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      Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999–2008

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          Abstract

          Surgery or blood transfusion had little effect on the incidence of sCJD.

          Abstract

          To elucidate the association between medical procedures and sporadic Creutzfeldt-Jakob disease (sCJD), we analyzed medical procedures (any surgical procedure, neurosurgery, ophthalmic surgery, and blood transfusion) for patients registered by the CJD Surveillance Committee in Japan during 1999–2008. We conducted an age-stratified case–control study with 753 sCJD patients and 210 controls and a study of patients who underwent neurosurgical or ophthalmic surgical procedures at the same hospital. Although the control group was relatively small, no evidence was found that prion disease was transmitted through the investigated medical procedures before onset of sCJD. After onset of sCJD, 4.5% of the sCJD patients underwent operations, including neurosurgical for 0.8% and ophthalmic for 1.9%; no special precautions against transmission of prion diseases were taken. Fortunately, we have not identified patients with prion disease attributed to these operations. Our findings indicate that surgical procedures or blood transfusion had little effect on the incidence of sCJD.

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          Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.

          P Parchi, A. Giese, S Capellari … (1999)
          Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.
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            Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease.

            E. Mitrová, E. Hewer, Luiz G. Klug … (2006)
            To validate the provisional findings of a number of smaller studies and explore additional determinants of characteristic diagnostic investigation results across the entire clinical spectrum of sporadic Creutzfeldt-Jakob disease (CJD), an international collaborative study was undertaken comprising 2451 pathologically confirmed (definite) patients. We assessed the influence of age at disease onset, illness duration, prion protein gene (PRNP) codon 129 polymorphism (either methionine or valine) and molecular sub-type on the diagnostic sensitivity of EEG, cerebral MRI and the CSF 14-3-3 immunoassay. For EEG and CSF 14-3-3 protein detection, we also assessed the influence of the time point in a patient's illness at which the investigation was performed on the likelihood of a typical or positive result. Analysis included a large subset of patients (n = 743) in whom molecular sub-typing had been performed using a combination of the PRNP codon 129 polymorphism and the form of protease resistant prion protein [type 1 or 2 according to Parchi et al. (Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.)] present in the brain. Findings for the whole group paralleled the subset with molecular sub-typing data available, showing that age at disease onset and disease duration were independent determinants of typical changes on EEG, while illness duration significantly influenced positive CSF 14-3-3 protein detection; changes on brain MRI were not influenced by either of these clinical parameters, but overall, imaging data were less complete and consequently conclusions are more tentative. In addition to age at disease onset and illness duration, molecular sub-type was re-affirmed as an important independent determinant of investigation results. In multivariate analyses that included molecular sub-type, time point of the investigation during a patient's illness was found not to influence the occurrence of a typical or positive EEG or CSF 14-3-3 protein result. A typical EEG was most often seen in MM1 patients and was significantly less likely in the MV1, MV2 and VV2 sub-types, whereas VV2 patients had an increased likelihood of a typical brain MRI. Overall, the CSF 14-3-3 immunoassay was the most frequently positive investigation (88.1%) but performed significantly less well in the very uncommon MV2 and MM2 sub-types. Our findings confirm a number of determinants of principal investigation results in sporadic CJD and underscore the importance of recognizing these pre-test limitations before accepting the diagnosis excluded or confirmed. Combinations of investigations offer the best chance of detection, especially for the less common molecular sub-types such as MV2 and MM2.
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              Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering.

              Parker C. Gibbs, Judith C Masters, D Asher … (1979)
              The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate that such clustering does occur. Fifteen percent of the cases were of the familial type, suggesting a genetic susceptibility to infection. Iatrogenic transmission by corneal transplantation and neurosurgical operations has occurred, and the possibility is raised that previous surgery or preexisting neurological operations has occurred, and the possibility is raised that previous surgery or preexisting neurological disease may be associated with an increased risk of developing CJD. It remains to be determined whether the virus of CJD is maintained only by patient-to-patient transmission, has a zoonotic reservoir such as scrapie, or causes widespread latent infection of man that is occasionally activated.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Infect Dis
                Journal ID (publisher-id): EID
                Title: Emerging Infectious Diseases
                Publisher: Centers for Disease Control and Prevention
                ISSN (Print): 1080-6040
                ISSN (Electronic): 1080-6059
                Publication date (Print): February 2009
                Volume: 15
                Issue: 2
                Pages: 265-271
                Affiliations
                [1]Kanazawa University Graduate School of Medical Science, Kanazawa, Japan (T. Hamaguchi, M. Noguchi-Shinohara, I. Nozaki, M. Yamada)
                [2]Jichi Medical University, Shimotsuke, Japan (Y. Nakamura)
                [3]Kohnodai Hospital, Ichikawa, Japan (T. Sato)
                [4]Tohoku University Graduate School of Medicine, Sendai, Japan (T. Kitamoto)
                [5]Tokyo Medical and Dental University, Tokyo, Japan (H. Mizusawa)
                [6]Creutzfeldt-Jakob Disease Surveillance Committee, Japan (Y. Nakamura, T. Sato, J. Mizusawa, T. Kitamoto, M. Yamada)
                Author notes
                Address for correspondence: Masahito Yamada, Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1, Takara-machi, Kanazawa 920-8640, Japan; email: m-yamada@ 123456med.kanazawa-u.ac.jp
                Article
                Publisher ID: 08-0749
                DOI: 10.3201/eid1502.080749
                PMC ID: 2657619
                PubMed ID: 19193271
                SO-VID: 281a5b6b-6b5e-4788-b8e0-536d7c322967
                History
                Categories
                Subject: Research

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: medical procedure,prion,ophthalmic surgery,creutzfeldt-jakob disease,blood transfusion,japan,research,neurosurgery,surgery
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                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: medical procedure, prion, ophthalmic surgery, creutzfeldt-jakob disease, blood transfusion, japan, research, neurosurgery, surgery

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