CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy)
Last reviewed 01/2018
CADASIL stands for cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy. This is a familial dementia syndrome characterised by migraine, adult-onset stroke and dementia (1).
- CADASIL is a hereditary microangiopathy caused by mutations in the NOTCH3 gene on chromosome 19
- microangiopathy is characterised by degeneration and disappearance of vascular smooth muscle cells and depositions of granular osmiophilic material (GOM), which is not amyloid, atherosclerotic, mineral or metallic in nature
patients can be found to have additional (genetic or non-genetic) cardiovascular
risk factors. These will interact with the stroke risk associated with CADASIL
- for example, a report found that smoking in CADASIL patients increased the risk of stroke (2)
- main features of CADASIL are
- ischaemic episodes, cognitive deficits, migraine with aura, and psychiatric disorders
of the disease is probably around 100%
- however expression varies in age of onset, severity of clinical symptoms, and progression, between families, as well as within members of the same family
- median age of onset of stroke in men is 50.7 years and in women 52.5 years of age
- an ischaemic episode (TIA or stroke) occurs in at least 70–85% of patients. Most patients continue to experience recurrent ischemic episodes
- cognitive deficits do not seem to be present before 35 years of age and there is marked variation in cognitive impairment in patients over 45 years of age
- approximately three quarters have dementia at the time of death
- about one quarter of NOTCH3 mutation carriers in a CADASIL study population were found to have a positive medical history for acute MI and/or current pathological Q-waves on electrocardiogram.
- Joutel A. et al.. Notch 3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 387: 288-92.
- Tonk M, Haan J. A review of genetic causes of ischemic and hemorrhagic stroke. J Neurol Sci. 2007.