Vasculopathic changes of CADASIL can be focal in skin biopsies

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leuk oencephalopathy (CADASIL) is a newly described cause of vascular dementia. Pathologic examination shows multiple small infarcts in the deep cerebral w hite matter together with a nonatherosclerotic, nonamyloid angiopathy invol ving the media of Small cerebral arteries. Ultrastructurally, characteristi c granular material is present in the basal lamina of vascular smooth muscl e cells in cerebral and extracerebral blood vessels. The ultrastructural ch anges have also been demonstrated in skin biopsies of affected patients; co nsequently, some investigators have recently recommended skin biopsies for the diagnosis of CADASIL. This study describes a 54-year-old male with a fa mily history for strokes who had clinical and radiological features suggest ive of CADASIL. A skin biopsy was performed to confirm the diagnosis. Initi ally, the characteristic vasculopathic changes of CADASIL were not identifi ed within small blood vessel walls. However, multiple deeper sections in ot her areas showed electron-dense material associated with vascular smooth mu scle cells, characteristic of CADASIL. Subsequent genetic testing demonstra ted 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 us eful adjunct in the diagnosis of CADASIL. However, as illustrated by this c ase, the findings may be focal, requiring a thorough evaluation of the enti re biopsy specimen.