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Investigations for CADASIL

BRAIN SCANS (MRI)

A magnetic resonance imaging brain scan (MRI) is usually performed and shows characteristic appearances with abnormalities in the deeper parts of the brain known as the white matter (they appear as white on this example).

Involvement of certain brain areas including a region called the anterior temporal lobe appears to be a useful guide to the diagnosis. This is a safe scan that involves no radiation but some people find it rather claustrophobic. 

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MRI scan of Healthy Brain

 

 

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Typical MRI scan of a brain with CADASIL

 

 

GENETIC TESTING

If we can detect a genetic abnormality by diagnostic genetic testing, we can be 100% sure that someone has CADASIL. In CADASIL the abnormalities that occur are all within one gene which is called the NOTCH3 gene.  However, this gene is made up of many thousands of building blocks (base pairs).  In CADASIL, there is an abnormality (mutation) in only one of these.  It can be a very time-consuming process, excluding an abnormality in the whole gene which is made up of 33 different parts, known as exons.  For this reason routine genetic testing of the whole gene, is not offered in CADASIL. Research has shown that most of the abnormalities tend to occur in certain parts of the gene. The St Georges’s laboratory now screens exons  2, 3, 4, 5, 6, 8, 11, 18, 19 & 22.  By doing this we are able to detect around 90% of NOTCH3 gene changes in a UK population.

If one member of a family has CADASIL, any other member of the same family that also has CADASIL, will have exactly the same underlying genetic abnormality.  If we know where the abnormality is, we can much more easily determine whether it is present.  Therefore, once we’ve found the underlying abnormality within a particular family, it is relatively easy to determine whether other family members are affected or may become affected in the future. This is known as ‘predictive genetic testing’.

 

Click here to go to Genetic Testing page

 

SKIN BIOPSY

CADASIL results in characteristic changes in the blood vessels.  For obvious reasons it is difficult to look at the blood vessels within the brain.  However, even though CADASIL itself only produces symptoms within the brain, abnormalities within the blood vessels can be seen elsewhere in the body. The easiest place to look for these is in the skin.  A very small skin biopsy is performed under local anaesthetic. We carry this out as an outpatient procedure in our CADASIL clinic. Because we now carry out more extensive genetic testing, we tend to only perform skin biopsy if genetic testing has been negative and if the diagnosis is still uncertain.

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It is important this is processed in a special way allowing it to be looked at under high magnification using an electron microscope.  Under this magnification, in patients with CADASIL, one can frequently see abnormal collections of material called GOM (Granular Osmiophilic Material) as shown by the arrows in the figure.  If  GOM is present we can be almost certain that the individual does have CADASIL.  However, in our experience the skin biopsy can be normal even in patients with definite CADASIL.  It appears that GOM can be detected on skin biopsy in 60-80% of CADASIL patients.

 

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