The role of serum biomarkers in differential diagnosis of epileptic seizures, functional/cognitive seizure and syncope: A prospective cohort study

Objective

Differentiating epileptic seizures (ES) from other transient loss of consciousness including syncope and Functional/Cognitive Seizure (FCS) poses significant challenges in emergency settings. Laboratory biomarkers have emerged as valuable tools in enhancing diagnostic precision. This study evaluates the diagnostic performance of serum biomarkers, including phosphate, lactate, prolactin, and ammonia, in distinguishing ES from FCS and related conditions.

Methods

A cohort of 99 patients presenting with transient loss of consciousness was analyzed. Group 1 included ES patients (n = 56), and Group 2 included FCS and presyncope/syncope cases (n = 43). Serum levels of phosphate, lactate, prolactin, and ammonia were measured within the first hour of admission. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curves, and multivariable logistic regression was performed to identify independent predictors.

Results

Serum phosphate levels ≤ 2.74 mg/dL demonstrated the highest diagnostic value (sensitivity: 82.1 %, specificity: 79.1 %, AUC=0.835). Lactate > 3.52 mmol/L exhibited high specificity (93.0 %) and moderate sensitivity (60.7 %) for ES (AUC=0.812). Prolactin > 15.55 ng/mL and ammonia > 60 μmol/L were also significant predictors, with specificities of 83.7 % and 88.4 %, respectively. Multivariable analysis confirmed serum phosphate, lactate, prolactin, and ammonia as independent predictors. The combined model achieved an AUC of 0.946, indicating excellent diagnostic performance.

Conclusion

This study highlights the diagnostic utility of serum biomarkers in differentiating ES from FCS. The findings underscore the potential for integrating simple, accessible biomarkers into clinical workflows to improve diagnostic accuracy. Further research is warranted to validate these results across diverse populations.