[Usefulness of the 14-3-3 test for the diagnosis of sCJD evaluated by a Spanish reference center]. / Utilidad del inmunoensayo de la proteína 14-3-3 en el diagnóstico de la enfermedad de Creutzfeldt-Jakob examinada desde un centro de referencia nacional.

INTRODUCTION: The performance of the 14-3-3 protein test has been shown to be adequate for sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis in selected populations, but its routine validity has been questioned. METHODS: One thousand and sixty-eight patients with clinically suspected sCJD were analyzed in a Spanish reference center. In order to explore the influence of the clinical context on the performance of the immunoassay, the patients were classified at sample reception according to the World Health Organization (WHO) diagnostic criteria excluding the 14-3-3 test results. The yield of the immunoassay was evaluated in each subgroup with criteria of probable, possible sCJD or non-sCJD. RESULTS: In the set of patients with suspicion of sCJD the inclusion of the 14-3-3 test produces a significant increase in the diagnosis certainty (positive likelihood ratio: 10.1) compared to the WHO's criteria, excluding the 14-3-3 test. For patients classified at sample reception as probable sCJD (n=166), possible sCJD (n=129) and non-sCJD (n=773), the positive predictive values for the test were 98.4%, 97.5% and 31%, and the negative predictive values were 22.2%, 73.4% and 100%, respectively. CONCLUSIONS: The predictive values of the assay vary according to the previous diagnostic certainty. Therefore, in order to interpret correctly the test, it is necessary to evaluate the degree of initial clinical suspicion of the patient at the moment of the cerebrospinal fluid (CSF) extraction. This study offers up-to-date information, referenced to the Spanish population, and in useful format, and it is intended to serve as a guideline for 14-3-3 test results interpretation to the clinicians in our community.

Utilidad del inmunoensayo de la proteína 14-3-3 en el diagnóstico de la enfermedad de Creutzfeldt-Jakob examinada desde un centro de referencia nacional / Usefulness of the 14-3-3 test for the diagnosis of sCJD evaluated by a Spanish reference center

Introducción. El inmunoensayo de la proteína 14-3-3 en líquido cefalorraquídeo (LCR) muestra un rendimiento óptimo para el diagnóstico de la enfermedad de Creutzfeldt- Jakob esporádica (ECJe) en poblaciones seleccionadas, pero su validez en la práctica rutinaria ha sido cuestionada. Método. Se estudiaron 1.068 pacientes con sospecha de ECJe procedentes de distintas instituciones españolas. Para explorar la influencia del contexto clínico sobre la validez del inmunoensayo los pacientes fueron clasificados en el momento de la recepción de la muestra de acuerdo con los criterios de certeza diagnóstica establecidos por la Organización Mundial de la Salud (OMS), excluyendo la prueba de la proteína 14-3-3. El rendimiento del immunoensayo se evaluó en cada subgrupo con criterios de ECJe probable, posible o no ECJe. Resultados. En el conjunto de pacientes con sospecha de ECJe la inclusión del inmunoensayo supone un aumento significativo en la certeza diagnóstica (razón de verosimilitud positiva: 10,1) sobre los criterios de la OMS sin incluir dicha prueba. En los subgrupos de pacientes clasificados a la recepción de la muestra como ECJe probable (n=166), ECJe posible (n=129) y no ECJe (n=773) los valores predictivos positivos de la prueba de la proteína 14-3-3 fueron 98,4, 97,5 y 31% y los valores predictivos negativos fueron 22,2, 73,4 y 100%, respectivamente. Conclusiones. Los valores predictivos de la prueba varían según el grado de certeza diagnóstica previa de cada paciente. Por ello, para interpretar correctamente el ensayo es necesario valorar el grado de sospecha clínica del paciente en el momento de la extracción del LCR. Este estudio pretende facilitar la interpretación de los resultados de la prueba de la proteína 14-3-3 a los especialistas clínicos, ofreciendo una información actualizada, referenciada a la población española y en formato de utilidad práctica (AU)

Introduction: The performance of the 14-3-3 protein test has been shown to be adequate for sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis in selected populations, but its routine validity has been questioned. Methods: One thousand and sixty-eight patients with clinically suspected sCJD were analyzed in a Spanish reference center. In order to explore the influence of the clinical context on the performance of the immunoassay, the patients were classified at sample reception according to the World Health Organization (WHO) diagnostic criteria excluding the 14-3-3 test results. The yield of the immunoassay was evaluated in each subgroup with criteria of probable, possible sCJD or non-sCJD. Results: In the set of patients with suspicion of sCJD the inclusion of the 14-3-3 test produces a significant increase in the diagnosis certainty (positive likelihood ratio: 10.1) compared to the WHO's criteria, excluding the 14-3-3 test. For patients classified at sample reception as probable sCJD (n=166), possible sCJD (n=129) and non-sCJD (n=773), the positive predictive values for the test were 98.4%, 97.5% and 31%, and the negative predictive values were 22.2%, 73.4% and 100%, respectively. Conclusions: The predictive values of the assay vary according to the previous diagnostic certainty. Therefore, in order to interpret correctly the test, it is necessary to evaluate the degree of initial clinical suspicion of the patient at the moment of the cerebrospinal fluid (CSF) extraction. This study offers up-to-date information, referenced to the Spanish population, and in useful format, and it is intended to serve as a guideline for 14-3-3 test results interpretation to the clinicians in our community (AU)