CADASIL

Missense mutations in the Notch3 gene cause CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and lenkoencephalopathy). Notch is a type I integral membrane protein proteolytically processed in its extracellular domain by fnrin and the metalloproteinase knzbanian. The signal transduction cascade... 

Many individuals with LA also harbor lacunar and/or cortical infarcts. Presence of LA serves as an intermediate surrogate both for ischemic stroke and intracerebral hemorrhage as they all share similar risk factors and similar pathophysiological mechanisms (Inzitari 2003). LA is widely found in dementing illnesses, such as Alzheimer s disease, vascular dementia, and cerebral autosomal dominant arteri-opathy with subcortical infarcts and leukoencepha-lopathy (CADASIL). Failure of blood supply in the... 

Fig. 13.4. Transverse FLAIR images of a CADASIL patient. Note the location of white matter lesions in the external capsule and close to the temporal pole anterior to the frontal horns of the lateral ventricles...

Auer DP, Putz B, Gossl C, Elbel G, Gasser T, Dichgans M (2001) Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy MR imaging study with statistical parametric group comparison. Radiology 218 443-451... 

Joutel A, Andreux F, Gaulis S, Domenga V, Cecillon M, Bat-tail N, Piga N, Chapon F, Godfrain C, Tournier-Lasserve E (2000) The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients. J Clin Invest 105 597-605... 

O Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS (2001) MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology 56 628-634... 

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)... 

Fig. 3.1. Investigations from a patient with CADASIL (see text). Electron micrographs (a, b) of muscle shows thickening of the basal lamina of the small blood vessels and the presence of dense eosinophilic material magnetic resonance brain imaging shows widespread leukoaraiosis (c).

Dichgans M, Mayer M, Uttner I et al. (1998). The phenotypic spectrum of CADASIL clinical fuidings in 102 cases. Annals of Neurology 44 731-739... 

Dubroca C, Lacombe P, Domenga V etal. (2005). Impaired vascular mechanotransduction in a transgenic mouse model of CADASIL arteriopathy. Stroke 36 113-117... 

Ebke M, Dichgans M, Bergmann M etal. (1997). CADASIL skin biopsy allows diagnosis in early stages. Acta Neurology Scandinavica 95 351-357... 

De novo mutation in the Notch3 gene causing CADASIL. Annals of Neurology 47 388-391... 

Razvi SS M, Davidson R, Bone I et al. (2005). The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the west of Scotland. 

The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain 127 2031-2038... 

Sometimes arterial occlusion is demonstrated by angiography in migrainous stroke and the cause is hypothesized to be in-situ thrombosis complicating vasospasm. No provoking factors are known. Other possible causes of stroke in the context of headache must be considered carotid dissection, mitochondrial cytopathy, ruptured vascular malformation, antiphospholipid antibody syndrome and CADASIL (cerebral autosomal dominant arterio-pathy with subcortical infarcts and leukoencephalopathy). Migraine auras without headache may be confused with TIA (Ch. 8). 

Cerebral microbleeds are seen frequently in patients with primary intracerebral hemorrhage, less commonly in patients with ischemic stroke and rarely in healthy controls (Cordonnier et al. 2007). Risk factors for cerebral microbleeds include hypertension, increasing age, diabetes, cerebral amyloid angiopathy and, less commonly, cerebral autosomal dominant arteriopathy with silent infarcts and leukoaraiosis (CADASIL) (Cordoimier et al. 2007). It is unclear whether previous use of antiplatelet agents or anticoagulants is a risk factor for cerebral microbleeds. 

Buffon F, Porcher R, Hernandez K et al. (2006). Cognitive profile in CADASIL. Journal of Neurology, Neurosurgery and Psychiatry 77 175-180... 

Damage within a network of white matter regions underlies executive dysfunction in CADASIL. Neurology 65 1584-1590... 

CADASIL affects small arteries. It is a rare disorder resulting from Notch3 gene mutations (chromosome 19). Characteristic vascular changes can be identified in brain, skin, and muscle biopsy specimens. By light microscopy, the affected vessels have a thickened appearance, and basophilic granular material is seen by H E stain. This material is PAS positive. It displaces... 

Cerebral ischemic injury is a common cause of dementia in older adults. Combination cases of vascular dementia and Alzheimer disease are also quite frequent. Vascular causes of dementia include subcortical vascular dementia, multi-infarct dementia, ischemic dementia, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and leuko-araiosis (see the Cerebrovascular Diseases section earlier in this chapter). ... 

Markus HS, Martin RJ, Simpson MA, et al. Diagnostic strategies in CADASIL. Neurology. 2002 59 1134-1138. 

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