Diagnosis of the disease

Today, diagnosis of the disease is based on brain examination under MRI (Magnetic Resonance Imaging). If MRI shows lesions indicative of CADASIL,   especially if there are pre-existing cases in the same family, then a genetic test will be performed to confirm the diagnosis.

When the general practitioner observes symptoms such as migraines with aura, psychomotor retardation, walking disorders etc., the physician would refer the patient to a neurologist.

More emphasis will be directed to a probable diagnostic of CADASIL if the patient belongs to a family with pre-existing cases.

MRI is a commonly used tool in neurology; its resulting images may show characteristics leading to an assumption of CADASIL, even if the patient has no one in the family with this disease.

Magnetic Resonance Imaging (MRI)

The patient would undergo a painless test inside a device that produces a strong magnetic field, to obtain cut images of the brain.  

In the case of CADASIL, MRI would show diffuse lesions in white matter area of the brain. Lesions may usually appear around 20 or 30 years old and are always present after the age of 35 years in all patients carrying a mutation of NOTCH3 gene. Characteristic signs of the disease can be observed on MRI many years before these lesions result in symptoms and disorders. The extent of abnormalities on MRI increases as patients become older. All this points to the existence of a leukoencephalopathy (disease of white brain matter) leading eventually to cerebrovascular accidents or strokes. 

Genetic Testing

In 1996, the NOTCH3 gene, responsible for the disease, was identified on chromosome 19. This discovery has enabled the development of a diagnostic test of CADASIL, via genetic analysis of blood samples.

 Patients may fall under the following 2 situations:

 
• The patient has symptoms indicative of CADASIL.

In this case, the genetic test is conducted only after an MRI exam. The objective of the test is to confirm the diagnosis.

• When the patient belongs to a previously identified family, genetic testing is aimed at detecting the mutation already identified in this family.

• When the patient belongs to a new family, the test is aimed at detecting a mutation on the most common areas and throughout the NOTCH3 gene.

• The patient shows no symptoms but a family member is suffering from CADASIL

 In this case, a screening test may be requested to see if the patient carries the same gene mutation.

Requirements:

• Patient must be over 18 years old.

• Patient has given voluntary and informed consent to the test.

Currently, genetic tests are carried out in France only under certain strict conditions. Before blood samples can be taken from any asymptomatic person, a multidisciplinary review must be scheduled with three specialists:

• A neurologist with expertise on the disease explains about CADASIL and gives  information about the clinical exam.

• A geneticist explains about the test and what the results mean.

• A psychologist follows-up on the patient’s questions about the disease, his/her psychological state and ability to understand the diagnosis.

The test is then performed after a reflection period of one to two months.

This test must be performed in a specialized center. Its reliability is close to 100%.

Diagnosis and Ethics

The request for genetic diagnosis by a person who does not present any symptoms, although being related to a family affected by CADASIL, must require close follow-up, due to the fact that the disease currently does not have any treatment. This process must only occur  after periods of precise education and reflection. It must take part within a specialized center with the help of a geneticist, a psychologist and a neurologist. ♦