Difference between revisions of "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy"

From Libre Pathology
Jump to navigation Jump to search
(redirect)
 
(split out)
 
Line 1: Line 1:
#redirect [[Neuropathology#Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy]]
'''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]]

Latest revision as of 06:51, 9 December 2014

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.
  • 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:

Skin biopsy diagnosis

  • Can be diagnosed on a skin biopsy.[7]

Electron microscopy

  • Granular osmiophilic material (GOM).

See also

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.