Cerebral Pathology in Hepatolenticular Degeneration (Wilson Disease)

Abstract

Introduction. Hepatolenticular degeneration (HLD), or Wilson disease, is one of the severe progressive hereditary disorders of the nervous system. A number of questions regarding its pathogenesis and pathology are the subject of in-depth research. The aim of the study was to examine cerebral pathology and determine the leading factors in its pathogenesis in the autopsy cases of HLD. Materials and methods. A postmortem study was carried out in 15 deceased patients (14–35 years old) with HLD. In all cases, clinical diagnosis was based on the characteristic signs of CNS and liver damage, presence of the Kayser–Fleischer corneal ring, and specific biochemical abnormalities in copper and protein metabolism. A set of histological, neurohistological, and histochemical staining methods was used, including the histochemical study of copper after the fixation of brain slices in rubeanic acid. Results. In all cases, severe microcirculatory changes were found in the brain, characteristic of the angiotoxic component of HLD, with impaired vessel permeability and the development of persistent edema and spongiform changes in brain tissue. Changes were more often found in the basal nuclei area, as well as in the white matter of the cerebral hemispheres, cerebellum, and pons. The cytotoxic component of HLD was evident in the same regions of the brain, represented by degenerative changes in astrocytes and neurons, often ending in their death. The most frequent form of pathology was the appearance of Alzheimer type II glia with ‘naked’ nuclei, and much less frequently, Alzheimer type I glia. The histochemical study showed deposits of copper granules in the endothelial cells of microvessels, Alzheimer type II glia, and neurons – predominantly in the globus pallidus and the caudate nucleus. Conclusion. A set of pathogenic factors plays an essential role in the pathogenesis of the brain damage in HLD: the toxic effect of copper on the brain, the damage to and impaired permeability of the blood-brain barrier, severe metabolic disturbances caused by liver failure, and brain hypoxia.