[Clinicopathological characteristics of Creutzfeldt-Jakob disease with a PrP V180I mutation and M129V polymorphism on different alleles].

We report an 80-year-old Japanese man with histologically-diagnosed Creutzfeldt-Jakob disease (CJD). The patient was admitted to our neurological unit because of sudden onset motor aphasia-like symptoms and right hemiparesis. His medical and family histories were unremarkable, and he had taken no medications. Urine, blood counts and blood chemistry were all within normal limits. Cerebrospinal fluid was normal except for elevation of neuron specific enolase (29.9 ng/ml). High-signal intensity was demonstrated in the cortex of the left temporal lobe on T2-weighted MRI images, and the lesion swelled during the initial stage of the disease. There was no enhancement with Gd-DTPA. Serial MRI showed that the high-signal lesion had spread into the bilateral cerebral cortex. The patient developed myoclonus followed by akinetic mutism within 6 months of onset. Consecutive EEGs revealed no periodic synchronous discharge (PSD). He died of pneumonia 21 months after of admission. Autopsy revealed spongiform changes in the cerebral cortex with Kuru plaques, confirming the diagnosis of CJD. The Cerebellar cortex was well preserved. The high-signal lesions corresponded to the spongiform changes in the cerebral cortex. Immunohistochemical analysis showed weak synaptic prion staining. Prion protein (PrP) gene analysis of genomic DNA isolated from the autopsied brain by polymerase chain reaction, the restriction fragment length polymorphisms, and direct sequencing revealed a point mutation (Val-->Ile) at codon 180 and a polymorphism (Met/Val) at codon 129 on different alleles. A few CJD patients with point mutations in codon 180 of the PrP gene have been reported. Combination of the codon 180 point mutation and codon 129 polymorphism may yield an atypical clinicopathological form of CJD that includes late onset, negative PSD, and atypical MRI findings, with preservation of the cerebellar cortex.