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.

Gerstmann-Sträussler-Scheinker Disease (Pro102Leu) Presenting as Rapidly Progressive Dementia

Genetic prion diseases account for about 10-15% of all cases of human prion disease and are caused by mutations in the prion protein gene. Gerstmann-Sträussler-Scheinker (GSS) disease is a rare genetic prion disease, which is characterized by slowly progressive cerebellar ataxia and the occurrence of cognitive decline in the later stage. P102L is the most common mutation in GSS. We report a patient with a P102L mutation that initially manifested as rapidly progressive dementia without cerebellar symptoms.

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease / Elevada variabilidade fenotípica na doença de Gerstmann-Sträussler-Scheinker

ABSTRACT Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

RESUMO A doença de Gerstmann-Sträussler-Scheinker é uma doença priônica genética, cuja mutação mais frequente é p.Pro102Leu. Descrevem-se dados clínicos, moleculares e neuropatológicos de sete indivíduos em duas famílias não relacionadas com p.Pro102Leu. Diferenças notáveis entre os pacientes em relação à idade de início, duração da doença e apresentação clínica foram encontradas. Na primeira família, dois pacientes apresentaram demência rapidamente progressiva e três apresentaram fenótipo de ataxia com idade variáveis de início e duração da doença. Nesta família, a idade de início entre mãe e filha diferiu em 39 anos. Na segunda família, fenótipos diferentes foram observados e idades precoces de início dos sintomas foram associadas à heterozigose no códon 129. Não houve diferença em relação ao genótipo do gene da apoE. O genótipo do códon 129 não foi responsável pela variabilidade clínica; heterozigose no códon 129 esteve associada ao início precoce da doença. O exame neuropatológico em dois pacientes confirmou presença de placas típicas e imunohistoquímica para PrPsc.

A Case of Gerstmann-Straussler-Scheinker Disease

BACKGROUND: Gerstmann-Straussler-Scheinker disease (GSS) is a type of human transmissible spongiform encephalopathy (TSE) that is determined genetically. CASE REPORT: A 46-year-old woman presented with a slowly progressive ataxic gait and cognitive decline. She was alert but did not cooperate well due to severe dementia and dysarthria. High signal intensities in the cerebral cortices were evident in MRI, especially in diffusion-weighted images (DWI). A prion protein gene (PRNP) analysis revealed a P102L (proline-to-leucine) mutation in codon 102. CONCLUSIONS: This is the first reported case of GSS (confirmed by PRNP analysis) in Korea. Distinctive MRI findings are also presented.

Enfermedades priónicas / Prion diseases

Las enfermedades priónicas son procesos neurodegenerativos producidos por el metabolismo aberrante de una proteína priónica, que afectan a seres humanos y animales durante un período de incubación prolongado, con carácter transmisible y evolución clínica fatal. Entre sus manifestaciones clínicas sobresalen: demencia, ataxia, insomnio, paraplejías, parestesias y conductas anormales. El principal hallazgo anatomopatológico es el aspecto espongiforme del cerebro de animales y personas infectados, causado por la acumulación de las proteínas priónicas en las neuronas, donde forman placas amiloides. No hay tratamiento que cure, mejore o controle los síntomas y signos de estas afecciones, por lo cual existen al respecto numerosas interrogantes y opiniones controvertidas en la comunidad científica mundial; razones todas que justificaron continuar polemizando en este artículo.

Prion diseases are neurodegenerative processes occurred by aberrant metabolism of a prion protein that affect humans and animals during a long period of incubation, with transmissible character and fatal clinical course. Among their clinical manifestations are insanity, ataxia, insomnia, and paraplegias, paresthesias and abnormal behaviors. The main patological finding is the spongiform aspect of the infected animal and human brain caused by accumulation of prion proteins in the neurons, where they form amyloid plaques. There is not treatment that cures, improves or controls symptoms and signs of these conditions, therefore several questions and different opinions in this regard raise in the world scientific community that justified to continue arguing in this paper.

Human prion diseases: molecular and clinical phenotypes

Human prian diseases are sporadic, acquired, and genetic neurodegenerative conditions characterized by brain accumulation and deposition of pathological prion protein. These disorders are highly heterogeneous and display a wide range of clinicopathological phenotypes. This well-known phenotypic heterogeneity is thought to be determined by two main disease modifiers: [i] the genotype at polymorphic codon 129 of the prion protein gene [PRNP], allowing three possible combinations, and [ii] the physicochemical properties of the pathological prion protein, or PrPSc, existing under distinct conformational variants. In addition to PrPSc conformation, glycosylation site occupancy of PrPSc at Asp 181 and Asp 197, and truncated PrP fragments may influence the biological properties of prion strains. Here we review molecular and clinical phenotypes encountered in human prion diseases

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.

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

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

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.