Neurofilament Light Chain Levels Are Predictive of Clinical Conversion in Radiologically Isolated Syndrome

Manon Rival, Eric Thouvenot, Lucile Du Trieu De Terdonck, Sabine Laurent-Chabalier, Christophe Demattei, Ugur Uygunoglu, Giovanni Castelnovo, Mikael Cohen, Darin T. Okuda, Orhun H. Kantarci, Daniel Pelletier, Christina Azevedo, Philippe Marin, Sylvain Lehmann, Aksel Siva, Thibault Mura, Christine Lebrun-Frenay

Research output: Contribution to journalArticlepeer-review


Background and ObjectivesTo evaluate the predictive value of serum neurofilament light chain (sNfL) and CSF NfL (cNfL) in patients with radiologically isolated syndrome (RIS) for evidence of disease activity (EDA) and clinical conversion (CC).MethodssNfL and cNfL were measured at RIS diagnosis by single-molecule array (Simoa). The risk of EDA and CC according to sNfL and cNfL was evaluated using the Kaplan-Meier analysis and multivariate Cox regression models including age, spinal cord (SC) or infratentorial lesions, oligoclonal bands, CSF chitinase 3-like protein 1, and CSF white blood cells.ResultsSixty-one patients with RIS were included. At diagnosis, sNfL and cNfL were correlated (Spearman r = 0.78, p < 0.001). During follow-up, 47 patients with RIS showed EDA and 36 patients showed CC (median time 12.6 months, 1-86). When compared with low levels, medium and high cNfL (>260 pg/mL) and sNfL (>5.0 pg/mL) levels were predictive of EDA (log rank, p < 0.01 and p = 0.02, respectively). Medium-high cNfL levels were predictive of CC (log rank, p < 0.01). In Cox regression models, cNfL and sNfL were independent factors of EDA, while SC lesions, cNfL, and sNfL were independent factors of CC.DiscussioncNfL >260 pg/mL and sNfL >5.0 pg/mL at diagnosis are independent predictive factors of EDA and CC in RIS. Although cNfL predicts disease activity better, sNfL is more accessible than cNfL and can be considered when a lumbar puncture is not performed.Classification of EvidenceThis study provides Class II evidence that in people with radiologic isolated syndrome (RIS), initial serum and CSF NfL levels are associated with subsequent evidence of disease activity or clinical conversion.

Original languageEnglish (US)
Article numbere200044
JournalNeurology: Neuroimmunology and NeuroInflammation
Issue number1
StatePublished - Jan 24 2023

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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