Prion disease develops when normal
prion proteins change into transmissible abnormal
prion proteins and the converted
proteins accumulate in the brain. The Japanese
Creutzfeldt-Jakob Disease (CJD) Surveillance Committee has identified 1320 patients with
prion diseases in the 10 years since 1999 (classified into 3 types: sporadic, 77.2%; hereditary, 16.7%; and environmentally acquired, 6.1%). Compared with patients in other countries, a relatively larger number of Japanese patients characteristically have dura mater graft-associated CJD and hereditary
prion diseases. All the environmentally acquired cases, except 1 case of variant CJD, were acquired from dura grafts. Although most patients were diagnosed with a classical subtype of
sporadic CJD (sCJD), whose features include rapidly progressing
dementia,
myoclonus, hyperintensity in the cerebral cortex and basal ganglia in diffusion-weighted magnetic resonance imaging, and periodic synchronous discharge in electroencephalography, the number of cases with atypical symptoms, such as MM2 (0.8%), MV2 (0.2%), VV1 (0%), and VV2 (0.2%) subtypes of sCJD cases, was not negligible. Appropriate diagnosis should be made based on clinical features, neuroradiological findings, CSF findings (14-3-3 and total
tau proteins), and genetic analysis of polymorphisms. Hereditary
prion diseases are classified into 3 major phenotypes: familial CJD (fCJD); Gerstmann-Straeussler-Scheinker disease (GSS), which mainly presents as
spinocerebellar ataxia; and
fatal familial insomnia. Many mutations of the
prion protein gene have been identified, but V180I (fCJD), P102L (GSS), and E200K (fCJD) mutations were the most common among the fCJD cases in Japan. Without a family history, genetic testing is necessary to distinguish even seemingly "
sporadic" CJD from fCJD. Accurate diagnosis is important for clarification of the pathological process, prevention of
secondary infection, and also psychological support.