Diagnostic approach in a patient with Creutzfeldt-Jakob disease / Abordagem diagnóstica em uma paciente com doença de Creutzfeldt-Jakob

ABSTRACT Prion diseases are an important cause of rapidly progressive dementias. Among them, the most common is sporadic Creutzfeldt-Jakob disease (CJD). It is a rare and incurable disease, with rapid progression to death. Objective: To describe the diagnostic approach of a patient with Creutzfeldt-Jakob disease. Methods: The diagnosis is established through the clinical picture associated with characteristic changes in the brain magnetic resonance imaging, the electroencephalogram, and analysis of specific changes in the cerebrospinal fluid. Results: The present report describes the case of a 53-year-old patient in the city of Fortaleza-CE. The diagnosis was made based on the clinical condition and through diagnostic tests, including 14-3-3 protein and RT QUIC analysis. Differential diagnosis was performed with other rapidly progressive causes, such as infectious and immune-mediated diseases. Conclusions: The diagnosis of probable sporadic CJD was established.

RESUMO As doenças priônicas são uma importante causa de demências rapidamente progressivas. Entre elas, a mais comum é a doença de Creutzfeldt-Jakob (DCJ) esporádica. É uma enfermidade rara e incurável, com rápida progressão para óbito. Objetivo: Descrever a abordagem diagnóstica de uma paciente com doença de Creutzfeldt-Jakob. Métodos: O diagnóstico é estabelecido pelo quadro clínico associado a alterações características na ressonância magnética cerebral, no eletroencefalograma e pela análise de alterações específicas no líquido cefalorraquidiano. Resultados: O presente relato descreve o caso de um paciente de 53 anos na cidade de Fortaleza (CE). O diagnóstico foi feito com base na condição clínica e por meio de testes diagnósticos, incluindo proteína 14-3-3 e análise Real-Time Quaking-Induced Conversion (RT QUIC). O diagnóstico diferencial foi realizado com outras causas rapidamente progressivas, como doenças infecciosas e imunomediadas. Conclusões: Por fim, foi estabelecido o diagnóstico de provável DCJ esporádica.

Genetic Prion Disease: Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease / 神经科学通报·英文版

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50-59 year group. Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt-Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.

Creutzfeldt-Jakob disease: one hundred years of participation in the design of the transmissible spongiform encephalopathies / Doença de Creutzfeldt-Jakob: cem anos de participação no desenho das encefalopatias espongiformes transmissíveis

Creutzfeldt and Jakob's disease (CJD) has its initial milestone in the publication issued 100 years ago that precipitated its better clinical-pathological and etiological understanding. Now, it is established that it belongs to the group of the prion diseases or transmissible spongiform encephalopathies family. CJD is itself divided into several types, the most common being sporadic that is further subdivided according to the anatomoclinical expression, but mainly due to its aetiology regarding prionic protein or genotype.

A doença de Creutzfeldt e Jakob (CJD) tem seu marco inicial na publicação emitida há 100 anos que precipitou seu melhor entendimento clínico- patológico e etiológico. Agora, está estabelecido que pertence ao grupo da família das doenças de príons ou encefalopatias espongiformes transmissíveis. A própria CJD se divide em vários tipos, sendo o mais comum o esporádico que também se subdivide de acordo com a expressão anatomoclínica, mas principalmente devido à sua etiologia em relação à proteína priônica ou genótipo.

La fantástica historia de la increíble prion / The fantastic story of the incredible prion

Resumen Desde el scrapie de la oveja a la encefalopatía espongiforme bovina y desde el kuru a la enfermedad de Creutzfeldt-Jakob, tenaces investigadores buscaron los misteriosos agentes de estos desórdenes neurológicos, hasta que Stanley Prusiner descubriera y describiera las priones en los ochenta, obteniendo el Premio Nobel en 1997. Pero, este no fue el final de esta fantástica historia de la increible proteina designada prion por Prusiner, porque ahora, la investigación en neurociencia ha encontrado proteínas prion-like jugando un importante papel en la génesis de la memoria a largo plazo.

Abstract From the scrapie of the sheep to the bovine spongiform encephalitis, and from the kuru to the Creutzfeldt-Jakob disease, tenacious investigators searched for the mysterious agent of these neurological disorders, till Stanley Prusiner discovered and described the prion in the eighties, wining the Nobel Prize in 1997. But this was not the end of the fantastic history of the incredible protein designed prion by Prusiner, because now the investigation on neuroscience has founded prion-like proteins playing an important role in the genesis of the long-term memory.

Heidenhain variant of Creutzfeldt-Jakob disease in Brazil: a case report / Variante Heidenhain da Doença de Creutzfeldt-Jakob no Brasil: um relato de caso

Creutzfeldt-Jakob disease (CJD) is a rare spongiform encephalopathy characterized by a rapid neurodegenerative progress, caused by a misfolded variant of the cellular prion protein (PrP) known as PrPSc. The clinical presentation of sCJD includes a wide range of neurological signs of cortical, subcortical, or cerebellar origin, either isolated or in various combinations. Due to this protean clinical presentation form, sCJD must be distinguished from other dementias. In this case report, we discuss the Heidenhain variant of Creutzfeldt-Jakob disease (HvCJD), a rare variant characterized by early visual symptoms and typical findings in imaging scans. Our patient presented rapidly progressive dementia and a history of visual hallucinations. As for other prion diseases, only symptomatic treatment is available for HvCJD. Thirty years of clinical investigation of patients with prion disease have resulted in little progress in either defining or evaluating potential treatments.

A doença de Creutzfeldt-Jakob (DCJ) é uma encefalopatia rara caracterizada por rápida progressão neurodegenerativa, causada pelo enovelamento incorreto da proteína priônica celular (PrP), conhecido como PrPSc. O quadro clínico da DCJ esporádica inclui um amplo espectro de sinais neurológicos de origens cortical, subcortical ou cerebelar, seja de forma isolada, seja combinada. Por causa da sua apresentação clínica variável, a DCJ esporádica deve ser distinguida de outras demências. Neste relato de caso, discutimos a variante Heidenhain da DCJ (vHDCJ), uma variante rara caracterizada por sintomas visuais precoces e características específicas no exame de imagem. Nossa paciente apresentou demência rapidamente progressiva e histórico de alucinações visuais. Assim como para as demais doenças priônicas, apenas o tratamento sintomático está disponível para a vHDCJ. Trinta anos de investigação clínica de pacientes com doença priônica têm resultado em pouco progresso, seja definindo os potenciais tratamentos, seja avaliando-os.

Enfermedad de Creutzfeldt-Jakob. Presentación de un caso y revisión de la literatura / Creutzfeldt-Jakob Disease. Case Report and Literature Review / Doença de Creutzfeldt-Jakob. Apresentação de caso e revisão da literatura

Resumen: La enfermedad de Creutzfeldt-Jakob (ECJ) es una patología neurodegenerativa transmisible, producida por una proteína anómala infectante denominada prion. Junto con el kuru, el insomnio familiar fatal y el síndrome de Gerstmann-Stráussler-Scheinker, configura el grupo de las llamadas encefalopatías espongiformes. La ECJ es la forma más común en el ser humano: se calcula que afecta a una persona por cada millón, a nivel mundial, y la mayoría de los pacientes presenta síntomas clásicos de demencia y mioclonías, asociadas a cambios específicos en el electroencefalograma (EEG). Conforme la enfermedad progresa, el cuadro demencial empeora y pueden presentarse síntomas visuales, cerebelosos, piramidales y extrapiramidales. El diagnóstico definitivo se logra demostrando la degeneración espongiforme de las neuronas en histopatología. La ECJ siempre es mortal y no tiene tratamiento específico: cerca del 90% de los pacientes fallece dentro del primer año después del diagnóstico. En este artículo, se reporta el caso de un paciente con ECJ esporádica probable, de acuerdo con los criterios diagnósticos actuales de la OMS y se da a conocer una revisión de la literatura.

Abstract: Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative pathology produced by an infecting abnormal protein called prion. Together with kuru, fatal familial insomnia, and Gerstmann-Stráussler-Scheinker syndrome, it forms the group of so-called spongiform encephalopathies. CJD is the most common form in humans: it is estimated to affect one person per million worldwide and most patients have classic symptoms of dementia and myoclonus, associated with specific changes in the electroencephalogram (EEG). As the disease progresses, the dementia condition worsens and visual, cerebellar, pyramidal, and extrapyramidal symptoms may develop. The final diagnosis is achieved by proving the spongiform degeneration of neurons in the histopathology. CJD is always fatal and has no specific treatment: about 90 % of patients die within the first year of diagnosis. This article reports the case of a patient with probable sporadic CJD, following current who diagnostic criteria, and provides a literature review.

Resumo: A doença de Creutzfeldt-Jakob (DCJ) é uma doença patologia neurodegenerativa transmissível, produzida por uma proteína anormal infectante denominada prion. Juntamente com o kuru, a Insónia familiar fatal e a síndrome de Gerstmann-Stráussler-Scheinker, forma o grupo das chamadas encefalopatias espongiformes. A DCJ é a forma mais comum em humanos: estima-se que ela afete uma em cada um milhão de pessoas em todo o mundo, e a maioria dos pacientes apresenta sintomas clássicos de demência e mioclonia, associados a alterações específicas no eletroencefalograma (EEG). À medida que a doença progride, o quadro de demência piora e podem surgir sintomas visuais, ce-rebelares, piramidais e extrapiramidais. O diagnóstico definitivo é obtido por meio da demonstração da degeneração espongiforme dos neurónios na histopatologia. A dcj é sempre fatal e não possui tratamento específico: cerca de 90% dos pacientes morrem no primeiro ano após o diagnóstico. Neste artigo, é relatado o caso de um paciente com dcj esporádica provável, de acordo com os atuais critérios de diagnóstico da oms, e é apresentada uma revisão da literatura.

Enfermedad por priones, encefalopatía espongiforme humana y enfermedad de Creutzfeldt-Jakob / Prion induced spongiform encephalopathy of Creutzfeldt-Jakob disease

The infectious protein or prion (PrPSC) is a transmissible and replicable polypeptide, which arises from an abnormal folding of the PrP protein, by unknown mechanisms and without changes in the primary sequence of its amino acids. Its new spatial disposition arises from the substitution of its alpha helices by beta bands, which increase its structural stability, avoiding its complete proteolysis, resulting in a residual accumulation of prions. These prions induce the misfolding of normal PrP protein, generating their exponential increase, leading to a disturbance of neuronal homeostasis which results in the development of the fatal spongiform encephalopathy of the Creutzfeldt-Jakob disease (CJD). This is the most prevalent human prion disease, and 90% of cases are sporadic, suggesting the endogenous genesis of prions. There are different types of prions, identified based on the genetic variance of codon 129 amino acids of the prion protein. Meteonin (M) and Valine (V)), associated with the result of their enzymatic proteolysis, define prions type 1 (21 kDa) and type 2 (19 kDa). The Classical form of CJD produced by MM1 prion occurs in 70% of the cases. The Cerebellar form originated by the VV2 prion occurs in 15% of cases, the form with Kuru plates, associated with the prion MV2 occurs in 5%, and the Vacuolar, related to the MM2 prion occurs in 4%. CJD is always characterized by behavioral, motor, cognitive, and vision alterations and by findings in magnetic resonance imaging, electroencephalogram and cerebrospinal fluid that define each clinical and neuropathological form.

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.

Traceability of animal protein byproducts in ruminants by multivariate analysis of isotope ratio mass spectrometry to prevent transmission of prion diseases

Ruminant feed containing animal byproduct proteins (ABPs) is prohibited in many countries due to its risk of transmitting prion diseases (PD). In most cases the entire herd is sacrificed, which causes great harm to the producer countries by preventing their exportation of ruminant derived-products. Methods: We used stable isotope ratio mass spectrometry (IRMS) of carbon (13C/12C) and nitrogen (15N/14N) to trace the animal protein in the blood of 15 buffaloes (Bubalus bubalis) divided into three experimental groups: 1 - received only vegetable protein (VP) during 117 days; 2 - received animal and vegetable protein (AVP); and 3 - received animal and vegetable protein with animal protein subsequently removed (AVPR). Groups 2 and 3 received diets containing 13.7% bovine meat and bone meal (MBM) added to a vegetable diet (from days 21-117 in the AVP group and until day 47 in the AVPR group, when MBM was removed). Results: On the 36th day, differences were detectable in the feeding profile (p <0.01) among the three experimental groups, which remained for a further 49 days (85th day). The AVPR group showed isotopic rate reversibility on the 110th day by presenting values similar to those in the control group (VP) (p> 0.05), indicating that it took 63 days to eliminate MBM in this group. Total atoms exchange (> 95%) of 13C and 15N was observed through incorporation of the diet into the AVP and AVPR groups. Conclusions: IRMS is an accurate and sensitive technique for tracing the feeding profile of ruminants through blood analysis, thus enabling investigation of ABP use. enabling investigation of ABP use.(AU)

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.

Re-transmissibility of mouse-adapted ME7 scrapie strain to ovine PrP transgenic mice

Scrapie is a mammalian transmissible spongiform encephalopathy or prion disease that predominantly affects sheep and goats. Scrapie has been shown to overcome the species barrier via experimental infection of other rodents. To confirm the re-transmissibility of the mouse-adapted ME7 scrapie strain to ovine prion protein (PrP) transgenic mice, mice of an ovinized transgenic mouse line carrying the Suffolk sheep PrP gene that contained the A₁₃₆ R₁₅₄ Q₁₇₁/ARQ allele were intracerebrally inoculated with brain homogenates obtained from terminally ill ME7-infected C57BL/6J mice. Herein, we report that the mouse-adapted ME7 scrapie strain was successfully re-transmitted to the transgenic mice expressing ovine PrP. In addition, we observed changes in the incubation period, glycoform profile, and pattern of scrapie PrP (PrP(Sc)) deposition in the affected brains. PrP(Sc) deposition in the hippocampal region of the brain of 2nd-passaged ovine PrP transgenic mice was accompanied by plaque formation. These results reveal that the mouse-adapted ME7 scrapie strain has the capacity to act as a template for the conversion of ovine normal monomeric precursors into a pathogenic form in ovine PrP transgenic mice. The change in glycoform pattern and the deposition of plaques in the hippocampal region of the brain of the 2nd-passaged PrP transgenic mice are most likely cellular PrP species dependent rather than being ME7 scrapie strain encoded.

Complex proteinopathies and neurodegeneration: insights from the study of transmissible spongiform encephalopathies / Proteinopatías complejas y neurodegeneración: conocimientos obtenidos del estudio de las encefalopatías espongiformes transmisibles

ABSTRACT Protein misfolding diseases are usually associated with deposits of single "key" proteins that somehow drive the pathology; β-amyloid and hyperphosphorylated tau accumulate in Alzheimer's disease, α-synuclein in Parkinson's disease, or abnormal prion protein (PrPTSE) in transmissible spongiform encephalopathies (TSEs or prion diseases). However, in some diseases more than two proteins accumulate in the same brain. These diseases might be considered "complex" proteinopathies. We have studied models of TSEs (to explore deposits of PrPTSE and of "secondary proteins") infecting different strains and doses of TSE agent, factors that control incubation period, duration of illness and histopathology. Model TSEs allowed us to investigate whether different features of histopathology are independent of PrPTSE or appear as a secondary result of PrPTSE. Better understanding the complex proteinopathies may help to explain the wide spectrum of degenerative diseases and why some overlap clinically and histopathologically. These studies might also improve diagnosis and eventually even suggest new treatments for human neurodegenerative diseases.

RESUMEN La acumulación de proteínas con conformación anormal es observada en numerosas enfermedades degenerativas del sistema nervioso. Tales enfermedades están generalmente asociadas con el depósito de una proteína que es importante para la patogenia de la enfermedad; amiloide-β e hiperfosforilación de tau en la Enfermedad de Alzheimer, α-sinucleína en la Enfermedad de Parkinson, y acúmulo de proteína prion anormal (PrPTSE) en las encefalopatías espongiformes transmisibles (EET). Sin embargo, en algunas enfermedades más de dos proteínas se acumulan en el sistema nervioso central. Estas enfermedades pueden considerarse "proteinopatías complejas". Hemos estudiado varios modelos de EET para analizar los depósitos de PrPTSE y la posible acumulación de otras proteínas (que podríamos llamar "proteínas secundarias"). La relación entre proteínas mal plegadas y neurodegeneración no es claro. La mayor parte de las enfermedades neurodegenerativas evolucionan por décadas; por lo tanto los acúmulos proteicos podrían generar diferentes efectos patogénicos en los diferentes estadios de la enfermedad. Alternativamente los acúmulos proteicos podrían ser el resultado de alteraciones del sistema nervioso y no su causa. Dado que la etiología de las ETT es relativamente bien conocido y es atribuido a infección por agentes autoreplicantes que generan malformacion de la proteína prion normal (la isoforma patologica, PrPTSE, propuesta como el agente infeccioso) hemos estudiado varios modelos animales, cepas de agente infectante y dosis del agente causal de ETT. Estos factores controlan el período de incubación, duración de la enfermedad e histopatología. Los modelos animales estudiados nos han permitido investigar si las diferentes características histopatológicas son independientes de PrPTSE o podrían ser secundarias a la acumulación de la misma. Un mejor conocimiento de las proteinopatías complejas podría ayudar a analizar el espectro de enfermedades degenerativas y a su vez, investigar el motivo de la superposición clínico-patológico en algunas de ellas. Estos estudios podrían ayudar en el diagnóstico y eventualmente sugerir nuevas posibles terapéuticas para las enfermedades neurodegenerativas humanas.

Ubiquitin C-terminal Hydrolase L1 Regulates Lipid Raft-dependent Endocytosis

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons, and gathering evidence indicates that UCH-L1 may play pathogenic roles in many neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease (PD). Additionally, lipid rafts have attracted interest in neurodegeneration as playing a common role in many neurodegenerative diseases. In the present study, we demonstrated that UCH-L1 associates with lipid rafts as with other PD-associated gene products. In addition, UCH-L1 regulates lipid raft-dependent endocytosis and it is not dependent on the expression and degradation of caveolin-1 or flotillin-1. Finally, UCH-L1 regulates cell-to-cell transmission of α-synuclein. This study provides evidence that many PD-associated gene products share common signaling pathways to explain the pathogenesis of PD.

Clinics in diagnostic imaging (193). Sporadic Creutzfeldt-Jakob disease (sCJD)

A 68-year-old man presented with a three-week history of rapidly progressive dementia, gait ataxia and myoclonus. Subsequent electroencephalography showed periodic sharp wave complexes, and cerebrospinal fluid assay revealed the presence of a 14-3-3 protein. A probable diagnosis of sporadic Creutzfeldt-Jakob disease was made, which was further supported by magnetic resonance (MR) imaging of the brain showing asymmetric signal abnormality in the cerebral cortices and basal ganglia. The aetiology, clinical features, diagnostic criteria, various MR imaging patterns and radiologic differential diagnosis of sporadic Creutzfeldt-Jakob disease are discussed in this article.

Calcium homeostasis modulator 1 ( CALHM1 ) polymorphisms in cattle

The calcium homeostasis modulator 1 gene (CALHM1), which is located on chromosome 10 in humans and on chromosome 26 in cattle, is a transmembrane glycoprotein that controls the cytosolic calcium concentrations. Altered calcium homeostasis has been associated with several neurodegenerative disorders, including Alzheimer's disease (AD). In a recent study, single nucleotide polymorphisms (SNPs) of CALHM1 have been associated with sporadic Creutzfeldt-Jakob disease (CJD). The protein sequence of human CALHM1 shows 93% homology with bovine CALHM1. Although SNPs of human CALHM1 have been correlated with human prion disease, polymorphisms of the bovine CALHM1 gene have not been reported in cattle thus far. To investigate polymorphisms of the bovine CALHM1 gene in Korean native cattle, we analyzed the open reading frame (ORF) of this gene in 175 Hanwoo and 141 Holstein cattle. We observed five SNPs: c.219C>T (rs380966453), c.357C>T (rs385969338), and c.869A>G (rs516301908) within the ORF region of two exons; and c.552+92A>G (rs481706737) and c.553-3A>C (rs448524869) in the intron of bovine CALHM1. Among the three SNPs that are in the ORF region of bovine CALHM1, the genotype and allele frequencies of the c.869A>G (p.His290Arg) and c.219C>T (p.Asn73Asn) SNPs were significantly different between Hanwoo and Holstein cattle (P<0.0001). Haplotype analysis showed that haplotypes ht2, ht3 and ht5 were also significantly different in these two cattle breeds. This study provides the first genetic analysis of the bovine CALHM1 gene in cattle.(AU)

Manifestaciones psiquiátricas por priones. Una revisión narrativa / Psychiatric manifestations by prions. A narrative review

Las enfermedades priónicas son un grupo de enfermedades neurodegenerativas raras y rápidamente progresivas que causan síntomas neuropsiquiátricos diversos. Estas enfermedades se describieron hace más de 200 arios, y con el tiempo se reconoció que los animales eran portadores de esta alteración; sin embargo, hasta finales de los noventa este problema conmocionó Europa, ya que para entonces la enfermedad había cruzado la barrera de especie y podía afectar al hombre. La polémica fue mayor al atribuirse la alteración a una proteína con capacidad infecciosa. El proceso patológico común se caracteriza por la conversión de la proteína priónica celular normal (PsPc) a una forma anómala y patológica (PrPSc). En el ser humano se han clasificado como padecimientos idiopáticos, hereditarios o adquiridos por la exposición a material exógeno con contenido priónico. La manifestación neurológica más sobresaliente de las prionopatías consiste en la aparición de una demencia rápidamente progresiva asociada a mioclonías y ataxia cerebelosa, además de síntomas extrapiramidales. Los síntomas psiquiátricos ocurren en etapas tempranas de la enfermedad y su presencia, además de la valoración de factores de riesgo, puede contribuir al diagnóstico oportuno de este síndrome. Clásicamente los síntomas psiquiátricos se han agrupado en tres categorías: síntomas afectivos, alteraciones de la motricidad y síntomas psicóticos. Este tipo de manifestaciones suele aparecer durante un periodo prodrómico previo a los signos neurológicos y consiste en la aparición de aislamiento social, ideas delirantes, irritabilidad/agresión, alucinaciones predominantemente visuales, ansiedad y depresión, así como otros menos frecuentes. El diagnóstico definitivo requiere de un estudio post mortem. La posibilidad de que un número mayor de casos pueda ocurrir en los próximos años o que en muchos pacientes no se haya considerado el diagnóstico es una realidad. En opinión de los autores de este trabajo, los psiquiatras debemos tener conocimiento de los síntomas de esta enfermedad. El objetivo de esta investigación es evaluar las alteraciones neuropsiquiátricas presentes en las prionopatías y, en particular, determinar si las manifestaciones psiquiátricas en conjunto integran un cuadro clínico que apunte al diagnóstico de estas enfermedades, aunque en primer término se revisan aspectos taxonómicos, patogénicos y patológicos. Como elemento agregado en este trabajo, los autores hacen algunas consideraciones diagnósticas basadas en la evidencia científica disponible hasta el momento. Los descriptores controlados aplicados a la búsqueda bibliográfica son los utilizados para indexación de artículos científicos en las bases de datos. Las bases de datos y EMBASE, aunque también se empleó PsycInfo. Los descriptores empleados son: enfermedades priónicas, trastornos psicóticos, depresión, trastornos afectivos, patología, clasificación, proteína priónica, historia, manifestaciones neurológicas y manifestaciones psiquiátricas. Los criterios de selección de material fueron cualitativos. Como conclusión y con base en la extensa bibliografía revisada, los autores plantean que el periodo en que hay más evidencia de alteraciones en la esfera mental se denomine «fase de síntomas psiquiátricos¼, la cual puede extenderse por algunos meses (hasta 4). Los síntomas afectivos son los más característicos de dicha fase. Como conclusiones, se considera que la identificación de estos síntomas en un paciente con factores de riesgo de sufrir esta enfermedad contribuiría a la identificación temprana del padecimiento y normaría qué pautas seguir ante la sospecha del diagnóstico de este grupo de trastornos, sobre todo con la idea de mejorar la calidad de vida de estos pacientes.

Prion diseases are a group of rare and rapidly progressive neurodegenerative conditions that may cause neuropsychiatric symptoms. This group of diseases has been described since the 18th century, but they were recognized decades later, when it became clear that the humans were affected by infected animals. There was controversy when the problem was attributed to a single protein with infective capacity. The common pathological process is characterized by the conversion of the normal cellular prion protein into an abnormal form. In humans, the illness has been classified as idiopathic, inherited and acquired through exposure to exogenous material containing abnormal prions. The most prominent neurological manifestation of prion diseases is the emergence of a rapidly progressive dementia, mioclonus associated with cerebellar ataxia and also extra pyramidal symptoms. Psychiatric symptoms occur in early stages of the illness and can contribute to timely diagnosis of this syndrome. Psychiatric symptoms have traditionally been grouped in three categories: affective symptoms, impaired motor function and psychotic symptoms. Such events usually occur during the prodromal period prior to the neurological manifestations and consists in the presence of social isolation, onset of delusions, irritability/aggression, visual hallucinations, anxiety and depression, and less frequent first-rank symptoms among others. Definite diagnosis requires post mortem examination. The possibility that a large number of cases may occur in the next years or that many cases have not been considered with this diagnosis is a fact. In our opinion, psychiatrists should be aware of symptoms of this disease. The main objective of this research consisted of assessing the correlation between this disturbance and neuro-psychiatric symptoms and particularly if this psychiatric manifestations integrate a clinical picture suggestive for the diagnosis of these diseases, but firstly reviewed taxonomic, pathogenic and pathological aspects. The authors of this project also added an element in relation to some diagnostic considerations based on scientific evidence. For the search controlled descriptors applied to the research for indexing scientific articles in databases were used. The electronic data bases used were PubMed, EMBASE and also PsycInfo. The descriptors were prion diseases, psychotic disorders, depression, mood disorders, pathology, classification, prion protein, history, neurological manifestations, and psychiatric manifestations. The selection criteria for the material were qualitative. To conclude, and based on the extensive literature review, the authors propose that the period where the evidence is more robust for mental impaired is named "psychiatric symptoms phase, which can be extended for a few months, being the psychiatric affective symptoms the most characteristic of this phase. In conclusion, we considered that the identification of these symptoms in a patient with risk factors for developing the disease will contribute to the early identification, and would regulate the guidelines in suspected diagnosis of this group of disorders. The intention is provide a better quality of life to the sick people.

Processamento de cabos de laringoscópio: revisão integrativa / Procesamiento de los mangos del laringoscopio: revisión integradora / Laryngoscope handles reprocessing: integrative review

Objetivo: Estudo de revisão integrativa da literatura científica com base na seguinte questão norteadora: ?Qual o tipo de processamento necessário para a segurança do reuso do cabo de laringoscópio??. Método: Foi realizada uma revisão integrativa utilizando os portais e as bases Pubmed, Embase, Scopus, Web of Science e CINAHL. Resultado: Foram identificados sete estudos experimentais cujos resultados demonstraram indefinição da classificação do cabo de laringoscópio quanto ao risco de causar infecção, comprovada pela diversidade de métodos de processamento. Conclusão: Conclui-se que os cabos de laringoscópio não podem ser considerados materiais independentes das lâminas e, portanto, são materiais semicríticos. Levando-se em conta a carga microbiana e orgânica identificada nesta revisão, o processamento mínimo recomendado é a limpeza seguida de desinfecção de alto nível. Um inventário pequeno e a falta de acesso às tecnologias para processamento não são razões aceitáveis para recomendações improvisadas, evitando assim a certificação e propagação de más práticas.

Objetivo: Estudio de una revisión integradora de la literatura científica basándose en la siguiente pregunta de investigación: ?¿Cuál tipo de procesamiento se requiere para la seguridad de la reutilización del mango del laringoscopio??. Método: Se hizo una revisión integradora utilizando los portales y las bases PubMed, Embase, Scopus, Web of Science y CINAHL. Resultados: Fueron identificados siete estudios experimentales cuyos resultados demostraron una indefinición de la clasificación del mango del laringoscopio en relación al riesgo de causar infección, comprobado por la variedad de métodos de procesamiento. Conclusión: Los mangos del laringoscopio no pueden ser considerados materiales independientes de las láminas y, por lo tanto, son materiales semicríticos. Teniendo en cuenta las cargas microbiana y orgánica identificadas en esta revisión, el procesamiento mínimo recomendado es la limpieza seguida de la desinfección de alto nivel. Un inventario pequeño y la falta de acceso a las tecnologías al procesamiento no son razones aceptables para las recomendaciones improvisadas, evitándose así la certificación y la propagación de más prácticas.

Objective: This is a integrative review study of the scientific literature based on the following guiding question: ?What kind of processing is required for the safety reuse of the laryngoscope handle?? Method: It was made an integrative review using the portals and basis Pubmed, Embase, Scopus, Web of Science and CINAHL. Results: Seven experimental studies were found and the results showed the uncertainty of the classification of the laryngoscope handle, as the risk of causing infection, proven by the diversity of reprocessing methods identified. Conclusion: We concluded that the laryngoscope handles cannot be considered apart of the blades and, therefore, they are semi-critical materials. Considering the microbial and the organic load identified in this review, the recommended minimal processing is cleaning, followed by the high-level disinfection. A small inventory and the lack of access to technologies for reprocessing are not acceptable reasons for improvised recommendations, thus avoiding the certification and the spread of the bad practices.

Estimation of the size of the iatrogenic Creutzfeldt-Jakob disease outbreak associated with cadaveric dura mater grafts in Korea / 한국역학회지

OBJECTIVES: This study estimated the overall incidence of iatrogenic Creutzfeldt-Jakob disease (iCJD) based on dura graft cases in Korea using a mathematical model. METHODS: We estimated the number of annual dura grafts performed between 1980 and 1995 by applying the proportion of dura grafts recorded by the Health Insurance Review Agency claim dataset in Korea to the number of nationwide neurosurgery cases. The distribution of the incubation period was assumed to fall under a Weibull distribution with density function or a log-logistic distribution with density function. RESULTS: The total number of neurosurgery procedures performed from 1980 to 1995 was estimated to be 263,945, and among those operations, 37% used dura graft products. Between the years of 1980 and 2020, our model predicted that the total number of iCJD cases would be between 14.9 and 33.2 (95% confidence interval [CI], 13.4 to 50.9). Notably, we estimated that the cumulative number of iCJD cases caused by dura grafts between 1980 and 2011 was approximately 13.3 to 27.3 (95% CI, 12.2 to 40.6). CONCLUSIONS: Based on our model, we postulate that the incidence of iCJD will sharply decline from 2012 to 2020. However, additional new cases are still expected, which necessitates a strong national surveillance system.

Real-Time Quaking-Induced Conversion Analysis for the Diagnosis of Sporadic Creutzfeldt-Jakob Disease in Korea

BACKGROUND AND PURPOSE: The level of 14-3-3 protein in the cerebrospinal fluid (CSF) is increased in Creutzfeldt-Jakob disease (CJD) patients, which has led to it being used as a clinical biomarker for the ante-mortem diagnosis of human prion diseases. However, the specificity of the 14-3-3 protein is less reliable for CJD diagnosis. Newly developed assays including real-time quaking-induced conversion (RT-QuIC) have made it possible to detect the PrPSc-like abnormal prion isoform with a high sensitivity in animal and human specimens that might contain a minute amount of PrP(Sc) due to in vitro prion replication. METHODS: This study applied a highly sensitive RT-QuIC assay using recombinant human PrP to detect PrP(Sc) in the CSF of 81 patients with sporadic CJD (sCJD) in Korea. RESULTS: RT-QuIC analysis of the CSF samples based on the expression levels of 14-3-3 and total tau proteins revealed positivity in 62 of 81 sCJD patients (sensitivity of 76.5%) but no positive results in the 100 non-CJD patients. CONCLUSIONS: The sensitivity of the RT-QuIC in this study was similar to that in some previous reports, and the specificity of RT-QuIC was higher than that of 14-3-3 in CSF, suggesting that RT-QuIC analysis can complement the weakness of the specificity of 14-3-3 for the diagnosis of sCJD. These results indicate that RT-QuIC might be very useful for the rapid and specific diagnosis of sCJD and provide a practical novel method for the ante-mortem diagnosis of human prion diseases.