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.

Encefalopatia espongiforme e príon inseridos em discussão de caso como decorrência do interrogatório meticuloso consecutivo à anamnese / Spongiform encephalopathy prion and inserted into case discussion as a result of meticulous interrogation subsequent to the interview

Contexto e objetivo: Revelações surpreendentes resultam do interrogatório, consecutivo à anamnese, promovendo considerações que enriquecem o conhecimento de professor e aluno.Estudo e local: Ensino curricular de Doenças Infecciosas e Parasitárias na Enfermaria do Departamento de Medicina da Escola Paulista de Medicina - Universidade Federal de São Paulo.Método: Programa para ensino de doutorandos e residentes sobre possíveis diagnósticos de pacientes recém-admitidos, com participação dos docentes ativos e dos aposentados, em atuação voluntária.Resultado: Exemplificação de como um por menor na história do doente pode ampliar o ensino.Conclusão: É conveniente proceder interrogatório detalhista que direcione a diagnose.

Enfermedades prion / Prion diseases

Las enfermedades prion son un grupo se desordenes degenerativos del sistema nervioso central que comparten características patológicas crónicas y progresivas. Los agentes causales son un grupo de proteínas infectantes sin presencia de ácidos nucleicos. El objetivo de realizar esta revisión es dar a conocer: qué son las enfermedades priónicas, además de aportar datos sobre su fisiopatología, clasificación, modos de transmisión a si como cuadro clínico, diagnóstico y posible tratamiento para lograr una mayor comprensión de estas patologías. Normalmente en nuestro organismo existen proteínas llamadas proteínas priónicas (PrP) las mismas que poseen un nivel de estructuración de tipo hélice alfa que es susceptible a la lisis por proteasas; la patogénesis de estas proteínas se producen cuando aparece una mutación o un cambio conformacional inducido por PrP patógena de otro individuo lo cual altera su estructura tridimensional haciendo imposible su lisis enzimática y su consecuente acumulación en los tejidos afectados, originando así las enfermedades priónicas.

The prion diseases are a group of degenerative disorders of the central nervous system that have chronic and progressive pathological characteristics in common. These diseases are caused by infectious agents called prion. A prion is a small proteinaceous infectious particle which resists inactivation by procedures that modify nucleic acids. The objective of this article is to understand the different aspects of these diseases and to contribute data about its physiopathology, classification, clinical signs and symptoms, diagnosis and treatment to. There exists a cellular protein known as cellular prion protein PrP that have alpha helix structure susceptible to lysis by protease. The pathogenesis of these proteins are produced when the mutation causes a change in the folding pattern of these protein which makes it resistant to the action of proteases and causes it to precipitate as insoluble amyloid. It accumulates in the affected tissue and causes the disease.

A history of kuru

Kuru is placed in its geographic and linguistic setting in the Eastern Highlands of Papua New Guinea. The epidemic of kuru has declined over the period 1957 to 2005 from more than 200 deaths a year to 1 or none. Since transmission of the kuru prion agent through the mortuary practice of transumption ceased by the early 1960s, the continuation of the epidemic into the present century demonstrates the long incubation periods that are possible in human prion diseases. Several histories of kuru are portrayed, from the different perspectives of the Fore people, of the scientists striving to elucidate the disease, of those engaged in research on prions, and of humans confronting the implications of kuru-like epidemics in the remote past. Kuru has connections to bovine spongiform encephalopathy through intraspecies recycling. The influence of host genetics on the incubation period in kuru may help to predict the shape of the still ongoing epidemic of variant Creutzfeldt-Jakob disease.

Ayer, hoy y mañana, la teoria del Prión / Prion Theory: Yesterday, today and tomorrow

Existe un grupo de enfermedades causadas por anormalidades en el procesamiento de las proteinas. Kuru, Scrapie y el síndrome de Creutzfeld-Jackob corresponden a este tipo de enfermedades de caracter degenerativo del sistema nervioso estudiadas en este artìculo cuyo reporte da cuenta de investigaciones en la tribu Fore de Nueva Guinea, donde se presentan casos de la primera de ellas con un impacto en dicha comunidad por disminución de su poblaciòn por causa del Kuru. Priones fue el nombre asignado por B. Prusiner cuya fenomenología se registra en esta investigación sobre esta variedad de enfermedades neurodegenerativas con componente genético, infeccioso o esporàdico resultante de dicha infección involucrando procesos anormales de proteinas naturales

Clinical Features of Other Dementias

Dementias can be calssified into cortical, subcortical, cortical-subcortical and multifocal ones based on the major pathological distribution within the brain. The literatures of recent knowledge about clinical features of other dementias than Alzheimer's and vascular ones, which were most frequently experienced by many clinicians were reviewed. That is, cortical dementias such as Pick's disease, frontal lobe type dementia and non-Alzheimer's type lobar atrophy including fronto-temporal dementia, progressive dysphasia, fronto-temporal dementia with motor neuron disease, and alcohol-related dementia were reviewed. Subcortical dementias such as dementias accompanying Parkinson's disease, Huntington's disease and progressive supranuclear palsy, and cortical-subcortical dementias such as Lewy body dementiaq and cortical-basal degeneration were also reviewed. As multifocal dementias, prion dementias including KUru, Creutzfeldt-Jakob disease, fatal familial insomnia and Gerstmann-Strussler-Sheinker syndrone, and AIDS dementia were also reviewed.

Kuru and "new variant" CJD.

Acquired transmissible spongiform encephalopathies in humans include Kuru (a disease which was associated with ritualistic cannibalism in Papua New Guinea), iatrogenic Creutzfeldt-Jakob disease and a newly recognized variant form of Creutzfeldt-Jakob disease (nvCJD). Clinical and neuropathological features of nvCJD are reminiscent of Kuru: early and progressive cerebellar ataxia and numerous characteristic Kuru-type amyloid plaques surrounded by spongiform change. In contrast to typical cases of sporadic CJD, Kuru and nvCJD affect young patients. The newly recognized form of CJD has been identified in ten young people in the UK in 1996, approximately 10 years after the beginning of the bovine spongiform encephalopathy (BSE) epidemic in the UK. Molecular analysis has shown that nvCJD has strain characteristics that are distinct from other types of CJD but similar to those of BSE. In the UK an estimated half a million BSE-infected cows entered the human food chain before the bovine offal ban of 1989. To be effective the oral route probably requires high-infectivity titers which are encountered only in the brain, spinal cord and eyes of naturally infected cows. In patients with Kuru, titers of more than 10(8) infectious doses per gram were reported in the brain tissues. As a result of the estimated very long incubation period of nvCJD (10 to 30 years or more) the predicted nvCJD epidemic will have the shape of a normal distribution curve with a peak expected in 2009. The epidemic may extend until 2030. There is already an example to illustrate such a curve in its descending line: the decline of Kuru deaths following the interruption of ritual cannibalism.

Enfermedades por priones / Prion's disease

La autoreplicación del prion cumple un papel esencial en la patogenia de este grupo de afecciones caracterizadas por la producción de encefalopatías espongiformes, tanto en los casos determinados por un factor genético hereditario como en los provocados por iatrogenia o posiblemente por la ingestión de alimentos o sustancias contaminadas. En ambos casos la producción de una variante conformacional de la proteína prion plantea incógnitas por su mecanismo de replicación sin la intervención de DNA o RNA. Finalmente la implicancia de la epidemia en el ganado bovino aparecida hace más de 10 años en inglaterra, resulta inquietante a la luz de la nueva variante de este origen comunicada en 1996 en los seres humanos.

Public health aspects of human and animal spongiform encephalopathies

This group of re-emerging human and animal diseases has recently attracted much attention, as well as concern, both in the scientific world and among the general public. In this paper the various public health aspects of these diseases are discussed. The epidemiology, both in human beings and animals, has been reviewed and the causative agents described. Diagnosis, pathology, prevention and control are addressed, showing how the risk to animals and human beings could be minimized

Spongiform encephalophathies [SE]: transmissible or neurodegenerative diseases

Spongiform encephalopathies [SE] are a group of disorders of the central nervous system which affects both animals and humans. These disorders include Creutzfeldt-Jacob disease [CJD], Gerstmann-Strassler-Scheinker syndrome [GSS], Kuru, Scrapie, bovine SE and others. These various entities are linked by characteristic pathology which include; spongiform change, neuronal loss and astrocytic gliosis as well as prolonged incubation period often extending to years and the possibility of sharing the same transmissible agent/s. In this article, the most recent data on SE disease is reviewed and especially its link to humans

Demencias por priones: revisión histórica, clínica y avances / Prion dementias: historical and clinical review and advances

Este artículo resume los aspectos históricos sobre la investigación de los nuevos agentes de la neurobiología llamados "Priones" y describe clínicamente las tres entidades morbosas humanas producidas por priones más importantes, así como los primeros y últimos hallazgos en cada una de ellas. En la primera parte, el autor hace una breve reseña sobre los principales acontecimientos históricos en la investigación relacionada a los priones, en general. Luego se aboca al estudio de Kuru, de la Enfermedad de Creutzfeldt-Jacob y de la Enfermedad de Gerstmann-Strãussler-Scheinker. Por último, abora el tópico controvertido de la imbrincación o superposición de los síndromes clínicos que se presentan en la práctica clínica de aquellas llamadas "Demencias Transmisibles", intentando una explicación actual.

This article summarizes the historic aspects about the investigation of the new neurobiologic agents called "Prions" and describes clinically three of the most important morbid human entities caused by prions as well as the first and last discoveries in each one. In the first part, the author makes a brief annotation about the main historic events in the prion-related investigation, in general. Afterwards, he approaches the study of Kuru, the Creutzfeldt-Jacob Disease and Gerstmann-Strãussler-Scheinker Disease. Finally, he addresses the convertible topic of clinical syndromes overlappng that are present in the clinical practice of those called "Transmissible Dementians", trying to present a plausible explanation.

Virus, virinos o priones? / Virus, virines or prions

La presencia de un agente infeccioso en ciertos desórdenes degenerativos del SNC caracterizados por vacuolización de las neuronas, pérdida de las terminaciones dendríticas y proliferación de los astrocitos quedó establecida por su naturaleza transmisible. Al microscopio electrónico no se detectan partículas virales, postulándose la existencia de un agente viral no-convencional. En el hombre las enfermedades asociadas a estos agentes son el Kuru y el Creutzfeld-Jakob, habiéndose usado como modelo el Scrapie de las ovejas. Además del aspecto espongiforme del cerebro, estas enfermedades se caracterizan por presentar un largo período de incubación y ausencia de respuesta inmune. Histológicamente se ha observado la presencia de fibrillas asociadas a scrapie (SAF), las que también se detectan en el Kuru y el Creutzfeld-Jakob, postulándose que serían el agente infeccioso. Con el agente Scrapie adaptado a hamster se ha logrado purificar extensamente una proteína infectiva de bajo peso molecular, denominada PRION, la que sería codificada por un gen celular. Aún no se ha logrado esclarecer si los priones contienen ácido nuclaico, ni si serían homologables a SAF a pesar que se polimerizan en bastones