Changing clinical patterns and increasing prevalence in CADASIL

Area of Science:

• Neurology
• Genetics
• Vascular Biology

Background:

• Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic small vessel disease leading to recurrent strokes.
• Phenotypic variability exists, with early descriptions suggesting dementia and disability onset in the fifth decade.

Purpose of the Study:

• To determine the prevalence and clinical characteristics of CADASIL in the west of Scotland.
• To investigate the impact of diagnostic timing on clinical outcomes.

Main Methods:

• Retrospective review of clinical records from a specialist CADASIL clinic.
• Analysis of NOTCH3 mutations and pedigree data to estimate prevalence.
• Stratification of patients by age and date of diagnosis to assess clinical outcomes.

Main Results:

• Identified 49 pedigrees with 21 different NOTCH3 mutations, predominantly in exon 4.
• Established a disease prevalence of 4.6 per 100,000 adults in Glasgow.
• Observed a median age of first stroke in women of 57 years, and a later age of stroke onset in men diagnosed more recently (56 years vs. 46 years).
• Found that 38% of patients over 58 were living independently and 61% were mobile without aids.

Conclusions:

• CADASIL prevalence is at least 4.6 per 100,000 adults, with mutation prevalence at 10.7 per 100,000.
• The median age of first stroke may be later than previously reported.
• CADASIL should be considered in the differential diagnosis of stroke, even in older individuals.