Kuru-type Plaques Research Articles

Sporadic Creutzfeld-Jakob Disease: A Four-Year Evolution Case with Heterozygosity at Codon 129 and Kuru Plaques

A 55-year-old man was first evaluated after a one-year evolution of rapidly progressive dementia. The neurological examination showed MMSE 23/30 with impairment of multiple cognitive domains (memory, executive function, praxis and visuospatial), frontal release signs and pyramidalism. EEG revealed mild generalised slowing without periodic discharges. CSF analysis was negative for 14-3-3 protein. MRI showed hyperintense signals involving the dorsofrontal and parieto-occipital cortices and both medial thalamus which were particularly evident on DWI sequence. The motor and sensory primary cortices remained unaffected. Genotyping of the prion protein gen identified heterozygosis methionine-valine at codon 129 and no mutations. The patient developed progressive worsening in the behavioural, cognitive and motor domains that left him in a state of akinetic mutism for a few months before death, which occurred four years after the clinical onset. A pathological study demonstrated spongiform changes, gliosis, neuronal loss and Kuru-type plaques. Immunohistochemistry exhibited a synaptic pattern with focal plaques. A western Blot analysis was not possible, but an atypical long-duration MV2 sporadic Creutzfeldt-Jakob was the most probable diagnosis.

Atypical neuropathological sCJD‐MM phenotype with abundant white matter Kuru‐type plaques sparing the cerebellar cortex

We describe an atypical neuropatholgical phenotype of sporadic Creutzfeldt-Jakob disease (sCJD) in a 64-year-old man presenting with a 5-month history of rapidly progressive dementia, comprising behavioral disturbances, memory complaints, disorientation and language alterations. MRI showed diffuse atrophy and hyperintensities in parietal, occipital, temporal and frontal cortices and left caudate nucleus on T2-weighted and fluid-attenuated inversion recovery images. No typical EEG alterations were observed. Repeated 14-3-3 assay was positive after a first negative test. Neuropathology showed classical CJD changes with small cortical foci of large confluent vacuoles and relatively well-preserved cerebellar cortex. The most striking feature was the presence of abundant Kuru-type plaques in both cerebral cortex and subcortical white matter. Sparse Kuru-type plaques were also seen in cerebellum, although only in white matter. Immunohistochemistry showed, in addition to unicentric plaques, diffuse synaptic and patchy perivacuolar, as well as plaque-like and periaxonal pathological prion protein deposits (PrP(res) ). Western blot studies demonstrated the co-occurrence of PrP(res) types 1 and 2 in frontal cortex and a relatively weak type 2 signal in cerebellum. PRNP genotyping revealed methionine homozygosity at codon 129 and excluded mutations. This case shows a previously undescribed combination of histopathological features which preclude its classification according to the current phenotypic and molecular sCJD classification. The observation demonstrates that Kuru-type amyloid plaques mainly involving the cerebral white matter may also occur in sCJD cases with short clinical course and the co-existence of PrP(res) types 1 and 2. This case further highlights the complexity of the correlations between histopathological phenotype and PrP(res) isotype in prion diseases.

Long-duration sCJD with PRNP codon 129 methionine homozygosity and cerebral cortical plaques

The authors investigated a 40-year-old woman who presented with ataxia and dementia with little progression for over 40 months. The results of a CSF 14-3-3 protein and EEG study did not reveal major abnormalities. Brain MRI showed increased signal intensity over the occipital cortex in diffusion-weighted imaging. To our knowledge, this is the longest MM-type sporadic Creutzfeldt-Jakob disease case with cortical kuru-type plaques.

Basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease.

To determine the correlation of clinical and pathologic features with prion protein (PrP) gene polymorphism at codon 129 and with biochemical characteristics of the protease-resistant PrP (PrPres) in sporadic Creutzfeldt-Jakob disease (CJD). Clinical data acquisition, determination of the codon 129 genotype of the PrP gene, brain pathologic study, and immunoblot analysis of crude brain extracts were carried out in 14 patients. The first group of 10 subjects showed the classic clinical triad, with dementia, myoclonus, and periodic sharp waves on EEG. None of the subjects had amyloid plaques, but PrP immunoreactivity was of diffuse synaptic type in the cerebellar cortex. All subjects were methionine-methionine at codon 129 and the PrPres had a biochemical profile of type 1 (unglycosylated band of 21.5 kD). A second group of three patients showed cerebellar ataxia and later dementia. Periodic sharp waves on EEG were absent. PrP amyloid plaques predominated in the cerebellar cortex, along with diffuse PrP immunoreactivity. These subjects were valine-valine at codon 129 and had a type 2 PrPres (unglycosylated band of 19.4 kD). In the last patient cerebellar ataxia and dementia appeared simultaneously. Many Kuru-type plaques were present in the cerebellar cortex; many PrP amyloid plaques were present in the basal ganglia. This patient was methionine-valine at codon 129 and the PrPres was of type 1. The codon 129 genotype is only one of the factors determining CJD phenotype, and the biochemical pattern of PrP has no direct correlation with this phenotype.

Creutzfeldt-Jakob disease with long duration and panencephalopathic lesions: Molecular analysis of one case

A 49-year-old woman presented with isolated aphasia followed by dementia and ataxia with a duration of 4 years. Histopathologically there was panencephalic involvement, status spongiosus, and kuru-type plaques. Molecular analysis showed heterozygosity at codon 129 in the prion protein (PrP) gene, and type 2 protease-resistant PrP. The comparison between this case and those previously reported suggests that the panencephalopathic variant of Creutzfeldt-Jakob disease (CJD) is an aspecific end-stage condition displayed by most if not all CJD variants in individual patients with an unusually prolonged course.