Magnetic Resonance Imaging in E200K and V210I Mutations of the Prion Protein Gene

Abstract

Magnetic resonance imaging (MRI), with diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR), is a useful diagnostic investigation for Creutzfeldt-Jakob disease (CJD). Amendment of the diagnostic criteria for sporadic CJD (sCJD) to include defined MRI alterations has just recently been proposed. We analyzed MRI scans with FLAIR and/or DWI available of 29 patients with the E200K or the V210I mutation, and a control group of 29 sCJD patients to compare the MRI lesion profile and evaluate the applicability of new MRI criteria to genetic CJD patients. FLAIR images of all 29 patients and controls and DWI images of 15 genetic CJD and 13 sCJD were rated by 2 neuroradiologists blinded to diagnosis and genetic testing. In genetic CJD (gCJD) patients, hyperintensities on FLAIR could be found in the putamen in 55% and the caudate nucleus in 66% and on DWI in 33% and 60%, respectively. Lesion profile and frequency of hyperintensities did not differ significantly from the findings in sCJD. New diagnostic MRI criteria yield similar sensitivity for gCJD and sCJD, being 79% and 72%, respectively. MRI provides useful information in E200K and V210I gCJD patients. The alterations strongly resembled those seen in sCJD, once again demonstrating the similarity of the clinical syndrome in patients with these particular mutations.

Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease

“…The differential diagnosis of human prion diseases can be often challenging due to the phenotypic heterogeneity of the disease. Prion disease biomarker tests developed in the last two decades allow the detection of symptomatic sCJD and genetic prion disease cases, with PRNP sequence variations mimicking the sporadic phenotype (e.g., PRNP-E200K and PRNP-V210I) with high accuracy [27,[29][30][31][32][33]. In contrast, very few studies have assessed the accuracy of the same biomarker tests in iCJD.…”

Neuroimaging in Dementia

“…210 In gJCD, MRI often resembles sJCD. 208,233,234 In FFI, such prototypical MRI findings of sJCD are usually absent, but can show atrophy. [234][235][236] In GSS, cerebellar or global atrophy can be found, whereas FLAIR, DWI, and ADC abnormalities are uncommon.…”

“Atypical” atypical parkinsonism: New genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy—A diagnostic guide

“…A). MRI in these cases shows bilateral hyperintensities in the putamen and caudate in T2, fluid‐attenuated inversion‐recovery (FLAIR), and diffusion‐weighted imaging (DWI) sequences, which is not the case in PSP . Obviously a positive 14‐3‐3 and tau protein level in the CSF, with periodic electroencephalography (EEG) patterns, raises suspicion of a prion disease, but these may be initially normal; therefore, clinical clues are very important to suspect this disorder.…”