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Risk of Clinical Events in Presymptomatic Familial Cerebral Cavernous Malformations.

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Clinical Impact of NOTCH3 Variant Location After First Stroke in CADASIL.

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<i>COL4A1</i> and <i>COL4A2</i> Gene Duplication or Triplication as a Genetic Cause of Cerebral Small Vessel Disease in Adults.

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CADASIL: yesterday, today, tomorrow.

H Chabriat1,2,3, A Joutel3,4, E Tournier-Lasserve2,3,5

  • 1Department of Neurology and CERVCO, Reference Center for Rare Vascular Diseases of the Eye and Brain, Hôpital Lariboisiére, APHP, Paris, France.

European Journal of Neurology
|April 30, 2020
PubMed
Summary
This summary is machine-generated.

Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common genetic small vessel disease. Research has identified NOTCH3 gene mutations and outlined the disease

Keywords:
CADASILMRI brain lesionsNOTCH3 genecognitive disorders and dementiagenetic and inherited disordersleukodystrophiesneurological disordersstroke cerebrovascular diseases and cerebral circulation

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Area of Science:

  • Neurology
  • Genetics
  • Pathophysiology

Background:

  • CADASIL, an archetypal small vessel disease of the brain, has been researched for over 40 years.
  • Recognized as the most common genetic cerebral small vessel disease.
  • The Brain Prize in 2019 highlighted CADASIL research milestones.

Purpose of the Study:

  • To review the discovery and research history of CADASIL.
  • To highlight key findings in understanding CADASIL pathophysiology and genetics.
  • To emphasize the ongoing need for therapeutic development.

Main Methods:

  • Discovery through family studies of initial clinical cases.
  • Identification of NOTCH3 gene mutations.
  • Development of genetic testing and animal models.

Main Results:

  • Established CADASIL as the most common genetic cerebral small vessel disease.
  • Described the natural history from silent lesions to severe disability and dementia.
  • Demonstrated the role of matrix proteins in pathophysiology.
  • Facilitated discovery of other monogenic small vessel diseases.

Conclusions:

  • CADASIL is widely recognized, but its mechanisms require further elucidation.
  • Understanding disease mechanisms is crucial for developing effective therapeutics.
  • Ongoing global research will advance CADASIL knowledge and cerebral small vessel disorder research.