Today’s video is on the subject of stroke and in particular cryptogenic strokes. 

A stroke is often a devastating occurrence for several reasons:

  1. A stroke can be life threatening and stroke is widely recognised as a leading cause of death worldwide
  2. A stroke can be disabling and can destroy a person’s quality of life
  3. A stroke can recur and cause more damage/death the next time.

It is therefore crucial to identify the cause of stroke and treat the underlying cause wherever possible.

Strokes are characterised by death of brain cells as a result of disruption of blood supply to those cells.

There are 2 major causes/ types of stroke

  1. Haemorrhagic – which accounts for 17% of all cases
  2. Ischaemic – which accounts for 83% of all cases.

In hemorrhagic strokes, there is a bleed and therefore the blood that would have gone to supply the brain cells goes somewhere else. In addition, because the brain lies within an enclosed space, the accumulating blood can actually cause pressure on the brain and damage it even further.

In Ischaemic strokes, there is some sort of blockage either in the major vessels that take the blood (this is called large vessel atherosclerosis)  to the brain or even in the smaller vessels (called small vessel occlusion). It is also possible that a blood clot may form somewhere else in the body and then can get dislodged and find its way into the vessels leading to the brain and can get lodged in one of the vessels and therefore disrupt the blood supply and cause brain cell death. This is called cardioembolism. Conditions such as AFib are often said to be associated with stroke as a consequence of cardioembolism.

In 15-40% of patients however, no obvious cause is found for the stroke on basic investigations. These patients are described as having had a cryptogenic stroke. 

A cryptogenic stroke can be particularly distressing for many reasons.

Firstly, cryptogenic strokes have a higher incidence in younger patients (< 45 years of age). Secondly, unless a cause is found it is difficult to be reassured that the treatment offered is truly reducing the recurrence of a second event. Thirdly the stroke may be the first symptom of something even more sinister such as malignancy or vasculitis.

It is therefore really important that such patients are subjected to a rigorous set of assessments  which extend beyond the basic investigations. In this video, I am going to discuss some of the important questions to ask and investigations to consider in patients with cryptogenic stroke that may help delineate an aetiology. 

  1. It is important to think of whether the neck has been manipulated in some way recently. In addition a recent dental or invasive procedure may be relevant. Also intravenous drug abuse and recent pregnancy is also very important to mention.
  2. In terms of symptoms, it is important to mention other symptoms that you may have noticed such as recent fatigue, claudication pains in the legs (which can suggest vasculitis). Also worth thinking of things like weight loss and night sweats which may signify underlying malignancy.
  3. It is also very important to mention a history of high blood pressure, diabetes, elevated cholesterol, family history of premature heart disease, stroke or even sudden death.
  4. When the doctor is examining the patient, it is important that he feels the pulses in both hands and measures the blood pressure in both arms. He should also listen very carefully to the neck and the heart for bruits and murmurs.

In terms of scans it is important to do a comprehensive set of imaging for the brain and the blood vessels around the head and neck. 

All patients who are admitted with a stroke should have an urgent CT scan of the head. This is important for several reasons.

  1. It will help delineate between hemorrhagic and ischemic stroke. This is important because if it is an ischemic stroke then you want to relieve the obstruction and this often requires blood thinners which could make a bleed worse
  2. In patients with an ischemic stroke, you can give a clot busting agent which can certainly help break the clot or obstruction but can make bleeding significantly worse.

When the CT scan is negative and doesn’t show an obvious stroke, it becomes important not to stop just there but do an MRI scan. Sometimes when the damage is in the posterior lobe of the brain, it may be missed on a CT scan and therefore an MRI scan is necessary.

The next step is to look at the blood vessels leading to the brain and in particular, the blood vessels in the neck (which are the carotid arteries). There are a variety of ways to look at these.

  1. Ultrasound – this is easily available, very portable and usually a very low risk investigation. Nevertheless, the views are often a little fuzzy and the quality is very dependent on the person doing the scan.
  2. CT angiography is quick and widely available but involves radiation exposure and also contrast exposure which could potentially date the kidneys in patients with already damaged kidneys.
  3. MR angiography on the other hand does not require contrast or radiation exposure but is very time consuming and requires even more specialised equipment.

The reason it is so important to look at the neck vessels is that there is evidence that if there is blockage of the big vessels then it may be possible to reduce the damage by mechanically fishing out the clot in the big vessels. Previously it was thought that this was only beneficial in 1 6 hour window, some studies are suggesting that it could be beneficial even if performed beyond 6 hours (up to 16 hours)

The next step is to study the heart in detail.

All patients should have a 12 lead ECG and be put on a 24 hour heart monitor whilst in hospital. The main reason is to look for the presence of atrial fibrillation which is associated with stagnation of blood within the heart with consequent clot formation. When AF is seen, it leads to a change in management. Patients are prescribed anticoagulants rather than simple antiplatelet agents. However just because an ECG and 24 hour monitoring does not show AF does not mean that one can reliably exclude AF as a possible cause for the stroke. In an ideal world you want to monitor the heart for a longer period. The question is how long should you monitor the heart for to feel sure that AF is definitely not present. 

Some studies have looked at this and they found that AF was detected in 3.2% of patients with a 24 hour monitor but if that monitoring period was extended to 30 days, AF was detected in 16.1% of patients. If you use an implantable device which is inserted under the chest and can stay on the patient for up to 2 years, the pick up of AF was 7.3 fold greater. Unfortunately many centres due to economic reasons will only offer 24 hours or at most 7 days recording and this is why if you are someone who has had a cryptogenic stroke, you should definitely insist on having either a 30 day monitor or even better, a REVEAL device. Remember if the stroke was due to a blood clot being dislodged from the heart then the standard stroke treatment (antiplatelets) will not adequately cover the risk of another stroke. 

It is also important for patients to have some form of imaging on the heart. This is to look for any mainly 4 things:

  1. To visualise a clot within the heart – which may sit in a small beak shaped structure of the atrium called atrial appendage or even in the ventricle.
  2. To look for any masses or tumours within the heart which may break off and go to the brain
  3. To look for vegetations which may result from an infection on one of the heart valves.
  4. To look for any shunts within the heart. If there is a shunt then it is possible that a small clot in the legs for example can go to the right heart, cross over through the shunt, go to the left heart and get dislodged from there and get stuck in the brain. It is true to say that a significant proportion of the population (about 20-25%) have a tiny hole in the hearts known as a PFO and just because you have a PFO clearly doesn’t mean you have a higher risk of strokes but nevertheless in people with a cryptogenic stroke, a coexisting PFO can provide a possible mechanism for the blood clot to go to the brain.

In terms of imaging, we usually start off with echocardiography (ultrasound assessment of the heart). Whilst this is readily available and fairly easy, it gives fuzzy images and is very dependent on body habitus. Also echocardiography itself does not visualise a small PFO or even clot in the left atrial appendage. A better test to look for a PFO is a bubble contrast echo. In this test, tiny air bubbles are injected into a vein. The microbubbles opacity the right heart and if there is a tiny shunt then the microbubbles can be seen in the left heart. If there is no shunt then the microbubbles are pushed by the right heart into the lungs where they dissipate and none are seen in the left heart. When a shunt is seen then sometimes it can be closed with keyhole surgery and this intervention may reduce the risk of another stroke.

Another way of imaging the heart is via a transesophageal echocardiogram. This is an invasive procedure and requires an ultrasound probe to be inserted into the food pipe under sedation. As the food pipe is geographically very close to the back of the heart, we are able to see the heart very clearly using this technique. A TOE is the best way of looking for clot within the atrial appendage.

IF there is nothing found on the heart scans, it is important next to study the blood itself. If the blood is rendered ‘thicker’ or more clottable, then this could also provide a mechanism for the stroke. There are a variety of hypercoagulable conditions. These include Antiphospholipid syndrome, bone marrow abnormalities, and malignancy. Primary thrombophilia can be the cause of 1-4% of cryptogenic strokes and 1 in 7 patients are found to have thrombophilia. 

Sometimes despite all these tests, we are never able to work out why the stroke happened. Nevertheless it is hugely important to be as rigorous as possible in looking for a cause.

As a cardiologist, I would always recommend prolonged heart monitoring of at least 30 days and ideally even longer and a bubble contrast echo in any patients with a cryptogenic stroke. 

I hope you found this blog useful.  I would love to hear from you as to whether you found this video helpful or not. This is the link to the video.

Stroke

 

Once again, thank you for doing all that you do for me.

Keywords: Cryptogenic strokes; AF; Afib; PFO; stroke; blood clots; thrombophilia; Antiphospholipid syndrome. 

 

References:

Mendirichaga et al, Evaluation of Cryptogenic stroke; American College of Cardiology 2019