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


METHODS
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.
Sanchez-Juan
Pascual
P
Department of Epidemiology and Biostatistics, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands.
Sánchez-Valle
Raquel
R
Green
Alison
A
Ladogana
Anna
A
Cuadrado-Corrales
Natividad
N
Mitrová
Eva
E
Stoeck
Kathrina
K
Sklaviadis
Theodoros
T
Kulczycki
Jerzy
J
Hess
Klaus
K
Krasnianski
Anna
A
Equestre
Michele
M
Slivarichová
Danka
D
Saiz
Albert
A
Calero
Miguel
M
Pocchiari
Maurizio
M
Knight
Richard
R
van Duijn
Cornelia M
CM
Zerr
Inga
I
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid; D017668:Age of Onset; D000368:Aged; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D018450:Disease Progression; D005060:Europe; D005260:Female; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid; D018709:Statistics, Nonparametric; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
D048948:14-3-3 Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase