Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant microvasculopathy characterized by recurrent lacunar and subcortical white matter ischemic strokes and vascular dementia in young and middle age patients without known vascular risk factors. There is disproportionate cortical hypometabolism.
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CADASIL is an autosomal dominant trait, with patients typically becoming symptomatic in adulthood (30 to 50 years of age).
Presentation is usually with recurrent transient ischemic attacks (TIAs) or strokes in multiple vascular territories. Presenile dementia and migraines develop in the third-to-fourth decades of life. Clinically, CADASIL often has a similar presentation to migraines and may also have auras. Depression, psychosis, pseudobulbar palsy and focal neurological defects as well as seizures are also seen 2,3.
CADASIL results from a mutation on chromosome 19p13.12 involving the NOTCH3 gene, and as the name implies is inherited as an autosomal dominant trait. It results in small vessel and arteriole stenosis secondary to fibrotic thickening of the basement membrane of the vessels; the pathological hallmark is the deposition of granular osmiophilic material in close relation to the vascular smooth muscle cells 7.
An angiopathy of small and middle sized arteries is characteristic, without atherosclerosis or amyloid deposition 3. Diagnosis requires genetic identification of the mutated gene 4.
CT is non-specific, demonstrating white matter regions of low attenuation.
MRI is the investigation of choice, often demonstrating widespread confluent white matter hyperintensities on T2-weighted images 2. More circumscribed T2 hyperintense lesions are also seen in the basal ganglia, thalamus and pons 3.
Although the subcortical white matter can be diffusely involved, in the initial course of the disease involvement of the anterior temporal lobe (86%) and external capsule (93%) are classical 2. There is relative sparing of the occipital and orbitofrontal subcortical white matter 2, subcortical U-fibers and cortex 3.
Cerebral microhemorrhages have been reported to occur in ~45% (range 25-70%) of cases without a characteristic distribution 1.
Eventually, cerebral atrophy ensues, which correlates well with the degree of cognitive decline.
Treatment and prognosis
Typically the disease has a variable but progressive course leading to death between 50 to 70 years of age 2,4.
General imaging differential considerations include:
multiple early age infarcts from a hypercoagulable state
cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)
think of it in younger patients with small vessel ischemic white matter change
predilection for anterior temporal lobe white matter is a distinctive feature
sparing of the cortex and subcortical U-fibers is typical
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- 7. Di Donato I, Bianchi S, De Stefano N, Dichgans M, et-al. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects. (2017) BMC Medicine. 15 (1): 41. doi:10.1186/s12916-017-0778-8 - Pubmed