CADASIL: hereditary disease of arteries causing brain infarcts and dementia.
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.
Kalimo
H
H
Department of Pathology; Division of Geriatric Medicine, Karolinska Institutet, Huddinge Hospital, Huddinge, Sweden.
Viitanen
M
M
Amberla
K
K
Juvonen
V
V
Marttila
R
R
Pöyhönen
M
M
Rinne
J O
JO
Savontaus
M
M
Tuisku
S
S
Winblad
B
B
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