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

J Stroke Cerebrovasc Dis. 2016 Aug;25(8):e128-30. doi: 10.1016/j.jstrokecerebrovasdis.2016.05.013. Epub 2016 May 27.

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.

Keywords: C323W; CADASIL; dysautoregulation; exon 6; infarct.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Brain Infarction / etiology*
  • CADASIL / complications*
  • CADASIL / diagnostic imaging
  • CADASIL / genetics*
  • Cysteine / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neuroimaging
  • Receptor, Notch3 / genetics*
  • Tryptophan / genetics

Substances

  • Receptor, Notch3
  • Tryptophan
  • Cysteine