title: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy with a Novel NOTCH3 Cys323Trp Mutation Presenting Border-Zone Infarcts: A Case Report and Literature Review.
abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary and progressive small-vessel disease caused by NOTCH3 mutations, pathologically characterized by the degeneration of vascular mural cells, white matter changes, and ischemic strokes. Recently, dysautoregulation has received increasing attention regarding the pathogenesis of stroke in CADASIL. Here, we report a CADASIL case with a novel Cys323Trp mutation in the NOTCH3 gene, which suggests a close relationship between hemodynamic factors and clustering of cerebral infarctions in CADASIL. A 47-year-old male patient presented with internal border-zone infarcts in the bilateral hemispheres and was diagnosed with CADASIL by the presence of granular osmiophilic material and the accumulation of the Notch3 extracellular domain around small vessels. A literature review revealed 7 reports of similar CADASIL cases with clustering of cerebral infarctions related to blood pressure fluctuations. Not only large-artery stenosis but also small-vessel pathologies potentiate watershed infarctions, which might be triggered by hemodynamic fluctuation due to cerebral dysautoregulation.
authors.affiliation: Department of Neurology, Saiseikai Noe Hospital, Osaka, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Tojima
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita, Japan. Electronic address: saitosa@ncvc.go.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Neurology, Kyoto Prefectual University of Medicine, Kyoto, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Department of Neurology, Saiseikai Noe Hospital, Osaka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Fukuda
mesh_terms: D020520:Brain Infarction / Q000209:etiology*; D046589:CADASIL / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D003545:Cysteine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D059906:Neuroimaging; D000071656:Receptor, Notch3 / Q000235:genetics*; D014364:Tryptophan / Q000235:genetics
chemical_list: D000071656:Receptor, Notch3; D014364:Tryptophan; D003545:Cysteine
keywords: C323W; CADASIL; dysautoregulation; exon 6; infarct