Progress in Explaining the Unknown

Over the past few years, stroke has dropped from the third-leading cause of death to the fifth. While that’s good news, stroke remains a leading cause of disability. Each year there are almost 800,000 new or recurrent strokes. (Learn about the major types of stroke.)

A stroke happens when a part of the brain stops functioning properly as a result of blood flow being cut off to part of it. The lack of oxygen and nutrients injures or kills brain cells and ultimately impacts the functions the group of cells were responsible for, often resulting in limb weakness or paralysis, communication challenges or other serious deficits. While there are only three major types of stroke, there are many causes.

The most common causes of strokes due to blood vessel blockage from a clot (ischemic) are heart problems like atrial fibrillation, hardening of the arteries (atherosclerosis) and smallvessel 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, 25 percent to 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.

 Nobody likes uncertainty around their health, and an unexplained stroke is the definition of uncertainty.

Dr. Mitch Elkind

Cryptogenic strokes always refer to ischemic strokes, and the mystery is the origin of the stroke. Most stroke patients 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.

"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 it in the arteries and in the heart," said Mitch Elkind, professor of neurology and epidemiology at Columbia University Medical Center.

The heart is evaluated by an ultrasound examination called an echocardiogram. An "echo" can reveal valve problems, enlarged chambers, evidence of blood clots, even tumors. 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 an echocardiogram of the back of the heart may be performed. "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. Problems can arise, however, when that blood contains a clot. Learn more about PFOs and stroke.

There may be cases where a person who has a PFO might be labeled as having a stroke of unknown origin. "Although there is … evidence to suggest that PFO can cause strokes in some patients, 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."

Nobody likes uncertainty around their health, and an unexplained stroke is the definition of uncertainty. "I would say 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. Physicians have known for more then 50 years that AFib 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 rub: 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 the 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. An accurate diagnosis is important because there are medications and treatments that reduce the risk of stroke in AFib patients.

Cryptogenic stroke patients should be assessed and, if necessary, treated for all other possible stroke risks. "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 everybody who’s had a stroke 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."

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, 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 allows patients and caregivers to connect with others living in similar situations.

The AHA/ASA also has an online community called the Support Network with a section dedicated to cryptogenic stroke survivors and their family caregivers. The goal is to connect people living with stroke and heart disease with others who are going through similar experiences.

Cryptogenic TIA

Bill Benedict with great-grandson Connor

Bill Benedict, 79, of Ithaca, New York, has had two stents and a mitral valve replacement. About a year ago he felt odd and went to the hospital for tests. "I don’t remember much about that," he said, "but they did a bunch of tests and told me I’d had a transient ischemic attack (TIA), but no cause was found."

A month later, he was sitting at the kitchen table with his wife, Dorothy, and daughter Susan when he started feeling strange. "I was dizzy and disoriented and terribly nauseated. I felt like I was mumbling," he said. Dorothy called 911 and he took an ambulance ride. On a gurney at the hospital, Dorothy asked him a question. "I remember thinking clearly about the answer, but I could tell from her response that I wasn’t making any sense," he recalled. They rushed him for more testing, but again the diagnosis was TIA of unknown cause.

This was more than a little concerning given his heart history as well as an older brother who’d had a stroke a few years before. "It was quite scary not to know," he said.

About a month later, he was at his cardiologist’s office, and she suggested that the cause of the TIAs might be AFib. She suggested he have a small heart monitor inserted in his chest. This monitor is about the size of a key and is put under the skin over the heart. It automatically detects and records abnormal heart rhythms.

Benedict agreed, and the monitor was inserted in January 2015. In April, it recorded an AFib incident that lasted about 90 seconds. He did not feel anything, but his cardiologist was able to see when it had happened at his next appointment. As a result, he is now taking blood thinners. Discovering AFib via monitoring doesn’t necessarily mean it was the cause of an unexplained stroke but diagnosing and treating AFib is important for reducing the risk of recurring stroke regardless.

"I think the heart monitor was a good recommendation by my cardiologist," he said. "I feel much better with this in me. It’s a relief."

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