Serum Neurofilament Light Chain Levels and Myelin Oligodendrocyte Glycoprotein Antibodies in Pediatric Acquired Demyelinating Syndromes

Abstract

Introduction: The relationship between serum neurofilament light chain (sNfL) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) status has not been yet investigated in children with the acquired demyelinating syndrome (ADS).Objective and Methods: The sNfL levels and MOG-Abs were measured by ultrasensitive single-molecule array and cell-based assay in a cohort of 37 children with ADS and negativity for serum anti-aquaporin 4 (AQP4) antibodies. The sNfL levels were compared in MOG-Ab+/MOG-Ab– and in two subgroups MOG-Ab+ with/without encephalopathy.Results: About 40% ADS resulted in MOG-Ab+. MOG-Ab+ were younger at sampling (median = 9.8; range = 2.17–17.5 vs. 14.7/9–17; p = 0.002) with lower frequency of cerebrospinal fluid oligoclonal bands positivity (27% vs. 70%; p = 0.013) compared to MOG-Ab–. About 53% of MOG-Ab+ presented encephalopathy at onset, 1/22 of MOG-Ab– (p = 0.0006). Higher sNfL levels (p = 0.0001) were found in MOG-Ab+ (median/range = 11.11/6.8–1,129) and MOG-Ab– (median/range = 11.6/4.3–788) compared to age-matched controls (median/range = 2.98/1–4.53), without significant difference. MOG-Ab+ with encephalopathy resulted significantly younger at sampling (median/range: 4.5/2.17–11.17 vs. 14.16/9.8–17.5; p = 0.004), had higher sNfL levels (median/range:75.24/9.1–1,129 vs. 10.22/6.83–50.53; p = 0.04), and showed a trend for higher MOG-Ab titer (0.28/0.04–0.69 vs. 0.05/0.04–0.28; p = 0.1) in comparison to those without encephalopathy.Discussion: We confirmed high sNfL levels in pediatric ADS independently from the MOG-Ab status. Encephalopathy at onset is associated more frequently with MOG Ab+ children with higher sNfL levels and MOG titer. These findings suggest a role of acute demyelination in association with axonal damage in the pathogenesis of encephalopathy in pediatric ADS.

Linking Plasma Amyloid Beta and Neurofilament Light Chain to Intracortical Myelin Content in Cognitively Normal Older Adults

“…Multiple lines of evidence indirectly support this hypothesis in humans. For instance, recent experiments have revealed associations between high serum NfL levels and MRI markers of myelin damage in multiple sclerosis (Yik et al, 2022), pediatric acquired demyelinating syndrome (Simone et al, 2021), and X-linked adrenoleukodystrophy (Weinhofer et al, 2021). Our results add further support to this hypothesis, showing a negative relationship between plasma NfL levels and intracortical myelin content of the right insular cortex, a lightly myelinated cortical region that has shown increased vulnerability in aging (Hu et al, 2014), preclinical (Cantero et al, 2020) and prodromal AD (Cantero et al, 2017).…”

Early blood neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels associate with different disease courses of myelin oligodendrocyte glycoprotein-associated disease in children

“…Similar results were found in MOGAD adult patients in the study of Mariotto et al , 31 as well as more recently in paediatric patients. 40 , 41 In our MOGNR subgroup of patients, NfL levels were higher than in the MOGR subgroup and significantly higher than in control patients. The higher levels of NfL in MOGNR could be related to the higher neuroinflammation in these patients.…”

Serum and Cerebrospinal Fluid Biomarkers in Neuromyelitis Optica Spectrum Disorder and Myelin Oligodendrocyte Glycoprotein Associated Disease

“…In MOGAD, sNfL values are associated with EDSS ( 117 , 124 , 125 ), are higher in pediatric patients presenting with encephalopathy ( 130 ) and both sGFAP and sNfL have been found to be associated with a recent brain lesion ( 124 ). In addition, tau concentration has been found to be associated with EDSS ( 125 ).…”