Computer-assisted three-dimensional image analysis of cerebral amyloid angiopathy.

Microaneurysms and fibrinoid necrosis of cerebral cortical arteries have been reported to be related to the pathogenesis of intracerebral hemorrhage associated with cerebral amyloid angiopathy. To elucidate the pathogenesis of such vascular lesions, we conducted the present study. Five hundred serial sections from brain tissue of a patient with severe amyloid angiopathy and intracerebral hemorrhage were analyzed histologically and immunohistochemically. Three-dimensional reconstructions of the vascular lesions were performed using a computer-assisted image analysis system. The microaneurysms were found to develop in small cortical arteries with diameters of about 40 to 50 microns. They were spindle-shaped dilatations, with a maximum diameter of about 200 microns, and appeared within vascular segments bearing severe amyloid deposition. In the walls of the aneurysms, the intima was thickened, and the media and adventitia showed thinning and disruption. Fibrinoid necrosis was found in the vascular walls of the most dilated, middle portions of the aneurysm. The vascular walls undergoing fibrinoid necrosis did not show any beta/A4 or cystatin C but presented with fibrinogen-like immunoreactivities, indicating invasion of plasma components. These results suggested the following sequential events for the pathogenesis of the cerebral amyloid angiopathy-associated vascular lesions leading to hemorrhage: (1) damage of the media and adventitia due to severe amyloid deposition results in dilatation of the cortical arteries, (2) the vascular dilatation progresses and is accompanied by thickening of the intima and disruption of the media and adventitia (microaneurysm formation), (3) plasma components invade to the vascular wall (fibrinoid necrosis), and (4) finally, hemorrhage develops.