Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, abbreviated CADASIL, is a rare genetic disorder that predisposes to cerebral infarcts and may explain a stroke in a young individual.
General
- Autosomal dominant disorder - as the name implies.[1]
- Causes strokes in 40-50 year-old.
- Cerebral microbleeds - common.
- Associated with increased risk of intracerebral hemorrhage.[2]
- Characteristic MRI findings - present in asymptomatic individuals with mutation.
- Increased risk of myocardial infarction.[3]
Note:
- There is also an autosomal recessive form - CARASIL.[4]
Etiology
- Mutation of Notch 3 gene.[5]
- Diagnosis: proven Notch 3 mutation.
Microscopic
Features:
- +/-Subcortical infarcts.
- Patches of (non-myelinated) tissue within the white matter deep to the cortex with abundant macrophages.
- Blood vessels typically have a basophilic granularity.[6]
IHC
- Notch 3: smooth muscle and pericytes punctate +ve.[3]
Notes:
- No cortical involvement -- this is unlike multiple sclerosis.
DDx:
- Amyloidosis.
- Binswanger's disease - multi-infarct dementia affecting subcortical white matter.
- Often diagnosed as Alzheimer's disease in the past.
Notch 3 staining in CADASIL. (WC/Nephron)
Skin biopsy diagnosis
- Can be diagnosed on a skin biopsy.[7]
Electron microscopy
- Granular osmiophilic material (GOM).
See also
References
- ↑ Tikka, S.; Mykkänen, K.; Ruchoux, MM.; Bergholm, R.; Junna, M.; Pöyhönen, M.; Yki-Järvinen, H.; Joutel, A. et al. (Apr 2009). "Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients.". Brain 132 (Pt 4): 933-9. doi:10.1093/brain/awn364. PMID 19174371.
- ↑ Choi, JC.; Kang, SY.; Kang, JH.; Park, JK. (Dec 2006). "Intracerebral hemorrhages in CADASIL.". Neurology 67 (11): 2042-4. doi:10.1212/01.wnl.0000246601.70918.06. PMID 17135568.
- ↑ Jump up to: 3.0 3.1 Lesnik Oberstein SA, Jukema JW, Van Duinen SG, et al. (July 2003). "Myocardial infarction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)". Medicine (Baltimore) 82 (4): 251–6. doi:10.1097/01.md.0000085054.63483.40. PMID 12861102.
- ↑ Fukutake, T.. "Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification.". J Stroke Cerebrovasc Dis 20 (2): 85-93. doi:10.1016/j.jstrokecerebrovasdis.2010.11.008. PMID 21215656.
- ↑ Kalaria, RN.; Viitanen, M.; Kalimo, H.; Dichgans, M.; Tabira, T. (Nov 2004). "The pathogenesis of CADASIL: an update.". J Neurol Sci 226 (1-2): 35-9. doi:10.1016/j.jns.2004.09.008. PMID 15537516.
- ↑ Kleinschmidt-DeMasters BK, Prayson RA (November 2006). "An algorithmic approach to the brain biopsy--part I". Arch. Pathol. Lab. Med. 130 (11): 1630–8. PMID 17076524.
- ↑ Joutel A, Favrole P, Labauge P, et al. (December 2001). "Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis". Lancet 358 (9298): 2049–51. doi:10.1016/S0140-6736(01)07142-2. PMID 11755616.