Correlating diffusion-weighted MRI intensity with type 2 pathology in mixed MM-type sporadic Creutzfeldt-Jakob disease

概要

Introduction: Although the sporadic Creutzfeldt-Jakob disease (sCJD) subtypes, with their distinctive clinicopathological features, have been identified based on two types of the abnormal prion protein (PrPSc), type 1 and type 2, and polymorphic codon 129 [1], there have been cases of both PrPSc types being present [2][3]. Because the clinical features in mixed PrPSc type sCJD were somewhat similar to the dominant PrPSc type but varied [4], the antemortem identification of both PrPSc types is not possible. On the other hand, the mixed PrPSc type features, especially in MM-type sCJD, have been best identified with neuropathological examination; the MM1-type involves fine vacuole-type spongiform change (FV), whereas the MM2C-type involves large confluent vacuole-type spongiform change (LCV) [5]. Our aim in this study was to predict the concurrence of MM-type sCJD with another type of PrPSc in the same individual before death and to reveal the relationship of clinical features and radiological findings in pathologically-mixed MM-type sCJD cases. We conducted both a retrospective clinicopathological case series and a regional systemic study to compare the pattern of spongiform change with hyperintensity on magnetic resonance diffusion-weighted imaging (DWI). This is the first study to statistically indicate the correlation of DWI intensity with the pattern of spongiform change.

Materials and Methods: We retrospectively identified seven MM-type sCJD cases with both fine vacuole-type spongiform (FV) and large confluent vacuole-type spongiform change (LCV) among 49 sCJD cases between 2008 and 2016. We reviewed clinical features, pathological findings, and radiological abnormalities in these seven cases. We also conducted a regional systemic study with 27 cortical subdivisions per hemisphere in 5 brains to associate the spongiform-change pattern with hyperintensity on DWI using the signal intensity index (SII).

Results: In the case series study, the one patient with dominant LCV showed longer disease duration, later onset of typical symptoms, no periodic sharp wave complexes in electroencephalography, and negative 14-3-3 protein findings compared to the six FV-dominant patients. LCV-dominant lesions tended to show higher intensity on DWI than did the FV-dominant lesions in respective patients. In the regional systemic study, LCV-dominant regions showed significantly higher SII on DWI than did the FV-dominant regions.

Conclusions: Mixed MM-type sCJD generally showed the clinical features of the phenotype that was dominant in pathological distribution. The SII may be clinically useful for investigating the concurrence of PrPSc type 2 in cases with the typical clinical course of MM1-type sCJD.