CADASIL causes small blood vessel walls to choke up, especially in the brain. This causes small bleeds and shuts down blood flow, which leads to death in a cluster of neurons (brain cells)—a small stroke. Often the process is slow, so the person does not recognize it as a sudden event—it’s just a change over time. At first, the brain can compensate for the cell loss, but in time, the damage builds up and dementia becomes apparent.
What Is CADASIL?
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited condition. It becomes apparent in early adulthood. First symptoms often are migraine headaches and mood swings. Transient ischemic attacks—brief episodes of narrowly circumscribed brain failure, such as weakness in an arm, or confusion—may also occur. Sometimes it mimics multiple sclerosis. Memory problems may show up as early as in the early 30s. It is an important but infrequent cause of dementia.
Previously it has been called hereditary multi-infarct dementia, chronic familial vascular encephalopathy, and familial subcortical dementia.
The defect is in NOTCH3, a gene on chromosome 19 that was first described in Drosophilia fruit flies. In CADASIL, the gene is mutant. The abnormal gene is not expressed in all parts of the body; it occurs mostly in the lining cells of small to medium arteries.
The condition is a dominantly inherited—if either parent had it, the child has a 50% chance of getting it. De novo mutations, that is, mutations not inherited, are rare.
How is It Diagnosed?
There are no specific generally available tests. Gene testing can be done, but is not widely available yet. Brain MRIs usually show a particular pattern: periventricullar white matter lesions in a younger person, usually involving frontal and temporal lobes, and subinsular white matter changes. T2-signal-abnormalities in the white matter of the temporal pole and T2-signal-abnormalities in the external capsule are said to be characteristic. Some investigators are testing to see if a skin biopsy might reveal the mutant gene. With the electron microscope, dense granules may be seen in arterioles.
How is It Treated?
There is no specific treatment. Some experts recommend vigorous protection of blood vessels (e.g., control blood pressure) but evidence of value has not accumulated. Angiography and anticoagulants are contraindicated (should not be done) in CADASIL; small bleeds are the problem, and angiography or anticoagulants may provoke bleeds into the brain, that is, cause strokes. Similarly, smoking increases the risk of strokes.
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