Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrP^Sc deposits in the brain

We report a case of human prion disease of 29 months duration in a 74-year-old Japanese man. The disease started with progressive sleeplessness and dementia. MRI showed gradually progressive cerebral atrophy. Neuronal loss, spongiform change and gliosis were evident in the thalamus and cerebral cortex, as well as in the striatum and amygdaloid nucleus. In the cerebellar cortex, mild-to-moderate depletion of Pukinje cells and spongiform change were observed. Mild neuronal loss in the inferior olivary nucleus was also seen. Immunohistochemistry revealed widespread perivacuolar deposits of abnormal prion protein (PrP^Sc) in the cerebral cortex, thalamus, basal ganglia, and brainstem, and minimal plaque-like deposits of PrP^Sc in the cerebellar cortex. In the cerebellar plaque-like deposits, the presence of amyloid fibrils was confirmed ultrastructurally. The entire pathology appeared to lie halfway between those of CJD and fatal insomnia, and further demonstrated the relationship between spongiform degeneration and PrP^Sc deposits, especially in the diseased thalamus. By immunoblotting, the thalamus was shown to contain the lowest amount of PrP^SC among the brain regions examined. The PrP^Sc of type 2, in which the ratio of the three glycoforms was compatible with that of sporadic fatal insomnia (MM2-thalamic variant) reported previously, was also demonstrated. Analysis of the prion protein gene (PRNP) showed no mutation, and homozygosity for methionine at codon 129. In conclusion, we considered that this patient had been suffering from sporadic, pathologically atypical fatal insomnia.