Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 Apr:102:105072.
doi: 10.1016/j.ebiom.2024.105072. Epub 2024 Mar 22.

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome

Sander J van Tilburg  1 , Charlotte E Teunissen  2 , Carolien C H M Maas  3 , Robin C M Thomma  4 , Christa Walgaard  5 , Hans Heijst  2 , Ruth Huizinga  1 , Pieter A van Doorn  5 , Bart C Jacobs  6
Affiliations
Randomized Controlled Trial

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome

Sander J van Tilburg et al. EBioMedicine. 2024 Apr.

Abstract

Background: Neurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes in serum NfL in patients with Guillain-Barré syndrome (GBS) in relation to disease severity, electrophysiological subtype, treatment response, and prognosis.

Methods: We included patients with GBS who participated in a double-blind, randomised, placebo-controlled trial that evaluated the effects of a second course of intravenous immunoglobulin (IVIg) on clinical outcomes. Serum NfL levels were measured before initiation of treatment and at one, two, four, and twelve weeks using a Simoa HD-X Analyzer. Serum NfL dynamics were analysed using linear mixed-effects models. Logistic regression was employed to determine the associations of serum NfL with clinical outcome and the prognostic value of serum NfL after correcting for known prognostic markers included in the modified Erasmus GBS Outcome Score (mEGOS).

Findings: NfL levels were tested in serum from 281 patients. Serum NfL dynamics were associated with disease severity and electrophysiological subtype. Strong associations were found between high levels of serum NfL at two weeks and inability to walk unaided at four weeks (OR = 1.74, 95% CI = 1.27-2.45), and high serum NfL levels at four weeks and inability to walk unaided at 26 weeks (OR = 2.79, 95% CI = 1.72-4.90). Baseline serum NfL had the most significant prognostic value for ability to walk, independent of predictors included in the mEGOS. The time to regain ability to walk unaided was significantly longer for patients with highest serum NfL levels at baseline (p = 0.0048) and week 2 (p < 0.0001). No differences in serum NfL were observed between patients that received a second IVIg course vs. IVIg and placebo.

Interpretation: Serum NfL levels are associated with disease severity, axonal involvement, and poor outcome in GBS. Serum NfL potentially represents a biomarker to monitor neuronal damage in GBS and an intermediate endpoint to evaluate the effects of treatment.

Funding: Prinses Beatrix Spierfonds W.OR19-24.

Keywords: Biomarker; Guillain-Barré syndrome; Longitudinal; Neurofilament light chain; Prognosis.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests Research of CT is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), Innovative Medicines Initiatives 3TR (Horizon 2020, grant no 831434) EPND (IMI 2 Joint Undertaking (JU), grant No. 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance), Alzheimer Drug Discovery Foundation, Alzheimer Association, Health Holland, the Dutch Research Council (ZonMW), The Selfridges Group Foundation, Alzheimer Netherlands. CT is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW2 (#73305095007) and Health ∼ Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). CT is recipient of TAP-dementia, a ZonMw funded project (#10510032120003) in the context of the Dutch National Dementia Strategy. CT performed contract research for ADx Neurosciences, AC-Immune, Aribio, Axon Neurosciences, Beckman–Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly Fujirebio, Grifols, Instant Nano Biosensors, Merck, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Siemens, Toyama, and Vivoryon. CT received payment or honoraria for lectures, presentations or educational events from Roche, Novo Nordisk and Grifols. All payments were made to her institution. CT serves on editorial boards of Medidact Neurologie/Springer; and in Neurology: Neuroimmunology & Neuroinflammation. She is editor of Alzheimer Research and Therapy. RH reports institutional funding from the GBS-CIDP Foundation International, Stichting GBS, T2B collaboration project funded by PPP Allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) under project number LSHM18055-SGF to stimulate public-private partnerships and co-financing by health foundations that are part of the SGF, NIH, and PANDIA collaboration project co-funded by BÜHLMANN Laboratories AG and the PPP Allowance made available by Health ∼ Holland, Top Sector Life Sciences & Health, to Prinses Beatrix Spierfonds to stimulate public-private partnerships under project number LSHM23017-SGF. She serves as editorial board member of the Journal of the Peripheral Nervous System and was board member of the Inflammatory Neuropathy Consortium. PD reports grants from the Prinses Beatrix Spierfonds and Sanquin to conduct the SID-GBS trial. PD reports consulting fees from Annexon and Roche, all paid to the institution. PD participates on a Data Safety Monitoring Board or Advisory Board for Argenx, Hansa, Octapharma and Sanofi. All fees go to the institution. He reports an unpaid leadership role in the Peripheral Nerve Society (PNS) and serves on the Medical advisory board for the GBS/CIDP Foundation International. BJ reports institutional funding from the GBS-CIDP Foundation International, Stichting GBS, Horizon 2020 (EU), Grifols, CSL-Behring, Annexon, Hoffmann-la Roche, Hansa Biopharma, BÜHLMANN Laboratories. BJ received institutional royalties, licences or consulting fees from Hansa Biopharma, Annexon and Hoffmann-la Roche. BJ received support from the GBS-CIDP Foundation International to cover travel expenses for their conference. BJ serves an unpaid role in the global Medical advisory board for the GBS-CIDP Foundation International, in the scientific review committee of Stichting MS research, and the scientific review committee of the Erasmus MC. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Serum NfL levels during the course of disease in patients with GBS. a) Evolution of serum NfL in patients with GBS. A jitter of ±0.5 days was allowed. Two samples taken after 100 days were omitted. The red line represents the locally weighted scatterplot smoothing (LOESS) curve. b) Similar to a), but colours represent the NCS subtype. Samples taken after 40 days were omitted. Data for ‘not assessed’ and ‘normal’ NCS variants are not shown in this figure. Grey lines connect samples from the same patient. Abbreviations: NCS, Nerve conduction studies; NfL, Neurofilament light chain.
Fig. 2
Fig. 2
Mixed-effects models for the evolution of serum NfL in patients with GBS. a) Estimated effect of NCS subtype on the dynamics of NfL. Age, MRC-SS, and GBS-DS were set on the median. b) Estimated effect of disease severity on the dynamics of NfL. Age was set on the median; NCS subtype, on ‘demyelinating’. Continuous lines represent the estimated NfL levels; the dashed lines represent the 95% confidence interval of the estimate. Abbreviations: NCS, Nerve conduction studies; NfL, Neurofilament light chain; MRC-SS, Medical Research Council sum score; GBS-DS, Guillain-Barré syndrome disability score.
Fig. 3
Fig. 3
Time-to-event analysis for the ability to walk unaided in patients with GBS. Patients were stratified into quartiles based on their serum NfL levels at two visits: study entry (a), and week 2 (b). The p-values were obtained using the log-rank test. Abbreviation: NfL, Neurofilament light chain.
Fig. 4
Fig. 4
Estimated effect of treatment on serum NfL levels. Treatment group, placebo or a second IVIg course (SID), was included in the mixed-effects models (Model 2, Supplementary Material). Effect plots were stratified for NCS. Continuous lines represent the estimated NfL levels; the dashed lines represent the 95% confidence interval of the estimate. Abbreviations: NfL, Neurofilament light chain; NCS, Nerve conduction studies; SID, Second IVIg dose.
See this image and copyright information in PMC

References

    1. Leonhard S.E., Mandarakas M.R., Gondim F.A.A., et al. Diagnosis and management of Guillain–Barré syndrome in ten steps. Nat Rev Neurol. 2019;15(11):671–683. - PMC - PubMed
    1. Willison H.J., Jacobs B.C., van Doorn P.A. Guillain-Barré syndrome. Lancet. 2016;388(10045):717–727. - PubMed
    1. Hughes R.A.C., Swan A.V., van Doorn P.A. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2014;2014(9) - PMC - PubMed
    1. Doets A.Y., Lingsma H.F., Walgaard C., et al. Predicting outcome in Guillain-Barré syndrome. Neurology. 2022;98(5):e518. - PMC - PubMed
    1. Walgaard C., Lingsma H.F., Ruts L., van Doorn P.A., Steyerberg E.W., Jacobs B.C. Early recognition of poor prognosis in Guillain-Barre syndrome. Neurology. 2011;76(11):968–975. - PMC - PubMed

Publication types