Prion diseases are neurodegenerative illnesses due to the accumulation of small infectious pathogens containing
protein but apparently lacking
nucleic acid, which have long incubation periods and progress inexorably once clinical symptoms appear.
Prions are uniquely resistant to a number of normal decontaminating procedures. The prionopathies [
Kuru,
Creutzfeldt-Jakob disease (CJD) and its variants, Gerstmann-Sträussler-Scheinker (GSS) syndrome and
fatal familial insomnia (FFI)] result from accumulation of abnormal
isoforms of the
prion protein in the brains of normal animals on both neuronal and non-neuronal cells. The accumulation of this
protein or fragments of it in neurons leads to apoptosis and cell death. There is a strong link between mutations in the gene encoding the normal
prion protein in humans (PRNP) - located on the short arm of chromosome 20 - and forms of
prion disease with a familial predisposition (familial CJD, GSS, FFI). Clinically a prionopathy should be suspected in any case of a fast progressing
dementia with
ataxia,
myoclonus, or in individuals with pathological
insomnia associated with
dysautonomia. Magnetic resonance imaging, identification of the
14-3-3 protein in the cerebrospinal fluid, tonsil biopsy and genetic studies have been used for in vivo diagnosis circumventing the need of brain biopsy. Histopathology, however, remains the only conclusive method to reach a confident diagnosis. Unfortunately, despite numerous treatment efforts, prionopathies remain short-lasting and fatal diseases.