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Difference between revisions of "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy"
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (view source)
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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.<ref name=pmid19174371>{{Cite journal | last1 = Tikka | first1 = S. | last2 = Mykkänen | first2 = K. | last3 = Ruchoux | first3 = MM. | last4 = Bergholm | first4 = R. | last5 = Junna | first5 = M. | last6 = Pöyhönen | first6 = M. | last7 = Yki-Järvinen | first7 = H. | last8 = Joutel | first8 = A. | last9 = Viitanen | first9 = M. | title = Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients. | journal = Brain | volume = 132 | issue = Pt 4 | pages = 933-9 | month = Apr | year = 2009 | doi = 10.1093/brain/awn364 | PMID = 19174371 }} | |||
</ref> | |||
*Causes strokes in 40-50 year-old. | |||
*Cerebral microbleeds - common. | |||
**Associated with increased risk of [[intracerebral hemorrhage]].<ref name=pmid17135568>{{Cite journal | last1 = Choi | first1 = JC. | last2 = Kang | first2 = SY. | last3 = Kang | first3 = JH. | last4 = Park | first4 = JK. | title = Intracerebral hemorrhages in CADASIL. | journal = Neurology | volume = 67 | issue = 11 | pages = 2042-4 | month = Dec | year = 2006 | doi = 10.1212/01.wnl.0000246601.70918.06 | PMID = 17135568 }}</ref> | |||
*Characteristic MRI findings - present in asymptomatic individuals with mutation. | |||
*Increased risk of [[heart|myocardial infarction]].<ref name=pmid12861102>{{cite journal |author=Lesnik Oberstein SA, Jukema JW, Van Duinen SG, ''et al.'' |title=Myocardial infarction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) |journal=Medicine (Baltimore) |volume=82 |issue=4 |pages=251–6 |year=2003 |month=July |pmid=12861102 |doi=10.1097/01.md.0000085054.63483.40 |url=}}</ref> | |||
Note: | |||
*There is also an autosomal recessive form - CARASIL.<ref name=pmid21215656>{{Cite journal | last1 = Fukutake | first1 = T. | title = Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. | journal = J Stroke Cerebrovasc Dis | volume = 20 | issue = 2 | pages = 85-93 | month = | year = | doi = 10.1016/j.jstrokecerebrovasdis.2010.11.008 | PMID = 21215656 }}</ref> | |||
===Etiology=== | |||
*Mutation of ''Notch 3'' gene.<ref name=pmid15537516>{{Cite journal | last1 = Kalaria | first1 = RN. | last2 = Viitanen | first2 = M. | last3 = Kalimo | first3 = H. | last4 = Dichgans | first4 = M. | last5 = Tabira | first5 = T. | title = The pathogenesis of CADASIL: an update. | journal = J Neurol Sci | volume = 226 | issue = 1-2 | pages = 35-9 | month = Nov | year = 2004 | doi = 10.1016/j.jns.2004.09.008 | PMID = 15537516 }}</ref> | |||
**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.<ref name=pmid17076524>{{cite journal |author=Kleinschmidt-DeMasters BK, Prayson RA |title=An algorithmic approach to the brain biopsy--part I |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=11 |pages=1630–8 |year=2006 |month=November |pmid=17076524 |doi= |url=}}</ref> | |||
==IHC== | |||
*Notch 3: smooth muscle and pericytes punctate +ve.<ref name=pmid12861102/> | |||
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. | |||
<gallery> | |||
Image:CADASIL_-_very_high_mag.jpg | Notch 3 staining in CADASIL. (WC/Nephron) | |||
</gallery> | |||
===Skin biopsy diagnosis=== | |||
*Can be diagnosed on a skin biopsy.<ref name=pmid11755616 >{{cite journal |author=Joutel A, Favrole P, Labauge P, ''et al.'' |title=Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis |journal=Lancet |volume=358 |issue=9298 |pages=2049–51 |year=2001 |month=December |pmid=11755616 |doi=10.1016/S0140-6736(01)07142-2 |url=}}</ref> | |||
==Electron microscopy== | |||
*Granular osmiophilic material (GOM). | |||
==See also== | |||
*[[Neuropathology]]. | |||
==References== | |||
{{Reflist|2}} | |||
[[Category:Diagnosis]] | [[Category:Diagnosis]] | ||
[[Category:Neuropathology]] | |||