scholarly journals Rapidly Progressing Sporadic Creutzfeldt-Jakob Disease Presenting as a Stroke

2018 ◽  
Vol 10 (3) ◽  
pp. 261-265 ◽  
Author(s):  
Maxim Oliver ◽  
Lisa Dyke ◽  
Alex Rico ◽  
Mario Madruga ◽  
Jorge Parellada ◽  
...  
Keyword(s):  
Prion Disease ◽  
Neurological Disorders ◽  
Hospice Care ◽  
Clinical Suspicion ◽  
Spongiform Encephalopathy ◽  
Medical Procedures ◽  
Human Prion Disease ◽  
Progressive Dementia ◽  
History Of ◽  
Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, fatal human prion disease that is characterized by progressive dementia and neurologic degeneration. It can mimic multiple other neurological disorders, and a high index of clinical suspicion is necessary to make a diagnosis. A 74-year-old woman with a 3-month history of a stroke and progressive neurologic deterioration was found to have sCJD. She expired within a week of her diagnosis. Autopsy revealed spongiform encephalopathy consistent with prion disease, and genetic analysis revealed 129 polymorphism and no pathologic mutation, confirming the diagnosis of nonfamilial human prion disease. No pathologic evidence of a stroke was found. Awareness of the disease by clinicians is important not only at the time of initial presentation but also during the following months. Since there is no treatment, invasive medical procedures should be limited to only those that are required for either diagnosis or hospice care.

scholarly journals Kuru, the First Human Prion Disease

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 232 ◽  
Author(s):  
Paweł Liberski ◽  
Agata Gajos ◽  
Beata Sikorska ◽  
Shirley Lindenbaum
Keyword(s):  
Electron Microscopy ◽  
Confocal Microscopy ◽  
Prion Disease ◽  
Amyloid Plaques ◽  
Human Medicine ◽  
Spongiform Encephalopathy ◽  
Biomedical Sciences ◽  
Human Prion Disease ◽  
History Of ◽  
Jakob Disease

Kuru, the first human prion disease was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, we summarize the history of this seminal discovery, its anthropological background, epidemiology, clinical picture, neuropathology, and molecular genetics. We provide descriptions of electron microscopy and confocal microscopy of kuru amyloid plaques retrieved from a paraffin-embedded block of an old kuru case, named Kupenota. The discovery of kuru opened new vistas of human medicine and was pivotal in the subsequent transmission of Creutzfeldt–Jakob disease, as well as the relevance that bovine spongiform encephalopathy had for transmission to humans. The transmission of kuru was one of the greatest contributions to biomedical sciences of the 20th century.

scholarly journals Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2019

2020 ◽  
Vol 44 ◽  
Author(s):  
Christiane Stehmann ◽  
Matteo Senesi ◽  
Shannon Sarros ◽  
Amelia McGlade ◽  
Marion Simpson ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Annual Number ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Prospective Surveillance ◽  
Jakob Disease ◽  
Neuropathological Examination

Nationwide surveillance of Creutzfeldt-Jakob disease and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2019. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2019, 513 domestic CSF specimens were referred for 14-3-3 protein testing and 85 persons with suspected human prion disease were formally added to the national register. As of 31 December 2019, just under half (42 cases) of the 85 suspect case notifications remain classified as ‘incomplete’; 16 cases were excluded through either detailed clinical follow-up (3 cases) or neuropathological examination (13 cases); 20 cases were classified as ‘definite’ and seven as ‘probable’ prion disease. For 2019, sixty-three percent of all suspected human prion disease related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. Two possibly causal novel prion protein gene (PRNP) sequence variations were identified. Keywords: Creutzfeldt-Jakob disease, prion disease, transmissible spongiform encephalopathy, disease surveillance

scholarly journals Study protocol for enhanced CJD surveillance in the 65+ years population group in Scotland: an observational neuropathological screening study of banked brain tissue donations for evidence of prion disease

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e033744
Author(s):  
Alexander Howard Peden ◽  
Lovney Kanguru ◽  
Diane L Ritchie ◽  
Colin Smith ◽  
Anna M Molesworth
Keyword(s):  
Brain Tissue ◽  
Prion Disease ◽  
Age Of Onset ◽  
Population Group ◽  
Immunohistochemical Analysis ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Tissue Samples ◽  
Jakob Disease ◽  
The Uk

IntroductionCreutzfeldt-Jakob disease (CJD) is a human prion disease that occurs in sporadic, genetic and acquired forms. Variant CJD (vCJD) is an acquired form first identified in 1996 in the UK. To date, 178 cases of vCJD have been reported in the UK, most of which have been associated with dietary exposure to the bovine spongiform encephalopathy agent. Most vCJD cases have a young age of onset, with a median age at death of 28 years. In the UK, suspected cases of vCJD are reported to the UK National Creutzfeldt-Jakob Disease Research & Surveillance Unit (NCJDRSU). There is, however, a concern that the national surveillance system might be missing some cases of vCJD or other forms of human prion disease, particularly in the older population, perhaps because of atypical clinical presentation. This study aims to establish whether there is unrecognised prion disease in people aged 65 years and above in the Scottish population by screening banked brain tissue donated to the Edinburgh Brain Bank (EBB).MethodsNeuropathological screening of prospective and retrospective brain tissue samples is performed. This involves histopathological and immunohistochemical analysis and prion protein biochemical analysis. During the study, descriptive statistics are used to describe the study population, including the demographics and clinical, pathological and referral characteristics. Controlling for confounders, univariate and multivariate analyses will be used to compare select characteristics of newly identified suspect cases with previously confirmed cases referred to the NCJDRSU.Ethics and disseminationBrain tissue donations to EBB are made voluntarily by the relatives of patients, with consent for use in research. The EBB has ethical approval to provide tissue samples to research projects (REC reference 16/ES/0084). The findings of this study will be disseminated in meetings, conferences, workshops and as peer-reviewed publications.Trial registration numbers10/S1402/69 and 10/S1402/70

scholarly journals RNA editing alterations define manifestation of prion diseases

2019 ◽  
Vol 116 (39) ◽  
pp. 19727-19735 ◽  
Author(s):  
Eirini Kanata ◽  
Franc Llorens ◽  
Dimitra Dafou ◽  
Athanasios Dimitriadis ◽  
Katrin Thüne ◽  
...  
Keyword(s):  
Disease Progression ◽  
Rna Editing ◽  
Prion Disease ◽  
Prion Diseases ◽  
Rapid Progression ◽  
Human Prion Disease ◽  
Progressive Dementia ◽  
Molecular Alterations ◽  
Jakob Disease ◽  
Subtype A

Prion diseases are fatal neurodegenerative disorders caused by misfolding of the normal prion protein into an infectious cellular pathogen. Clinically characterized by rapidly progressive dementia and accounting for 85% of human prion disease cases, sporadic Creutzfeldt–Jakob disease (sCJD) is the prevalent human prion disease. Although sCJD neuropathological hallmarks are well-known, associated molecular alterations are elusive due to rapid progression and absence of preclinical stages. To investigate transcriptome alterations during disease progression, we utilized tg340-PRNP129MM mice infected with postmortem material from sCJD patients of the most susceptible genotype (MM1 subtype), a sCJD model that faithfully recapitulates the molecular and pathological alterations of the human disease. Here we report that transcriptomic analyses from brain cortex in the context of disease progression, reveal epitranscriptomic alterations (specifically altered RNA edited pathway profiles, eg., ER stress, lysosome) that are characteristic and possibly protective mainly for preclinical and clinical disease stages. Our results implicate regulatory epitranscriptomic mechanisms in prion disease neuropathogenesis, whereby RNA-editing targets in a humanized sCJD mouse model were confirmed in pathological human autopsy material.

The neuroepidemiology of human prion disease

2020 ◽  
pp. 367-378
Author(s):  
Patrick JM Urwin ◽  
Anna M Molesworth
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Prion Protein Gene ◽  
Human Prion Disease ◽  
Disease States ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Sporadic Disease

Human prion diseases comprise a number of rare and fatal neurodegenerative conditions that result from the accumulation in the central nervous system of an abnormal form of a naturally occurring protein, called the prion protein. The diseases occur in genetic, sporadic, and acquired forms: genetic disease is associated with mutations in the prion protein gene (PRNP); sporadic disease is thought to result from a spontaneous protein misfolding event; acquired disease results from transmission of infection from an animal or another human. The potential transmissibility of the prion in any of these forms, either in disease states or during the incubation period, has implications for public health. Here we focus on Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), although we will also discuss other forms of human prion disease.

scholarly journals Mutant PrPSc Conformers Induced by a Synthetic Peptide and Several Prion Strains

2004 ◽  
Vol 78 (4) ◽  
pp. 2088-2099 ◽  
Author(s):  
Patrick Tremblay ◽  
Haydn L. Ball ◽  
Kiyotoshi Kaneko ◽  
Darlene Groth ◽  
Ramanujan S. Hegde ◽  
...  
Keyword(s):  
Prion Disease ◽  
Synthetic Peptide ◽  
Biologically Active ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Prion Strains ◽  
Protease Digestion ◽  
Brain Extracts ◽  
Low Levels ◽  
Prp Gene

ABSTRACT Gerstmann-Sträussler-Scheinker (GSS) disease is a dominantly inherited, human prion disease caused by a mutation in the prion protein (PrP) gene. One mutation causing GSS is P102L, denoted P101L in mouse PrP (MoPrP). In a line of transgenic mice denoted Tg2866, the P101L mutation in MoPrP produced neurodegeneration when expressed at high levels. MoPrPSc(P101L) was detected both by the conformation-dependent immunoassay and after protease digestion at 4°C. Transmission of prions from the brains of Tg2866 mice to those of Tg196 mice expressing low levels of MoPrP(P101L) was accompanied by accumulation of protease-resistant MoPrPSc(P101L) that had previously escaped detection due to its low concentration. This conformer exhibited characteristics similar to those found in brain tissue from GSS patients. Earlier, we demonstrated that a synthetic peptide harboring the P101L mutation and folded into a β-rich conformation initiates GSS in Tg196 mice (29). Here we report that this peptide-induced disease can be serially passaged in Tg196 mice and that the PrP conformers accompanying disease progression are conformationally indistinguishable from MoPrPSc(P101L) found in Tg2866 mice developing spontaneous prion disease. In contrast to GSS prions, the 301V, RML, and 139A prion strains produced large amounts of protease-resistant PrPSc in the brains of Tg196 mice. Our results argue that MoPrPSc(P101L) may exist in at least several different conformations, each of which is biologically active. Such conformations occurred spontaneously in Tg2866 mice expressing high levels of MoPrPC(P101L) as well as in Tg196 mice expressing low levels of MoPrPC(P101L) that were inoculated with brain extracts from ill Tg2866 mice, with a synthetic peptide with the P101L mutation and folded into a β-rich structure, or with prions recovered from sheep with scrapie or cattle with bovine spongiform encephalopathy.

scholarly journals Prion disease: advances in diagnosis and treatment

2005 ◽  
Vol 4 (10) ◽  
pp. 273-278
Author(s):  
Steve Dealler
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Disease ◽  
Transmissible Spongiform Encephalopathies ◽  
The Political ◽  
Spongiform Encephalopathy ◽  
Potential Treatment ◽  
Spongiform Encephalopathies ◽  
Current State ◽  
Jakob Disease ◽  
Pentosan Polysulphate

Steve Dealler is a medical microbiologist with Morecambe Bay Hospitals NHS Trust. His work on on the diagnosis, epidemiology and potential treatment of transmissible spongiform encephalopathies has brought him inter-national recognition. He has been at the forefront of work on the epidemiology of human food containing the vector for bovine spongiform encephalopathy (BSE), and the development of prophylaxis against variant Creutzfeldt-Jakob disease (vCJD). He is currently working on a potential treatment, pentosan polysulphate. Here he describes the current state of knowledge in the battle against this devastating disease and the political inertia that frustrated earlier attempts to prevent the epidemic.

scholarly journals Case Report: Creutzfeld- Jakob disease, onset with ataxia and absence of dementia

2021 ◽  
Author(s):  
Lucas de Oliveira Pinto Bertoldi ◽  
Beatriz Cassarotti ◽  
Isabela Silva Souza ◽  
Alana Strucker Barbosa ◽  
Eduardo Silveira Marques Branco ◽  
...  
Keyword(s):  
Case Report ◽  
Cognitive Deficit ◽  
Disease Onset ◽  
Abdominal Distension ◽  
Initial Assessment ◽  
Progressive Dementia ◽  
Mri Scan ◽  
History Of ◽  
Jakob Disease ◽  
Low Incidence

Context: Creutzfeld Jakob disease, a rare prion disease that leads to rapidly progressive dementia and movement disorders, through its pathophysiology will determine brain damage. Regardless of the cause, the course of the disease will be rapid and will invariably lead to death. Objective: The reason why the case is described is due to the low incidence of this disease and its unusual course in the case described. Case report: A 67-year-old male, had a personal history of smoking and obesity . Referred to our service due to sudden ataxia, in the presence of an unchanged MRI scan. The first sympton started when he woke up with a dizzying and inability to walk due to imbalance. In the initial assessment, the patient had appendicular ataxia in all 4 limbs, with an examination of his mental status without changes. New head MRI exam showing alterations compatible with CJD. Interned with hipotheses diagnoses of Wilson’s disease, encephalitis or CJD, he developed abdominal distension with surgical need and immediately after the procedure he already presented a comatose, spastic, and myoclonic condition compatible with the final phase of CJD, later protein 14-3-3 was found in the CSF. Conclusions: CJD, usually presents with rapidly progressive cognitive deficit associated with movement disorder. In the case presented, initially there was no change in cognition and after an urgent surgical procedure, there was an important advance in a shorter than expected period for the disease.

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