Nowadays diagnosis of this disease is based on MRI brain exam (Magnetic Resonance Imaging). If MRI exams detect brain lesions typical of Cadasil, a fortiori with corroborating evidence of family clinical history, then a genetic test can be prescribed to confirm the diagnosis.
MRI Exam (Magnetic Resonance Imaging)
This painless exam obtains cut-view images of the brain by placing the patient in a device that produces a strong magnetic field. In contrast with scanning devices, this exam does not expose the patient to risks of X-rays.
In case of Cadasil, MRI scans show spread lesions in the white matter of the brain. The lesions generally appear between the ages of 20 and 30 years and they are consistently present after the age of 35 in all subjects who carry the Notch3 gene mutation. These characteristic MRI signals may be observed many years well before the first signs of disorders and symptoms. The extent of these abnormalities observed in MRI exams increases with age. They account for existence of a leukoencephalopathy leading eventually to a series of cerebrovascular accidents or strokes.
In 1996, the NOTCH3 gene which is responsible for the disease was identified on chromosome 19. This discovery has made possible the development of a diagnostic test of Cadasil through genetic analysis of blood samples.
Testing may occur under these two situations:
· The test is prescribed for diagnostic purpose on a patient who exhibits manifestations symptomatic of Cadasil. In this case, genetic testing proceeds only after an MRI scan (exam of the cerebral white matter) and with the patient’s permission. The purpose of the test is to confirm the diagnosis suspected by the doctor.
o When the patient belongs to a previously known family in the program, genetic test is carried out to detect the mutation which has already been identified within the patient’s family.
o When the patient does not belong to a known family, the test is performed in the first stage to detect one of the more common mutations of the disease.
o When the diagnosis appears highly probable, a screening study of the entire Notch3 gene may deem necessary but this process is time-consuming, expensive and may take months to complete.
· The subject does not exhibit any symptoms; however a family member is suffering from Cadasil: in this case, a screening test may be requested to determine if the subject is a carrier of the mutated gene.
Pre-Conditions for Genetic Testing
In practice, genetic screening tests are performed in France under these certain conditions:
· Patient must be over the age of 18.
· Patient’s written informed consent prior to the test.
· Consultation with a specialist neurologist for explanations about the Cadasil disease and undergo of a clinical assessment.
· Consultation with a geneticist about nature of the test and interpretation of results.
· Consultation with a psychologist for an evaluation of the patient’s thoughts, his/her questions concerning to the disease, psychological state of mind and ability to handle a complex diagnosis.
Once these conditions have been met, the test is carried out after a reflective waiting period of one to two months.
The test must be performed in an accredited specialized clinic. The test reliability margin is close to 100%. In effect, there is a high demand for information but few people have undergone genetic testing for screening diagnostic purpose.
This test is performed on a small artery sample collected under the skin or a muscle. Even though Cadasil manifests solely in neurological symptoms, alterations are also observed in vascular walls of small arteries of muscles or the skin. This test is no longer performed today.
Diagnosis and Ethics Considerations
The request for genetic diagnosis by an individual related to a family affected by Cadasil but nevertheless not showing any clinical signs of the disease must be subject to a monitoring process especially since there is no specific treatment for this disease. The request must proceed only after a period of thorough assessment and reflection. It must only be performed in an accredited specialized clinic under the supervision of a geneticist, a psychologist and a neurologist. ♦