Keywords: pfo migraines
Description: Cryptogenic stroke is a diagnosis of exclusion. These are strokes that occur in people who are usually less than 55 years old, without an identifiable cause. Our sensitivity to these events has been
Cryptogenic stroke is a diagnosis of exclusion. These are strokes that occur in people who are usually less than 55 years old, without an identifiable cause. Our sensitivity to these events has been heightened because of the new definitions of a transient ischemic attack. Transient ischemic attack (TIA) is a clinical diagnosis of a neurologic deficit without MRI abnormalities: if there is an MRI abnormality, whether or not that person is symptomatic, it is now defined as a stroke. With these new definitions, and the sensitivity of MRI, we are seeing more cryptogenic strokes.
It has been hypothesized that many cryptogenic strokes are caused by small emboli that travel from the legs to the right atrium; during straining (such as a Valsalva maneuver) these emboli can go across a PFO into the left atrium and then travel to the brain, producing a stroke. The problem is that these are very small emboli, approximately 1 to 3 mm, and we can't actually show these small emboli crossing from right to left. However, large emboli have been observed by echocardiography to be trapped in the PFO. So the diagnosis of cryptogenic stroke is a diagnosis of exclusion that is impossible to verify.
What is the scope of the problem? Of the 700,000 strokes per year in the United States, 80% of them are ischemic, and 20% of those are defined as cryptogenic. The prevalence of PFO among this cryptogenic stroke population is about 40% to 50%; in the general population, it's only about 20%. Current estimates are that somewhere between 30,000 and 60,000 strokes per year in the U.S. are caused by paradoxical embolism through a PFO.
There are some other fascinating associations: scuba divers with PFOs are more susceptible to decompression illness. Platypnea-orthodeoxia is a condition of desaturation that occurs when you're standing up but not when you're lying down; these patients are quite symptomatic, with arterial saturations in the low 80s. They also frequently have PFOs; if you close the PFO, the arterial desaturation is alleviated.
Fat emboli during orthopedic surgery or air emboli during neurosurgery may also travel through the venous system. If you don't have a PFO, the fat or the air is trapped in the lungs and doesn't cause much of a problem unless it's massive; but if you have a PFO, then the embolus can go from right to left atrium up to the brain, with devastating neurologic consequences.
There are several treatment alternatives for cryptogenic stroke ( Table I ). Warfarin has been used for years, but it is uncertain that this reduces the risk of events, which is still 2% to 8% per year. Antiplatelet therapy appears to be of equivalent value to warfarin. The WARS trial looked at over 2,000 patients with stroke of uncertain origin (atrial fibrillation and high-grade carotid stenosis were excluded); the recurrence rate was quite high—8% per year—but not all of these patients had PFOs. There was a substudy of 630 patients in WARS who were evaluated by transesophageal echocardiography; PFO was significantly more common in patients with cryptogenic stroke. In a subset analysis, they separated patients into those who had a PFO from those patients who did not have a PFO, and then segregated them according to age. Remember, cryptogenic stroke is usually defined as occurring in patients less than 55 years of age; above age 55, strokes are generally felt to be more likely due to atherosclerosis. Interestingly, though, in the lowest age group (<55), the incidence of recurrent stroke or death tended to be lower in patients with a PFO, and it was about equal in the 55 to 65 age range. But above age 65 into the 80s, patients were 3 times more likely to have a stroke or death if a PFO was present, even accounting for other risk factors usually associated with atherosclerosis. As you get older, you probably have more venous emboli and your right atrial pressure goes up, raising the risk of PFO-mediated embolic events to the point where, in the elderly, that risk may be just as important as underlying atherosclerotic disease. These are all observational data at present, but the concept is fascinating and needs to be tested. Perhaps all elderly patients with stroke should be getting their PFOs closed in addition to getting their carotid arteries cleaned out.