Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. An inherited form of vascular dementia that strikes relatively young adults of both sexes and is characterized by multiple strokes, dementia, migraine-like headaches, and psychiatric disturbances. CADASIL is due to mutation of a gene called NOTCH3 located on chromosome 19. Also called hereditary multi-infarct dementia. The phenotypic presentation is variable but remarkable for a high frequency of migraine with aura. Magnetic resonance images show a microangiopathic pattern of lesions. Prominent involvement of the temporopolar white matter and involvement of the temporopolar arcuate fibers are conspicuous findings seen in many patients.
Individuals with CADASIL can suffer from anxiety or depression. Depression is very frequent after any stroke and usually improves with time and treatment if necessary. However, occasionally, depression may occur before any other symptoms of CADASIL. Rarely, seizures (epilepsy) occurs as part of CADASIL. Over time, as the disease progresses, memory problems may occur and if these become severe, they are likely to occur in the 50’s or 60’s. An unusual feature is the onset of confusion and reduced consciousness over a period of hours or days, sometimes with fever and seizures; this often follows a migraine attack. It recovers completely over one to two weeks.
A person with CADASIL generally does not show symptoms until mid-life (40s-50s), though some cases have been identified where symptoms appear in the 20s. Though symptoms and course of disease can vary dramatically, the initial symptoms are generally migraine and MRI abnormalities. Over the next decades as the disease advances, strokes and dementia are common symptoms. Death generally occurs 10-20 years within the onset of symptoms.
CADASIL is caused by mutations in a gene called Notch3, which is a protein that is involved in determining cell fate; for example, it might determine that a particular cell will be the type of cell that is present in the wall of a blood vessel, or that it will be a liver cell. Mutation in Notch3 causes the Notch3 protein to accumulate abnormally in brain vessels and peripheral tissue arteries. This also leads to diffuse loss of myelin throughout the brain, as well as deep infarcts in the white matter.
CADASIL is an autosomal dominant disease, which means that a single mutated copy of the Notch3 gene overrides the one “good” copy, producing disease
This means that if a parent is affected, any children of that parent have a 50% chance of having the disorder as well. If the child receives the mutated gene, the child has a 100% chance of getting CADASIL.
No specific treatment is available. However, anti-platelet agents such as aspirin, Aggrenox, or Plavix 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.
We still do not know whether CADASIL patients benefit from treatment with “blood thinning” medications that are often used to help prevent stroke. Your neurologist may recommend that you take a low-dose aspirin or a similar medication daily to try to prevent a stroke. Warfarin (coumadin) and TPA (to dissolve blood clots) should be avoided because they increase the risk of bleeding in the brain. Triptans to treat migraine should also be avoided because they increase the risk of stroke.