Neurofilament light (NfL) as biomarker in serum and CSF in status epilepticus

Abstract

Objective We explored the potential of neurofilament light chain (NfL) in serum and cerebrospinal fluid as a biomarker for neurodestruction in status epilepticus. Methods In a retrospective analysis, we measured NfL in serum and cerebrospinal fluid samples of patients with status epilepticus using a highly sensitive single-molecule array technique (Simoa). Status epilepticus was diagnosed according to ILAE criteria. Additionally, we employed an alternative classification with more emphasis on the course of status epilepticus. We used data from three large control groups to compare NfL in status epilepticus versus neurologically healthy controls. Results We included 28 patients (mean age: 69.4 years, SD: 15 years) with a median status duration of 44 h (IQR: 80 h). Twenty-one patients (75%) suffered from convulsive status epilepticus and seven (25%) from non-convulsive status epilepticus. Six patients died (21%). Cerebrospinal fluid and serum NfL concentrations showed a high correlation (r = 0.73, p < 0.001, Pearson). The main determinant of NfL concentration was the status duration. NfL concentrations did not differ between convulsive status epilepticus and convulsive status epilepticus classified according to the ILAE or to the alternative classification without and with adjusting for status duration and time between status onset and sampling. We found no association of NfL concentration with death, treatment refractoriness, or prognostic scores. Conclusion The results suggest that neurodestruction in status epilepticus measured by NfL is mainly determined by status duration, not status type nor therapy refractoriness. Therefore, our results suggest that regarding neurodestruction convulsive and non-convulsive status epilepticus are both neurological emergencies of comparable urgency.

Fluid Biomarkers of Neuro-Glial Injury in Human Status Epilepticus: A Systematic Review

“…These findings were recently replicated by a German group [65]. Their study also showed significantly elevated sNfL levels in patients with SE compared to healthy controls.…”

“…An important advantage of NfL is its reliability in measurement in serum/blood. Additionally, two studies on humans [63,65] and a preclinical study [60] have demonstrated a close and optimal correlation between the peripheral and central compartments.…”

Evaluation of neurofilament light chain as a biomarker in dogs with structural and idiopathic epilepsy

“…Therefore, a clinical need exists for readily available and non‐invasive serum biomarkers that could assist with discrimination of genetic vs structural causes of epilepsy or identification of epileptic patients that recently have experienced seizures. Serum NfL concentrations are increased in humans experiencing status epilepticus compared to both healthy people and those with epilepsy who experience occasional isolated seizures 9,10 . Furthermore, serum NfL concentrations in humans correlate well with CSF concentrations in numerous neurological diseases, and thus serum NfL concentrations generally are considered reliable biomarkers for CNS disease 10,11 …”

“…Serum NfL concentrations are increased in humans experiencing status epilepticus compared to both healthy people and those with epilepsy who experience occasional isolated seizures 9,10 . Furthermore, serum NfL concentrations in humans correlate well with CSF concentrations in numerous neurological diseases, and thus serum NfL concentrations generally are considered reliable biomarkers for CNS disease 10,11 …”

“…9,10 Furthermore, serum NfL concentrations in humans correlate well with CSF concentrations in numerous neurological diseases, and thus serum NfL concentrations generally are considered reliable biomarkers for CNS disease. 10,11 Our objective was to evaluate NfL as a serum biomarker for epilepsy in dogs. Our primary hypothesis was that serum NfL concentrations would be significantly higher in dogs with SE compared to those with IE.…”