Serum Neurofilament Levels in Children With Febrile Seizures and in Controls

Abstract

Objective Neuroaxonal damage is reflected by serum neurofilament light chain (sNfL) values in a variety of acute and degenerative diseases of the brain. The aim of this study was to investigate the impact of febrile and epileptic seizures on sNfL, serum copeptin, and prolactin levels in children compared with children with febrile infections without convulsions. Methods A prospective cross-sectional study was performed in children aging 6 months to 5 years presenting with fever (controls, n = 61), febrile seizures (FS, n = 78), or epileptic seizures (ES, n = 16) at our emergency department. sNfL, copeptin, and prolactin were measured within a few hours after the event in addition to standard clinical, neurophysiological, and laboratory assessment. All children were followed up for at least 1 year after presentation concerning recurrent seizures. Results Serum copeptin values were on average 4.1-fold higher in FS and 3.2-fold higher in ES compared with controls (both p < 0.01). Serum prolactin values were on average 1.3-fold higher in FS compared with controls ( p < 0.01) and without difference between ES and controls. There was no significant difference of mean sNfL values (95% CI) between all three groups, FS 21.7 pg/ml (19.6–23.9), ES 17.7 pg/ml (13.8–21.6), and controls 23.4 pg/ml (19.2–27.4). In multivariable analysis, age was the most important predictor of sNfL, followed by sex and C reactive protein. Neither the duration of seizures nor the time elapsed from seizure onset to blood sampling had an impact on sNfL. None of the three biomarkers were related to recurrent seizures. Significance Serum neurofilament light is not elevated during short recovery time after FS when compared with children presenting febrile infections without seizures. We demonstrate an age-dependent decrease of sNfL from early childhood until school age. In contrast to sNfL levels, copeptin and prolactin serum levels are elevated after FS.

Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies

“…These increases accompany hippocampal atrophy in cognitively healthy older adults, which has suggested possible AD-independent, ageexpected hippocampal decline (Idland et al, 2017). However, younger children have higher serum NfL levels than older children reaching the lowest level between the age of 10 and 15 years, then increasing in a linear fashion until the age of 60 years and accelerating non-linearly afterward (Evers et al, 2020;Khalil et al, 2020;Reinert et al, 2020). There are various proposed bases for serum NfL elevation in aging, including subclinical senescence with greater neuronal apoptosis (Khalil et al, 2020) and increased disruption of blood-brain barrier (Sweeney et al, 2018).…”

Cerebrospinal fluid neurofilament light levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment

“…This observation is supported by a previous study which reported that serum NfL was not altered in children with febrile seizures. 12 However, it had also previously been reported that NfL may reflect the contribution of seizure status to CLN3 disease severity. 13 The lowest NfL levels in this cohort was in the atypical patient 667.…”

Neurological symptoms and blood neurofilament light levels

“…11,[13][14][15][16] Of note, there are few studies that also looked at NfL in epilepsy, and partial or generalized epileptic seizures were not associated with an increase in NfL levels but status epilepticus resulted in increased NfL. 17,18 Avoiding the increase in blood neurofilaments or decreasing their levels could be a relevant aspect for assessing the efficacy of forthcoming treatments-as shown in multiple sclerosis (MS) (Table 1). 19…”

“…Thus, the second sample taken few days after the event will not show a change in NfL levels if the cognition was altered for example because of Alzheimer disease (AD), Parkinson disease (PD), or vascular dementia 11,13‐16 . Of note, there are few studies that also looked at NfL in epilepsy, and partial or generalized epileptic seizures were not associated with an increase in NfL levels but status epilepticus resulted in increased NfL 17,18 . Avoiding the increase in blood neurofilaments or decreasing their levels could be a relevant aspect for assessing the efficacy of forthcoming treatments—as shown in multiple sclerosis (MS) (Table 1).…”