title: CADASIL: hereditary disease of arteries causing brain infarcts and dementia.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) begins with migraine with aura in approximately one-third of the patients. More severe symptoms of recurrent strokes usually appear at 30-50 years of age. However, well before the first stroke, CADASIL may be diagnosed on the basis of characteristic hyperintensities in T2-weighted magnetic resonance images. Multiple lacunar infarcts located mainly in the basal ganglia and frontal white matter lead to a cognitive decline and finally to dementia. These infarcts result from a thickening and fibrosis of the walls of the small and medium-sized penetrating arteries with consequent obliteration and/or thrombosis. Although the symptoms are almost exclusively neurological, the arteriopathy is generalized. Thus, basophilic, periodic acid-Schiff-positive and, in electron microscopy, osmiophilic material accumulates between degenerating smooth muscle cells. This occurs even in dermal arteries, which renders skin a useful target for diagnostic biopsy. Presently, no specific therapy is available. CADASIL is caused by missense point mutations in the Notch3 gene, which encodes a transmembrane receptor protein. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular, N-terminal domain of the molecule, which most probably results in conformational alteration. The function of Notch3 in adults and the pathogenesis of CADASIL are still unknown.
authors.affiliation: Department of Pathology; Division of Geriatric Medicine, Karolinska Institutet, Huddinge Hospital, Huddinge, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Kalimo
authors.forename: M
authors.initials: M
authors.lastname: Viitanen
authors.forename: K
authors.initials: K
authors.lastname: Amberla
authors.forename: V
authors.initials: V
authors.lastname: Juvonen
authors.forename: R
authors.initials: R
authors.lastname: Marttila
authors.forename: M
authors.initials: M
authors.lastname: Pöyhönen
authors.forename: J O
authors.initials: JO
authors.lastname: Rinne
authors.forename: M
authors.initials: M
authors.lastname: Savontaus
authors.forename: S
authors.initials: S
authors.lastname: Tuisku
authors.forename: B
authors.initials: B
authors.lastname: Winblad
mesh_terms: D002539:Cerebral Arterial Diseases / Q000235:genetics* / Q000473:pathology*; D002544:Cerebral Infarction / Q000235:genetics* / Q000473:pathology*; D003704:Dementia / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000235:genetics* / Q000473:pathology*; D013577:Syndrome