Cryptogenic Stroke: Stroke of Unknown Cause

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A stroke is the death of brain tissue, usually produced by the interruption of blood flow to part of the brain. Common vascular problems that can lead to stroke include thrombosis (clotting) of blood vessels in the brain, embolus (a blood clot that travels to the brain and lodges there), and local problems involving blood vessels in the brain, such as an aneurysm or inflammation.

After someone has had a stroke, the doctor will attempt to determine the specific cause, since the underlying cause of a stroke often determines the best therapy. In up to 40 percent of cases, however, no specific cause can be identified. A stroke of unknown cause is termed a cryptogenic stroke. (The term “cryptogenic” simply indicates that the cause is cryptic, or perplexing.)

When Are Strokes Called Cryptogenic?

After a stroke, sometimes it can be quite difficult to determine whether the interruption of blood flow that produced the stroke was caused by a blood clot that formed in place (thrombus), a blood clot that traveled to the brain from elsewhere (embolus), or some other vascular problem.

A stroke should not be called cryptogenic until a full evaluation has been done without yielding a specific cause. In general, such an evaluation should include brain imaging (with a CT scan or MRI scan), imaging of the blood vessels that supply the brain (carotid duplex or transcranial Doppler studies), and possibly angiography.

In addition, a complete echocardiographic study of the heart should be done, looking for cardiac sources of an embolus. Potential cardiac sources include blood clots in the heart (usually in the left atrium), patent foramen ovale (PFO), an aneurysm of the atrial septumatrial fibrillation, or mitral valve prolapse (MVP). If no cause has been identified after this thorough evaluation, the stroke is deemed to be cryptogenic.

The actual causes of cryptogenic strokes (if they could be identified) are multiple, and people who are labeled as having a cryptogenic stroke are a heterogeneous group. As medical science improves its ability to identify the cause of strokes in individual patients, the number of people who are said to have a cryptogenic stroke will fall.

Who Gets a Cryptogenic Stroke?

The profile of patients who have suffered cryptogenic strokes is generally the same as patients who have suffered strokes of identifiable causes. They tend to be older people who have the typical risk factors for cardiovascular disease.

Cryptogenic strokes are seen equally in men and women. They may be more common in blacks and Hispanics. While cryptogenic strokes in younger people (under age 50) get a lot of attention from doctors and in the medical literature, studies suggest that the actual age distribution of cryptogenic strokes is the same as for non-cryptogenic strokes. That is, the ability to identify the cause of stroke in younger people is just about the same as it is in older people.

What Is the Outlook After Cryptogenic Stroke?

In general, the prognosis of a patient who has suffered a cryptogenic stroke appears to be somewhat better than for non-cryptogenic strokes. Still, the 2-year rate of recurrent stroke averages 15 - 20 percent.

Since treatment to prevent recurrent stroke depends on the cause of the stroke (anticoagulation with warfarin after embolic stroke, antiplatelet therapy with aspirin or clopidogrel after thrombotic stroke), the best therapy after a cryptogenic stroke is unclear. The consensus among experts at this point, however, leans toward using antiplatelet therapy.

The PFO Controversy
One of the more controversial aspects of cryptogenic strokes is the question of how often they are caused by a Patent Foramen Ovale (PFOs), otherwise known as a hole in the heart. Undoubtedly some cryptogenic strokes are produced by blood clots that cross a PFO, enter the circulation, and travel to the brain. However, this phenomenon is quite rare, while PFOs are very common. (PFOs can be identified in up to 25% of all individuals by echocardiography.)

Probably, for this reason, studies that have evaluated the potential benefits of using PFO closure devices in patients who have had cryptogenic strokes have been disappointing - no reduction in subsequent strokes has been identified. At the same time, the procedures used to close PFOs expose patients to the potential of serious side effects.

It is still likely that in certain patients, closing PFOs would probably be beneficial. But at this point, there no proven method for determining which patients with cryptogenic stroke and PFO would benefit from PFO closure.

However, a recent study suggests that by employing a transcranial Doppler study, in conjunction with a bubble study, doctors can begin to detect those particular patients in whom cryptogenic strokes might have been caused by a PFO.  Further studies will be needed to assess whether closing the PFO will reduce subsequent strokes in this subset of patients.

The bottom line, though, is that the routine closure of PFOs in patients with cryptogenic stroke cannot be justified today.  The American Academy of Neurology in 2016 warned against routinely offering PFO closure to people who have suffered cryptogenic strokes.

Atrial Fibrillation and Cryptogenic Stroke

Atrial fibrillation is a well-known cause of embolic stroke, and patients with atrial fibrillation generally need to be anticoagulated.

Recent evidence suggests that a substantial minority of patients with cryptogenic stroke may have “subclinical” atrial fibrillation - that is, episodes of atrial fibrillation that do not cause significant symptoms, and therefore go unrecognized. Further, there is data suggesting that that long-term ambulatory cardiac monitoring may be useful in identifying subclinical atrial fibrillation in patients who have had a cryptogenic stroke. In these patients, presumably, as in other patients with atrial fibrillation, anticoagulation would likely reduce the risk of recurrent stroke.

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