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 Creutz-feldt-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 interpreted with caution, especially in young patients or those who are MV at codon 129.