[Prion diseases : Creutzfeldt-Jakob and differential diagnoses].

Prions are unprecedented infectious pathogens that cause a group of rare and inevitably fatal neurodegenerative diseases, affecting approximately 1 person per 1 million inhabitants worldwide each year. These diseases include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, fatal insomnia (FI) and variably protease-sensitive prionopathy (VPSPr), all of which involve a conformational change of normal cellular prion protein (PrPC) into abnormal scrapie prion protein (PrPSc) through a posttranslational process. This structural change is associated with profound alterations in the physicochemical properties of PrPC, making the molecule resistant to proteolysis. The conformational alteration of PrPC can occur either due to spontaneous conversion, dominant mutations in the prion protein gene (PRNP) which codes for PrPC or due to an infection with the pathogenic isoform PrPSc from exogenous sources. There is general consensus that PrPC serves as the substrate for the conversion to abnormal PrPSc. The latter multiplies exponentially and accumulates in the brain, forming deposits which are associated with the neurodegenerative changes. Although the understanding of the main causes of prion-induced neurodegeneration is still limited, the spread of PrPSc and neurotoxic signal transfer in the pathogenic process of prions appear to show an interaction. Prion diseases sometimes have long incubation times but also short clinical trajectories. Sporadic and genetic forms occur worldwide of which genetic forms are associated with mutations in PRNP. Zoonotic forms of prion diseases are also associated with bovine diseases. Substantial progress has been made in the diagnosis of these disorders and the diagnostics include magnetic resonance imaging (MRI) and laboratory investigations, particularly of the cerebrospinal fluid.