A rare case of Sporadic Creutzfeldt-Jakob disease at a remote mountain hospital in the Indian Himalayan Region.

Sporadic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative spongiform encephalopathy that causes neuronal derangement secondary to prion protein. Its initial diagnosis is often complex and challenging due to non-specific clinical presentation, lack of awareness, and low clinical suspicion. This disease is invariably fatal, and most patients die within 12 months of presentation. Definite diagnosis of prion disease requires neuropathological analysis, usually done at autopsy. Here, we present the autopsy findings of a 57-year-old male patient, illustrating the complexity of diagnosing this disease early in the clinical course and the need for a broad differential diagnosis at the onset.

A rare case of Sporadic Creutzfeldt-Jakob disease at a remote mountain hospital in the Indian Himalayan Region

ABSTRACT Sporadic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative spongiform encephalopathy that causes neuronal derangement secondary to prion protein. Its initial diagnosis is often complex and challenging due to non-specific clinical presentation, lack of awareness, and low clinical suspicion. This disease is invariably fatal, and most patients die within 12 months of presentation. Definite diagnosis of prion disease requires neuropathological analysis, usually done at autopsy. Here, we present the autopsy findings of a 57-year-old male patient, illustrating the complexity of diagnosing this disease early in the clinical course and the need for a broad differential diagnosis at the onset.

Doença de Creutzfeltd-Jakob esporádica sem demência: relato de caso / Sporadic Creutzfeldt-Jakob disease without dementia: a case report

Resumo A doença de Creutzfeldt-Jakob é uma condição rara causada por príons. Embora a forma mais notória da doença seja a infecciosa, a forma mais comum é a chamada esporádica, onde ocorre a transformação de proteínas citoplasmáticas das células gliais em príons. Caracteriza-se por uma demência rapidamente progressiva cujo diagnóstico pode ser feito com grande precisão por meio de sinais clínicos, alterações típicas na ressonância magnética de crânio e o exame Real-Time Quaking-Induced Conversion (Rt-QuIC) no líquido cefalorraquidiano. Relatamos um caso da doença sem distúrbios cognitivos, mas com outros sinais clínicos comuns como anormalidades comportamentais, ataxia, reações extrapiramidais e mioclonia; observamos ainda alterações típicas na ressonância magnética do crânio (alterações de sinal afetando áreas dos lobos parietal e temporal) e um Rt-QuIC fortemente positivo. Entendemos que o relato do caso possa servir de alerta para que outros profissionais de saúde possam reconhecer a doença, aumentando as possibilidades de um diagnóstico mais preciso em casos semelhantes.

Abstract Creutzfeldt-Jakob disease is a rare condition caused by prions. Although the infectious form of the disease is the most well-known, the most common form is the so-called sporadic type, where the transformation of cytoplasmic proteins from glial cells into prions occurs. The disease is characterized by rapidly progressive dementia whose diagnosis can be made with great accuracy based on clinical signs, typical changes on magnetic resonance imaging and real-time quaking-induced conversion (Rt-QuIC) testing in cerebrospinal fluid. We report a case of the disease without cognitive disorders in the initial phase, but with other common clinical signs including behavioral abnormalities, ataxia, extrapyramidal features, and myoclonus; typical changes on magnetic resonance imaging of the skull (signal alterations affecting parietal and temporal lobes areas) and strongly positive Rt-QuIC test. This case report can serve to alert other health professionals on recognizing the disease and contribute to a more accurate diagnosis in similar cases.

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.

Case Report: Neurodegenerative Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Infection, a Report of Three Cases: Creutzfeldt-Jakob Disease, Rapidly Progressive Alzheimer's Disease, and Frontotemporal Dementia.

The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurodegenerative diseases is yet to be fully clarified. Rapid worsening and even new-onset cases of those disorders have been reported in association with coronavirus disease 2019 (COVID-19). We describe three cases of neurodegenerative diseases in patients with SARS-CoV-2: a case of Creutzfeldt-Jakob disease during the COVID-19 acute phase, to our knowledge, is the second one described in the literature; a rapidly progressive Alzheimer's Disease; and a patient with frontotemporal dementia, and a quick decline of both cognitive and behavioral domains. This report suggests an association between SARS-CoV-2 infection and a higher probability of developing or accelerating neurodegenerative chronic neurologic conditions. We reinforce the need for a close cognitive follow-up in the aftermath of Sars-Cov2 infection.

Case Report: Three Case Reports of Rapidly Progressive Dementias and Narrative Review.

Rapidly progressive dementia (RPD) is a heterogeneous group of diseases characterized by cognitive impairment and other neurological disorders developed in a short span of fewer than 2 years. Currently viewed as new and infrequent entities, most medical personnel have little understanding of it. Nevertheless, they significantly compromise many patients' quality of life. Here, we drive 3 clinical cases that evolve as RPD with different etiologies. Case 1: 70-year-old woman presented to the emergency with neuropsychiatric syndrome for 18 days. The researchers identified inflammatory cerebrospinal fluid (CSF), protein 14-3-3-positive T-tau protein, MRI: T2 and FLAIR hyperintensities in bilateral caudate nuclei with diffusion restriction, EEG shows a generalized periodic pattern with triphasic wave morphology. Case 2: 29-year-old man with cognitive impairment and faciobrachial dystonia seizure. The diagnosis was confirmed by achieving elevated antibodies against voltage-gated potassium channels. Case 3: A 49-year-old woman with encephalopathy and myoclonic seizures; EEG and MRI showed subtle changes. The patient also had a normal CSF but a positive CBA serologic NMDA-R antibody test. We described fundamental aspects of RPD to allow made differential diagnoses in patients with cognitive impairment and encephalopathy. Establishing an early and accurate diagnosis can benefit patients with RPD etiologies that are treatable and even reversible, decreasing in morbidity and mortality.

The role of microglia in prion diseases and possible therapeutic targets: a literature review.

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that leads to progressive neurodegeneration due to gliosis, vacuolation of central nervous system tissue, and loss of neurons. Microglia play a crucial role in maintaining Central Nervous System (CNS) homoeostasis, both in health and disease, through phagocytosis and cytokine production. In the context of CJD, the immunomodulatory function of microglia turns it into a cell of particular interest. Microglia would be activated by infectious prion proteins, initially acquiring a phagocytic and anti-inflammatory profile (M2), and producing cytokines such as IL-4, IL-10, and TGF-ß. Therefore, microglia are seen as a key target for the development of new treatment approaches, with many emerging strategies to guide it towards a beneficial role upon neuroinflammation, by manipulating its metabolic pathways. In such a setting, many cellular targets in microglia that can be involved in phenotype modulation, such as membrane receptors, have been identified and pointed out as possible targets for further experiments and therapeutic approaches. In this article, we review the major findings about the role of microglia in CJD, including its relationship to some risk factors associated with the development of the disease. Furthermore, considering its central role in neural immunity, we explore microglial connection with other elements of the immune system and cell signalling, such as inflammasomes, the complement and purinergic systems, and the latest finding strategies to guide these cells from harmful to beneficial roles.

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.

Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Creutzfeldt-Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-ß (Aß), alpha synuclein (α-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of Aß, α-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.

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.

Second-Generation RT-QuIC Assay for the Diagnosis of Creutzfeldt-Jakob Disease Patients in Brazil.

The recent development of IQ-CSF, the second generation of real-time quaking-induced conversion (RT-QuIC) using cerebrospinal fluid (CSF), for the diagnosis of Creutzfeldt-Jakob Disease (CJD) represents a major diagnostic advance in the field. Highly accurate results have been reported with encouraging reproducibility among different centers. However, availability is still insufficient, and only a few research centers have access to the method in developing countries. In Brazil, we have had 603 suspected cases of CJD since 2005, when surveillance started. Of these, 404 were undiagnosed. This lack of diagnosis is due, among other factors, to the lack of a reference center for the diagnosis of these diseases in Brazil, resulting in some of these samples being sent abroad for analysis. The aim of this research study is to report the pilot use of IQ-CSF in a small cohort of Brazilian patients with possible or probable CJD, implementing a reference center in the country. We stored CSF samples from patients with possible, probable or genetic CJD (one case) during the time frame of December 2016 through June 2018. All CSF samples were processed according to standardized protocols without access to the clinical data. Eight patients presented to our team with rapidly progressive dementia and typical neurological signs of CJD. We used CSF samples from seven patients with other neurological conditions as negative controls. Five out of seven suspected cases had positive tests; two cases showed inconclusive results. Among controls, there was one false-positive (a CSF sample from a 5-year-old child with leukemia under treatment). The occurrence of a false positive in one of the negative control samples raises the possibility of the presence of interfering components in the CSF sample from patients with non-neurodegenerative pathologies. Our pilot results illustrate the feasibility of having CJD CSF samples tested in Brazilian centers and highlight the importance of interinstitutional collaboration to pursue a higher diagnostic accuracy in CJD in Brazil and Latin America.

A Complete and State of the Art Pre-mortem Diagnostic Approach to Creutzfeldt-Jakob Disease: A Case Report.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and rapidly progressive form of dementia caused by the spread of a prion protein within the brain. Its real incidence is unknown since its definitive diagnosis requires histopathological analysis of brain specimens. However, novel tests that detect prion proteins in cerebrospinal fluid samples, such as the real-time quaking-induced conversion (RT-QuIC) technique, now allow the pre-mortem diagnosis of sCJD. Here, we report the first case of sCJD confirmed by RT-QuIC in Latin America, providing evidence of its diagnostic performance and clinical correlation.

Enfermedad de Creutzfeldt-Jakob / Creutzfeldt-Jakob disease

Resumen: La enfermedad de Creutzfeldt-Jakob es una afección neuroselectiva y neurodegenerativa, de curso fatal, poco frecuente, que representa un desafío para el diagnóstico clínico. Se comunica el caso de un paciente de 52 años de edad con antecedente de ingesta de mamíferos silvestres durante su vida, con cuadro de disminución de la agudeza visual, demencia rápidamente progresiva, mioclonías, movimientos anormales y disfunción motora; con estudios auxiliares de diagnóstico diferencial dentro de parámetros normales y la determinación de la proteína TAU reactiva.

Abstract: Creutzfeldt-Jakob disease is a neuroselective and neurodegenerative illness, with fatal course, which is rare and represents a challenge for clinical diagnosis. This paper reports the case of a 52-year-old male with a history of ingestion of wild mam- mals during his life, with a picture of diminished visual acuity, rapidly progressive dementia, myoclonus, abnormal movements and motor dysfunction; with auxiliary studies of differential diagnosis within normal parameters and the determination of reactive TAU protein.

Case series of Creutzfeldt-Jakob disease in a third-level hospital in Quito.

BACKGROUND: Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder that affects mammals and humans. The prevalence of this disease in the United States is 0.5 to 1 per million inhabitants. So far in Ecuador, we do not know what the prevalence or incidence is, and only one case report has been written. CASE PRESENTATION: We present a case series of Creutzfeldt-Jakob disease in a third-level hospital in Quito. The average age of symptom onset in our patients was 58.8 years. The male to female ratio was 1:1. Two patients began with cognitive/behavioral symptoms, while 4 patients began with focal neurological signs; 1 case with ataxia, 2 with gait disorders and 1 with vertigo and headache. All of the patients had the clinical features established by the World Health Organization. In addition, the entire cohort was positive for the 14-3-3 protein in cerebrospinal fluid, and had high signal abnormalities in caudate and putamen nucleus in DWI and FLAIR IRM. Only in one case, did we reach a definitive diagnosis through a pathological study. All other cases had a probable diagnosis. In this series of cases, 6 out of 6 patients died. The average time from the onset of the symptoms to death in this cohort was 13 months. CONCLUSION: This is the first report of a series of cases of Creutzfeldt-Jakob disease in Quito. Although definitive diagnosis must be histopathological, there are ancillary tests currently available that have allowed us to obtain a diagnosis of the disease.

Prion disease.

Genetic prion diseases (gPrDs) are caused by autosomal-dominant mutations in the prion protein gene (PRNP). Although the first PRNP mutations identified, and most since, are PRNP missense, octapeptide repeat insertions, deletion and nonsense mutations have now also been shown to cause gPrD. Based on clinicopathologic features of familial disease, gPrDs historically have been classified into three forms: familial Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. This classification, however, occurred prior to the identification of PRNP, and although these forms are still recognized, classification now is somewhat more complex. Clinical manifestations, and even pathology, are known to be more heterogeneous and varied than the historic three phenotypic classifications. Most gPrDs either present rapidly with progression of dementia, ataxia, myoclonus, and other motor features leading to death in few months or present more slowly, declining over a few years with mild cognitive impairment, ataxia, or parkinsonism and later dementia; a few very rare mutations, however, present over years to decades with neuropsychiatric disorders and systemic symptoms (gastrointestinal disorders and neuropathy). In this chapter, we review the broad phenotypic spectrum of PRNP mutations causing gPrDs.

Arm Levitation as Initial Manifestation of Creutzfeldt-Jakob Disease: Case Report and Review of the Literature.

Background: Arm levitation is an involuntary elevation of the upper limb, a manifestation of the alien-limb phenomenon. It has rarely been reported in Creutzfeldt-Jakob disease (CJD), less so as an initial manifestation. Case Report: We report a 56-year-old right-handed man with rapidly progressive gait ataxia and involuntary elevation of the left upper limb. During the next few weeks, the patient developed cognitive impairment, apraxia, visual hallucinations, and myoclonus. He met diagnostic criteria for CJD. We evaluated additional published cases of early-appearance of alien-limb phenomenon in the context of CJD; there were 22 such cases and alien-limb phenomenon was the first and exclusive manifestation in only five of them. Discussion: Arm levitation may be a distinct presentation of CJD, appearing earlier than other clinical features.

First case of V180I rare mutation in a Brazilian patient with Creutzfeldt-Jakob disease.

Here, we report the first case of V180I rare mutation in a Brazilian woman whose clinical condition started with memory impairment for recent events and insomnia with 2 months of evolution, without any other alterations in neurological examination. Both the electroencephalogram (EEG) and the routine biochemical examination of cerebrospinal fluid (CSF) were normal. CSF 14-3-3 protein search was positive. Magnetic resonance imaging (MRI) of the encephalon showed findings suggestive of Creutzfeldt-Jakob disease, confirmed by sequencing of PRNP gene that reveal V180I mutation also homozygosity for methionine at codon 129 (M129M).

Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature.

Although prion diseases are generally thought to present as rapidly progressive dementias with survival of only a few months, the phenotypic spectrum for genetic prion diseases (gPrDs) is much broader. The majority have a rapid decline with short survival, but many patients with gPrDs present as slowly progressive ataxic or parkinsonian disorders with progression over a few to several years. A few very rare mutations even present as neuropsychiatric disorders, sometimes with systemic symptoms such as gastrointestinal disorders and neuropathy, progressing over years to decades. gPrDs are caused by mutations in the prion protein gene (PRNP), and have been historically classified based on their clinicopathological features as genetic Jakob-Creutzfeldt disease (gJCD), Gerstmann-Sträussler-Scheinker (GSS), or Fatal Familial Insomnia (FFI). Mutations in PRNP can be missense, nonsense, and octapeptide repeat insertions or a deletion, and present with diverse clinical features, sensitivities of ancillary testing, and neuropathological findings. We present the UCSF gPrD cohort, including 129 symptomatic patients referred to and/or seen at UCSF between 2001 and 2016, and compare the clinical features of the gPrDs from 22 mutations identified in our cohort with data from the literature, as well as perform a literature review on most other mutations not represented in our cohort. E200K is the most common mutation worldwide, is associated with gJCD, and was the most common in the UCSF cohort. Among the GSS-associated mutations, P102L is the most commonly reported and was also the most common at UCSF. We also had several octapeptide repeat insertions (OPRI), a rare nonsense mutation (Q160X), and three novel mutations (K194E, E200G, and A224V) in our UCSF cohort. © 2016 Wiley Periodicals, Inc.