Article Text

Download PDFPDF
CASE REPORT
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) presenting with stroke in a young man
  1. Louise Dunphy1,
  2. Amir Rani2,
  3. Yaw Duodu2 and
  4. Yousef Behnam2
  1. 1 Surgery, Milton Keynes University Hospital, Milton Keynes, UK
  2. 2 Stroke Medicine, Milton Keynes University Hospital, Milton Keynes, UK
  1. Correspondence to Dr Louise Dunphy, Louise.Dunphy{at}doctors.org.uk

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene which maps to the short arm of chromosome 19 and encodes the NOTCH3 receptor protein, predominantly expressed in adults by vascular smooth muscle cells and pericytes. The receptor has a large extracellular domain with 34 epidermal growth factor-like repeats encoded by exons 2–24, the site at which CADASIL mutations are most commonly found. Migraine with aura is often the earliest feature of the disease, with an increased susceptibility to cortical spreading depression suggested as a possible aetiological mechanism. Stroke, acute encephalopathy and cognitive impairment can also occur. Hypertension and smoking are associated with early age of onset of stroke. It diffusely affects white matter, with distinct findings on T2- weighted MRI, involving the external capsule, anterior poles of the temporal lobe and superior frontal gyri, displaying a characteristic pattern of leucoencephalopathy. Affected individuals have a reduced life expectancy. An effective treatment for CADASIL is not available. The authors describe a 35-year-old manwith an unremarkable medical history, presenting to the emergency department with slurred speech and increased confusion 3 days following a fall. He was a smoker and consumed 16 units of alcohol weekly. He was hypertensive and tachycardic. Physical examination confirmed increased tone in his lower limbs and dysarthria. His CT head showed severe cerebral atrophy, multiple small old infarcts and moderate background microvascular disease. Further investigation with an MRI head confirmed multiple white matter abnormalities with microhaemorrhages. The possibility of a hereditary vasculopathy was rendered as the appearances were thought consistent with a diagnosis of CADASIL. Genetic testing identified the NOTCH3 gene thus confirming the diagnosis. This paper provides an overview of the aetiology, clinical presentation, pathogenesis, investigations and management of CADASIL.

  • stroke
  • dementia
  • vascular
View Full Text

Statistics from Altmetric.com

Footnotes

  • Contributors LD: wrote the case report; AR: literature search; YD: editing; YB: editing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Obtained.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.