Original articles
European surveillance on Creutzfeldt-Jakob disease: a case-control study for medical risk factors

https://doi.org/10.1016/S0895-4356(99)00207-3Get rights and content

Abstract

Medical risk factors for Creutzfeldt-Jakob disease (CJD) were analyzed in a prospective ongoing case-control study based on European CJD surveillance. Detailed data on past and recent medical history were analyzed in 405 cases and controls matched by sex, age, and hospital. Data were correlated with polymorphism at codon 129 of the prion protein gene. Our analysis did not support a number of previously reported associations and failed to identify any common medical risk factor for CJD. Although not statistically significant, brain surgery was associated with an increased risk of CJD. A detailed medical history should be obtained in every suspected CJD case in order to identify iatrogenic sources of CJD.

Introduction

Creutzfeldt-Jakob disease (CJD) is the most common transmissible spongiform encephalopathy in humans [1]. Most cases of CJD are considered to be sporadic; 10–15% are familial [2]. Iatrogenic transmission from case to case has been described mainly via neurosurgical procedures, dura mater transplants, corneal grafts, treatment by pituitary-derived human growth hormone, and gonadotropin 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. Further iatrogenic cases have occurred in patients with implantation of stereotactic EEG electrodes [13]. Dura mater transplants have caused over 60 cases of iatrogenic CJD when used in neurosurgery 14, 15, 16, 17. Little is known about infectivity of blood and blood products. Although there is no proven case of CJD transmission by blood or blood products in humans to date, the risk assessment is problematic [18]. The risk factors for developing the sporadic form of CJD are not yet established. Associations of CJD with physical injuries, ocular tonometry, and surgery have been reported in previous epidemiological surveys 16, 17. Neurological or psychiatric diseases 19, 20 have been found more often in cases than in controls and flu-like illnesses have been reported immediately to preceed the onset of CJD [21]. However, previous studies have been limited by small sample size. In this report, pooled data from the European CJD surveillance study 22, 23, 24, 25, 26 were used to assess in detail the risk of CJD in relation to medical risk factors 22, 23, 24, 25, 26.

Section snippets

Patients and methods

Registries of CJD cases were established in Belgium, France, Germany, Italy, the Netherlands, and the United Kingdom [24]. The European CJD surveillance study was based on these registries and was carried out to monitor the incidence of CJD in the European Community. Based on this surveillance, a case-control study was conducted aiming to assess possible risk factors for CJD [22]. Suspected cases were notified to each national CJD unit. The suspected case was seen by a research physician who

Results

Detailed data on medical history are analyzed in 405 cases and controls. The description of cases and controls is given in a previous article [22]. According to standardized classification criteria [19], patients were classified clinically as probable CJD in 206 cases, and neuropathologically confirmed as definite CJD in 199 cases. The diagnoses of the controls are given in Table 1.

Discussion

The etiology of CJD is not adequately understood. Modes of transmission from human to human have been identified in a small number of patients through medical procedures 7, 27, 28, 29. These cases are therefore designated as iatrogenic forms of CJD. Various medical risk factors for sporadic CJD have been described in previous case-controls studies (Table 7). As CJD is a rare neurological disorder, these studies are hampered by a limited statistical power 19, 25, 26, 30. Pooled data from the

Acknowledgements

The research was done under the auspices of the EU Concerted Action on the Epidemiology of CJD funded through the BIOMED1 programme. We thank Hanneke de Breeijen and Michael Koenders for their help in data management and data analysis and Heino Diringer and Paul Brown for advice. We also thank Jean-Philippe Deslys, Dominique Dormont, Jean-Jacques Hauw, Jean-Louis Laplanche, and Véronique Sazdovitch for cooperation in the French study, which was supported by the Intitut National de la Santé et

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