Clinical features and diagnosis of human prion diseases

Abstract

Human prion diseases are a group of progressive, fatal encephalopathies united by their similar neuropathological features, their potential transmissibility and a core molecular feature: a conformational change in prion protein. They exist in sporadic/idiopathic, genetic and acquired forms. The clinical features vary according to a number of factors, including cause and the prion protein genotype of the affected individual. Common features include dementia, cerebellar ataxia and involuntary movements. There is no absolute clinical diagnostic test; definitive diagnosis is neuropathological. However, MRI, electroencephalogram, cerebrospinal fluid protein tests, genetic tests and tonsil biopsy, can be very helpful in supporting a clinical diagnosis. The development of a noninvasive diagnostic test (e.g., on blood) would be very helpful in terms of easier, earlier clinical diagnosis, as well as having other applications (such as blood donor screening or population infection prevalence surveys). A relatively new technique (protein misfolding cyclic amplification) holds promise as such a test. Various therapeutic approaches have been suggested, but there is no current effective treatment and there are significant problems in the assessment of any candidate therapies.