CREUTZFELDT-JAKOBS DISEASE

Creutzfeldt-Jakob's disease is a transmissible encephalopathy manifest ing with dementia and motor disturbances, which usually progresses rap idly and is lethal within months. It occurs mainly sporadically, but i t can also be transmitted by proteinaceous infective particles called prions. The diagnosis has to rely on clinical symptoms, EEG and brain biopsy being the most suitable additional examinations. No therapy is yet known. ''Naturally'' occurring transmission has not been observed: all transmitted cases reported so far have been iatrogenic and follow ed administration of cadaveric hypophyseal hormones, transplantation o f tissue from CNS or related organs, or brain surgery with contaminate d instruments. Remarkable discoveries in the past decades with respect to the molecular and genetic characterization of the transmissible pa thogen have led to a new understanding of the disease. The infective a gent appears to be an abnormal isoform of a physiologically occuring p rotein: the cellular prion (PrPc). The crucial pathogenetic event is t he conformational conversion of PrPc into its pathological isoform (Pr Psc), an event thought to be triggered autocatalytically by the infect ious agent itself. The disease can be elicited in experimental animals by inoculation of PrPsc. In the sporadic cases of Creutzfeldt-Jakob's disease, PrPsc is thought to arise through spontaneous conversion of PrPc. A growing body of evidence indicates that specific alleles of th e prion gene confer a genetic predisposition to Creutzfeldt-Jakob's di sease and to related pathologies.