Cryptogenic Stoke: A Stroke of Unknown Cause

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 Cryptogenic Stoke: A Stroke of Unknown Cause

Common Classifications of Stroke Cause

When a person has damage to the brain from a lack of blood flow, this is considered an ischemic stroke. While great attention is appropriately placed on how to best treat the stroke immediately to improve outcome, equally as importance is finding the cause of the stroke to prevent having another stroke.

We know that having had a stroke is a major risk factor for having another stroke. While there are steps that can be taken to reduce stroke risk in general, knowing the cause of a stroke can help the Vascular Neurologist tailor medications and interventions to best prevent another stroke. Not all strokes are equal, and stroke prevention is not all equal.



The most common causes of stroke can be categorized as:

Stroke due to cardioembolism, or a blood clot that started in the heart traveling to the brain. A common example of this is atrial fibrillation, where the top chamber of the heart quivers and clots can form in the nooks and crannies. These clots can then pass to the brain to cause stroke.

Stroke due to large vessel atherothromboembolism, or a blockage in a large artery that causes a lack of blood flow in the brain. One example of this is carotid stenosis, or narrowing of the major blood vessel in the front part of the neck due to plaque from cholesterol and high blood pressure.

Brain blood clot medical concept as 3D illustration blood cells blocked by an artery blockage thrombus causing a blockage of blood flow to the neurology anatomy. 

Stroke due to large vessel atherothromboembolism, or a blockage in a large artery that causes a lack of blood flow in the brain. One example of this is carotid stenosis, or narrowing of the major blood vessel in the front part of the neck due to plaque from cholesterol and high blood pressure.

Stroke due to small vessel occlusive disease, or a narrowing or blockage in the tiny arteries in the brain. These blood vessels are very sensitive to the effects of high blood sugar and high blood pressure and when narrowed can lead to small strokes in the deeper parts of the brain, termed lacunar strokes.Strokes due to uncommon known causes. This can include things such as tearing of a blood vessel called an arterial dissection, genetic conditions that cause clots to form in arteries, autoimmune conditions causing inflammation in the blood vessels, drug abuse, or other causes.

Cryptogenic stroke, or sometimes referenced as stroke of undetermined origin.

Cryptogenic Stroke: What Does This Mean?

What does this term Cryptogenic actually mean? It sounds impressive and rare. It is difficult for patients to understand. “Crypto” comes from a Greek base, meaning “hidden.” “Geni”c also is derived from Greek, meaning “origin” or “cause.” In the end, this complex word simply signifies that the origin of the stroke is still hidden – yet to be discovered. Cryptogenic stroke does not mean that the origin is necessarily impossible to find, but it is merely still hidden. It is the role of the expert Vascular Neurologist – or Stroke Neurologist – to pursue all the appropriate advanced testing to try to discover this cause and inform the treatment to prevent another stroke.

Are Cryptogenic Strokes Rare?

Frustratingly, cryptogenic strokes are quite common – at least initially. Multiple scientific medical studies have shown that up to 1 out of every 4 strokes is termed cryptogenic at the time of discharge from the hospital.

This is why it is of the utmost importance to have later follow up with a Vascular Neurologist to pursue further testing to find the cause. Finding a cause may make the difference between having another stroke with disability or maintaining a healthy brain with full function.

Culprits for Cryptogenic Stroke

Atrial fibrillation

As mentioned above, atrial fibrillation is where the top chamber of the heart quivers and does not pump well, so clots can form there and then travel to the brain to cause stroke. Many people who have atrial fibrillation have no symptoms due to this and do not feel any “fluttering” or palpitations in their chest.

  • While a heart monitor may be in place for the few days the patient is in the hospital after stroke, the yield of finding atrial fibrillation is low in that short duration. The longer that monitoring is done, the more likely it is that atrial fibrillation will be found. Heart monitoring for a month increases the chance of finding atrial fibrillation by more than 500%. For this reason, a surface heart monitor that usually involves a sticker placed on the chest and a wireless receiver will commonly be done in the setting of cryptogenic stroke. If the suspicion is high, the Vascular Neurologist will occasionally pursue an implanted heart monitor to evaluate for atrial fibrillation for up to 3 years.
  • if atrial fibrillation is found the person would most likely be better protected from further stroke by a transition to a stronger blood thinner or anticoagulant such as Eliquis, Xarelto, Pradaxa, or Coumadin.

Aortic atheroma

  • As mentioned above, atrial fibrillation is where the top chamber of the heart quivers and does not pump well, so clots can form there and then travel to the brain to cause stroke. Many people who have atrial fibrillation have no symptoms due to this and do not feel any “fluttering” or palpitations in their chest.
  • The aorta is the major blood vessel coming off the top of the heart to supply blood flow to the brain and entire body. The first portion is called the “ascending aorta.”
  • Occasionally, a plaque or atheroma can attach to the aorta here. When brisk blood flow goes past this from the heart, small pieces can break off and travel to the brain to cause ischemic stroke
  • Aortic atheromas are often not seen on routine echocardiograms – or ultrasounds of the heart – done with the test probe against the chest during hospitalizations for stroke.
  • The Vascular Neurologist may consider a more detailed ultrasound of the heart and aorta, called a transesophageal echocardiogram (TEE), where the test probe is swallowed and held against the heart and aorta to get a much better picture and evaluate for any atheroma

Finding atrial fibrillation changes stroke prevention significantly. While the average cryptogenic stroke patient will be on aspirin

  • The presence of an atheroma can significant change management for stroke prevention, as typically multiple antiplatelet medications will then be used together and occasionally a procedure may be considered to address this.

Paradoxical embolism from a shunt

  • A “shunt” is present when blood flow can travel across the vasculature without going through the lungs. This can be due to a variety of structural issues, but the most common is called a patent foramen ovale (PFO)
  • A PFO is a hole in the top part of the heart that all people have as they develop in the mother’s womb, but in about 80% of people closes on its own after birth. When a PFO is still present later in life, it is considered a congenital heart defect, which means a heart structure problem since birth. In contrast to other congenital heart defects, PFOs do not cause significant problems with oxygen levels or growth, as they are typically quite small. As the person likely has no symptoms, most people with a PFO do not know that they have it.
  • Occasionally, this small PFO can allow a blood clot from the legs or elsewhere to pass through the top part of the heart without being filtered out by the lungs, then traveling to the brain and causing ischemic stroke.
  • If a PFO is larger or associated with a weakness in the wall in the top of the heart, it can be called an atrial
  • septal aneurysm, where there is more “floppiness” in the tissue that can lead to clot formation at the site itself, causing stroke.
  • Occasionally, the shunt may be found closer to the lungs in what is considered a pulmonary arteriovenous malformation
  • Your Vascular Neurologist will likely consider doing more testing to evaluate for a shunt, such as a “bubble study,” CT angiogram of the chest, or occasionally a heart catherization.
  • If a PFO is found and thought to be the cause of the stroke, stronger blood thinners or a minimally invasive heart procedure to correct the defect will help prevent any further stroke.

Hypercoagulable state

  • A hypercoagulable state is a situation in which a person has a clotting disorder that makes them more likely to form clots, which can cause ischemic stroke
  • One category of this is genetic or inherited clotting disorders. This includes things like Factor V Leiden mutations or Prothrombin 20210a mutations.
  • Another category is due to acquired clotting disorders from autoimmune conditions. Antiphospholipid antibody syndrome is associated with lupus and causes someone to be very likely to form blood clots unless they are placed on strong blood thinners.
  • Finally, certain underlying and sometimes undiagnosed cancers can cause someone to be more likely to form clots. For this reason, certain people with cryptogenic stroke should undergo screening for any underlying cancers.
  • If one of these hypercoagulable conditions is discovered, the person will benefit from going on a stronger anticoagulant blood thinner to prevent stroke. The typical aspirin alone would not adequately prevent further stroke.

A Forefront of Stroke Care

When it comes to cryptogenic stroke, there are likely causes of stroke that are not yet fully understood or discovered. This is an exciting area on the forefront of neurology with ongoing research. There are a couple theories that seem most promising:

  • Atrial cardiopathy
    • It is thought that some people may have an atrium – the top chamber of the heart – that does not pump or empty well, but without the abnormal heart rhythm of atrial fibrillation. This may lead to clot formation as a cause for stroke. This can be evaluated with an electrocardiogram (EKG) assessing the electrical system of the heart, echocardiogram (ultrasound of the heart) taking measurements of the heart, or by certain blood tests.
    • There are major ongoing clinical trials identifying these patients and seeing if they are best served by an anticoagulant strong blood thinner to prevent stroke, as would be used in atrial fibrillation.
  • Substenotic cerebrovascular disease
    • Substenotic cerebrovascular disease refers to a narrowing in a blood vessel in the head or neck that does not meet the percentage of narrowing to be considered “significant.”
    • For example, with carotid stenosis typically a surgery would be pursued only if the degree of narrowing is greater than 60% and causing the stroke, based on previous clinical trials.
    • However, there are theories that the degree of stenosis is not the only important factor, and there may be other factors such as clot type or composition that can affect likelihood of causing stroke.
    • It is being investigated if advanced magnetic resonance imaging (MRI) vessel-wall sequences or monitoring for microembolism (tiny clots passing to the brain) with continuous transcranial doppler ultrasound can help identify people whose strokes were caused by a plaque in a blood vessel, even if that percentage of narrowing is not “significant.” These people may then benefit from a procedure on that blood vessel to address the plaque.

Cryptogenic stroke is a common phenomenon where there is no clear answer for what caused the stroke on initial review. However, we should not stop there, as that can leave someone at risk for having another stroke. Partner with a qualified Vascular Neurologist through NeuroX to do the right tests to find the hidden cause and help you avoid having another stroke.


About Dr.Watson

Dr. Watson is an avid researcher and has published numerous articles in healthcare niche, especially in neurology. His research combined with his experience provide a unique and accurate look into neurological issues and related topics.

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NeuroX is a project of American TelePhysicians, founded in 2020 in Jacksonville, Florida, intending to become a complete & comprehensive neuro & psych care portal. NeuroX provides both patients and providers the resources and tools needed to ensure outstanding integrated neurological, psychological & psychiatric clinical care with efficiency and cost savings.

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