Creutzfeldt-Jakob disease with the M232R mutation in the prion protein gene in two cases showing different disease courses: a clinicopathological study

We report two autopsy cases of Creutzfeldt-Jakob disease (CJD) with the M232R mutation of the prion protein (PrP) gene that exhibited different clinicopathological features (age at death, 64/54 years; disease duration, 13/26 months). Both cases showed myoclonus, hyperintensity on diffusion-weighted MRI, and increased 14-3-3 protein in the cerebrospinal fluid. The initial sign in each case was memory disturbance and abnormal pharyngeal sensation, respectively. In the first case, the disease progressed rapidly with akinetic mutism developing 6 months after onset, while it occurred 23 months after onset in the second case. Pathologically, both cases had severe neuronal loss with gliosis and spongiform change in the cerebral cortex, basal ganglia, and cerebellum. PrP deposition was the diffuse synaptic type in the first case, but the second case had both diffuse synaptic and perivacuolar types. PrP(sc) immunoblotting revealed a type 1 band pattern in the first case, but both types 1 and 2 in the second case. Based on these findings, together with the results in previous CJD cases with M232R, we noted the possibility that the presence of type 2 PrP(sc) may be associated with both morphological features of PrP deposition and slow disease progression in this genetic prion disease.