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The Lancet. Infectious Diseases Jan 2020Creutzfeldt-Jakob disease (CJD) is a fatal disease presenting with rapidly progressive dementia, and most patients die within a year of clinical onset. CJD poses a...
Creutzfeldt-Jakob disease (CJD) is a fatal disease presenting with rapidly progressive dementia, and most patients die within a year of clinical onset. CJD poses a potential risk of iatrogenic transmission, as it can incubate asymptomatically in humans for decades before becoming clinically apparent. In this Review, we sought evidence to understand the current iatrogenic risk of CJD to public health by examining global evidence on all forms of CJD, including clinical incidence and prevalence of subclinical disease. We found that although CJD, particularly iatrogenic CJD, is rare, the incidence of sporadic CJD is increasing. Incubation periods as long as 40 years have been observed, and all genotypes have now been shown to be susceptible to CJD. Clinicians and surveillance programmes should maintain awareness of CJD to mitigate future incidences of its transmission. Awareness is particularly relevant for sporadic CJD, which occurs in older people in whom clinical presentation could resemble rapidly developing dementia.
Topics: Adult; Aged; Aged, 80 and over; Creutzfeldt-Jakob Syndrome; Female; Humans; Iatrogenic Disease; Incidence; Infectious Disease Incubation Period; Male; Middle Aged; Prevalence; Risk Assessment; Young Adult
PubMed: 31876504
DOI: 10.1016/S1473-3099(19)30615-2 -
Progress in Neurobiology Nov 2019While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across...
While the root causes for individual neurodegenerative diseases are distinct, many shared pathological features and mechanisms contribute to neurodegeneration across diseases. Altered levels of microRNAs, small non-coding RNAs involved in post transcriptional regulation of gene expression, are reported for numerous neurodegenerative diseases. Yet, comparison between diseases to uncover commonly dysregulated microRNAs during neurodegeneration in general is lagging. We performed a systematic review of peer-reviewed publications describing differential microRNA expression in neurodegenerative diseases and related animal models. We compiled the results from studies covering the prevalent neurodegenerative diseases in the literature: Alzheimer's disease, amyotrophic lateral sclerosis, age-related macular degeneration, ataxia, dementia, myotonic dystrophy, epilepsy, glaucoma, Huntington's disease, multiple sclerosis, Parkinson's disease, and prion disorders. MicroRNAs which were dysregulated most often in these diseases and their models included miR-9-5p, miR-21-5p, the miR-29 family, miR-132-3p, miR-124-3p, miR-146a-5p, miR-155-5p, and miR-223-3p. Common pathways targeted by these predominant miRNAs were identified and revealed great functional overlap across diseases. We also identified a strong role for each microRNA in both the neural and immune components of diseases. microRNAs regulate broad networks of genes and identifying microRNAs commonly dysregulated across neurodegenerative diseases could cultivate novel hypotheses related to common molecular mechanisms underlying neurodegeneration.
Topics: Animals; Brain; Disease Models, Animal; Gene Expression Regulation; Humans; MicroRNAs; Neurodegenerative Diseases
PubMed: 31356849
DOI: 10.1016/j.pneurobio.2019.101664 -
International Journal of Molecular... Dec 2022Genetic Creutzfeldt-Jakob disease (gCJD) is a subtype of genetic prion diseases (gPrDs) caused by the accumulation of mutated pathological prion proteins (PrP). gCJD has... (Review)
Review
Genetic Creutzfeldt-Jakob disease (gCJD) is a subtype of genetic prion diseases (gPrDs) caused by the accumulation of mutated pathological prion proteins (PrP). gCJD has a phenotypic similarity with sporadic CJD (sCJD). In Japan, gCJD with a Val to Ile substitution at codon 180 (V180I-gCJD) is the most frequent gPrD, while the mutation is extremely rare in countries other than Japan and Korea. In this article, we aim to review previously elucidated clinical and biochemical features of V180I-gCJD, expecting to advance the understanding of this unique subtype in gCJD. Compared to classical sCJD, specific clinical features of V180I-gCJD include older age at onset, a relatively slow progression of dementia, and a lower positivity for developing myoclonus, cerebellar, pyramidal signs, and visual disturbance. Diffuse edematous ribboning hyperintensity of the cerebral cortex, without occipital lobes in diffusion-weighted magnetic resonance imaging, is also specific. Laboratory data reveal the low positivity of PrP in the cerebrospinal fluid and periodic sharp wave complexes on an electroencephalogram. Most patients with V180I-gCJD have been reported to have no family history, probably due to the older age at onset, and clinical and biochemical features indicate the specific phenotype associated with the prion protein gene mutation.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Prion Proteins; Prions; Codon; Mutation
PubMed: 36499498
DOI: 10.3390/ijms232315172 -
Clinical Implant Dentistry and Related... Oct 2013Despite the causal association between variant Creutzfeldt - Jakob disease and bovine spongiform encephalopathy (BSE), bovine origin graft materials are widely used... (Review)
Review
BACKGROUND
Despite the causal association between variant Creutzfeldt - Jakob disease and bovine spongiform encephalopathy (BSE), bovine origin graft materials are widely used during dental surgical procedures. The aim of this study was to assess the risk of BSE transmission through anorganic bovine bone substitutes.
METHODS
Electronic database of MEDLINE was searched to identify relevant studies regarding our focused questions, presence of BSE prion infectivity in raw bovine bone, BSE prion inactivation by bone substitute manufacturing process, protein contents in anorganic bovine bone substitutes, and validity of current BSE diagnostic methods. Search terms yielded 1,704 titles. After title/abstract screening and duplicates removal, 36 full-text articles were screened for inclusion.
RESULTS
A total of 16 studies were included in the final analysis. No eligible studies were identified regarding the efficacy of BSE prion inactivation by the treatments used for anorganic bovine bone manufacturing. BSE infectivity and PrP(Sc) , pathological prion, were detected in bovine bone marrow and serum samples. Proteins were detected in Tutoplast® (bovine), Bio-Oss®, and tibia samples treated at the similar condition for Bio-Oss deproteinization. Inconsistent results of different BSE diagnostic tests were not unusual findings (Iwata et al. 2006; Arnold et al. 2007; Murayama et al. 2010), and a study by Balkema-Buschmann and colleagues showed an apparent discrepancy between BSE infectivity and detection of PrP(27-30), the current surrogate marker for prion disease infectivity.
CONCLUSION
This review indicates that bovine-derived graft biomaterials may carry a risk of prion transmission to patients.
Topics: Animals; Bone Substitutes; Cattle; Encephalopathy, Bovine Spongiform; Risk Factors
PubMed: 22171533
DOI: 10.1111/j.1708-8208.2011.00407.x -
Neurology Apr 2008The potential threat of a large outbreak of variant Creutzfeldt-Jakob disease initiated a proliferation of research into the understanding and treatment of human prion... (Review)
Review
BACKGROUND
The potential threat of a large outbreak of variant Creutzfeldt-Jakob disease initiated a proliferation of research into the understanding and treatment of human prion disease. However, clinical research is at an early stage with a pressing need for objective evaluation of treatments to inform the design of future studies.
METHODS
We aimed to summarize existing research on outcomes of patients with prion disease, considering any published clinical study and patient series with data on disease progression. Methods were prespecified in a protocol and studies were identified from systematic searches of multiple sources.
RESULTS
One randomized trial was identified. Many studies were flawed or poorly reported, and therefore interpreted cautiously. One hundred forty published patient series revealed wide ranges in disease duration for each of the prion diseases. Thirty-three studies described the use of 14 drugs, 10 which were reported in single studies of three or fewer patients and one which was reported for two individual cases. Effects of four drugs were examined in more detail, with mixed results. The only current reliable evidence is from the single randomized trial suggesting that flupirtine may slow cognitive decline. Based on published information identified by this review, survival of most treated patients is within the ranges reported in the untreated patient series.
CONCLUSIONS
Thirty years of clinical investigation of patients with prion disease has resulted in little progress in either defining or evaluating potential treatments. Disease course and treatment of all patients must be evaluated within a structured framework, preferably within randomized controlled trials.
Topics: Aminopyridines; Analgesics; Clinical Trials as Topic; Creutzfeldt-Jakob Syndrome; Disease Progression; Drug Evaluation, Preclinical; Humans; Neuropharmacology; Prion Diseases; Survival Rate; Treatment Failure
PubMed: 18391159
DOI: 10.1212/01.wnl.0000308955.25760.c2 -
Journal of Alzheimer's Disease : JAD 2022Creutzfeldt-Jakob disease (CJD) can be difficult to distinguish clinically from some non-prion neurological diseases. Previous studies have reported markedly increased... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Creutzfeldt-Jakob disease (CJD) can be difficult to distinguish clinically from some non-prion neurological diseases. Previous studies have reported markedly increased levels of α-synuclein in cerebrospinal fluid (CSF) of CJD patients, indicating that it is a potential diagnostic biomarker.
OBJECTIVE
The aim of this study was to assess the diagnostic power of CSF α-synuclein in discriminating CJD from non-prion disorders.
METHODS
The Ovid MEDLINE, Cochrane, and Embase databases were searched for articles published on or before February 25, 2022, using the search term (prion diseases OR Creutzfeldt-Jakob syndrome) AND (synuclein OR α-synuclein). The difference in CSF α-synuclein levels between CJD and non-prion diseases was calculated using random-effects models (I2 > 50%) or fixed-effects models (I2 < 50%) in terms of standardized mean difference (SMD) and 95% confidence interval (CI). The publication bias was estimated using funnel plots and the Egger's test.
RESULTS
Ten studies were included in this study. The concentrations of CSF α-synuclein were significantly higher in CJD patients compared to total non-prion controls (SMD = 1.98, 95% CI 1.60 to 2.36, p < 0.00001), tauopathies (SMD = 1.34, 95% CI 0.99 to 1.68, p < 0.00001), synucleinopathies (SMD = 1.78, 95% CI 1.11 to 2.44, p < 0.00001), or Alzheimer's (SMD = 1.14, 95% CI 0.95 to 1.33, p < 0.00001). CSF α-synuclein could distinguish CJD from non-prion diseases with overall sensitivity of 89% (95% CI 80-95%), specificity of 92% (95% CI 86-95%), and AUC of 0.96 (95% CI: 0.94-0.97).
CONCLUSION
CSF α-synuclein has excellent diagnostic value in discriminating CJD from non-prion neurological diseases. Given the high heterogeneity among the included studies, further studies are needed to confirm its clinical utility.
Topics: Biomarkers; Creutzfeldt-Jakob Syndrome; Humans; Prion Diseases; alpha-Synuclein
PubMed: 35912746
DOI: 10.3233/JAD-220425 -
Journal of Clinical Medicine Research Mar 2018Tonometry has been identified as a common method for measuring the intraocular pressure in patients. The direct contact between the tonometer and the eye may contribute... (Review)
Review
Tonometry has been identified as a common method for measuring the intraocular pressure in patients. The direct contact between the tonometer and the eye may contribute to the risk of cross infection, especially of viral particles, from one patient to another. A systematic review was undertaken to address the likelihood of human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and prion diseases transmission through the use of tonometers. Additionally, a comparison of the current tonometer disinfection methods is provided to assist with identifying which technique effectively reduces the risk of disease transmission. An electronic literature search was conducted using the following databases: Web of Science, EMBASE, CINAHL, SCOPUS, Biosis Previews, Cochrane Library, PubMed, and Google Scholar. Dissertation indexes were also searched, and these included: Dissertations and Abstracts, and Dissertations and Abstracts - UK/Ireland. Additionally, the Clinicaltrials.gov trial registry was searched to identify any other relevant literature. Two independent reviewers critically appraised the articles retrieved through the literature search. In total, 11 unique studies were deemed relevant for this systematic review. The available evidence demonstrated that the use of tonometers contributes to the transmission of these infectious diseases . The results also demonstrated variability in determining the most effective tonometer sterilization technique against these infectious diseases . There was limited evidence available regarding the transmission of HIV, hepatitis B, hepatitis C, and prion diseases through the use of tonometers. Additionally, due to the variability regarding the most effective sterilization techniques, it is difficult to identify which sterilization technique is most effective or adequately effective against these infectious diseases. Future research studies regarding infectious disease transmission through tonometry and sterilization techniques should be completed to more adequately inform infectious disease control guidelines.
PubMed: 29416571
DOI: 10.14740/jocmr3294w -
Euro Surveillance : Bulletin Europeen... Oct 2017Sporadic Creutzfeldt-Jakob disease (sCJD) is potentially transmissible to humans. (Review)
Review
BACKGROUND
Sporadic Creutzfeldt-Jakob disease (sCJD) is potentially transmissible to humans.
OBJECTIVE
This study aimed to summarise and rate the quality of the evidence of the association between surgery and sCJD.
DESIGN AND METHODS
Firstly, we conducted systematic reviews and meta-analyses of case-control studies with major surgical procedures as exposures under study. To assess quality of evidence, we used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Secondly, we conducted a systematic review of sCJD case reports after sharing neurosurgical instruments.
RESULTS
Thirteen case-control studies met the inclusion criteria for the systematic review of case-control studies. sCJD was positively associated with heart surgery, heart and vascular surgery and eye surgery, negatively associated with tonsillectomy and appendectomy, and not associated with neurosurgery or unspecified major surgery. The overall quality of evidence was rated as very low. A single case-control study with a low risk of bias found a strong association between surgery conducted more than 20 years before disease onset and sCJD. Seven cases were described as potentially transmitted by reused neurosurgical instruments.
CONCLUSION
The association between surgery and sCJD remains uncertain. Measures currently recommended for preventing sCJD transmission should be strongly maintained. Future studies should focus on the potential association between sCJD and surgery undergone a long time previously.
Topics: Creutzfeldt-Jakob Syndrome; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Prion Diseases; Surgical Instruments; Surgical Procedures, Operative
PubMed: 29090678
DOI: 10.2807/1560-7917.ES.2017.22.43.16-00806 -
The Neurologist Mar 2017Creutzfeldt-Jacob disease (CJD) is a human prion disease generally characterized by subacute changes in behavior and intellectual function, often followed by ataxia,... (Review)
Review
BACKGROUND
Creutzfeldt-Jacob disease (CJD) is a human prion disease generally characterized by subacute changes in behavior and intellectual function, often followed by ataxia, vision changes, and myoclonus. Ten percent of cases may present atypically, both symptomatically and in respect to initial investigations.
METHODS
We report a case of CJD mimicking acute stroke and review all similar cases in the magnetic resonance imaging era reported in English, identified through a PubMed and SCOPUS search.
RESULTS
A 68-year-old woman presented with an acute left parietal syndrome, initially referred as a left middle cerebral artery territory stroke. Structural imaging was unremarkable and focal electroencephalogram changes suggested nonconvulsive status epilepticus. Subsequent clinical progression, with the development of cortical high signal on diffusion-weighted imaging and positive 14-3-3 protein in the cerebrospinal fluid, confirmed a diagnosis of CJD. Review of the literature identified 14 further cases mimicking both anterior and posterior stroke syndromes.
CONCLUSIONS
CJD develops primarily within a population in whom stroke risk factors are common and represents a rare but important stroke mimic. Negative vascular imaging in elderly patients with apparent acute stroke syndromes should prompt diagnostic review including consideration of prion diseases.
Topics: Aged; Brain; Cognition Disorders; Creutzfeldt-Jakob Syndrome; Disease Progression; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Stroke
PubMed: 28248914
DOI: 10.1097/NRL.0000000000000107 -
Arquivos de Neuro-psiquiatria Aug 2022The Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy that manifests as a rapidly progressive dementia syndrome. Currently, CJD has no cure, and many... (Review)
Review
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: , , , , , , , and , with the Boolean operators and . 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.
Topics: Aminopyridines; Creutzfeldt-Jakob Syndrome; Doxycycline; Humans; Pentosan Sulfuric Polyester; Prion Diseases; Quinacrine
PubMed: 36252593
DOI: 10.1055/s-0042-1755341