anomalies of the inferior vena cava in patients with iliac venous thrombosis. Ann Intern Med 2002;136:37–41.

    PubMed  Google Scholar 

  72. Fraser D, Moody A, Morgan P, Martel A, Davidson I. Diagnosis of lower-limb deep venous thrombosis: A prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med 2002;136:89–98.

    PubMed  Google Scholar 

  73. Fraser D, Moody A, Davidson I, Martel A, Morgan P. Deep venous thrombosis: Diagnosis by using venous enhanced subtracted peak arterial MR venography versus conventional venography. Radiology 2003;226:812–820.

    PubMed  Google Scholar 

  74. Puls R, Hosten N, Bock J, et al. Signal-enhanced color Doppler sonography of deep venous thrombosis in the lower limbs and pelvis. J Ultrasound Med 1999;18:185–190.

    PubMed  Google Scholar 

  75. Comess K, DeRook F, Beach K, Lytle N, Golby A, Albers G. Transesophageal echocardiography and carotid ultrasound in patients with cerebral ischemia: Prevalence of findings and recurrent stroke risk. J Am Coll Cardiol 1994;23:1598–1603.

    PubMed  Google Scholar 

  76. Mas J-L, Zuber M, the French Study Group on Patent Foramen Ovale and Atrial Septal Aneurysm. Recurrent cerebrovascular events in patients with patent foramen ovale, atrial septal aneurysm, or both and cryptogenic stroke or transient ischemic attack. Am Heart J 1995;130:1083–1088.

    Article  PubMed  Google Scholar 

  77. Bogousslavsky J, Garazi S, Jeanrenaud X, Aebisher N, Van Melle G, the Lausanne Stroke with Paradoxical Embolism Study Group. Stroke recurrence in patients with patent foramen ovale: The Lausanne study. Neurology 1996;46:1301–1305.

    PubMed  Google Scholar 

  78. Tong D, Becker K. Patent foramen ovale and recurrent stroke: Closure is the best option: No. Stroke 2004;35:804–805.

    Article  PubMed  Google Scholar 

  79. McGaw D, Harper R. Patent foramen ovale and cryptogenic cerebral infarction. Intern Med J 2001;31:42–47.

    Article  PubMed  Google Scholar 

  80. Berthet K, Lavergne T, Cohen A, et al. Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause. Stroke 2000;31:398–403.

    PubMed  Google Scholar 

  81. Ay H, Buonanno F, Abraham S, Kistler J, Koroshetz W. An electrocardiographic criterion for diagnosis of patent foramen ovale associated with ischemic stroke. Stroke 1998;29:1393–1397.

    PubMed  Google Scholar 

  82. Dearani J, Ugurlu B, Danielson G, Daly R, McGregor C, Mullany C, Puga F, Orszulak T, Anderson B, Brown R, Schaff H. Surgical patent foramen ovale closure for prevention of paradoxical embolism-related cerebrovascular ischemic events. Circulation 1999;100:II171–175.

    PubMed  Google Scholar 

  83. Albers G, Amarenco P, Easton J, Sacco R, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126:483S–512S.

    Article  PubMed  Google Scholar 

  84. Orgera M, O'Malley P, Taylor A. Secondary prevention of cerebral ischemia in patent foramen ovale: Systematic review and meta-analysis. South Med J 2001;94:699–703.

    PubMed  Google Scholar 

  85. Nendaz M, Sarasin F, Junod A, Bogousslavsky J. Preventing stroke recurrence in patients with patent foramen ovale: Antithrombotic therapy, foramen closure, or therapeutic abstention? A decision analytic perspective. Am Heart J 1998;135:532–541.

    PubMed  Google Scholar 

  86. Furlan A. Patent foramen ovale and recurrent stroke: Closure is the best option: Yes. Stroke 2004;35:803–804.

    Article  PubMed  Google Scholar 

  87. Wu L, Malouf J, Dearani J, et al. Patent foramen ovale in cryptogenic stroke: Current understanding and management options. Arch Intern Med 2004;164:950–956.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, UC Irvine Medical Center, University of CA-Irvine, Orange, CA, 92868-4280

    Steven C. Cramer MD

  2. Department of Neurology, UC Irvine Medical Center, University of CA-Irvine, 101 The City Drive South, Bldg 53, Rm 203, Orange, CA, 92868-4280

    Steven C. Cramer MD

Authors
  1. Steven C. Cramer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven C. Cramer MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cramer, S.C. Patent Foramen Ovale and Stroke: Prognosis and Treatment in Young Adults. J Thromb Thrombolysis 20, 85–91 (2005). https://doi.org/10.1007/s11239-005-3202-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-005-3202-8

Key Words

Search

Navigation