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.

Conclusion: Results from this study suggested that increased DWI signals could reflect severe spongiform changes in CJD180 patients.

Fig. 1

Axial T₂- (a) and diffusion-weighted (b) MR images from the 3 CJD cases with the V180I mutation, revealing extensive cortical hyperintensity lesions. Hyperintense signals in the bilateral caudate nucleus and putamen are also demonstrated, but these are subtle compared with the cortical lesions. Medial regions of the occipital lobes are not involved.

Fig. 2

SPECT analysis in case 1 (CJD180). a ¹²³I-IMP SPECT demonstrated decreased uptake. b eZIS analysis in SPECT performed using ^99mTc-ECD. c 3DSRT analysis in SPECT performed using ^99mTc-ECD.

Fig. 3

¹H-MRS in case 1 exhibits decreased cortical gray matter NAA/Cr.

Fig. 4

Pathological findings in the right frontal lobe of case 1 reveal severe spongiform changes and neuronal loss. However, astrocytic gliosis, accumulation of PrP^Sc, and microglial activation are less apparent in the cerebral cortex. a HE staining. b CD68 staining. c S100b protein staining (× 10). d S100b protein staining (× 200).