Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts

Definition

Definition of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, usually called CADASIL, is an inherited condition that causes stroke and other impairments. The resulting blood vessel damage can cause migraines and other impairments of normal brain function. Later in life, the damaged blood vessels can cause reduced blood flow to various tissues in the body (ischemia). Although the severity of symptoms varies among those affected, people with CADASIL typically have more than one stroke in their lifetime. Recurrent strokes can progressively damage the brain, causing loss of intellectual function (dementia).

Symptoms

Symptoms of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts
This condition affects blood flow in small blood vessels, particularly in the brain. An abnormality in the muscle cells surrounding these blood vessels (vascular smooth muscle cells) gradually destroys these cells.

Causes

Causes of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts
Mutations in the NOTCH3 gene cause CADASIL. The NOTCH3 gene provides instructions for producing the Notch3 receptor protein, which is important for the normal function and survival of vascular smooth muscle cells. When certain molecules attach (bind) to Notch3 receptors, the receptors send signals to the nucleus of the cell. These signals then turn on (activate) particular genes within vascular smooth muscle cells.

NOTCH3 gene mutations lead to the production of an abnormal Notch3 receptor protein that affects the function and survival of vascular smooth muscle cells. Disruption of Notch3 functioning can lead to the self-destruction (apoptosis) of these cells.

Diagnosis

Diagnosis of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts
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. These white matter lesions are also seen in asymptomatic individuals with the mutated gene. While MRI is not used to diagnose CADASIL, it can show the progression of white matter changes even decades before onset of symptoms.

Treatment

Treatment of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts
No specific treatment is available. However, anti-platelet agents such as aspirin, Dipyridamole, or clopidogrel might slow down the disease and help prevent strokes. Given the propensity for cardiovascular and cerebrovascular complications, minimizing vascular risk factors and implementing therapy for primary or secondary prevention of stroke and myocardial infarction seems prudent. Stopping oral contraceptive pills is justified particularly in cases with migraine with aura. Aggressive treatment of hypercholesterolemia and hypertension is reasonable although the utility of statins and antihypertensive agents in the absence cardiovascular risk factors is unknown. Homocysteine levels are elevated in CADASIL and treatment with folic acid is reasonable. Anti-platelet therapy appears justifiable whereas anticoagulation may be inadvisable given the propensity for microhemorrhages. Administering tPA following onset of stroke is not advised for CADASIL patients, due to increased risk of microhemorrhages. Warfarin (Coumadin) should be avoided. Some CADASIL patients have used L-Arginine, a naturally occurring amino acid, to ease symptoms such as headache. Aricept, normally used for Alzheimer's Disease, has been shown to improve executive functioning in CADASIL patients.

Prognosis

Prognosis of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts
Consult with your doctor.

Prevention

Prevention of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts
Consult with your doctor.