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.
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 2. More circumscribed 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
- subcortical arteriosclerotic encephalopathy (SAE)
- Susac syndrome
- CNS vasculitis
- COL4A1 brain small-vessel disease
- myotonic dystrophy type 1
- 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
- 1. Blitstein MK, Tung GA. MRI of cerebral microhemorrhages. AJR Am J Roentgenol. 2007;189 (3): 720-5. doi:10.2214/AJR.07.2249 - Pubmed citation
- 2. Yousry TA, Seelos K, Mayer M et-al. Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). AJNR Am J Neuroradiol. 1999;20 (1): 91-100. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 3. Auer DP, Pütz B, Gössl C et-al. Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison. Radiology. 2001;218 (2): 443-51. Radiology (full text) - Pubmed citation
- 4. Bohlega S, Al Shubili A, Edris A et-al. CADASIL in Arabs: clinical and genetic findings. BMC Med. Genet. 2007;8 : 67. doi:10.1186/1471-2350-8-67 - Free text at pubmed - Pubmed citation
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- 6. Liem MK, Lesnik Oberstein SA, Haan J, van der Neut IL, van den Boom R, Ferrari MD, van Buchem MA, van der Grond J. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: progression of MR abnormalities in prospective 7-year follow-up study. (2008) Radiology. 249 (3): 964-71. doi:10.1148/radiol.2492080357 - Pubmed
- 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