CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts & leukoencephalopathy)
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Epidemiology
- affects relatively young adults of both sexes
Pathology
- notch-3 deposits in blood vessel walls
- ischemic infarcts, lacunes & diffuse leukoencephalopathy
Genetics
- autosomal dominant
- linked to chromosome 19q12[2], notch-3 homolog gene on chromosome 9p13.2-p13.1. (?)
- > 200 NOTCH3 mutations have been described
- most involve point mutations leading to gain or loss of Cys
- R141C mutation in exon 4 in the NOTCH3 gene (case report)[3]
- mutations affect highly conserved Cys within EGF-like repeat domains in the extracellular part of the receptor
Clinical manifestations
- migraine with aura[3] generally 1st manifestation
- 5X more common than in general population[3]
- subcortical ischemic events
- vascular dementia
- mood changes
- severe depression, apathy, occasional manic episodes[3]
Radiology
- MRI abonormalities present by age 35 (100%)
- white matter & microangiopathic changes
- temporal pole most characteristic
Complications
- increased risk for hemorrhage
Differential diagnosis
Management
- no specific treatment is available for CADASIL[3]
- avoid vasoconstrictor agents
- triptans may be safe
- anticonvulsant & beta-blocker may be used for migraine prophylaxis
- treat cardiovascular risk factors
- statin, antiplatelet agents
- avoid anticoagulants because of increased risk for hemorrhage[3]
- acetazolamide 250 mg BID + aspirin 300 mg QD
- escitalopram 10 mg QD (case report[3])
More general terms
Additional terms
- CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts & leukoencephalopathy)
- notch-3 (Drosophila) homolog protein (NOTCH3)
References
- ↑ Joutel et al. Nature 383:707-10 1996 Tournier-Lasserve et al. Nature Genetics 3:256-9 1993
- ↑ 2.0 2.1 Kalaria RN, Viitanen M, Kalimo H, Dichgans M, Tabira T; The CADASIL Group of Vas-Cog. The pathogenesis of CADASIL: an update. J Neurol Sci. 2004 Nov 15;226(1-2):35-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15537516
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Toro J, Duque A, Reyes S, Patino J. Case Challenge: A Man with Migraine and Behavioral Changes. NEJM Journal Watch. Sept 12, 2017 Case Conclusion: A Man with Migraine and Behavioral Changes. NEJM Journal Watch. Sept 26, 2017 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
- ↑ Di Donato I, Bianchi S, De Stefano N 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. BMC Med. 2017 Feb 24;15(1):41. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28231783 Free PMC Article