title: Atypical neuropathological sCJD-MM phenotype with abundant white matter Kuru-type plaques sparing the cerebellar cortex.
abstract: 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.
authors.affiliation: Neurological Tissue Bank of the Biobank-Hospital Clinic-IDIBAPS, Facultat de Medicina, Spain. ellen.gelpi@gmail.com
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.forename: Josep Ma
authors.initials: JM
authors.lastname: Soler Insa
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Saverioni
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.forename: Carlos
authors.initials: C
authors.lastname: Nos
authors.forename: Elena
authors.initials: E
authors.lastname: Martínez-Saez
authors.forename: Teresa
authors.initials: T
authors.lastname: Ribalta
authors.forename: Isidre
authors.initials: I
authors.lastname: Ferrer
authors.forename: Raquel
authors.initials: R
authors.lastname: Sanchez-Valle
mesh_terms: D002525:Cerebellar Cortex; D007562:Creutzfeldt-Jakob Syndrome / Q000150:complications / Q000473:pathology*; D017809:Fatal Outcome; D006801:Humans; D007729:Kuru / Q000150:complications / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010641:Phenotype