Microscopic Examination -- Rapidly Progressive Motor Weakness, Starting in Pregnancy


Spinal cord: There was marked loss of fibres from both the crossed and uncrossed corticospinal tracts, with more widespread loss of fibres from other spinal tracts including the spinocerebellar tracts (Figure 2a). Severe loss of anterior horn cells was seen at all levels of the spinal cord; loss of neurons from the Clarke's column nuclei was less marked (Figure 2b). Basophilic inclusions were noted in occasional remaining anterior horn cells and other neurons within the spinal cord (Figure 3). Hyaline inclusions and Bunina bodies were not seen. The posterior columns and dorsal root ganglia were well preserved.

Cerebrum: Scattered basophilic cytoplasmic inclusions were noted in the pyramidal neurons in many regions of the cortex, but most prominently within the frontal lobes, where there was also focal spongiosis of superficial lamina. Basophilic inclusions were also noted within the putamen, thalamus and globus pallidus.

Brain stem: Scattered basophilic inclusions were noted throughout the brain stem nuclei, including the substantia nigra (Figure 4a and Figure 4b), oculomotor nuclei, periaqueductal grey matter, pontine nuclei, locus cerulei, hypoglossal nuclei and inferior olivary nuclei. Neuronal loss from these regions appeared mild. There was marked fibre loss from the corticospinal tracts in the cerebral peduncles and medullary pyramids.

Cerebellum: This showed mild patchy loss of Purkinje cells and occasional axonal 'torpedoes'. Basophilic inclusions were noted within the dentate nucleus.

Inclusions: The inclusions had sharply demarcated, irregular or rounded outlines and showed marked basophilia with hematoxylin and eosin staining, sometimes with central areas pallor. Although some showed argyrophilia with a modified Bielchowsky preparation, most were unstained. They did not show fluorescence with ultraviolet light following thioflavin-S staining. Occasional inclusions showed speckled ubiquitin immunoreactivity (Figure 5a, arrow and Figure 5b), however, most were negative (Figure 5a, arrow head). Occasional inclusions also showed weak, often peripheral, immunoreactivity with an antibody to phosphorylated neurofilament (Figure 6, arrows). Immunoreactivity using antibodies to tau protein, alpha-synuclein and MAP-2 was not seen.

At electron microscopy the inclusions were well circumscribed, but not membrane bound (Figure 7a), and composed of a mixture of haphazardly arranged 15nm tubular structures, most of which appeared straight, 7nm filaments, membranous structures, granular material and what appeared to be degenerate neurosecretory granules (Figure 7b).


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