TY - JOUR
T1 - Clinicopathological and genetic studies of two further Italian families with cerebral autosomal dominant arteriopathy
AU - Malandrini, A.
AU - Carrera, P.
AU - Palmeri, S.
AU - Cavallaro, T.
AU - Fabrizi, G. M.
AU - Villanova, M.
AU - Fattapposta, M.
AU - Vismara, L.
AU - Brancolini, V.
AU - Tanganelli, P.
AU - Calì, A.
AU - Morocutti, C.
AU - Zeviani, M.
AU - Ferrari, M.
AU - Guazzi, G. C.
PY - 1996/8
Y1 - 1996/8
N2 - We report on two Italian families with an early-adult onset autosomal dominant disorder, characterized by leukoencephalopathy, migraine, psychiatric disturbances, stroke and dementia. These findings fulfill the diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome. Moreover, to confirm the CADASIL gene location to 19p12, we performed a linkage analysis with four microsatellite markers. The results of the genetic study gave positive but not significant led scores, indicating only weak evidence of a linkage with 19p12. In one autopsy case, we found extensive ischemic changes due to the selective involvement of the small muscular arteries of the cerebral white matter. The lesions consisted of a thickening of the media with deposition of granular eosinophilic material. Ultrastructural examination of the arterial walls showed graded damage to smooth muscle cells, mostly of the longitudinal layer, and an abnormal proliferation of basal lamina components. Immunocytochemical analysis showed strong reactivity using antibodies to collagen IV and smooth myosin proteins. The results suggest a primary involvement of the smooth muscle cells of small cerebral arteries, with a secondary alteration of basal lamina components and elastic tissue.
AB - We report on two Italian families with an early-adult onset autosomal dominant disorder, characterized by leukoencephalopathy, migraine, psychiatric disturbances, stroke and dementia. These findings fulfill the diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome. Moreover, to confirm the CADASIL gene location to 19p12, we performed a linkage analysis with four microsatellite markers. The results of the genetic study gave positive but not significant led scores, indicating only weak evidence of a linkage with 19p12. In one autopsy case, we found extensive ischemic changes due to the selective involvement of the small muscular arteries of the cerebral white matter. The lesions consisted of a thickening of the media with deposition of granular eosinophilic material. Ultrastructural examination of the arterial walls showed graded damage to smooth muscle cells, mostly of the longitudinal layer, and an abnormal proliferation of basal lamina components. Immunocytochemical analysis showed strong reactivity using antibodies to collagen IV and smooth myosin proteins. The results suggest a primary involvement of the smooth muscle cells of small cerebral arteries, with a secondary alteration of basal lamina components and elastic tissue.
KW - CADASIL
KW - Cerebral arteriopathy
KW - Leukoencephalopathy
KW - Smooth muscle cell
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U2 - 10.1007/s004010050498
DO - 10.1007/s004010050498
M3 - Article
C2 - 8841656
AN - SCOPUS:8944257612
VL - 92
SP - 115
EP - 122
JO - Acta Neuropathologica
JF - Acta Neuropathologica
SN - 0001-6322
IS - 2
ER -