Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and right-to-left shunt: lack of evidence for an association in a prevalence study

Eur Neurol. 2009;61(1):46-9. doi: 10.1159/000165350. Epub 2008 Oct 24.

Abstract

Background/aims: Up to more than 50% of cryptogenetic stroke patients and patients with migraine with aura (MA) are found to have a right-to-left shunt (RLS), which is usually due to a patent foramen ovale. Moreover, both MA and stroke are cardinal features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Notch3 mutations have been suggested to induce an abnormally high incidence of atrial septal defects in a family harbouring an Arg141Cys pathogenetic mutation. We sought to determine the prevalence of RLS in CADASIL patients with different Notch3 mutations, both with and without migraine as a clinical feature.

Methods: Subjects with a molecular diagnosis of CADASIL were tested for the presence of an RLS by means of contrast-enhanced transcranial Doppler (TCD). The diagnosis of migraine was made according to the 2004 International Headache Classification.

Results: Sixteen CADASIL patients were tested; 6 had MA. Four patients displayed an RLS on contrast-enhanced TCD examination. Three of these patients had MA. Both patients with Arg141Cys displayed a large RLS.

Conclusion: We conclude that RLS is not necessarily linked to CADASIL as a comorbidity factor. Nevertheless, there could be a relation between RLS and specific Notch3 mutations, such as Arg141Cys.

MeSH terms

  • Adult
  • Aged
  • CADASIL / complications*
  • CADASIL / epidemiology
  • CADASIL / genetics
  • Female
  • Heart Septal Defects, Atrial / complications*
  • Heart Septal Defects, Atrial / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Migraine with Aura / complications*
  • Migraine with Aura / epidemiology
  • Mutation
  • Prevalence
  • Receptor, Notch3
  • Receptors, Notch / genetics
  • Ultrasonography, Doppler, Transcranial

Substances

  • NOTCH3 protein, human
  • Receptor, Notch3
  • Receptors, Notch