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Multicenter Study
. 2007 Jul;254(7):901-6.
doi: 10.1007/s00415-006-0472-9. Epub 2007 Mar 25.

Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosis

Pascual Sanchez-Juan  1 , Raquel Sánchez-Valle, Alison Green, Anna Ladogana, Natividad Cuadrado-Corrales, Eva Mitrová, Kathrina Stoeck, Theodoros Sklaviadis, Jerzy Kulczycki, Klaus Hess, Anna Krasnianski, Michele Equestre, Danka Slivarichová, Albert Saiz, Miguel Calero, Maurizio Pocchiari, Richard Knight, Cornelia M van Duijn, Inga Zerr
Affiliations
Multicenter Study

Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosis

Pascual Sanchez-Juan et al. J Neurol. 2007 Jul.

Abstract

Background: The analysis of markers in the cerebrospinal fluid (CSF) is useful in the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, the time at which the study of these markers is most sensitive remains controversal.

Objective: To assess the influence of time of sampling on the value of CSF tests in the diagnosis of sCJD.

Method: In the framework of a multinational European study, we studied the results of 14-3-3, S100b, neurone specific enolase (NSE) and tau protein in 833 CSF samples from sCJD patients at different stages of disease and in 66 sequentially repeated lumbar punctures (LP).

Results: 14-3-3 and tau protein tended to increase in sensitivity from onset (88%, 81%) to the advanced stage (91%, 90%). This was significant only in the methionine-valine (MV) heterozygous group of patients at codon 129. The absolute levels of S100b (p < 0.05), NSE and tau protein increased in the last stage of disease. High levels of tau protein, NSE and S100b were associated with shorter survival times (p < 0.01). Sixty-six sCJD patients underwent repeated LP. These sCJD patients were younger, had longer disease durations and were more frequently MV at codon 129 (p < 0.001) than the whole group. 14-3-3 sensitivity increased from 64% to 82% in the second LP (p = 0.025) and 88% sCJD patients had at least one positive result.

Conclusions: Sensitivity and absolute levels of CJD markers increased with disease progression and were modulated by the codon 129 genotype. Early negative results should be inter-preted with caution, especially in young patients or those who are MV at codon 129.

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Figures

Fig. 1
Fig. 1
Sensitivity of markers for sporadic Creutzfeldt-Jakob disease diagnosis in repeated lumbar punctures (LP) and combined results in both LP. LP = lumbar puncture, + = positive, NSE = neurone specific enolase, and = both LP+, or = either 1st or 2nd+
Fig. 2
Fig. 2
Levels of quantitative markers in repeated lumbar punctures. 1Differences between median levels were not significant. 2THe median S100b levels were different (p = 0.027). *Byk-Sangtec kit
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