Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism

J Neurol Sci. 2008 Dec 15;275(1-2):121-7. doi: 10.1016/j.jns.2008.08.018. Epub 2008 Sep 26.


Background: Patent foramen ovale (PFO) is an independent risk factor for cerebral infarction. Since ~25% of the population have a PFO, the simple association of PFO with stroke is not enough to establish the diagnosis of paradoxical embolism. We evaluated possible clinical clues to the diagnosis of paradoxical embolism.

Methods: Among patients with cryptogenic ischemic stroke (CS) who were investigated for a right-to-left shunt (RLS), we compared clinical, coagulation and biochemical parameters in patients with PFO versus without PFO.

Results: Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and 2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism (OR, 4.39; 95% CI, 1.23-15.69; p=0.023), prolonged travel (OR, 8.77; 95% CI, 1.775-43.3; p=0.008) , migraine (OR, 2.30: 95% CI, 1.07-4.92; p=0.031), a Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33; 95% CI, 1.15-9.64; p=0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26-16.2; p=0.018) were independently associated with PFO-associated cerebrovascular events. Patients with PFO had higher plasma total homocysteine levels than patients without PFO (8.9+/-3 versus 7.9+/-2.6 micromol/L respectively; p=0.021).

Conclusions: A history of DVT or pulmonary embolism, migraine, recent prolonged travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver preceding the event are clinical clues to the diagnosis of paradoxical embolism among patients with CS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Coagulation Tests / methods
  • Embolism, Paradoxical / complications*
  • Embolism, Paradoxical / diagnosis*
  • Embolism, Paradoxical / diagnostic imaging
  • Female
  • Foramen Ovale, Patent / complications*
  • Homocysteine / blood
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Stroke / complications*
  • Ultrasonography, Doppler, Transcranial
  • Vitamin B 12 / blood


  • Homocysteine
  • Vitamin B 12