Serum Biomarkers of Brain Injury in Diagnosis of Patients After Seizure in Emergency Department: A Systematic Review

Distinguishing seizures from other causes of transient loss of consciousness in the emergency department (ED) is challenging. This PRISMA-guided systematic review evaluated serum brain injury biomarkers for the acute diagnosis of seizures in adults. We searched PubMed and Web of Science for studies published between 2015 and 2025 and included 14 studies in which blood sampling occurred shortly after the event, reflecting the ED diagnostic window. Given the heterogeneity across studies, the overall certainty of the evidence was low. Neuron-specific enolase (NSE) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) were consistently elevated after epileptic seizures compared to healthy controls. NSE effectively differentiated seizures from syncope, while UCH-L1 and glial fibrillary acidic protein (GFAP) distinguished epileptic from psychogenic non-epileptic seizures (PNESs). Neurofilament light chain (NfL) remained stable after a single seizure but increased markedly in status epilepticus (SE). S100B and BDNF results were inconsistent. Although no single biomarker serves as a standalone test, NSE and UCH-L1 are promising complementary diagnostic tools for identifying epileptic seizures in adults. Furthermore, NfL is a strong candidate marker for SE, reflecting neuroaxonal injury. Larger prospective, standardized studies are needed before routine ED implementation.