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Magnetic Resonance Imaging (MRI)

Magnetic resonance imaging (MRI) is a method for making detailed images of the brain. In CADASIL, the MRI shows changes in the deep regions of the brain, particularly in the white matter. The white matter lies below the outer layers of the brain (the cortex or gray matter) and forms the connections among brain areas so that they work in a unified way. The blood supply to the white matter is provided by small blood vessels which make it especially vulnerable to CADASIL. Other disorders, such as multiple sclerosis, cause white matter changes that look similar on MRI, so CADASIL cannot be diagnosed from MRI alone. However, CADASIL might be suspected if the white matter changes are concentrated in certain brain areas (frontal lobes and/or temporal lobes).

MRI uses magnetic fields and radio waves to make its images and involves no x-rays or other forms of radiation. It is a safe and reliable test method with few health risks. However, it is not safe for people with pacemakers or certain other implanted medical devices or for people who may have small metal fragments or dust in their eyes. It is often helpful to have MRI scans repeated every few years to look for progression of the disease.

Genetic Testing

CADASIL is caused by a mutation (mistake) in the structure of the NOTCH3 gene. It turns out, however, that the mutation can take different forms, and that not all people with CADASIL have the same precise mutation. Within a family, all those affected with the disease will have the same NOTCH3 mutation. Detection of a mutation is considered 100% proof of the existence of the disease. Since the NOTCH3 gene is very large, the search for mutations can be complex. For this reason, if a mutation is known in a family, the laboratory may limit testing in individuals at risk to specific mutations. For initial testing in a family, the laboratory will sequence large segments of the NOTCH3 gene in search of a mutation.

Only a small amount of blood, which can be taken from a vein, is needed for genetic testing. In the United States, there is only one commercial laboratory that offers genetic testing for CADASIL. Your insurance may or may not cover the test. You and/or your physician can find more detailed information about the lab by visiting the Athena Diagnostics site.

A decision to test for a genetic disorder is an important and sometimes difficult one. Learning that you have a genetic disorder can be psychologically distressing and can have an impact on health insurance. Some people with symptoms may want to know – others may not. The decision to have the test can be even more difficult for healthy members of a CADASIL family. You should discuss your concerns with your doctor before having the test. Genetic counselors have special expertise in working with people with genetic disorders and may provide helpful advice and guidance in making your decisions.

Skin Biopsy

CADASIL causes characteristic changes in the blood vessels in almost all regions of the body. These vascular changes may be crucial in making a diagnosis but can only be seen under a powerful electron microscope. Since the blood vessels of the brain cannot be analyzed directly, microscopic examination is performed on the more readily accessible blood vessels in the skin. Under local anesthesia, a small piece of skin is taken from the upper arm or thigh and the resulting wound is closed with one or two sutures. The tissue sample is then sent to a facility that has an electron microscope. Under magnification, the changes typical of CADASIL can be seen in the vascular walls. One of these characteristics is called granular osmiophilic material, or GOM, which is thought to be made of clumps of excess protein. If such changes can be detected, the CADASIL diagnosis can be regarded as confirmed. The key limitation to skin biopsy is that there is a small chance that the disease could be missed if the skin specimen does not happen to contain any diseased blood vessels. • A skin biopsy may be helpful in a specialized laboratory if genetic testing is negative as the diagnosis of CADASIL is still considered likely by a CADASIL specialist.