Familial Creutzfeldt-Jakob disease with a V180I mutation: comparative analysis with pathological findings and diffusion-weighted images.
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.
Mutsukura
Kazuo
K
First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Satoh
Katsuya
K
Shirabe
Susumu
S
Tomita
Itsuro
I
Fukutome
Takayasu
T
Morikawa
Minoru
M
Iseki
Masachika
M
Sasaki
Kensuke
K
Shiaga
Yusei
Y
Kitamoto
Tetsuyuki
T
Eguchi
Katsumi
K
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
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