Prion Diseases: actual clinical and diagnostic aspects

Recently, the problem of neurodegenerative diseases in the medical community has become increasingly relevant. This is due to many factors: from insufficiently studied mechanisms of development of some nosological units to low awareness of medical workers. Among neurodegenerative diseases in humans, prions constitute a very specific group, which are infectious protein particles with a unique morphological structure and capable of causing a number of incurable diseases. Despite years of research, no optimal remedy has yet been found to treat them. This review examines the already studied aspects of prion diseases as a class, including small historical background, features of ethiology, pathogenesis, course and outcome of the most common of them, as well as existing research on experimental methods of diagnostics, treatment and prevention of prion infections.

Prionic diseases / Doencas prionicas

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.

Doenças priônicas são enfermidades neurodegenerativas devido ao acúmulo de pequenos agentes infecciosos compostos unicamente por proteína (prions), com longos períodos de incubação e de progressão inexorável para o óbito. Esses agentes são excepcionalmente resistentes aos processos habituais de descontaminação para germes e vírus. As prionopatias [Kuru, doença de Creutzfeldt-Jakob (CJD) e suas variantes, Síndrome de Gerstmann-Sträussler-Scheinker (GSS) e insônia familiar fatal (FFI)] resultam do acúmulo de isoformas anormais da proteína priônica no cérebro. Este acúmulo leva, em última análise, à apoptose e morte celular. Existe uma forte associação entre mutações no gene que codifica a proteína priônica normal em humanos (PRNP) - localizado no braço curto do cromossoma 20 - e formas genéticas destas doenças (CJD familiar, GSS, FFI). Clinicamente devemos suspeitar de uma prionopatia em qualquer caso de demência de rápida progressão, particularmente quando associadas a ataxia, mioclonias, ou em indivíduos com insônia patológica combinada com disautonomia. Métodos diagnósticos como ressonância magnética, pesquisa da proteína 14-3-3 no líquido cefalorraquiano, biópsia de amígdalas e estudos genéticos têm sido utilizados para diagnóstico in vivo, evitando-se assim a necessidade de biópsia cerebral. A despeito disso, a histopatologia continua a ser o único método conclusivo para se chegar a um diagnóstico definitivo. Infelizmente, apesar dos inúmeros esforços de tratamento, as prionopatias permanecem doenças de curta duração e fatais.