title: An autopsied case of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease presenting with hyperintensities on diffusion-weighted MRI before clinical onset.
abstract: A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram. Myoclonus was observed 8 weeks after clinical onset. The patient reached an akinetic mutism state and died 5 months after onset. Neuropathological examination showed widespread cerebral neocortical involvement of fine vacuole-type spongiform changes with large confluent vacuole-type spongiform changes. Spongiform degeneration with neuron loss and hypertrophic astrocytosis was also observed in the striatum and medial thalamus. The inferior olivary nucleus showed severe neuron loss with hypertrophic astrocytosis. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition with perivacuolar-type PrP deposition in the cerebral neocortex. Mild to moderate PrP deposition was also observed extensively in the basal ganglia, thalamus, cerebellum and brainstem, but it was not apparent in the inferior olivary nucleus. PrP gene analysis showed no mutations, and polymorphic codon 129 showed methionine homozygosity. Western blot analysis of protease-resistant PrP showed both type 1 scrapie type PrP (PrPSc) and type 2 PrPSc. Based on the relationship between the neuroimaging and pathological findings, we speculated that cerebral cortical lesions with large confluent vacuoles and type 2 PrPScwould show higher brightness and continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrPSc. We believe the present patient had a combined form of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD), which suggests a broader spectrum of sCJD clinicopathological findings.
authors.affiliation: Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Neurology, Oyamada Memorial Spa Hospital, Yokkaichi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Neurology, Oyamada Memorial Spa Hospital, Yokkaichi, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
authors.forename: Maya
authors.initials: M
authors.lastname: Mimuro
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
authors.affiliation: Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Nagakute, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000368:Aged; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D017809:Fatal Outcome; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D000072002:Prion Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D013788:Thalamus / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology
chemical_list: D000072002:Prion Proteins
keywords: Creutzfeldt-Jakob disease; MM2-cortical-type; MM2-thalamic-type; diffusion-weighted MRI; prion protein