ABSTRACT

Prion diseases are a group of unusual diseases affecting humans and animals (Table 17.1), which involve only the central nervous system (CNS) and always lead to a fatal outcome. The unique nature of prion diseases includes their pathogenesis, mode of transmission, and neuropathology. These diseases can be transmitted by a small fraction from the brain of a diseased individual. The ‘prion hypothesis’, advanced by Prusiner1 and recently reviewed by him,1 is now widely accepted. It maintains that the ‘infectious’ agent is an abnormal conformation of a naturally occurring protein. This harmless prion protein (PrPc) may transform into a protease-resistant form (PrPSc or PrPres), which is strongly linked to disease pathogenesis. Although most workers accept the ‘protein-only’ theory, others present data which they interpret as demonstrating that nucleic acids, or other unidentified agents, are also involved in the transmission of these diseases.2-6

The terminology of the diseases is still changing. The term ‘spongiform encephalopathy’ is inadequate, since in patients with fatal familial insomnia (FFI) as well as in those with dementia and spastic paraparesis (P1O5L) spongiosis is not seen. The term ‘transmissible encephalopathies’ is also problematic, since it is not always easy to demonstrate transmissibility. The term ‘prion diseases’ is preferable, because it concentrates on the unique features of these diseases and the central role played by prions in the pathogenesis (which may, however, be different in sporadic, transmitted and genetic cases).