Cryptogenic Stroke: Stroke of Unknown Cause

When somebody has a stroke, it means that some part of their brain tissue has died. Stroke is usually caused by the interruption of blood flow to part of the brain. Common vascular problems that can lead to stroke include a blood clot or problems involving blood vessels in the brain, such as an aneurysm or inflammation.

After a person 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. Up to 40% of the time, however, no specific cause for the stroke can be identified. A stroke whose cause remains unknown after a thorough evaluation is called a cryptogenic stroke. (The term “cryptogenic” simply means 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 the brain’s blood supply 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 medical evaluation has failed to reveal 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), possibly angiography, and several lab tests to test blood glucose, renal function, platelet function, and clotting function (PT/PTT/INR).

In addition, a complete echocardiographic study of the heart should be done, looking for potential cardiac sources of an embolus. Such cardiac sources include blood clots in the heart (usually in the left atrium), patent foramen ovale (PFO), an aneurysm of the atrial septum, atrial fibrillation, or mitral valve prolapse (MVP).

There are many potential underlying causes of cryptogenic strokes, and people labeled as having a cryptogenic stroke are a heterogeneous group. As medical science has improved, and our ability to identify the cause of a stroke has also improved, the number of people who are said to have a cryptogenic stroke has begun to fall. However, “cryptogenic stroke” remains a fairly common diagnosis.

Who Gets a Cryptogenic Stroke?

The profile of people who have suffered cryptogenic strokes is generally the same as for people who have suffered strokes of identifiable causes. They tend to be older individuals 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 Latinx people. While cryptogenic strokes in younger people (under age 50) get a lot of attention from doctors and researchers, studies suggest 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.

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. In general, these strokes tend to be smaller than non-cryptogenic strokes, and the long-term prognosis is somewhat better. Still, the two-year rate of recurrent stroke after a cryptogenic stroke averages 15% to 20%.

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 (PFO), a "hole" in the septum between the right and left sides of the heart. Undoubtedly, some cryptogenic strokes are produced by blood clots that cross a PFO 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.

However, some research 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.

At this point, most experts find it reasonable to perform PFO closure in people under 60 years of age who have had a cryptogenic stroke and a suspicious Doppler study. However, it is believed that the routine closure of PFOs in other people 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. 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 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.

For this reason, ambulatory monitoring should be performed on anyone who has had a cryptogenic stroke to look for episodes of atrial fibrillation.

A Word From Verywell

In a substantial minority of people who suffer from a stroke, no specific cause can be identified after a thorough medical evaluation. While people who have such a cryptogenic stroke generally have a better prognosis than those in whom a definitive cause is found, they should receive special attention looking for potential underlying causes, in particular, for possible patent foramen ovale or atrial fibrillation.