CLINICOPATHOLOGICAL AND GENETIC-STUDIES OF 2 FURTHER ITALIAN FAMILIESWITH CEREBRAL AUTOSOMAL-DOMINANT ARTERIOPATHY

We report on two Italian families with an early-adult onset autosomal dominant disorder, characterized by leukoencephalopathy, migraine, psy chiatric disturbances, stroke and dementia. These findings fulfill the diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome. More over, to confirm the CADASIL, gene location to 19p12, we performed a l inkage analysis with four microsatellite markers. The results of the g enetic study gave positive but not significant lod scores, indicating only weak evidence of a linkage with 19p12. In one autopsy case, we fo und extensive ischemic changes due to the selective involvement of the small muscular arteries of the cerebral white matter. The lesions con sisted of a thickening of the media with deposition of granular eosino philic material. Ultrastructural examination of the arterial walls sho wed graded damage to smooth muscle cells, mostly of the longitudinal l ayer, and an abnormal proliferation of basal lamina components. Immuno cytochemical analysis showed strong reactivity using antibodies to col lagen IV and smooth myosin proteins. The results suggest a primary inv olvement of the smooth muscle cells of small cerebral arteries, with a secondary alteration of basal lamina components and elastic tissue.