Compromiso sensitivo y polineuropatía periférica como manifestación inicial de enfermedad de Creutzfeldt-Jakob. A propósito de un caso

La enfermedad de Creutzfeldt-Jakob (ECJ) es una rara enfermedad neurodegenerativa con una alta incidencia en Chile respecto del resto del mundo. El cuadro se caracteriza principalmente por desarrollo de demencia rápidamente progresiva y diversos signos neurológicos inespecíficos, siendo el más frecuente la mioclonía. El caso que se describirá a continuación destaca por las manifestaciones iniciales atípicas que presentó el paciente, tales como compromiso sensitivo en región cráneo-cérvico-dorsal y polineuropatía periférica de extremidades inferiores (EEII), lo que significó un retraso en el diagnóstico clínico de la ECJ. Es importante conocer los diferentes síntomas y signos que pueden presentarse en el cuadro clínico de ECJ, tanto típicos como aquellos menos frecuentes, para así poder dar con el diagnóstico de la enfermedad en etapas más tempranas. De igual manera, es fundamental contar con herramientas diagnósticas como la detección de proteína 14-3-3 o proteína Tau en los centros de salud de nuestro país. Esto permitiría al equipo de salud, brindar un manejo de soporte adecuado y oportuno a estos pacientes.

Creutzfeldt-Jakob disease is a rare neurodegenerative disease with a high incidence in Chile compared to the rest of the world. The condition is mainly characterized by the development of rapidly progressive dementia and various nonspecific neurological signs, the most common being myoclonus. The case that will be described below stands out for the atypical initial manifestations that the patient presented, such as sensory compromise in the cranio-cervico-dorsal region and peripheral polyneuropathy of the lower extremities, which meant a delay in the clinical diagnosis of the disease. It is important to know the different symptoms and signs that can be present in the clinical picture of CJD, both typical and those less frequent, in order to be able to diagnose the disease in earlier stages. Similarly, it is essential to have diagnostic tools such as the detection of 14-3-3 protein or Tau protein in health centers in our country. This would allow the health team to provide adequate and timely support management to these patients.

Experiencia con la enfermedad de Creutzfeldt-Jakob de un único centro de referencia en México. Análisis de una serie de casos / Experience with Creutzfeldt-Jakob disease in a single referral center in Mexico. Case series

Resumen Introducción: La enfermedad de Creutzfeldt-Jakob (ECJ) es una enfermedad del sistema nervioso central rápidamente progresiva y mortal causada por priones. Objetivo: Presentar las principales características clínicas y paraclínicas de pacientes con probable ECJ en un centro de referencia de América Latina. Métodos: Estudio retrospectivo de pacientes diagnosticados con demencia rápidamente progresiva entre 2014 y 2019. Se incluyeron características clínicas, demográficas, del electroencefalograma, imágenes por resonancia magnética, proteína 14-3-3 y tomografía por emisión de positrones (PET), cuando estaba disponible. Resultados: Veinticuatro pacientes cumplieron con los criterios de ECJ esporádica (75 % mujeres), la edad media fue de 59.29 ± 11.67 años, la duración de la enfermedad desde el inicio de los síntomas hasta el ingreso hospitalario fue de 7.41 ± 6.54 meses y las primeras manifestaciones más comunes fueron las alteraciones del comportamiento (41.7 %). Los complejos de ondas delta prevalecieron en el electroencefalograma (54.2 %), la hiperintensidad cortical en la resonancia magnética (83.3 %) y el hipometabolismo frontal en la PET (37.5 %). En el análisis del líquido cefalorraquídeo, siete casos mostraron proteína tau total positiva; cinco, proteína 14-3-3 positiva; y tres, proteína tau hiperfosforilada positiva. Conclusiones: Existe importante heterogeneidad clínica en cuanto a los síntomas iniciales. Los hallazgos de las pruebas auxiliares coincidieron con los de otras series.

Abstract Introduction: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal central nervous system disease caused by prions. Objective: To present the main clinical and paraclinical characteristics of patients with probable CJD in a referral center of Latin America. Methods: Retrospective study of patients diagnosed with rapidly progressive dementia between 2014 and 2019. Clinical, demographic, electroencephalogram, magnetic resonance imaging, and 14-3-3 protein characteristics were included, as well as positron-emission tomography (PET) data when available. Results: Twenty-four patients met the criteria for sporadic CJD (75% were women). Mean age was 59.29 ± 11.67 years, while mean disease duration from symptom onset to hospital admission was 7.41 ± 6.54 months. The most common first symptom was behavioral changes (41.7%). Delta wave complexes prevailed (54.2%) on electroencephalogram, cortical hyperintensity (83.3%) on magnetic resonance and frontal hypometabolism (37.5%) on PET. Seven cases showed positive total Tau; five, positive 14-3-3 protein; and three, positive phosphorylated tau on cerebrospinal fluid analysis. Conclusions: There is significant clinical heterogeneity regarding initial symptoms. Auxiliary test findings were consistent with those of other series.

Creutzfeldt-Jakob disease: literature review based on three case reports / Doença de creutzfeldt-jakob: revisão da literatura baseada no relato de três casos

ABSTRACT. Creutzfeldt-Jakob disease (CJD) is one of the transmissible spongiform encephalopathies that lead to rapidly progressive dementia. CJD has a low prevalence, and the average survival is only 1 year after the onset of symptoms. As the patients with CJD develop rapidly progressive dementia, associated with myoclonus, visual or cerebellar problems, pyramidal or extrapyramidal features, and akinetic mutism, the hypothesis of CJD must be raised. Classic magnetic resonance imaging (MRI) findings are hypersignals in the caudate nucleus, putamen, and cortical region. CJD must be considered a differential diagnosis of other types of dementia, and there is no effective treatment for this disease. In this article, we present a literature review based on the report of three cases of the sporadic form of this disease.

RESUMO. A doença de Creutzfeldt-Jakob (DCJ) faz parte do grupo das encefalopatias espongiformes transmissíveis que levam a um quadro de demência rapidamente progressiva. A DCJ possui baixa prevalência, e a sobrevida média é de apenas um ano após o início dos sintomas. Diante de um paciente com demência rapidamente progressiva, associada a mioclonias, alterações visuais ou cerebelares, sinais piramidais ou extrapiramidais e mutismo acinético, a hipótese de DCJ deve ser levantada. Os achados clássicos na ressonância magnética são os hipersinais em núcleo caudado, putâmen e região cortical. A DCJ deve ser considerada como um diagnóstico diferencial de outros tipos de demência e não existe um tratamento eficaz para essa doença. Apresentamos neste artigo uma revisão da literatura baseada no relato de três casos da forma esporádica dessa doença.

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.

Systematic review of pharmacological management in Creutzfeldt-Jakob disease: no options so far? / Revisão sistemática do manejo farmacológico na doença de Creutzfeldt-Jakob: ainda sem opções?

Abstract Background The Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that manifests as a rapidly progressive dementia syndrome. Currently, CJD has no cure, and many patients die within the first year, but some drugs are being studied as options for managing this condition. Objective To evaluate the effectiveness of pharmacological treatments offered to patients with CJD as a means to increase survival and reduce cognitive deterioration. Methods A systematic review of the literature was performed using 4 independent reviewers and 1 extra reviewer to resolve possible divergences in the search and analysis of papers indexed in MedLINE (PubMed), SciELO and Lilacs databases. The Medical Subject Heading (MeSH) terms used were: prion diseases, Creutzfeldt-Jakob disease, pharmacologic therapy, therapeutics, quinacrine, doxycycline, flupirtine, and pentosan polysulfate, with the Boolean operators AND and OR. This search included controlled clinical trials, uncontrolled clinical trials, and case series published from the year 2000 onwards, in the English language. Results A total of 85 papers were found using the descriptors used. At the end of the selection analyses, 9 articles remained, which were analyzed fully and individually. Conclusions None of the drugs evaluated proved significantly effective in increasing survival in patients with CJD. Flupirtine appears to have a beneficial effect in reducing cognitive deterioration in patients with CJD. However, additional studies are needed to establish better evidence and therapeutic options for the management of patients with CJD.

Resumo Antecedentes A doença de Creutzfeldt-Jakob (DCJ) é uma encefalopatia espongiforme que se manifesta como síndrome demencial rapidamente progressiva. Atualmente, a DCJ não possui cura e muitos pacientes morrem no primeiro ano de doença, mas alguns medicamentos vêm sendo estudados como opções no manejo desta condição. Objetivo Avaliar a eficácia dos tratamentos farmacológicos oferecidos aos pacientes com DCJ no aumento de sobrevida e na redução da deterioração cognitiva. Métodos Foi realizada uma revisão sistemática da literatura utilizando 4 revisores independentes e 1 extra para resolver divergências eventuais na busca e na análise de trabalhos indexados nas bases de dados MedLINE (via PubMed), SciELO e Lilacs. Os termos Medical Subjects Heading (MeSH) utilizados foram: prion diseases, creutzfeldt jakob disease, pharmacologic therapy, therapeutics, quinacrine, doxycycline, flupirtine e pentosan polysulfate, com os operadores booleanos AND e OR. Essa pesquisa incluiu ensaios clínicos controlados, não controlados e séries de casos, publicados a partir do ano 2000 no idioma inglês. Resultados Ao todo, foram encontrados 85 trabalhos através dos descritores utilizados. Ao final das análises de seleção, restaram 9 artigos, que foram analisados na íntegra individualmente. Conclusões Nenhuma das drogas avaliadas se mostrou significativamente eficaz no aumento da sobrevida dos pacientes com DCJ. A flupirtina parece ter um efeito benéfico na redução da deterioração cognitiva dos pacientes com DCJ. Entretanto, estudos adicionais são necessários para o estabelecimento de melhores evidências e opções terapêuticas para o manejo dos pacientes com DCJ.

One case of Creutzfeldt-Jakob disease with restless leg syndrome as the first symptom and literature analysis / 中国基层医药

Objective:To analyze the clinical features and auxiliary examination results of sporadic Creutzfeldt-Jakob disease (sCJD) with restless leg syndrome (RLS) as the first symptom.Methods:The clinical features and auxiliary examination results of one case of sCJD who received treatment in Sichuan Mianyang 404 Hospital were analyzed based on relevant literature.Results:A 59-year-old woman of Han nationality who had sCJD with restless leg-like manifestation of the left lower limb for 18 days was included in this study. The patient was first treated in orthopedic department, but her symptom did not improve after treatment. Twenty days later, she was transferred to neurology department for further treatment. Her daily life and activities were not affected. Head magnetic resonance imaging, electroencephalography, cerebrospinal fluid routine examination and biochemical test results were normal. Five days later, the patient had mild left-sided ataxia, which then progressed rapidly, followed by right-sided ataxia, left-leg spasticity and adduction, involuntary movement, myoclonia, cognitive decline, akinetic mutism, repeated hyperthermia, repeated complex partial seizures. Two weeks later, head magnetic resonance imaging examination revealed hyperintense signal of the cingulate gyrus, frontal cortex and right island cortex on DWI, with cerebellar atrophy and three-phase electroencephalography wave. Four weeks later, CSF14-3-3 protein was positive, and no related genetic mutation in the prion protein gene was found. The duration from onset to death was about 8 months.Conclusion:sCJD is a common subtype of prion protein disease, and the condition can be stabilized for more than 1 month after the onset of RLS. There is no specificity in early clinical and auxiliary examinations, and neither dobutazine treatment nor neurotrophic treatment is effective. The disease progresses rapidly after 1 month, head MRI and EEG reexamination can reveal clues, and CSF14-3-3 protein can assist clinical diagnosis.

Mental disorder caused by prion disease misdiagnosed as depressive episode：a case report / 四川精神卫生

This paper reported a case of a 29-year-old male patient with mental disorder caused by prion disease was misdiagnosed as depressive episode with somatic symptoms. The patient's symptoms were initially predominantly psychiatric， with progressive worsening of somatic symptoms， and he died more than 1 year after his first onset. Prion disease caused various manifestations of mental symptoms， which can easily lead to missed diagnosis and misdiagnosis. This paper discussed the case， in order to provide references for the clinical diagnosis of mental disorder caused by prion disease.

Bilateral hearing loss as an initial presentation of Creutzfeldt-Jakob disease / Perda auditiva bilateral como uma apresentação inicial da doença de creutzfeldt-jakob

ABSTRACT. We reported a case of a 61-year-old male patient with anacusis, cerebellar syndrome, myoclonus, and frontal signs. The brain magnetic resonance imaging showed bilateral striated hyperintensity of the fluid-attenuated inversion recovery and restricted diffusion in the diffusion-weighted imaging and hypointense areas corresponding to the apparent diffusion coefficient in the cerebral cortex. The autopsy revealed positive immunohistochemistry for the PrPSc protein. Creutzfeldt-Jakob disease presenting with hearing loss is unusual.

RESUMO. Relatamos o caso de um paciente do sexo masculino, 61 anos, com anacusia, síndrome cerebelar, mioclonia e sinais frontais. A ressonância magnética cerebral mostrou hiperintensidade estriada bilateral do fluid-attenuated inversion recovery (FLAIR) e difusão restrita no diffusion-weighted imaging (DWI) e áreas hipointensas correspondendo ao coeficiente de difusão aparente no córtex cerebral. A autópsia revelou imuno-histoquímica positiva para a proteína PrPSc. A doença de Creutzfeldt-Jakob que se apresenta com perda auditiva é incomum.

Enfermedad de Creutzfeldt-Jakob: experiencia de 5 años en un hospital terciario de Chile / Creutzfeldt-Jakob disease, experience in 17 patients

Background: Creutzfeldt-Jakob disease (CJD) is a prion affection that typically produces a rapidly progressive dementia with different neurologic and extra-neurologic manifestations. Aim: To characterize clinical, imaging and electroencephalography findings in patients with a probable CJD. Patients and Methods: A case series study of patients admitted in the Neurology department at a public hospital, between 2014 and 2019. Demographic, clinical, imaging, and electroencephalographic data of patients with probable CJD were analyzed. Results: Seventeen patients aged 63 ± 11 years (53% women) with a probable CJD were gathered. The incidence was 4.7 cases/year per million inhabitants. Twenty four percent of patients had a family history of CJD. The median time between the onset of symptoms and the hospital admission was three months with a survival of four months. The most common clinical manifestations were an amnesic syndrome in 88%, myoclonus in 76%, frontal syndrome and ataxia in 71%. Brain MRI was abnormal in all patients. The preponderant finding was the involvement of the caudate nucleus in 82% of cases. In the EEG, 94% of patients had abnormalities. All had a theta-delta slowing as a base rhythm. The pseudo-periodic pattern was observed in the 29% and status epilepticus in 18%. Conclusions: In this group of patients we observed the heterogeneity of the clinical manifestations of the disease, the frequent imaging and electroencephalographic alterations and the short evolution time leading to death.

Un caso probable de enfermedad de Creutzfeldt-Jacob de variante esporádica con larga supervivencia en Perú

La enfermedad de Creutzfeldt-Jacob (ECJ) es la enfermedad por priones más común con una incidencia anual de 1 caso por un millón de habitantes. La ECJ tiene un mal pronóstico y el promedio de vida es de 4-6 meses. Solo se han reportado en la literatura 11 casos de ECJ en Perú. Presentamos el caso de un varón de 66 años con el diagnóstico probable de ECJ esporádico con sobrevida de 25 meses. Identificamos que el tiempo entre el inicio de la enfermedad hasta las mioclonías y hasta el mutismo acinético, la ausencia de hallazgos imagenológicos tempranos, el compromiso tardío de corteza y ganglios basales y la implementación de tratamientos de soporte son factores que podrían explicar a la sobrevida prolongada.

Creutzfeldt-Jakob disease (CJD) is the commonest human prion disease with a reported annual incidence rate of one per million worldwide. CJD has a bad prognosis, and the mean length of survival is 4-6 months. Only 11 cases have been reported in the literature from Peru. Thus, we report a case of a 66-year-old male patient with the diagnosis of probable sporadic CJD in whom the survival duration was of 25 months. We identify that the time from disease onset to myoclonus and to reach the akinetic mutism state, the absence of early imaging findings, the delayed cortical and basal ganglia involvement and the supportive therapies implemented were factors that could contribute for the long survival in this patient.

Analysis of the Electrophoretic Profiles of Prion Protein in Carcinous and Pericarcinous Lysates of Six Different Types of Cancers / 生物医学与环境科学（英文）

Objective@#To find the different electrophoretic profiles of prion protein in carcinous and individual pericarcinous tissues in lysates of gastric, colon, liver, lung, thyroid, and laryngeal cancers.@*Methods@#Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot were used to test the amounts and electrophoretic patterns of total PrP and the tolerance of PK (protease K) digestion among six various cancer tissue types.@*Results@#A mass of PrP signals with a large molecular weight were identified in the homogenates of peripheral tissues. The amounts and electrophoretic patterns of total PrP did not differ significantly between carcinous and pericarcinous tissues. PrPs in all types of the tested cancer samples were PK sensitive but showed diversity in the tolerance of PK digestion among various tissue types.@*Conclusions@#The study revealed that the included electrophoretic patterns of carcinous and pericarcinous tissues were almost similar. Unlike PrP-specific immunohistochemical assay, evaluation of PrP electrophoretic patterns in the peripheral organs and tissues by Western blot does not reflect tumor malignancy.

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.

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.

Demencia rápidamente progresiva, sobre el reporte de un caso de Creutzfeldt-Jakob / Rapidly Progressive Dementia, on a Creutzfeldt-Jakob Case Report

Resumen La enfermedad de Creutzfeldt-Jakob (ECJ) es una entidad neurodegenerativa, neuroselectiva y fatal con casi nulo reporte en México. Se presenta el caso de un paciente del sexo masculino de 40 años que inició de padecimiento con alteraciones de la memoria a corto plazo, episodios depresivos y labilidad emocional con tendencia a la irritabilidad, posteriormente se agregó desorientación espacial y disminución de fuerza del hemicuerpo izquierdo, lateropulsión en la marcha ipsilateral e insomnio, por lo cual fue ingresado al hospital por 40 días para abordaje diagnóstico. Durante su estancia hospitalaria se le realizaron diversos estudios siendo los más relevantes para el diagnóstico: resonancia magnética, la cual presentó "cintas corticales" e hiperintensidades en los núcleos de la base, ambos hallazgos altamente sugerentes de la patología, así como proteína 14-3-3 positiva, lo cual reafirmó el diagnóstico. Tras 15 meses del inicio de los síntomas neurológicos presentó un cuadro de neumonía adquirida en la comunidad, por lo cual fue admitido al hospital donde se diagnosticó absceso pulmonar y demencia rápidamente progresiva, finalmente el paciente falleció en el nosocomio por una sepsis de origen pulmonar, 18 meses después del inicio de los síntomas, no se realizó necropsia, esto de acuerdo con los estándares actuales del manejo de la enfermedad.

Abstract The Creutzfeldt-Jakob disease is a neurodegenerative, neuroselective and fatal entity, that is not usually reported in Mexico. We present a 40-year-old male patient who presents the onset of this illness, with short-term memory disorder, depressive episodes and emotional lability with a tendency to irritability. He also presents space disorientation, decreased strength of the left and lateral hemibody drive in the ipsilateral walk, and insomnia, for which he is admitted to the hospital during 40 days for diagnostic approach. Several studies were carried out during his hospital stay, the most relevant for the diagnosis: a magnetic resonance which presented "cortical ribboning" and hyperintensities in the nuclei of the base, both diagnosis highly suggested the pathology. The positive results to protein 14-3-3 reaffirmed the diagnosis. After 15 months of the onset of neurological symptoms, the patient presented symptoms of pneumonia, which lead to the hospitalization. During his stay, he presented a pulmonary abscess and rapid progressive dementia. The patient died in the hospital by a pulmonary sepsis 18 months after the onset of symptoms. No necropsy was performed, following the current standards for the disease management.

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.

Atypical Gerstmann-Sträussler-Scheinker syndrome caused by PRNP P102L mutation: a case report and literature review / 中华神经科杂志

Objective@#To improve the clinician′s recognition of Gerstmann-Sträussler-Scheinker syndrome (GSS).@*Methods@#The detailed clinical information, neuropsychological examination, cerebrospinal fluid examination, imaging characteristics, electroencephalogram examination and gene detection were analyzed in a case of GSS similar to Creutzfeldt-Jakob disease (CJD) in symptomatology. The differences between the two different prion diseases were compared in combination with the literature review.@*Results@#The patient is a 62-year-old woman, with cerebellar ataxia as the first symptom, followed by rapid dementia, accompanied by pyramidal and extrapyramidal signs. Magnetic resonance imaging showed hyper-intense signal in diffusion weighted imaging in caudatum and cortical ribboning, and protein 14-3-3 was negative. PRNP gene analysis showed P102L gene mutation.@*Conclusions@#The typical clinical manifestation of GSS is hereditary ataxia followed by cognitive decline of varying severity. Detection of PRNP plays an important role in the diagnosis of GSS.

Atypical Gerstmann-Str(a)ussler-Scheinker syndrome caused by PRNP P102L mutation: a case report and literature review / 中华神经科杂志

Objective To improve the clinician's recognition of Gerstmann-Str(a)ussler-Scheinker syndrome (GSS).Methods The detailed clinical information,neuropsychological examination,cerebrospinal fluid examination,imaging characteristics,electroencephalogram examination and gene detection were analyzed in a case of GSS similar to Creutzfeldt-Jakob disease (CJD) in symptomatology.The differences between the two different prion diseases were compared in combination with the literature review.Results The patient is a 62-year-old woman,with cerebellar ataxia as the first symptom,followed by rapid dementia,accompanied by pyramidal and extrapyramidal signs.Magnetic resonance imaging showed hyper-intense signal in diffusion weighted imaging in caudatum and cortical ribboning,and protein 14-3-3was negative.PRNP gene analysis showed P102L gene mutation.Conclusions The typical clinical manifestation of GSS is hereditary ataxia followed by cognitive decline of varying severity.Detection of PRNP plays an important role in the diagnosis of GSS.

Advances in genetics research in the pathogenesis of amyotrophic lateral sclerosis / 中南大学学报(医学版)

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease affecting the upper and lower motor neurons. It is characterized by progressive muscle weakness, atrophy and ultimate death due to dysphagia and dyspnea. There are many causes of ALS, among which the genetic factors show great relevance. Imbalance of protein homeostasis in neurons, prion-like proliferation and propagation of abnormal proteins, mitochondrial dysfunction, glutamate mediated excitotoxicity, and intraneuronal substance transport disorders are recognized as the pathogenesis.The study on gene mutation related to pathogenesis will bridge the molecular and cellular research of ALS, which can deepen the understanding of the occurrence and development of ALS and the role of gene mutation in ALS, and provide new ideas and enlightenment for the treatment of ALS.