When the Cause is Unknown

The first of a two-part series

Each year, there are about 800,000 new or recurrent strokes. That means there’s a stroke in the United States every 40 seconds. In the past few years, stroke has dropped from the third-leading cause of death to the fifth, but that’s still more than 137,000 deaths a year — 1 out of every 18 deaths, or one every four minutes.

A stroke interrupts blood flow to the brain and starves it of nutrients. The lack of oxygen and nutrients kills brain cells and ultimately impacts the functions those groups of cells were responsible for. While there are only three types of stroke — ischemic, hemorrhagic and transient ischemic accident (TIA) — there are many causes.

Eighty-seven percent of strokes are considered ischemic. They are caused by a blockage in a blood vessel to the brain or in it. These blockages are typically caused by heart problems like atrial fibrillation, hardening of the arteries (atherosclerosis) and small vessel disease. The primary cause of bleeding (hemorrhagic) strokes is chronic damage to blood vessels from high blood pressure (HBP). HBP increases the risk of either type of stroke — 77 percent of Americans treated for a first stroke have blood pressure over 140/90 mmHg.

Although two-thirds of strokes are explained by those causes, between 25 percent and 30 percent of ischemic strokes are unexplained.

In medical language, these are called "cryptogenic strokes." Up to 200,000 survivors annually don’t know what caused their strokes.

Cryptogenic strokes always refer to ischemic strokes, and what is unknown is the origin of the cause of the stroke. Stroke patients almost always receive some type of brain imaging, like a CT scan or an MRI. Strokes that are deep within the brain are often due to small blood vessel problems that result from high blood pressure or diabetes.

Dr. Mitch Elkind

"However, if the stroke is on the surface and looks like an embolism (clot) that came from somewhere else, and we don’t have a definite cause, then we have to go looking for [a blockage or other cause] in the arteries and in the heart," said Mitch Elkind, professor of neurology and epidemiology at Columbia University Medical Center.

An ultrasound examination, called an echocardiogram, is used to evaluate the heart. An "echo" can reveal heart valve problems, enlarged chambers of the heart, evidence of blood clots, even tumors within the heart. In addition, the carotid arteries and other blood vessels that go to the brain are evaluated by ultrasound or CT or magnetic resonance angiography. If these procedures don’t reveal the source of the clot, then they perform an echocardiogram of the back of the heart. "That’s often a place where blood clots hide out, in the left atrium or the left atrial appendage," Elkind said.

Some cryptogenic strokes may be caused by a hole in the heart called a patent foramen ovale (PFO). About a quarter of the population has this congenital heart defect. For the vast majority of the millions of people with a PFO, it is not a problem, even though blood can leak from the right atrium to the left. However, when that leaked blood contains a clot, problems can arise. (Learn more about PFOs and stroke.)

Patients who have a stroke and a PFO may be referred to as patients with a stroke of undetermined cause. "Although there is … evidence to suggest that PFO can cause strokes, it’s not considered a high risk source of stroke because PFO is so common," Elkind said. "Those people may have a PFO that may have caused their stroke, but because we can’t be certain of that, we say, ‘This may have been a cause but I’m going to consider you an unexplained stroke patient because I just can’t know for sure and I don’t want to miss something else.’ Once you label something as the cause, then you stop looking for any other reason." However, when a person experiences PFO and stroke, it is recommended that they be treated with aspirin even if their stroke isn’t specifically attributed to the PFO.

No one likes uncertainty around their health, and an unexplained stroke is the definition of uncertainty. "Patients have a sense of insecurity about it for the reasons that you would expect," Elkind said. "A stroke is a terrifying event, so it’s a scary and frustrating situation.

They will often seek additional opinions, which is always a good thing. I usually reassure those patients that when we don’t find the cause after (thorough) testing, that’s usually a pretty good sign that the chance of another stroke is quite low."

Another possible cause of unexplained strokes is paroxysmal (intermittent) atrial fibrillation. AFib is a quivering or irregular heartbeat. Physicians have known for more than 50 years that it can cause clots, but paroxysmal AFib has been difficult to diagnose because the arrhythmia may not happen while the patient is in the hospital being monitored, and there may be no other symptoms. "However, what doctors now understand is that a lot more people have AFib than we knew before," Elkind said.

Here’s the bad news: Patients with AFib are five times more likely to have strokes. Studies have shown that continuous cardiac monitoring of cryptogenic stroke patients helps physicians detect and diagnose AFib. With an accurate diagnosis, patients can receive treatment to prevent another stroke.

Today there are devices that allow for monitoring of heart rhythm for many weeks to months to help detect heart arrhythmias. In the past, patients were routinely monitored for only 24 hours, but recent evidence suggests that up to 20 percent of patients with stroke of unknown cause may demonstrate intermittent AFib as much as 30 days following a stroke.

Just because the cause is undetermined, doesn’t mean there’s nothing to be done. Cryptogenic stroke patients should be treated for all the other stroke risk factors. "We may put them on a medication that’s specifically for AFib or we may send somebody for surgery to open up a blocked carotid artery if that’s present," Elkind said. "That will treat the specific cause of that particular stroke, but at the same time, we want to reduce their overall burden of risk factors that could lead to future problems. So you have to quit smoking, you have to watch your diet. Just about every stroke survivor goes on a cholesterol medicine even if they have normal cholesterol, because we know those statin medications have other beneficial effects. Generally, we’re going to have people take at least a low dose of a blood pressure medication to get their blood pressure down even further. We also encourage exercise and all the other things we know that reduce risk in general."

For more information, download our free PDF, What's at the Heart of My Stroke? A Patient Guide to Understanding Cryptogenic Stroke.

See also: Part two of this series, Shedding More Light on Cryptogenic Stroke

Learn the warning signs of stroke.

Support for stroke and AFib patients and their loved ones

The American Heart Association/American Stroke Association, together with StopAfib.org, has created an online community, the My AFib Experience™. The community is designed to help AFib patients take charge of their condition. The My AFib Experience provides personalized tools to address the unique needs and experiences of those living with AFib, as well as allowing patients and caregivers to connect with others living in similar situations.

The AHA/ASA also has an online community called the Support Network. The goal is to connect people living with stroke and heart disease with others who are going through similar journeys.

Interview with the primary investigator of the study, "Cryptogenic Stroke and Underlying Atrial Fibrillation" presented at the International Stroke Conference 2014 in San Diego:


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Stroke Rehabilitation

Making the Best Decisions at Discharge After Stroke

The type of rehabilitation and support systems a survivor receives at discharge can strongly influence health outcomes and recovery. In this, the first part of a two-part series on stroke rehab, we offer guidance for the decision-making process required when it’s time to leave the hospital.

What to Expect from Outpatient Rehab

After stroke, about two-thirds of survivors receive some type of rehabilitation. Outpatient therapy may consist of Several types of therapy. Whether a patient is referred to inpatient or outpatient therapy depends on the level of medical care required.

What to Expect in Stroke Rehab

Following a stroke, about two-thirds of survivors receive some type rehabilitation. In this second of our two-part series, we want to alleviate some of the mystery, fear and anxiety around the inpatient rehab part of the stroke recovery journey.
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AHA-ASA Resources

The Support Network

When faced with challenges recovering from heart disease or stroke, it’s important to have emotional support. That is why we created a network to connect patients and loved ones with others during their journey.

Caregiver Guide to Stroke

The Caregiver Guide to Stroke is meant to help caregivers better navigate the recovery process and the financial and social implications of a stroke.

Stroke Support Group Finder

To find a group near you, simply enter your ZIP code and a mile radius. If your initial search does not pull up any groups, try

Tips for Daily Living Library

This volunteer-powered library gathers tips and ideas from stroke survivors, caregivers and healthcare professionals all over the country who’ve created or discovered adaptive and often innovative ways to get things done!

Stroke Family Warmline

The Warmline connects stroke survivors and their families with an ASA team member who can provide support, helpful information or just a listening ear.

Let's Talk About Stroke Patient Information Sheets

Let's Talk About Stroke is a series of downloadable patient information sheets, created by the American Stroke Association, that presents information in a question-and-answer format that's brief, easy to follow and easy to read.

Request Free Stroke Information Packets

Fill out this online form to request free information about a variety of post-stroke topics.
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Stroke & Parts of the Brain

When Stroke Affects the Occipital Lobe

Our occipital lobe, the smallest of the four lobes of the cerebral cortex, controls how we visually interpret our world.

When Stroke Affects the Cerebellum

The cerebellum contains 80 percent of our neurons. Its job seems to be to make things better. We talked with neuroscientist Jeremy Schmahmann about how stroke affects the “little brain.”

When Stroke Affects the Parietal Lobe

The parietal lobe helps us make sense of sensory information, like where our bodies and body parts are in space, our sense of touch, and the part of our vision that deals with the location of objects.

When Stroke Affects the Frontal Lobe

Of the four lobes that make up the cerebral cortex, the frontal lobe is the largest. It plays a huge role in many of the functions that make us human — memory, language, movement, judgment, abstract thinking.

When Stroke Affects the Temporal Lobe

The temporal lobe has several functions, mainly involved with memory, perception and language.

When Stroke Affects the Brain Stem

The brain stem serves as a bridge in the nervous system. It sits at the top of the spinal column in the center of the brain. When a stroke happens there, it can cause a few different deficits and, in the most severe cases, can lead to locked-in syndrome.

When Stroke Affects the Thalamus

The thalamus can be thought of as a "relay station," receiving signals from the brain’s outer regions (cerebral cortex), interpreting them, then sending them to other areas of the brain to complete their job.
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