Serum neurofilament light as biomarker of seizure‐related neuronal injury in status epilepticus

Giovannini, Giada; Bedin, Roberta; Ferraro, Diana; Vaudano, Anna Elisabetta; Mandrioli, Jessica; Meletti, Stefano

doi:10.1111/epi.17132

Cited by 24 publications

(35 citation statements)

References 13 publications

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“…First, we show that Simoa technology is sensitive and reliable enough to measure NfL in serum as a proxy for CSF in SE. This is a finding in line with the other paper on that topic by Giovannini and colleagues [ 6 ]. In both studies, even though Giovannini used a different method to measure NfL, the correlation between CSF and serum NfL values in SE patients is very similar.…”

Section: Discussionsupporting

confidence: 93%

“…If future studies confirm that non-convulsive SE too leads to significant neurodestruction, intensified treatment might be indicated. Additional findings are that NfL concentrations in most SE patients are higher than the age-adjusted 95th percentile of neurologically healthy controls which is in agreement with the only other study of NfL in SE [6]. Interestingly, the range of NfL concentrations overlapped between SE and controls also in this study [6].…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2023

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

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

et al. 2023

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“…Previous studies demonstrated that the average interictal NF-L levels in patients with drug-refractory epilepsy due to structural and other etiologies, genetic epilepsy, or temporal lobe epilepsy with hippocampal sclerosis are comparable to those in controls, although they can be slightly increased in some subpopulations of patients when using a cut-off level of 10 pg/mL [ 51 , 52 , 53 ]. Other studies, however, reported that patients with post-stroke epilepsy or epilepsy related to auto-immune encephalitis have chronically increased serum NF-L levels, even though the levels remain below 100 pg/mL [ 52 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…A recent study reported Increased serum NF-L levels in patients with status epilepticus (SE) when assessed within 48 h after the beginning of seizure activity [ 51 ]. In addition, elevated NF-L levels are associated with the development of treatment refractoriness and 30-day clinical worsening or death.…”

Section: Discussionmentioning

confidence: 99%

“…We consider it unlikely, however, that the occurrence of SE was a major contributor to the NF-L levels on D2. In humans, the SE-induced increase measured within 48 h after the start of SE, corresponding to the timeline of D2 plasma sampling in the present study, ranged from 13 pg/mL to 101 pg/mL [ 51 ]. In our animal cohort, the NF-L levels increased from 11 pg/mL to 5072 pg/mL, supporting the view that TBI rather than SE was the major contributor to the robust NF-L increase.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Heiskanen

Jääskeläinen

Manninen

et al. 2022

IJMS

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Plasma neurofilament light chain (NF-L) levels were assessed as a diagnostic biomarker for traumatic brain injury (TBI) and as a prognostic biomarker for somatomotor recovery, cognitive decline, and epileptogenesis. Rats with severe TBI induced by lateral fluid-percussion injury (n = 26, 13 with and 13 without epilepsy) or sham-operation (n = 8) were studied. During a 6-month follow-up, rats underwent magnetic resonance imaging (MRI) (day (D) 2, D7, and D21), composite neuroscore (D2, D6, and D14), Morris-water maze (D35–D39), and a 1-month-long video-electroencephalogram to detect unprovoked seizures during the 6th month. Plasma NF-L levels were assessed using a single-molecule assay at baseline (i.e., naïve animals) and on D2, D9, and D178 after TBI or a sham operation. Plasma NF-L levels were 483-fold higher on D2 (5072.0 ± 2007.0 pg/mL), 89-fold higher on D9 (930.3 ± 306.4 pg/mL), and 3-fold higher on D176 32.2 ± 8.9 pg/mL after TBI compared with baseline (10.5 ± 2.6 pg/mL; all p < 0.001). Plasma NF-L levels distinguished TBI rats from naïve animals at all time-points examined (area under the curve [AUC] 1.0, p < 0.001), and from sham-operated controls on D2 (AUC 1.0, p < 0.001). Plasma NF-L increases on D2 were associated with somatomotor impairment severity (ρ = −0.480, p < 0.05) and the cortical lesion extent in MRI (ρ = 0.401, p < 0.05). Plasma NF-L increases on D2 or D9 were associated with the cortical lesion extent in histologic sections at 6 months post-injury (ρ = 0.437 for D2; ρ = 0.393 for D9, p < 0.05). Plasma NF-L levels, however, did not predict somatomotor recovery, cognitive decline, or epileptogenesis (p > 0.05). Plasma NF-L levels represent a promising noninvasive translational diagnostic biomarker for acute TBI and a prognostic biomarker for post-injury somatomotor impairment and long-term structural brain damage.

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Serum neurofilament light chain in patients with epilepsy and cognitive impairment

Ueda

Suzuki

Hatanaka

et al. 2023

Epileptic Disorders

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Background:The neurofilament light chain (NfL) is receiving increased attention as a biomarker of neurological diseases, as NfL concentration elevated in the blood and cerebrospinal fluid after neuronal damage. However, few studies have addressed NfL in epilepsy. We aimed to investigate the alteration of serum NfL in adult patients with epilepsy, and the association between this biomarker and cognitive impairment. Methods: A total of 38 consecutive patients with epilepsy and 24 controls underwent cross-sectional measurement of serum NfL levels and cognitive testing using the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), the Frontal Assessment Battery (FAB), the Trail-Making Test, and the Stroop Color-Word Test. Statistical analysis was performed with Student's t-test to compare serum NfL levels between the epilepsy group and the control group, and with Spearman's correlation and agecorrected partial correlation analyses to evaluate the association between serum NfL level and cognitive impairment in epilepst patients.Results: There was no difference in serum NfL levels between the epilepsy and control groups (epilepsy [mean ± SD]: 17.3 ± 13.9 pg/mL; control: 17.7 ± 11.5 pg/mL; p = .92); however, the MoCA-J scores were lower in the epilepsy group (26.6 ± 3.1 vs. 28.1 ± 1.6; p = .03). The age-corrected partial correlation analysis showed a correlation between serum NfL level and cognitive test scores in the epilepsy group (MMSE: r s = −.63, p < .01; MoCA-J: r s = −.54, p < .01; FAB: r s = −.68, p < .01), whereas serum NfL levels were correlated exclusively with MMSE scores in the control group (r s = .44, p = .04). Significance:In adult epilepsy patients, the serum NfL level was not significantly elevated, but was correlated with cognitive test scores. Our findings suggest that serum NfL concentration could be an indicator of cognitive function in epilepsy patients.

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Serum neurofilament light as biomarker of seizure‐related neuronal injury in status epilepticus

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 24 publications

References 13 publications

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

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

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

Serum neurofilament light chain in patients with epilepsy and cognitive impairment

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