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. 2022 Oct 24;10(1):e200044.
doi: 10.1212/NXI.0000000000200044. Print 2023 Jan.

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

Manon Rival  1 , Eric Thouvenot  2 , Lucile Du Trieu de Terdonck  1 , Sabine Laurent-Chabalier  1 , Christophe Demattei  1 , Ugur Uygunoglu  1 , Giovanni Castelnovo  1 , Mikael Cohen  1 , Darin T Okuda  1 , Orhun H Kantarci  1 , Daniel Pelletier  1 , Christina Azevedo  1 , Philippe Marin  1 , Sylvain Lehmann  1 , Aksel Siva  1 , Thibault Mura  1 , Christine Lebrun-Frenay  1 ; SFSEP and RISC
Collaborators, Affiliations

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

Manon Rival et al. Neurol Neuroimmunol Neuroinflamm. .

Abstract

Background and objectives: To 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).

Methods: sNfL 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.

Results: Sixty-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.

Discussion: cNfL >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 evidence: This 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.

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Figures

Figure 1
Figure 1. Association of sNfL and cNfL Levels With Different Clinical, MRI, and CSF Parameters
(A) Correlation between sNfL and cNfL levels. (B) sNfL and the age of patients with RIS are not correlated. (C) sNfL levels are not significantly different in subgroups determined by sex, number of 2005 DIS criteria, spinal cord lesion, or OCB positive. (D) cNfL levels are not significantly different in subgroups determined by sex, 2005 DIS criteria, or spinal cord lesion. They are significantly elevated in RIS patients with OCB compared with those in others (*p = 0.02, Mann-Whitney test). cNfL = CSF neurofilament light chain; DIS = dissemination in space; NfL = neurofilament light chain; OCBs = oligoclonal bands; RIS = radiologically isolated syndrome; sNfL = serum neurofilament light chain.
Figure 2
Figure 2. Survival Curves for Evidence of Clinical Activity and Clinical Conversion According to Brain MRI and OCBs
Kaplan-Meier estimates of the probability of EDA and CC during follow-up are depicted as a function of the presence of IT lesions (A), SC lesions (B), the presence of OCBs (C), high levels of WBCs (D). CC = clinical conversion; EDA = evidence of disease activity; IT = infratentorial; OCBs = oligoclonal bands; SC = spinal cord; WBCs = white blood cells.
Figure 3
Figure 3. Survival Curves for Evidence of Clinical Activity and Clinical Conversion According to cNfL and sNfL
Kaplan-Meier estimates of the probability of EDA and CC during follow-up are depicted as a function of the presence of low (≤260 pg/mL), medium (260–710 pg/mL), or high (>710 pg/mL) cNfL levels (A, B) and low (≤5.0 pg/mL), medium (5.0–8.5 pg/mL), or high (>8.5 pg/mL) sNfL levels (C, D). CC = clinical conversion; cNfL = CSF neurofilament light chain; EDA = evidence of disease activity; sNfL = serum neurofilament light chain.
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