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The typical clinical manifestations of sporadic Creutzfeldt‐Jakob disease (sCJD) are rapid‐progressive dementia and myoclonus. However, the diagnosis of atypical sCJD can be challenging due to its wide phenotypic variations. We report an autopsy case of variably protease‐sensitive prionopathy (VPSPr) with Met/Met homogeneity at codon 129. An 81‐year‐old woman presented with memory loss without motor symptoms. Seventeen months after the onset, her spontaneous language production almost disappeared. Diffusion‐weighted images (DWI) showed hyperintensity in the cerebral cortex while electroencephalogram (EEG) showed nonspecific change. 14‐3‐3 protein and real‐time qualing‐induced conversion (RT‐QuIC) of cerebrospinal fluid were negative. She died at age 85, 3.5 years after the onset. Pathological investigation revealed spongiform change, severe neuronal loss, and gliosis in the cerebral cortex. Mild to moderate neuronal loss and gliosis were observed in the basal ganglia. PrP immunostaining revealed plaque‐like, dotlike, and synaptic structures in the cerebral cortex and small plaque‐like structures in the molecular layer of the cerebellum. Analysis of PRNP showed no pathogenic mutations, and Western blot examination revealed the lack of a diglycosylated band consistent with VPSPr. The present case, which is the first report on a VPSPr case in Japan, supports previously published evidence that VPSPr cases can present variable and nonspecific clinical presentations. Because a small number of VPSPr cases can show typical magnetic resonance imaging (MRI) change in sCJD. We should investigate the possibility of VPSPr in a differential diagnosis with atypical dementia that presented DWIs of high intensity in the cortex, even though 14‐3‐3 proteins and RT‐QuIC are both negative. In addition, VPSPr cases can take a longer clinical course compared to that of sCJD, and long‐term follow‐up is important. [ABSTRACT FROM AUTHOR]

Genetic Creutzfeldt‐Jakob disease (gCJD) with a V180I mutation (V180I gCJD) is the most common type of gCJD in Japan, characterized by an older age at onset, slower progression, and moderate to severe cortical degeneration with spongiform changes and sparing of the brainstem and cerebellum. Degeneration of the inferior olivary nucleus (IO) is rarely observed in patients with CJD but is known to occur in fatal familial insomnia (FFI) and MM2‐thalamic‐type sporadic CJD (sCJD‐MM2T) involving type 2 prion protein (M2T prion). Here we report on an 81‐year‐old Japanese woman who initially developed depressive symptoms followed by progressive cognitive impairment, myoclonus, and hallucinations and died after a clinical course of 23 months. Insomnia was not evident. Genetic analysis of the prion protein (PrP) identified a V180I mutation with methionine/valine heterozygosity at codon 129. Pathologic analysis demonstrated extensive spongiform degeneration, neuronal loss in the cortices, and weak synaptic‐type PrP deposition. Except for IO degeneration, the clinicopathologic features and Western blotting PrP band pattern were compatible with those of previously reported V180I gCJD cases. Quantitative analysis revealed that the neuronal density of the IO, especially in the dorsal area, was considerably reduced to the same extent as that of a patient with sCJD‐MM2T but preserved in other patients with V180I gCJD and sCJD‐MM1 (this patient, 2.3 ± 0.53/mm2; a patient with sCJD‐MM2T, 4.2 ± 2; a patient with V180I gCJD, 60.5 ± 9.3; and a patient with sCJD‐MM1, 84.5 ± 17.9). Use of the protein misfolding cyclic amplification (PMCA) method confirmed the presence of the M2T prion strain, suggesting that the latter might be associated with IO degeneration in V180I gCJD. Autopsy studies are necessary to better understand the nature of CJD, since even if patients present with the common clinical picture, pathologic analysis might provide new insights, as was the case here. [ABSTRACT FROM AUTHOR]

In Japan, because MV2‐type sporadic Creutzfeldt–Jakob disease (CJD) is rare, little is known about its clinical and neuropathological characteristics. An autopsy case of MV2K‐type sporadic CJD is presented, and the characteristic clinical, radiological, and neuropathological findings are discussed. The patient was a Japanese woman who died at the age of 72 years. Her initial symptom was rapidly progressive dementia. She then developed truncal ataxia and delusions. Approximately nine months after onset, she exhibited akinetic mutism. The total clinical course was 11 months. Magnetic resonance imaging revealed hyperintensity areas in the basal ganglia, thalamus, and hippocampus on diffusion‐weighted images. In the cerebral cortex, this finding was slight and inconspicuous. Electroencephalography revealed no periodic sharp wave complexes. Prion protein (PrP) gene analysis revealed no mutations, and polymorphic codon 129 exhibited methionine and valine heterozygosity. In the cerebrospinal fluid, levels of both total tau and 14‐3‐3 proteins were elevated. Grossly, the brain weighed 1050 g before fixation and exhibited diffuse cortical atrophy. On histopathological examination, extensive fine vacuole‐type spongiform degeneration was noted in the cerebral cortex. Numerous kuru plaques were observed in the cerebellum. PrP immunohistochemistry revealed extensive diffuse synaptic‐ and perineuronal‐type PrP deposits in the cerebral cortex. Kuru plaques were strongly immunoreactive for PrP. Western blot analysis of brain tissue samples revealed mixed type 2 and intermediate type. Systematic and comprehensive investigations of both clinical and neuropathological aspects are required for accurate diagnosis. [ABSTRACT FROM AUTHOR]