title: Familial Creutzfeldt-Jakob disease with a V180I mutation: comparative analysis with pathological findings and diffusion-weighted images.
abstract: BACKGROUND
  Diffusion-weighted imaging (DWI) has been reported to be a useful technique for diagnosing Creutzfeldt-Jakob disease (CJD). The present study reported DWI results in cases of familial CJD with a V180I mutation (CJD180) in the prion protein gene as well as neurological findings.
  
  
  METHODS
  A retrospective analysis of 3 patients with V180I was performed. Cerebrospinal fluid (CSF) analysis, brain MRI, single-photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS) were included. CSF was analyzed for biochemical markers, and each patient underwent brain MRI, SPECT, and MRS analysis. A brain biopsy from the frontal cortex, which corresponded to the area of increased DWI signals, was utilized for neuropathological analysis.
  
  
  RESULTS
  CSF analysis results revealed elevated total tau protein and the absence of 14-3-3 protein, as well as decreased concentrations of neuron-specific enolase, S100 protein, and prostaglandin E(2). All patients presented with unique MRI features. Brain biopsy showed severe spongiform morphology, but comparatively preserved neurons and mild astrocytic gliosis. Accumulations of PrP(Sc) were not detected using the 3F4 antibody, and microglial activation was subtle. SPECT revealed hypoperfusion throughout both hemispheres. MRS revealed a reduced N-acetyl aspartate/creatine ratio.
  
  
  CONCLUSIONS
  Results from this study suggested that increased DWI signals could reflect severe spongiform changes in CJD180 patients.
authors.affiliation: First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mutsukura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Satoh
authors.forename: Susumu
authors.initials: S
authors.lastname: Shirabe
authors.forename: Itsuro
authors.initials: I
authors.lastname: Tomita
authors.forename: Takayasu
authors.initials: T
authors.lastname: Fukutome
authors.forename: Minoru
authors.initials: M
authors.lastname: Morikawa
authors.forename: Masachika
authors.initials: M
authors.lastname: Iseki
authors.forename: Kensuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yusei
authors.initials: Y
authors.lastname: Shiaga
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology*; D003545:Cysteine / Q000031:analogs & derivatives; D038524:Diffusion Magnetic Resonance Imaging; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology / Q000523:psychology; D015609:Organotechnetium Compounds; D057178:Primary Progressive Nonfluent Aphasia / Q000209:etiology / Q000473:pathology / Q000523:psychology; D011725:Pyridines; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C473191:6-iodo-2-(4'-dimethylamino-)phenyl-imidazo(1,2-a)pyridine; D015415:Biomarkers; D015609:Organotechnetium Compounds; D011725:Pyridines; D019275:Radiopharmaceuticals; C059659:technetium Tc 99m bicisate; D003545:Cysteine