Neurofilament light chain and glial fibrillary acidic protein as diagnostic and prognostic biomarkers in epileptic seizures and epilepsy: A systematic review

Epileptology − with epilepsy as one of the most common neurological diseases − has an urgent need for easily accessible biomarkers to improve diagnosis, prognosis and therapeutic monitoring. Neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) have emerged as promising fluid biomarkers in various neurological disorders. Their potential role in epileptic seizures and epilepsy remains largely unexplored. To assess the current state of research on this topic we comprehensively searched the published literature for studies on GFAP and/or NfL in cerebrospinal fluid and/or blood in adult humans with epileptic seizures, status epilepticus or epilepsy (last data base search on 10th of May 2024). We identified a total of 2285 publications of which 19 fulfilled our search criteria. The studies targeted various outcomes such as prognosis in status epilepticus, differentiation of seizure semiology and etiology, differentiation of epileptic seizures from non-epileptic conditions, prediction of epilepsy in autoimmune epilepsy, after a stroke or after a first unprovoked seizure, the role of the time interval from seizure to sampling, the association with disease duration as well as seizure frequency and the influence of seizure suppressing medication. The results are heterogeneous but indicate promising applications for both NfL and GFAP in diagnosis and prognostication of patients with epileptic seizures and epilepsy. In the present review we summarize the current evidence, future perspectives, but also limitations, of NfL and GFAP as fluid biomarkers in epilepsy and epileptic seizures.