COMPUTER-ASSISTED 3-DIMENSIONAL IMAGE-ANALYSIS OF CEREBRAL AMYLOID ANGIOPATHY

Background and Purpose: Microaneurysms and fibrinoid necrosis of cereb ral cortical arteries have been reported to be related to the pathogen esis of intracerebral hemorrhage associated with cerebral amyloid angi opathy. To elucidate the pathogenesis of such vascular lesions. we con ducted the present study. Methods: Five hundred serial sections from b rain tissue of a patient with severe amyloid angiopathy and intracereb ral hemorrhage were analyzed histologically and immunohistochemically. Three-dimensional reconstructions of the vascular lesions were perfor med using a computer-assisted image analysis system. Results: The micr oaneurysms were found to develop in small cortical arteries with diame ters of about 40 to 50 mum. They were spindle-shaped dilatations, with a maximum diameter of about 200 mum, and appeared within vascular seg ments bearing severe amyloid deposition. In the walls of the aneurysms , the intima was thickened, and the media and adventitia showed thinni ng and disruption. Fibrinoid necrosis was found in the vascular walls of the most dilated, middle portions of the aneurysm. The vascular wal ls undergoing fibrinoid necrosis did not show any beta/A4 or cystatin C but presented with fibrinogen-like immunoreactivities, indicating in vasion of plasma components. Conclusions. These results suggested the following sequential events for the pathogenesis of the cerebral amylo id angiopathy-associated vascular lesions leading to hemorrhage: (1) d amage of the media and adventitia due to severe amyloid deposition res ults in dilatation of the cortical arteries, (2) the vascular dilatati on progresses and is accompanied by thickening of the intima and disru ption of the media and adventitia (microaneurysm formation), (3) plasm a components invade to the vascular wall (fibrinoid necrosis), and (4) finally, hemorrhage develops.