NOTCH3 and CADASIL: Although CADASIL is considered rare, with a reported disease prevalence of 4 per 100 000,5 6 a much higher frequency of typical cysteine-altering NOTCH3 variants was reported as 1 in 400 individuals.7 8 These could contribute to the risk of apparently sporadic lacunar stroke, but the clinical significance of these variants remains uncertain.