Recent advances in the pre-mortem diagnosis of Creutzfeldt-Jakob disease

Abstract

Included in the spectrum of human transmissible spongiform encephalopathies are Creutzfeldt-Jakob disease (CJD) and the new variant form (vCJD), Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, kuru and various less distinct neuropsychiatric disorders. Progress in our understanding of this group of disorders continues at a prodigious rate, although important vexing practical issues persist. The definitive confirmation of symptomatic prion disease still requires pathological examination, most reliably performed post-mortem. However, paralleling the recent advances in the molecular biological understanding of normal prion protein (PrP(c)) function and the pathophysiology of prion diseases, there have been worthwhile developments in the pre-mortem diagnosis of CJD. Efforts to develop less invasive but very reliable ante-mortem diagnostic tests have received an additional impetus because of the potential epidemic of vCJD. Historically, the ancillary investigation of most merit has been the EEG, whereas the recent advances have encompassed a broader range of technologies, including both magnetic resonance and radioisotopic neuroimaging, and immunoassays for a range of non-specific marker proteins in both CSF, and less commonly, blood. However, given the recent refinement of sophisticated immunoassays, it is envisaged that the pathognomonic, protease-resistant, disease-associated isoforms of the prion protein (PrPres) may soon be directly detectable in the blood and tissues of patients manifesting or incubating a spongiform encephalopathy.