DIAGNOSIS OF CREUTZFELDT-JAKOB-DISEASE BY 2-DIMENSIONAL GEL-ELECTROPHORESIS OF CEREBROSPINAL-FLUID

Background The diagnosis of Creutzfeldt-Jakob disease (CJD) is based o n clinical and electroencephalographic criteria which do not allow a r eliable diagnosis to be made during life. Methods Serum and cerebrospi nal fluid (CSF) samples were obtained after informed consent from rela tives of suspected cases of CJD referred to the German CJD surveillanc e unit. CSF samples from 58 definite (neuropathologically verified), 4 6 probable, and 34 possible CJD cases, and from 44 patients without CJ D were analysed by two-dimensional gel electrophoresis (2-DE). Two inv estigators blinded to clinical findings recorded the presence of two p roteins, p130/131. The kappa value for the level of agreement between these investigators was calculated. Results obtained were compared wit h the determination of neuron-specific enolase (NSE) in CSF. NSE conce ntrations of more than 35 ng/mL were considered indicative of CJD. Fin dings p130/131 was detected in 81% of definite (47/58), 80% of probabl e (37/46), 68% of possible (23/34) CJD cases, and in none of the other 44 cases, NSE concentrations of more than 35 ng/mL were seen in 79% o f definite (46/58), 80% of probable (37/46), 59% of possible (20/34) C JD cases, and 9% of other cases (4/43). The positive predictive value for 2-DE of CSF is 100% and the negative predictive value is 69%. The level of agreement for the detection of p130/131 by two evaluators in a subset of 141 2-DE gels was a kappa of 0.93 (95% Cl 0.86-0.99). Of 1 3 cases initially classified as possible and later reclassified as def inite, ten cases were identified correctly by the 2-DE analysis, indic ating a better diagnostic accuracy of this test compared with the curr ent clinical classification. None of nine cases classified as other by neuropathology had p130/131 in 2-DE. Interpretation 2-DE for p130/131 is a specific test for the diagnosis of CJD. These data suggest inclu ding detection of p130/131 as a criterion for the diagnosis of probabl e CJD in addition to the currently accepted criteria of a rapidly prog ressive dementia of less than 2 years duration, typical neurological s igns, and periodic sharp-wave complexes in the EEG.