An autopsied case of V180I Creutzfeldt-Jakob disease presenting with panencephalopathic-type pathology and a characteristic prion protein type.

A 73-year-old Japanese woman showed slowly progressive aphasia, apraxia and dementia. She had no family history of prion disease or dementia. One year later she showed parkinsonism and corticobasal degeneration was initially suspected. On MRI, the left temporal neocortex seemed swollen on T2-weighted images in the initial stage, and a later high-signal intensity region was observed in the cerebral cortex in diffusion-weighted images. The patient developed myoclonus and an akinetic mutism state 15 months and 22 months after onset, respectively. Consecutive electroencephalography revealed no periodic sharp-wave complexes. Prion protein (PrP) gene analysis revealed a valine to isoleucine point mutation at codon 180, and methionine homozygosity at codon 129. This patient's clinical symptoms and disease course were atypical for Creutzfeldt-Jakob disease (CJD), and a stable state with nasal tube-feeding lasted several years. She died of respiratory failure at the age of 81, 102 months after the onset. Autopsy revealed widespread spongiform degeneration with weak synaptic-type PrP deposition, confirming the diagnosis of genetic CJD. Neurons in the cerebral cortex were relatively preserved in number and hypertrophic astrocytosis was generally moderate for such long-term disease, but cerebral white matter showed diffuse severe myelin pallor with tissue rarefaction suggestive of panencephalopatic-type pathology. The cerebellar cortex was relatively well preserved with observation of mild spongiform change in the molecular layer, moderate neuron loss in the Purkinje neuron layer, and scattered small plaque-like PrP deposition. Western blot analysis of protease-resistant PrP showed a characteristic pattern without a diglycoform band. V180I CJD is an interesting form of genetic CJD with regards to the clinicopathologic, molecular and genetic findings.

An autopsy case of diffuse neurofibrillary tangles with calcification: early stage pathologic findings.

A 66-year-old man with no medically remarkable past or family history gradually showed personality changes, memory disturbance, sleeplessness and abnormal behavior. Neurologic examination showed no focal signs and neither parkinsonism nor cerebellar ataxia was recognized. He died 4 years after the onset of dementia due to chronic renal failure. Neuropathologic examination revealed neuronal loss and gliosis in the temporal cortex, particularly in the subiculum, parahippocampal gyrus and entorhinal cortex, and insular cortex. NFTs were observed to be widespread in the cerebral cortex, especially the temporal cortex and brainstem, while senile plaques were not observed. Gallyas-Braak silver staining revealed the presence of numerous NFTs, glial inclusions and neuropil threads throughout the cerebral neocortex, limbic system, hippocampus and brainstem. The subiculum showed the most severe involvement; severe atrophy, severe neuron loss, and numerous ghost tangles (extracellular NFTs) were apparent. Although NFTs contained both monoclonal anti-3repeat-tau antibody (RD3) and RD4 immunoreactivity, this differed between the intracellular NFTs and ghost tangles. RD3 immunoreactivity was mainly observed in ghost tangles and neuropil threads, whereas RD4 immunoreactivity was mainly observed in intracellular NFTs and glial inclusions. Calcification was also found to be widespread in the cerebral cortex and white matter, basal ganglia, thalamus, cerebellar cortex, white matter and dentate nucleus. These characteristic neuropathologic findings lead to the pathologic diagnosis of diffuse neurofibrillary tangles with calcification (DNTC). It is argued that this patient showed early stage pathologic signs of DNTC due to a short disease duration, which may provide clues regarding the progression of this rare disease.