Neurofilament light-chain (Nf-L) as a biomarker in seizures and status epilepticus of varying duration

BACKGROUND: Neurofilament light chain (Nf-L) is an established biomarker for neuronal damage and a prognostic parameter in many diseases of the central nervous system (CNS). In epilepsy, most studies have focused on Nf-L levels either in epileptic seizures or in status epilepticus. We sought to investigate the correlation between epileptic seizures of different duration and elevated Nf-L levels as a biomarker for neuroaxonal injury also considering methodological confounders in Nf-L measurement. METHODS: In adult patients, Nf-L was investigated in serum and/or cerebrospinal fluid (CSF) after a single epileptic seizure (51 patients), acute repetitive seizures (11 patients) or status epilepticus (20 patients) along with standard acute CSF parameters. In addition, ratios of Nf-L to age-adjusted reference intervals were calculated. RESULTS: In both serum and CSF, absolute Nf-L levels were significantly increased after status epilepticus compared to patients who experienced a single seizure (serum: p < 0.0001; CSF: p = 0.0008) or acute repetitive seizures (serum: p = 0.035 CSF: p = 0.045). Similarly, age-adjusted Nf-L ratios in serum were higher after status epilepticus (median = 1.68, interquartile range = 2.81) than after a single seizure (median = 0.67, interquartile range = 0.73; p = 0.039). Though ANOVA-testing indicated significant differences in CSF Nf-L ratios between the three groups (p = 0.040), pairwise post hoc testing was not significant. A moderate significant positive correlation was observed between the duration of status epilepticus and serum Nf-L concentrations (Pearson r = 0.48, p = 0.02). CONCLUSION: Our data indicate that single and acute repetitive seizures likely do not cause significant neuronal injury as assessed by Nf-L concentrations in serum and CSF. In contrast, status epilepticus is accompanied by a duration-dependent increase in serum Nf-L, which presumably reflects seizure-associated cellular injury and underlines the need for rapid and consistent antiseizure treatment.