ABSTRACT
Specific pathological hallmarks have been described in amyotrophic lateral sclerosis (ALS), which include motor neuronal loss, Bunina bodies (BBs) and skein like inclusions (SLIs). We investigated the relation between these three lesions in the cervical and lumbar anterior horns and the hypoglossal nuclei of 20 ALS patients and 9 controls using a quantitative light microscopy study. Immunohistochemistry with anti-cystatin C and anti-ubiquitin was used to detect the BBs and SLIs, respectively. A significant relation between the severity of neuronal loss and the proportion of SLI-containing neurons was found in the spinal cord, whereas no relation was found with BBs. We therefore propose that BBs and SLIs participate in two different steps of the cascade leading to neuronal loss.
Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Brain Stem/pathology , Cell Death/physiology , Cytoskeleton/pathology , Inclusion Bodies/pathology , Motor Neurons/pathology , Spinal Cord/pathology , Adult , Aged , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/physiopathology , Brain Stem/metabolism , Brain Stem/physiopathology , Cell Count , Cystatin C , Cystatins/metabolism , Cytoskeleton/metabolism , Female , Humans , Hypoglossal Nerve/metabolism , Hypoglossal Nerve/pathology , Hypoglossal Nerve/physiopathology , Immunohistochemistry , Inclusion Bodies/metabolism , Male , Middle Aged , Motor Neurons/metabolism , Spinal Cord/metabolism , Spinal Cord/physiopathology , Statistics as Topic , Ubiquitin/metabolismABSTRACT
For decades, drugs containing bismuth have been used to treat gastrointestinal disorders. Although a variety of adverse effects, including neurological syndromes, have been recorded, the biological/toxicological effects of bismuth ions are far from disclosed. Until recently, only quantitative assessments were possible, but resent research has made histochemical tracing of bismuth possible. The technique involves silver enhancement of bismuth crystallites by autometallography (AMG). In the present study, the localization of bismuth was traced by AMG in sections of paraffin-embedded brain tissue obtained by autopsy from 6 patients suffering from bismuth intoxication in a period ranging from 1975 through 1977. Tissue was analyzed at light and electron microscopical levels, and the presence of bismuth further confirmed by proton-induced x-ray emission (PIXE). Clinical data and bismuth concentrations in blood, cerebellum, and thalamus were measured by atomic absorption spectrophotometry (AAS) and are reported here. Histochemical analyses demonstrate that bismuth accumulated in neurons and glia cells in the brain regions examined (neocortex, cerebellum, thalamus, hippocampus). Cerebellar blood vessels stained most intensely. The PIXE and AAS data correlated with the histochemical staining patterns and intensities. At the ultrastructural level, bismuth was found to accumulate intracellularly in lysosomes and extracellularly in the basement membranes of some vessels.
