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. 1998 Feb 14;316(7131):577–582. doi: 10.1136/bmj.316.7131.577

Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study

Markus Otto a, Jens Wiltfang b, Ekkehard Schütz c, Inga Zerr a, Anke Otto a, Annette Pfahlberg d, Olaf Gefeller d, Manfred Uhr e, Armin Giese f, Thomas Weber g, Hans A Kretzschmar f, Sigrid Poser a
PMCID: PMC28459  PMID: 9518907

Abstract

Objective: To analyse serum concentrations of brain specific S100 protein in patients with Creutzfeldt-Jakob disease and in controls.

Design: Prospective case-control study.

Setting: National Creutzfeldt-Jakob disease surveillance unit.

Subjects: 224 patients referred to the surveillance unit with suspected Creutzfeldt-Jakob disease and 35 control patients without dementia.

Main outcome measure: Serum concentration of S100 protein in patients with Creutzfeldt-Jakob disease, in patients with other diseases causing dementia, and in the control group.

Results: Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65 were classed as definitely having the disease after neuropathological verification, an additional 6 were classed as definitely having the disease as a result of a genetic mutation, 43 as probably having the disease, 36 as possibly having the disease, and 74 patients were classed as having other disease. In the 108 patients classed as definitely or probably having Creutzfeldt-Jakob disease the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was significantly higher than concentrations found in the 74 patients classed as having other diseases (median 109 pg/ml; SD 177 pg/ml; P=0.0001). At a cut off point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95% confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%). There was a significant difference in survival at different concentrations of S100 in Kaplan-Meier curves (P=0.023).

Conclusion: Measurement of serum concentrations of S100 is a valuable tool which can be used more easily than tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob disease. More studies are needed to determine whether serial testing of serum S100 improves diagnostic accuracy.

Key messages

  • Creutzfeldt-Jakob disease is a rare, fatal neurodegenerative disease. Diagnosis is made clinically and neuropathologically

  • There is no serum test which allows the diagnosis to be made while the patient is alive

  • In this study raised serum concentrations of S100 protein were found in patients with Creutzfeldt-Jakob disease

  • Serum concentrations of S100 could be used with a sensitivity of 77.8% and a specificity of 81.1% to confirm Creutzfeldt-Jakob disease in the differential diagnosis of diseases that cause dementia

  • Serial measurement of S100 concentrations will enhance diagnostic accuracy

Full Text

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Acknowledgments

We thank Professor K Felgenhauer, department head, for encouraging us to do this work. We also thank the physicians who made site visits to the hospitals in the study: A Szudra, S Räcker, S Grosche, M Lantsch, W Murach, K Weidehaas, and C Riedemann. We thank M Bodemer, M Liebeskind, and Professor M Oellerich for technical assistance. We also thank B J Steinhoff, assistant professor, for re-evaluating the electroencephalograms. Parts of this work, especially the follow up of patients classified as having other disease, are based on a thesis by B Mollenhauer. We thank all physicians who reported suspected cases of Creutzfeldt-Jakob disease to the German Creutzfeldt-Jakob disease surveillance unit for providing clinical, neuroradiological, and biochemical data as well as for their help in obtaining serum samples. LIA-mat Sangtec100 kits were provided by Byk Sangtec, Dietzenbach, Germany.

See editorial by Pocchiari and p 593

Footnotes

Funding: This study was supported in part by a grant from the Bundesministerium für Gesundheit and by a grant from the VerUm Stiftung.

Conflict of interest: None.

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