Brain

Brain Advance Access published online on July 1, 2006
Brain, doi:10.1093/brain/awl159

This Article FREE Full Text (PDF) OA All Versions of this Article: 129/9/2278    most recent awl159v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Disclaimer Google Scholar Articles by Collins, S. J. Articles by Will, R. G. Search for Related Content PubMed PubMed Citation Articles by Collins, S. J. Articles by Will, R. G. Social Bookmarking          What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org
Received October 6, 2005
Revised May 9, 2006
Accepted May 16, 2006

Article

Determinants of diagnostic investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease

S. J. Collins ^{1 * *}, P. Sanchez-Juan ^{2 *}, C. L. Masters ¹, G. M. Klug ¹, C. van Duijn ², A. Poleggi ³, M. Pocchiari ³, S. Almonti ³, N. Cuadrado-Corrales ⁴, J. de Pedro-Cuesta ⁴, H. Budka ⁵, E. Gelpi ⁵, M. Glatzel ⁶, M. Tolnay ⁷, E. Hewer ⁷, I. Zerr ⁸, U. Heinemann ⁸, H. A. Kretszchmar ⁹, G. H. Jansen ¹⁰, E. Olsen ¹⁰, E. Mitrova ¹¹, A. Alpérovitch ¹², J.-P. Brandel ¹², J. Mackenzie ¹³, K. Murray ¹³, and R. G. Will ¹³

¹ Australian National Creutzfeldt-Jakob disease Registry, Department of Pathology, The University of Melbourne, Parkville, Vic., Australia
² Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands
³ National Registry of Creutzfeldt-Jakob disease, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita’, Rome, Italy
⁴ National HTSE Laboratory Unit at Centre of Microbiology and National HTSE Registry at Centre of Epidemiology, Instituto de Salud Carlos III, Calle Sinesio Delgado 6, Madrid, Spain
⁵ Austrian Reference Centre for Human Prion Diseases, Institute of Neurology, Medical University Vienna, Wien, Austria
⁶ Institute of Neuropathology and National Reference Center for Prion Diseases, University Hospital Zurich, Zurich, Switzerland; Present address: University Medical Center Hamburg-Eppendorf, Institute of Neuropathology, Hamburg, Germany
⁷ Institute of Neuropathology and National Reference Center for Prion Diseases, University Hospital Zurich, Zurich, Switzerland
⁸ Department of Neurology, Georg-August University, Göttingen, Germany
⁹ Department of Neuropathology, Ludwig-Maximilian University, Munich, Germany
¹⁰ Centre for Infectious Disease Prevention and Control, Public Health Agency of Canada, Ottawa, ON, Canada
¹¹ Institute of Preventive and Clinical Medicine, Research Base of Slovak Medical University, Bratislava, Slovak Republic
¹² U.708 INSERM, Hôpital de la Salpêtrière, Paris, France
¹³ National CJD Surveillance Unit, Western General Hospital, Edinburgh, UK

^* To whom correspondence should be addressed.
S. J. Collins, E-mail: stevenjc{at}unimelb.edu.au

	Abstract

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.

Keywords: sporadic CJD; diagnostic investigation results; molecular sub-typing.

---

^*These authors contributed equally to this work.
CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				I. Cali, R. Castellani, A. Alshekhlee, Y. Cohen, J. Blevins, J. Yuan, J. P. M. Langeveld, P. Parchi, J. G. Safar, W.-Q. Zou, et al. Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics Brain, October 1, 2009; 132(10): 2643 - 2658. [Abstract] [Full Text] [PDF]

				R. Lodi, P. Parchi, C. Tonon, D. Manners, S. Capellari, R. Strammiello, R. Rinaldi, C. Testa, E. Malucelli, B. Mostacci, et al. Magnetic resonance diagnostic markers in clinically sporadic prion disease: a combined brain magnetic resonance imaging and spectroscopy study Brain, October 1, 2009; 132(10): 2669 - 2679. [Abstract] [Full Text] [PDF]

				I. Zerr, K. Kallenberg, D. M. Summers, C. Romero, A. Taratuto, U. Heinemann, M. Breithaupt, D. Varges, B. Meissner, A. Ladogana, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease Brain, October 1, 2009; 132(10): 2659 - 2668. [Abstract] [Full Text] [PDF]

				V L Villemagne, C A McLean, K Reardon, A Boyd, V Lewis, G Klug, G Jones, D Baxendale, C L Masters, C C Rowe, et al. 11C-PiB PET studies in typical sporadic Creutzfeldt-Jakob disease J. Neurol. Neurosurg. Psychiatry, September 1, 2009; 80(9): 998 - 1001. [Abstract] [Full Text] [PDF]

				B. Meissner, K. Kallenberg, P. Sanchez-Juan, D. Collie, D. M. Summers, S. Almonti, S. J. Collins, P. Smith, P. Cras, G. H. Jansen, et al. MRI lesion profiles in sporadic Creutzfeldt-Jakob disease Neurology, June 9, 2009; 72(23): 1994 - 2001. [Abstract] [Full Text] [PDF]

				G. M. Klug, H. Wand, A. Boyd, M. Law, S. Whyte, J. Kaldor, C. L. Masters, and S. Collins Enhanced geographically restricted surveillance simulates sporadic Creutzfeldt-Jakob disease cluster Brain, February 1, 2009; 132(2): 493 - 501. [Abstract] [Full Text] [PDF]

				J. D.F Wadsworth, S. Joiner, J. M Linehan, E. A Asante, S. Brandner, and J. Collinge The origin of the prion agent of kuru: molecular and biological strain typing Phil Trans R Soc B, November 27, 2008; 363(1510): 3747 - 3753. [Abstract] [Full Text] [PDF]

				S. Brandner, J. Whitfield, K. Boone, A. Puwa, C. O'Malley, J. M Linehan, S. Joiner, F. Scaravilli, I. Calder, M. P. Alpers, et al. Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease Phil Trans R Soc B, November 27, 2008; 363(1510): 3755 - 3763. [Abstract] [Full Text] [PDF]

				B. Meissner, K. Kallenberg, P. Sanchez-Juan, A. Krasnianski, U. Heinemann, D. Varges, M. Knauth, and I. Zerr Isolated Cortical Signal Increase on MR Imaging as a Frequent Lesion Pattern in Sporadic Creutzfeldt-Jakob Disease AJNR Am. J. Neuroradiol., September 1, 2008; 29(8): 1519 - 1524. [Abstract] [Full Text] [PDF]

				J. D. F. Wadsworth, S. Joiner, J. M. Linehan, M. Desbruslais, K. Fox, S. Cooper, S. Cronier, E. A. Asante, S. Mead, S. Brandner, et al. Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice PNAS, March 11, 2008; 105(10): 3885 - 3890. [Abstract] [Full Text] [PDF]

				P. Brown Transmissible spongiform encephalopathy in the 21st century: Neuroscience for the clinical neurologist Neurology, February 26, 2008; 70(9): 713 - 722. [Full Text] [PDF]

				M. D. Geschwind, K. A. Josephs, J. E. Parisi, and B. M. Keegan A 54-year-old man with slowness of movement and confusion Neurology, November 6, 2007; 69(19): 1881 - 1887. [Full Text] [PDF]

				H.J. Tschampa, K. Kallenberg, H.A. Kretzschmar, B. Meissner, M. Knauth, H. Urbach, and I. Zerr Pattern of Cortical Changes in Sporadic Creutzfeldt-Jakob Disease AJNR Am. J. Neuroradiol., June 1, 2007; 28(6): 1114 - 1118. [Abstract] [Full Text] [PDF]

				U. Heinemann, A. Krasnianski, B. Meissner, D. Varges, K. Kallenberg, W. J. Schulz-Schaeffer, B. J. Steinhoff, E. M. Grasbon-Frodl, H. A. Kretzschmar, and I. Zerr Creutzfeldt-Jakob disease in Germany: a prospective 12-year surveillance Brain, May 1, 2007; 130(5): 1350 - 1359. [Abstract] [Full Text] [PDF]

				Diagnosis and Classification of Prion Diseases Journal Watch Neurology, November 7, 2006; 2006(1107): 1 - 1. [Full Text]

				M. W. Head and J. W. Ironside Sporadic Creutzfeldt-Jakob disease: further twists and turns in a convoluted protein. Brain, September 1, 2006; 129(Pt 9): 2238 - 2240. [Full Text] [PDF]

Online ISSN 1460-2156 - Print ISSN 0006-8950

Copyright © 2009 Guarantors of Brain

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics