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Abstract
Objective To explore the correlation between serum and CSF neurofilament light chain (NfL) and the association of NfL levels and future disease activity in pediatric patients with a first attack of acquired demyelinating syndromes (ADS).
Methods In total, 102 children <18 years with a first attack of CNS demyelination and 23 age-matched controls were included. Clinically definite multiple sclerosis (CDMS) was set as an endpoint for analysis. CSF NfL was tested by the commercially available ELISA (UmanDiagnostics); serum NfL (sNfL) was tested with a Simoa assay. Hazard ratios (HR) were calculated with Cox regression analysis.
Results Of the 102 patients, 47 (46%) were tested for CSF NfL. CSF and serum NfL correlated significantly in the total group (ρ 0.532, p < 0.001) and even more significantly in the subgroup of patients with future CDMS diagnosis (ρ 0.773, p < 0.001). sNfL was higher in patients than in controls (geometric mean 6.1 pg/mL, p < 0.001), and was highest in ADS presenting with encephalopathy (acute disseminated encephalomyelitis, n = 28, 100.4 pg/mL), followed by patients without encephalopathy (ADS−) with future CDMS diagnosis (n = 40, 32.5 pg/mL), and ADS− who remained monophasic (n = 34, 17.6 pg/mL). sNfL levels higher than a median of 26.7 pg/mL at baseline are associated with a shorter time to CDMS diagnosis in ADS− (p = 0.045). HR for CDMS diagnosis was 1.09 for each 10 pg/mL increase of sNfL, after correction for age, oligoclonal bands, and MRI measures (p = 0.012).
Conclusion The significant correlation between CSF and serum NfL strengthens its reliability as a peripheral marker of neuroaxonal damage. Higher sNfL levels at baseline were associated with higher probability of future CDMS diagnosis in ADS−.
Glossary
- ADEM=
- acute disseminated encephalomyelitis;
- ADS=
- acquired demyelinating syndromes;
- CDMS=
- clinically definite multiple sclerosis;
- CI=
- confidence interval;
- DMT=
- disease-modifying treatment;
- EDSS=
- Expanded Disability Status Scale;
- FU=
- follow-up;
- HR=
- hazard ratio;
- IgG=
- immunoglobulin G;
- IQR=
- interquartile range;
- IVMP=
- IV methylprednisolone;
- mAB=
- monoclonal antibody;
- MS=
- multiple sclerosis;
- NfL=
- neurofilament light chain;
- OCB=
- oligoclonal bands;
- ON=
- optic neuritis;
- SC=
- symptomatic control;
- sNfL=
- serum neurofilament light chain;
- TM=
- transverse myelitis
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work as co–last authors.
- Received August 28, 2018.
- Accepted in final form April 9, 2019.
- © 2019 American Academy of Neurology
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