This article presents an update on the clinical aspects of human
prion disease, including the wide spectrum of their presentations.
RECENT FINDINGS:
Prion diseases, a group of disorders caused by abnormally shaped
proteins called
prions, occur in sporadic (
Jakob-Creutzfeldt disease), genetic (genetic
Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker syndrome, and
fatal familial insomnia), and acquired (
kuru, variant
Jakob-Creutzfeldt disease, and iatrogenic
Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human
prion diseases. New antemortem potential diagnostic tests based on amplifying
prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human
prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with
dysautonomia and neuropathy and progressing to a frontal-executive
dementia with pathology of combined prionopathy and
tauopathy. Unfortunately, to date, all human
prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the
prion protein gene recently has been identified that appears to protect against
prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of
neurodegenerative disorders, might lead to potential treatments.
SUMMARY: Sporadic
Jakob-Creutzfeldt disease is the most common form of human
prion disease. Genetic
prion diseases, resulting from mutations in the
prion-related
protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired
prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and are becoming rarer as awareness of transmission risk has led to implementation of measures to prevent such occurrences.