Dialysis-associated encephalopathy: light and electron microscopic morphology and topography with evidence of aluminum by laser microprobe mass analysis

Recently we described silver-staining variants for the demonstration of beta/A4 amyloid and neurofibrillary tangles in senile dementia of Alzheimer type (SDAT). The same methods allowed, for the first time, the visualization of characteristic patterns and distinct morphological changes in human dialysis-associated encephalopathy. Light and electron microscopy demonstrated typical silver-stained inclusions in the cytoplasm of choroidal epithelium, glia and neurons. Performing laser microprobe mass analysis on en-bloc silver-stained semithin sections, evidence for significant amounts of aluminum was obtained within the lesions. Prominent aluminum-signals were obtained additionally in adjacent structures and nuclei of sections which were stained with toluidine-blue exclusively. Silver-stained paraffin sections of ten patients with a history of long-term hemodialysis were evaluated. The choroidal epithelium--obviously the most sensitive structure--showed black inclusions ranging from a few dots to a complete black staining of cells. Glial cells presented massive silver-stained deposits, which were restricted to the gray matter. Finally, neurons revealed numerous fine-granular black inclusions, scattered throughout the cytoplasm. Brain stem nuclei were primarily affected, but neurons within cortex, subcortical gray matter and spinal cord were also involved to various degrees; inclusions were not evident in the nucleus dentatus and the oliva inferior. Vessel-related deposits were found frequently. By electron microscopy the cytoplasm of neurons was filled either with large amounts of small electron-dense granules, or with lipofuscin granules, containing numerous irregular, non-membrane-bound inclusions. Massive electron-dense depositions were seen in the cytoplasm of choroidal epithelia and in proximity to nuclei of cortical astro- and oligodendroglia. The described neuronal changes and, in particular, alterations of choroidal epithelium and glia are completely different from characteristic plaques and tangles in SDAT.