Sometimes, even with extensive testing, the cause of a stroke can’t be determined. These strokes are called cryptogenic strokes.
Doctors are working to reduce the number of strokes that are classified as cryptogenic. They are doing this by screening for a possible cause, such as atrial fibrillation (AFib), and through more thorough evaluations, like 24-hour ECG monitoring and transesophageal echocardiography.
In many cases, a stroke is caused by a blood clot that blocks the flow of oxygen-rich blood to the brain. But in some cases, the cause of a stroke is unknown. These are called cryptogenic strokes, and they occur in 25-40% of ischemic strokes.
A cryptogenic stroke happens when a person experiences a transient ischemic attack (TIA) or stroke-like symptoms that last a few hours, but the cause is never discovered. It can also be a symptom of underlying conditions, such as a vascular disease or an arrhythmia.
Having a stroke or TIA is an emergency, and it’s important to seek medical attention immediately. The sooner treatment begins, the lower the risk of permanent damage.
Stroke patients often undergo a rigorous workup, including an extensive cardiac evaluation with electrocardiography, echocardiography and magnetic resonance imaging. However, despite this extensive testing, the cause of the stroke may remain unclear. This is known as cryptogenic stroke or idiopathic stroke.
Research suggests that a cryptogenic stroke can be due to a number of different factors, including heart valve problems, atrial fibrillation, complex aortic atherosclerosis and hypercoagulable states. One possible cause of cryptogenic stroke is a patent foramen ovale (PFO). This is a hole in the heart that’s present from birth but doesn’t close completely as people get older. People with PFO have an increased risk of having a paradoxical embolism from upstream veins through the PFO, which can lead to a stroke.
According to the latest data, a longer duration of continuous monitoring with implantable loop recorders can increase detection of silent AF and improve the diagnosis of a cryptogenic stroke. This may reduce the proportion of strokes misclassified as cryptogenic if it is widely implemented.
Identifying the underlying cause of a stroke can help doctors know which type of prevention is most effective for reducing the risk of another stroke or TIA in the future. For example, if the underlying condition is AFib, doctors can prescribe anticoagulation medications instead of antiplatelet therapy to decrease the chances of having another clot-related stroke. The right treatment can reduce the risk of a cryptogenic stroke by as much as 40%, so it’s crucial that all potential causes be investigated.
Cryptogenic stroke is defined by a lack of identifiable cause for the ischemic event. This may be due to a variety of reasons, including occult arterial or cardiac disease and unidentified subtypes of intracranial atherosclerosis. It is also possible that the clot or embolism was triggered by some unknown factor such as hypercoagulable states, vasculitis or even cancer. The work-up for these patients includes brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI), neurovascular imaging with CT angiography or MR angiography of the carotid artery, echocardiography, and transcranial Doppler studies of the vessels suspected of being involved in the event. Other investigations include blood tests for full blood count, clotting times, C-reactive protein and erythrocyte sedimentation rate, liver function, thyroid function, electrolytes, and lipid profile. In select patients, rapid plasmin reagin testing, erythrocyte sedimentation rate, thrombophilia screening, and genetic analysis can also be used to identify atypical causes of cryptogenic stroke.
In one study of 2555 patients who had a first cryptogenic TIA or stroke, 45% of patients remained cryptogenic at 12 months follow-up (figure 1). Among those that were identified as having the underlying cause of their stroke, AF/atrial fibrillation and cancer accounted for 29% and 17% of the cases respectively. Those remaining cryptogenic were younger, had lower CHA2DS2-VASc scores and mRS on admission, and were more likely to be smoking and to have dyslipidaemia. In addition, they had higher acute D-dimer levels compared with those whose etiology was ruled out.
This reflects the fact that they have a more complex and difficult to investigate underlying cause than those who had confirmed large artery disease, small vessel disease, or other known causes of stroke. Compared with those who had large artery disease, they had a similar 10-year risk of presumed cardioembolic stroke but had a lower risk of peripheral vascular disease. Acutely elevated NT-proBNP levels suggest the presence of an occult arterial or cardioembolic thromboembolic cause, and this explains why warfarin was more effective in these patients than aspirin in reducing their recurrent stroke risk (see appendix p 8). The diagnosis of a cryptogenic event is important because it increases the potential for secondary prevention.
Most strokes are ischemic, caused by blood clots blocking or damaging arteries that supply blood to the brain. Hemorrhagic strokes are less common and are caused by a ruptured blood vessel that leaks or breaks in the brain, causing bleeding. But sometimes, even with extensive testing, doctors can’t identify the cause of a stroke. When that happens, it’s called cryptogenic.
The first step in diagnosing a cryptogenic stroke is to evaluate the patient’s symptoms, history and risk factors. Doctors can then order tests to look for the underlying cause of the stroke. These tests and exams can help doctors see structural elements of the heart, brain and arteries, as well as measure heart behavior and blood composition.
These tests may include imaging of the blood vessels in and around the brain (CT or MRI), noninvasive testing of the carotid arteries to find plaques that could be contributing to the stroke (MRI, CT angiography, transthoracic echocardiography, aortic arch examination by ultrasound with TEE or MR) and long-term cardiac monitoring for atrial fibrillation (electrocardiogram and continuous long-term outpatient cardiac telemetry).
For some patients, advanced imaging techniques can reveal hidden abnormalities that would otherwise go undetected. For example, a study of symptomatic patients with asymptomatic carotid stenosis showed that the presence of a plaque in the adjacent segment of the artery was a strong predictor of future stroke (Kalibak et al., 2000).
Further testing may also be necessary in some cases to determine whether a specific condition is causing the stroke. For instance, an inherited or acquired condition known as thrombophilia can increase the risk of a stroke, so it’s important to check blood clotting factors and the condition of the aorta — the body’s main artery that extends from the heart — for any signs of damage or inflammation (Kopczak et al., 2019).
Depending on the results of these tests and exams, doctors can decide what treatment is appropriate for the cryptogenic stroke. For most people, that includes taking medications to prevent blood clots or slow the rate of blood clotting. The medications can be prescribed alone or in combination.
Many of the same treatments used to prevent another stroke in someone who’s had one are also effective for cryptogenic stroke. These include medication to stop blood cells, called platelets, from sticking together and forming clots in blood vessels. Medications to reduce cholesterol and other blood fats may also be prescribed.
In most cases, doctors don’t know the cause of a cryptogenic stroke and can’t treat it directly. But different tests and exams can help figure out what might have contributed to the stroke and identify ways to prevent it from happening again.
For example, people who have a type of irregular heartbeat called atrial fibrillation are at a higher risk for cryptogenic stroke and need to be treated with blood thinners. They may need to have an implanted device that keeps blood clots from forming.
Other underlying conditions that contribute to cryptogenic stroke can be treated with medications. These include a condition called thrombophilia, which is a genetic disorder that increases the chances of blood clots forming. It can be treated with anticoagulants, or blood thinners that reduce the chance of clots forming in the brain and other body organs.
Whether or not to treat a person for an underlying problem that’s causing a cryptogenic stroke is a personal decision made by the patient with the help of his or her family and doctor. For most people, long-term treatment will involve antiplatelet and/or anticoagulation therapy, but the exact medications prescribed will depend on the specific underlying condition found or suspected to have caused the stroke.
Research is ongoing to find out the best way to evaluate and treat people who have had a cryptogenic stroke. New tests, such as a blood test that measures levels of the protein NT-proBNP, are being investigated in the hopes that they will help identify more of the causes of cryptogenic stroke.
Ischemic strokes, caused by blood clots that block blood flow to the brain, account for about 85% of all strokes. But sometimes doctors can’t find a clear cause. These cases are called cryptogenic.
Most people with cryptogenic strokes get medications to prevent future blood clots. These include antiplatelet and/or anticoagulation therapy.
In most strokes, a blood clot blocks or ruptures a blood vessel and stops oxygen flow to the brain. But in about 1 in 4 strokes, doctors can’t find a clear cause. These are called cryptogenic strokes. Having one can cause serious problems, including weakness and difficulty walking. It can also lead to falls and trouble swallowing, which can lead to aspiration pneumonia. But with a good health care team and some targeted tests, you can help reduce your chances of another stroke.
Doctors use brain imaging to look for evidence of a blocked artery or bleeding in the brain. They can also do a blood test to check for clot-forming proteins and other signs of clotting. If the results aren’t clear, a doctor may recommend that you have more tests to check the electrical conductivity and structure of your heart. They might suggest transesophageal echocardiography (TTE) and Holter or ELR (seven-day ambulatory ECG monitoring) to check for atrial fibrillation.
Studies have shown that if you have a patent foramen ovale, which is common in older people, you are more likely to have an ischemic stroke than someone without the defect. So you might benefit from treatment with warfarin or aspirin to prevent another stroke. But you need to talk with your health care team about the benefits and risks of these treatments.
You can also have cryptogenic TIAs (transient ischemic attacks). These are similar to stroke but don’t result in a permanent or severe loss of function. If you have a TIA, it’s important to get treated right away because it can be a warning sign of a future stroke.
A stroke is a type of brain attack that occurs when a blood vessel supplying oxygen to the brain becomes blocked or narrowed. Most strokes are caused by clots that break off from a larger plaque in a blood vessel and travel to the brain, but sometimes, doctors cannot determine what causes a person’s stroke. These are known as cryptogenic strokes.
These strokes are still treated just like other strokes, but it’s important for people to know their risk factors so they can get medical attention right away. Some of the symptoms that can be associated with cryptogenic stroke include dizziness, loss of balance, and trouble speaking. The most common cause of a cryptogenic stroke is atrial fibrillation (AFib). This is an irregular heartbeat that increases your risk for stroke by 5x. Other common underlying conditions that can lead to a cryptogenic stroke include migraines, vascular tearing, or an unstable rupture of a mildly stenotic plaque in a blood vessel.
Despite how common these occurrences are, there is still hope for those who experience them. A 2016 study found that a stroke’s cause could be determined in more than half of the patients who experienced a cryptogenic stroke or transient ischemic attack (TIA). The researchers recommend that all cryptogenic stroke patients undergo extensive diagnostic tests and continuous cardiac rhythm monitoring using an implantable cardioverter-defibrillator (ICM) device.
This testing includes a full neurological examination and a comprehensive cardiovascular workup, including an ECG Holter or ELR, CHA2DS2-VASc score, invasive hemodynamic assessment, and transthoracic echocardiography. It also recommends screening for thrombophilic states and the use of an ICM device to monitor for atrial fibrillation. Detection of AF influences the therapeutic options for those without contraindications to oral anticoagulants, making this an essential test in all stroke and TIA patients.
Even with these tests and exams, it’s not always possible to determine what caused a person’s cryptogenic stroke. It is still a good idea to know the risk factors that they have for a stroke, though, because some of them are modifiable. These risk factors can be reduced through lifestyle changes and medication.
The brain controls the muscles in your face and mouth that help you speak. If a stroke affects this area, it can cause slurred or difficult-to-pronounce words (aphasia). It can also affect your coordination and clumsiness. Different areas of the brain control different abilities, so your symptoms depend on where in the brain the stroke occurred.
Cryptogenic Stroke symptoms may also include trouble walking or balance issues, or a loss of memory. In rare cases, a stroke can also cause seizures. If you have these symptoms, it’s important to see a doctor as soon as possible. These are signs of a severe stroke and you should be treated right away to reduce your risk of another stroke or heart attack.
A standard evaluation of ischaemic stroke or TIA includes neurological examination and assessment of common modifiable risk factors such as blood pressure, cholesterol and diabetes. In addition, 24-hour ECG monitoring and a transthoracic echocardiogram are performed to identify potential cardiac sources of ischaemic stroke, including intracardiac thrombus and valvular disease. In the absence of a clear small-vessel mechanism, further investigations are recommended, such as long-term cardiac rhythm monitoring with implantable monitoring devices, which have shown to be superior to conventional follow-up strategies for identifying atrial fibrillation (AF) in patients with cryptogenic stroke and TIA.
Approximately one third of strokes remain unexplained after extensive evaluation, and are classified as cryptogenic, or of unknown cause.1 The majority of these patients are younger and have fewer traditional vascular risk factors. Many of these patients have a cryptogenic embolic stroke of undetermined source (ESUS). Several mechanisms have been proposed for ESUS, such as occult cardioembolism from a patent foramen ovale, asymptomatic carotid stenosis, paroxysmal embolism, hypercoagulable or prothrombotic states and cardiac structural abnormalities.
However, further studies are needed to determine the long-term outcome and efficacy of antithrombotic and pharmacological therapies for patients with cryptogenic ischaemic stroke. Closure of a PFO and anticoagulation therapy have been reported to improve outcomes, particularly in patients with a cryptogenic embolic stroke associated with a high-risk PFO.
When someone has a stroke, their brain is not getting enough blood to supply it with oxygen. This is called an ischemic stroke, and it can happen because of a clot or because of something blocking a blood vessel in the brain (hemorrhage). Sometimes doctors can’t find what caused the ischemia. These are known as cryptogenic strokes. It’s important to understand what these strokes are so that they can be treated and prevented.
Some people have a cryptogenic stroke and don’t even know it. If you are worried about your family or friends, encourage them to see a doctor as soon as possible. They may need physical, occupational, or speech therapy to help them recover from their symptoms. It’s also important to talk about depression, which is a common complication of stroke and can lead to worsening of symptoms.
Cryptogenic strokes can occur in people of any age or gender, and they are more common in people with other health conditions like high blood pressure and diabetes. Some of the most important things you can do to prevent a cryptogenic stroke are to exercise regularly, maintain a healthy weight, control your blood sugar levels, and quit smoking.
A cryptogenic stroke can be difficult to diagnose, but ongoing research is improving methods for diagnosis and treatment. For example, a new study found that some cryptogenic strokes are caused by atrial fibrillation (AF), which is an irregular heartbeat that puts you at 5x the risk of stroke. The study recommends longer monitoring for AF, which can be done with a wearable device.
Another way to prevent a cryptogenic stroke is to get regular health screenings, especially for diabetes, high blood pressure, and cholesterol. These screenings can help you take action before a problem occurs. Lastly, you should talk to your doctor about lifestyle changes you can make to reduce your risk of a stroke. If you do have a cryptogenic stroke, there are medications that can help prevent a second stroke. These include aspirin, clopidogrel, and tPA. Talk to your doctor about what medications are best for you.
In most cases, a blood clot that blocks blood flow to the brain causes a stroke. But in about 20% of strokes, a specific cause can’t be found. These are known as cryptogenic strokes.
Scripps cardiologists use advanced testing to look for the underlying cause of stroke and other symptoms like TIA (transient ischemic attack, or ministroke). These tests can include an MRI or CT scan, echocardiograms and Holter monitoring.
A large portion of strokes occur when a blood clot blocks the flow of blood to an area in the brain, causing damage and loss of function. Most ischemic strokes are caused by atherosclerotic plaque build-up in the artery that leads away from the heart, which can rupture and cause a clot to reach the brain. However, sometimes doctors can’t find a specific cause of a stroke and consider it cryptogenic. Different tests and exams can help determine the cause, including an echocardiogram (an ultrasound of the heart), blood tests, CT scans of the head and brain, and MRI studies.
A 2016 study found that, while TIAs are often treated with anticoagulants and other preventive measures, cryptogenic strokes remain undiagnosed. As a result, patients are not being treated for conditions that may reduce their risk of another stroke, such as atrial fibrillation, valvular heart disease or diabetes, and have higher rates of disability and death.
One potential cause of a cryptogenic stroke is an undiagnosed patent foramen ovale (PFO), a condition where a hole in the heart allows blood to flow from the right side of the heart to the left. The hole is usually small, but in some people the opening is larger and can lead to a blood clot traveling through the PFO to the brain.
Whether or not this is the case, the PFO should be evaluated using an echocardiogram and a computed tomography angiography test. If the opening is detected, a closure device can be implanted to close it and reduce your risk of future strokes.
If you have had a cryptogenic stroke, our team of interventional cardiologists and neurologists will work together to assess your symptoms and determine the underlying cause of your stroke. Our experts will review your medical history, perform a physical examination and use imaging to look at the blood vessels in your neck and brain. We also use ambulatory ECG monitoring to detect episodes of atrial fibrillation and recommend treatment. We have the experience and expertise to offer a wide variety of treatments that can reduce your chances of having a cryptogenic stroke.
Atherosclerosis in the aortic arch is a relatively common cause of cryptogenic stroke. Plaques in the aortic arch can be dislodged from their parent vessel and migrate to embolic areas, including the brain. Until recently, carotid disease and atrial fibrillation were considered the major culprits in this group of patients, but data from stroke data banks suggest that plaques in the aortic arch can also play an important role (5-7). The presence of aortic arch atheroma in cases of unexplained stroke has been shown to confer an increased risk for subsequent ischemic events. This is particularly true when the plaques are large (>4 mm), and/or have mobile components. The occurrence of asymptomatic cerebral embolic signals in the presence of such lesions further supports the importance of this vascular territory as a potential source of ischemic events.
The aortic arch is a difficult vascular territory to evaluate, due to its location and the difficulty of accessing it with standard diagnostic techniques. However, aortic arch atheroma has been demonstrated to be associated with cryptogenic stroke in the past, and it is now recognized that this condition should be included among the list of possible causes of unexplained stroke.
In one study, aortic arch atheroma was shown to increase the risk of ischemic stroke by 61%, compared to non-aortic arch atherosclerosis alone. A similar association was found with the occurrence of asymptomatic embolic signals in the presence of aortic arch atheroma, confirming that these lesions are a significant source of ischemic events.
Several other factors contribute to the increased risk of aortic arch-associated ischemic events, including plaque thickness and the presence of mobile components. The latter feature is usually identified by the presence of pedunculated thrombi within aortic arch plaques on transesophageal echocardiography, and it is a strong predictor for future stroke in untreated patients. In addition, aortic arch atheroma with ulceration on the surface of the plaque increases the risk of ischemic events by over 40%.
The incidence of aortic arch-related embolic events can be significantly reduced by anticoagulation and/or antiplatelet therapy. Specifically, aspirin has been shown to reduce the risk of new arterial ischemic events in patients with aortic arch atheroma that have not yet undergone thrombolysis or surgery. In cases of recurrent ischemic stroke, aortic arch endarterectomy has been reported to be effective in reducing the number of recurrent emboli (8,9,11).
A stroke happens when blood flow to a part of your brain is blocked by a clot or when a weak blood vessel ruptures. In most cases, doctors can figure out the underlying cause of your stroke by doing a thorough medical workup and using different tests. But in a small number of cases — called cryptogenic strokes or strokes of unknown origin — no specific cause can be identified.
The good news is that researchers are continuing to uncover new ways to prevent cryptogenic strokes. In the meantime, it’s important for anyone who has suffered a stroke to get a thorough evaluation by doctors and to take action to reduce their risk.
Typically, doctors who are treating someone with cryptogenic stroke will start by doing a complete blood workup to see if there are any factors that could increase your chances of another stroke. They’ll also examine your neck and skull for signs of vascular malformations, such as aneurysms, and look at your brain tissue through brain imaging. They’ll also check for a number of heart conditions, including atrial fibrillation (AFib), which increases your risk of stroke five times more than normal.
In addition to these tests, you should have a comprehensive echocardiographic study to look for any cardiac sources of thromboembolic embolism, such as a patent foramen ovale (PFO), a ventricular septal defect or an aneurysm of the atrial septum. This can be done by doing a transesophageal echocardiogram. A PFO-related thrombus can also be diagnosed with venography of the lower extremities, such as a calf vein test.
At Scripps, our cardiologists have years of experience in diagnosing and treating these complicated heart cases. We’re the first on the West Coast to use an FDA-approved device to close a PFO and significantly reduce your risk of stroke. We’ve also used this device to help patients with other types of heart defects, such as a ventricular septal defect or an aortic arch atheroma. We also have extensive experience with a wide range of other heart devices and treatments for irregular heart rhythms.
A cryptogenic stroke occurs when a person suffers a stroke that can’t be linked to an obvious cause. These types of strokes account for about 25% of all ischemic strokes, which are caused by blood clots in the arteries that supply blood to the brain. Hemorrhagic strokes are the other type of stroke, and they occur when a weakened blood vessel ruptures in the brain. Both of these kinds of stroke can be prevented by taking steps to avoid the risks.
Doctors who are experienced in treating these patients can usually find the cause by a thorough evaluation. This might include examining the structure of the brain, vascular system and heart, looking at blood vessels through imaging and a variety of tests and exams that measure heart behavior and blood composition.
For example, doctors might check for a genetic disorder called thrombophilia, which means that your blood has an increased tendency to clot. If that’s the case, you may need to take anticoagulants to keep clots from forming in your arteries. They might also look for a condition called aortic arch atheroma, which is the development of fatty plaque (cholesterol) in the aorta, which is the body’s main artery.
A common irregular heartbeat, called atrial fibrillation, can also contribute to cryptogenic strokes. Doctors can detect AF using electrocardiograms, a cardiac catheterization test or the implantable cardioverter defibrillator device. But it can be hard to identify AF in someone who has had a stroke if the symptoms occurred while the person was asleep, or at work or other places away from the hospital.
Other conditions, like migraines or a vascular tearing, can also lead to a cryptogenic stroke. The best way to know if these are the cause is to see a doctor immediately after a stroke, so that treatment can begin before brain damage sets in.
Even if the doctors don’t find the cause of your stroke, you can help prevent another one by following healthy lifestyle recommendations and getting regular health screenings. These include eating well, exercising regularly and managing risk factors like high blood pressure and cholesterol levels.
