DIALYSIS-ASSOCIATED ENCEPHALOPATHY - LIGHT AND ELECTRON-MICROSCOPIC MORPHOLOGY AND TOPOGRAPHY WITH EVIDENCE OF ALUMINUM BY LASER MICROPROBEMASS ANALYSIS

Recently we described silver-staining variants for the demonstration o f beta/A4 amyloid and neurofibrillary tangles in senile dementia of Al zheimer type (SDAT). The same methods allowed, for the first time, the visualization of characteristical patterns and distinct morphological changes in human dialysis-associated encephalopathy. Light and electr on microscopy demonstrated typical silver-stained inclusions in the cy toplasm of choroidal epithelium, glia and neurons. Performing laser mi croprobe mass analysis on en-bloc silver-stained semithin sections, ev idence for significant amounts of aluminum was obtained within the les ions. Prominent aluminum-signals were obtained additionally in adjacen t structures and nuclei of sections which were stained with toluidin-b lue exclusively. Silver-stained paraffin sections of ten patients with a history of long-term hemodialysis were evaluated. The choroidal epi thelium - obviously the most sensitive structure - showed black inclus ions ranging from a few dots to a complete black staining of cells. Gl ial cells presented massive silver-stained deposits, which were restri cted to the gray matter. Finally, neurons revealed numerous fine-granu lar black inclusions, scattered throughout the cytoplasm. Brain stem n uclei were primarily affected, but neurons within cortex, subcortical gray matter and spinal cord were also involved to various degrees; inc lusions were not evident in the nucleus dentatus and the oliva inferio r. Vessel-related deposits were found frequently. By electron microsco py the cytoplasm of neurons was filled either with large amounts of sm all electron-dense granules, or with lipofuscin granules, containing n umerous irregular, non-membrane-bound inclusions. Massive electron-den se depositions were seen in the cytoplasm of choroidal epithelia and i n proximity to nuclei of cortical astro- and oligodendroglia. The desc ribed neuronal changes and, in particular, alterations of choroidal ep ithelium and glia are completely different from characteristic plaques and tangles in SDAT.