CADASIL is a autosomal dominant inherited cerebrovascular disease. It is the most common cause of hereditary vascular dementia and one of the most common causes of familial stroke in middle age.
The first symptoms appear at the age of approximately 45-50 years with recurrent subcortical ischemic strokes and cognitive deficits that progress to dementia. About one third of patients suffer from migraine with aura and mood swings. Both are usually preceded by stroke and the symptoms of dementia at about 30 years of age.
Psychiatric disorders are common and often manifest in depression, apathy, and personality changes. Less common symptoms are acute reversible encephalopathy (accompanied by headache, confusion and seizure), epilepsy and subclinical peripheral neuropathy.
The onset and course of the disease are variable.
In contrast to classic cerebral infarction, which is often caused by arteriosclerosis, mutations in the NOTCH3 gene (on chromosome 19) lead to cerebral non-arteriosclerotic and non-inflammatory microangiopathy (especially the blood vessels supplying the brain, but also the internal organs and the skin ).
The NOTCH3 protein is a membrane receptor that is expressed mainly by vascular smooth muscle cells and is involved in cell-cell interaction and apoptosis processes. The mutant protein increasingly forms multimers which are deposited in the vessel wall.
The prognosis of the disease is unfavorable, most patients become bedridden and in need of care. On average, patients die at the age of 68 years.