CEREBRAL AUTOSOMAL-DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY - STUDY OF 2 AMERICAN FAMILIES WITH PREDOMINANT DEMENTIA

Few European families have been reported with cerebral autosomal domin ant arteriopathy with subcortical infarcts and leukoencephalopathy (CA DASIL). We describe four patients from two independent American famili es. All four cases underwent comprehensive clinical, neuropsychologica l and pathological examination. Pathological data were correlated with clinical features. Dementia was a prominent and constant feature in a ll subjects. The families differed in phenotypical presentation and we analyzed possible pathological substrates that may account for the di fferences. Autopsy showed multiple ischemic infarcts in the white matt er, abnormal vasculature with thickening and degeneration of the vesse l wall. The clinical course in the first family was characterized by e arly dementia without stroke-like episodes; however, autopsy demonstra ted strokes in the basal ganglia and thalamus. The members of the seco nd family developed dementia later and had history of several clinical ly evident strokes. Pathological examination showed only widespread de generation of the white matter. Our study of two American families wit h CADASIL suggests that involvement of the basal ganglia and thalamus is important for early development of dementia and clinically can pres ent as a gradual dementia, resembling a neurodegenerative process. Sel ective damage of the white matter and central gray matter provides fur ther insight to the pathogenesis of vascular dementia. (C) 1997 Elsevi er Science B.V.