CONVENTIONAL MRI AND NOTCH3 GENE SCREENING IN SPORADIC CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a small vessels disease caused by mutations in the NOTCH3 gene,¹ is considered the most frequent cause of genetically determined stroke. The age at onset ranges between the fourth and the third decade, and the cardinal symptoms comprise stroke, migraine headaches with or without aura, and cognitive decline, with additional features including psychiatric disturbances and epileptic seizures.²

Imaging studies summarized the CADASIL pattern as a combination of T₂-hyperintensities in the periventricular white matter, anterior temporal pole, external capsule, basal ganglia, and brainstem.Hemosiderin deposits (microbleeds) have been described, primarily in the thalamic regions.^3,4

The extent of radiologic CADASIL abnormalities, however, greatly differs among subjects and increases with age⁴ or other factors, sometimes impeding identification of CADASIL in a subject. In patients with CADASIL, causative mutations have been reported spanning the NOTCH3 gene; since it is a quite expensive and time-consuming analysis,⁵ a common strategy is to perform a complete gene screening only on patients with a positive familial history of CADASIL.

We investigated whether sporadic patients with brain MRI suggestive of CADASIL may carry mutations in the entire NOTCH3 gene, even in the absence of a positive familial …