Clinical Q&As
Why are some people well with CADASIL until their seventies whereas others present with symptoms much earlier?
The severity of CADASIL can vary widely within families. For example, within one family one member may have strokes in their forties or fifties whilst another may still be well when they are seventy. We do not fully understand why this is the case. Our research has shown that common risk factors such as smoking and high blood pressure make stroke occur earlier in patients with CADASIL, but this does not fully account for the differences within families. Other unknown factors also contribute. There is some evidence that genes other than the NOTCH3 gene may alter the severity of the disease and we are carrying out research trying to identify which these genes are.
How do I distinguish between a migraine attack and a TIA/mini stroke?
Migraine attacks are usually accompanied by headache, a feeling of sickness, and often intolerance of bright light. In CADASIL migraine attacks are also usually accompanied by an aura. The aura can be visual (often bright or coloured lights), sensory (often a feeling of tingling), speech (often the inability to find words), confusion, and loss of power in an arm or leg.
Sometimes it can be difficult to distinguish an aura which can occur without headache, from a mini stroke. In a mini stroke in CADASIL the most common symptoms are loss of power down one side of the body, or loss of sensation down one side of the body. The abnormality tends to on at the same time in both the arm and leg. Visual symptoms and inability to find the right words do not occur in CADASIL stroke.
Sometimes loss of power and an abnormal sensation can be difficult to differentiate between TIA and migraine, but a helpful pointer is that the symptoms in migraine often occur in one part of the body (for example, the face) and then spread gradually to other parts (for example, the arm), whereas in stroke they all come on at the same time. Also migraine symptoms are often possible (e.g. a tingling) whereas in stroke symptoms are usually negative (e.g. an inability to feel).
Is one’s gait affected in CADASIL as it progresses?
Gait can be affected in CADASIL. If a CADASIL patient has a stroke then they can have a limp secondary to weakness. However, gait can occasionally be affected without a stroke in a syndrome called gait apraxia. This is where disruption of connections within the white matter in the brain alters the ability to coordinate one’s walking. This can result in an unsteady and wide based gait or sometimes an abnormal gait due to small steps.
Should antiplatelet agents such as Aspirin be prescribed in CADASIL?
Drugs such as Aspirin reduce the risk of recurrent stroke in people who have already had common stroke. We don’t know whether they have a similar effect in CADASIL. Our policy is usually to recommend Aspirin or a similar antiplatelet drug called Clopidogrel (Plavix) in CADASIL patients who have suffered a stroke, or who are over age forty. However the evidence for this is not strong.
We would advise patients not to take both Aspirin and Clopidogrel because this combination is associated with an increased risk of bleeding into the brain in people with diseases of the small blood vessels in the brain. Similarly, we would advise against taking Warfarin or one of the new oral anticoagulant drugs unless there is a good reason for it (such as atrial fibrillation).
I have CADASIL. Should I take the oral contraceptive pill?
The combined oral contraceptive pill (which contains estrogen and progestogen) is associated with an increased risk of stroke. Even though this is small, we would advise against taking it if you have CADASIL. The mini pill (progestogen only) is associated with a lower risk of stroke and would be a better option if oral contraception is used.
I have CADASIL. Is it safe to take hormone replacement therapy?
HRT for menopausal symptoms is associated with an increased risk of stroke, probably due to a slight increase in blood clotting. For this reason it is better to avoid it in patients who have CADASIL. However, if the menopausal symptoms are very severe, sometimes a decision may need to be made to take it despite the increased risk, but this should be discussed in detail with your doctor.
Should statins be prescribed in CADASIL?
Statins have been shown to reduce the risk of recurrent stroke in people with common stroke. The evidence that they work in stroke caused by disease of the small blood vessels in the brain is much less strong. There is no evidence to show whether they do, or don’t, help in CADASIL. Because of their benefit in common stroke we tend to recommend taking statins in CADASIL if the cholesterol is elevated although the evidence for this is not strong.
What lifestyle changes can help with CADASIL?
Because it has been shown that common cardiovascular risk factors such as smoking and high blood pressure worsen CADASIL we would recommend that a healthy lifestyle is adopted which reduces cardiovascular lifestyle factors. This includes maintaining a normal weight, having a healthy heart friendly diet (details of such a diet can be found on websites such as the British Heart Foundation), not smoking, and avoiding excessive alcohol.
Regular exercise reduces blood pressure and has also been shown to reduce the risk of common stroke. There is increasing evidence that regular exercise also protects the brain from cognitive decline and dementia and therefore we would strongly recommend this.
Are there any supplements that have been shown to help with CADASIL symptoms such as co-enzyme Q10, omega-3, L-arginine or B vitamins?
There is no evidence that any of these supplements help in CADASIL. It was suggested that L-arginine might improve CADASIL and this could possibly increase the blood flow to the brain in people with CADASIL. However there is no evidence from clinical trials that this improves the outcome.
In people who have very elevated homocysteine levels we sometimes recommend reducing these with B vitamins and folic acid.
In what way is CADASIL dementia different from Alzheimer’s disease?
CADASIL can cause cognitive problems and dementia by damaging the white matter in the brain through which pathways run connecting different regions of the brain. It therefore causes what we call a “disconnection syndrome” in which complex networks in the brain are disrupted. This tends to produce symptoms such as slowing of brain processes, and also difficulty in planning or multi-tasking. Sometimes attention is also affected. Memory problems can occur but are not such a prominent early feature of the disease.
In contrast, Alzheimer’s disease affects the cortex (outer surface) of the brain and tends to produce prominent memory and orientation problems earlier in the disease.
Can CADASIL affect libido?
Many diseases including CADASIL can affect libido when the disease becomes severe. Libido can also be greatly affected by psychological consequences of disease such as anxiety and depression. Therefore if you suffer from this symptom it is worth asking your doctor because if it is due to anxiety or depression treating this can improve libido.
Can CADASIL cause problems in children?
Occasionally children with CADASIL can develop migraine, but migraine is common in children and young adults anyway. Other than this CADASIL does not produce problems in children.
Can CADASIL alter personality?
Sometimes the cognitive problems in CADASIL can result in an apparent alteration in personality. It can make the sufferer lose motivation and interest in their previous activities; this is called apathy. Sometimes they can make the sufferer appear less tolerant and become angry more easily. These symptoms can be distressing for both the CADASIL patient and their family. Similar symptoms can also be produced by depression and therefore it is important to ask your doctor if they could be due to depression because this can respond to treatment.
Where can I find information on CADASIL?
On this website we hope to provide useful information on CADASIL which is presented in a clear and balanced fashion. There are also links to other sites at which information can be found. There are many sites which have additional information, but in some cases it is not balanced and could cause unnecessary worry or confusion for CADASIL sufferers and their families.
What happens after a diagnosis; should I have periodic reviews? If so, how frequently?
This is up to you and patient preferences vary. If people with a CADASIL diagnosis remain well we often review them, and this can be by telemedicine, on a yearly basis. If they are having problems we would review them more frequently. However, some people who have had a CADASIL gene diagnosis but remain well prefer not to be seen and to just get on with their life. This is an equally reasonable option. If this is the case it is important that you occasionally have your blood pressure checked by your GP and continue to practice a healthy lifestyle.
Is there a UK patients group for CADASIL?
CADASIL Support UK is fantastic charitable organisation and support group set up by those with CADASIL for others with CADASIL and their families. You can find them on Facebook under 'Cadasil Support UK' here and on their website here.
Research Q&As
Can I become involved in CADASIL research?
At The University of Cambridge we have an active CADASIL research programme. We collaborate with other groups throughout the UK who are interested in carrying out research in CADASIL.
Your permission is required for us to be allowed to contact you. If you would like to sign-up to be contacted about research, then please let Molly Henthorn know by emailing mmh64@medschl.cam.ac.uk.
When the researchers get in touch, they will provide you with a ‘Participant Information Sheet’, which contains all of the information about the study. They can help to answer any questions and discuss the study further with you. If you decide to take part, you will then be asked to sign a ‘Consent Form’, which states that you have read and understand all the information about the study and are happy to take part.
What is the focus of current research into CADASIL?
*All areas starred are those we are working on at Cambridge.
Do you get any benefits from taking part in research?
The main benefits of taking part in research are altruistic, to help us further our knowledge of the disease and increase the likelihood of us being able to treat it.
We are able to refund your travel expenses for you, but do not give you any other monetary benefit. Further, you do get time with the researchers in that area which provides you with an opportunity to ask questions. You will also receive a report back about the findings of the research study once it is all complete.
What are the drawbacks of taking part in research?
The main drawback for a lot of patients involved in our research is that it often requires you coming to Cambridge, which can be a long way for some patients. Further, the procedures that are involved in the research may not always be enjoyable. For example, if the research involves taking blood then you may not enjoy the blood test. Or if the research involves an MRI scan then some people can find this claustrophobic and noisy. Some studies that involve testing medications or other medical procedures can have some risk from the potential side effects, although we are currently not doing this type of study at Cambridge.
Every study is reviewed by an independent ethics committee before it is able to begin, to make sure that any risk is minimal and that the benefits outweigh any risks. Participants have all of the procedures and risk explained to them in an information sheet that they read before signing up to the study.
Can we help raise money for CADASIL research at Cambridge?
Medical research is very expensive . We are fortunate to receive support form a number of government and charity funders. However additional support is always very helpful to use in enabling us to carry out CADASIL research. We have a CADASIL fund which is run through the Addenbrooke’s Charitable Trust. This allows gift aid to be claimed back on donations which increases the amount we receive for donations from taxpayers. If you would like to donate you can find details here.