Vasculopathic changes of CADASIL can be focal in skin biopsies

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a newly described cause of vascular dementia. Pathologic examination shows multiple small infarcts in the deep cerebral white matter together with a nonatherosclerotic, nonamyloid angiopathy involving the media of small cerebral arteries. Ultrastructurally, characteristic granular material is present in the basal lamina of vascular smooth muscle cells in cerebral and extracerebral blood vessels. The ultrastructural changes have also been demonstrated in skin biopsies of affected patients; consequently, some investigators have recently recommended skin biopsies for the diagnosis of CADASIL. This study describes a 54-year-old male with a family history for strokes who had clinical and radiological features suggestive of CADASIL. A skin biopsy was performed to confirm the diagnosis. Initially, the characteristic vasculopathic changes of CADASIL were not identified within small blood vessel walls. However, multiple deeper sections in other areas showed electron-dense material associated with vascular smooth muscle cells, characteristic of CADASIL. Subsequent genetic testing demonstrated a single nucleotide substitution at position 659 on chromosome 19p13.1 causing an amino-acid change (Cys --> Phe), a finding indicative of CADASIL. The involvement of blood vessels within the dermis makes skin biopsy a useful adjunct in the diagnosis of CADASIL. However, as illustrated by this case, the findings may be focal, requiring a thorough evaluation of the entire biopsy specimen.