Read more about this disease, some with Classification – Types – Signs and symptoms – Genetics – Pathophysiology – Diagnosis – Screening – Prevention – Treatment and management – Cures and much more, some including pictures and video when available.
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the Notch 3 gene on chromosome 19.[1] The most common clinical manifestations are migraine headaches and transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.[2]
The underlying pathology of CADASIL is progressive degeneration of the smooth muscle cells in blood vessels. Mutations in the Notch 3 gene (on the short arm of chromosome 19) cause an abnormal accumulation of Notch 3 at the cytoplasmic membrane of vascular smooth-muscle cells both in cerebral and extracerebral vessels,[3] seen as granular osmiophilic deposits on electron microscopy.[4]
Interestingly, the Notch 3 gene is in the same locus as the gene for familial hemiplegic migraine.
CADASIL may start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 to 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and urinary incontinence.
MRIs show hypointensities on T1-weighted images and hyperintensities on T2-weighted images, usually multiple confluent white matter lesions of various sizes, are characteristic. These lesions are concentrated around the basal ganglia, periventricular white matter, and the pons, and are similar to those seen in Binswanger disease.[2][5] These white matter lesions are also seen in asymptomatic individuals with the mutated gene.[6] While MRI is not used to diagnose CADASIL, it can show the progression of white matter changes even decades before onset of symptoms.
The most definitive diagnostic tool is a blood test to screen for the mutated Notch 3; Though costly, some insurance companies do cover the cost if deemed medically necessary. Since CADASIL is a systemic arteriopathy, evidence of blood vessel damage is seen in small- and medium-sized arteries. Therefore, skin biopsies have been used for diagnosis;[7] however, this method is less reliable than the blood screen.
[tubepress mode=’tag’, tagValue=’CADASIL’]