Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis

Author:

Brune Synne1,Høgestøl Einar A2ORCID,de Rodez Benavent Sigrid A3,Berg-Hansen Pål4,Beyer Mona K5,Leikfoss Ingvild Sørum6,Bos Steffan D7,Sowa Piotr8,Brunborg Cathrine9,Andorra Magi10ORCID,Pulido Valdeolivas Irene10ORCID,Asseyer Susanna11ORCID,Brandt Alexander12ORCID,Chien Claudia12ORCID,Scheel Michael13,Blennow Kaj14,Zetterberg Henrik15,Kerlero de Rosbo Nicole16,Paul Friedemann12,Uccelli Antonio17ORCID,Villoslada Pablo10ORCID,Berge Tone18,Harbo Hanne F7

Affiliation:

1. Institute of clinical Medicine, University of Oslo, Oslo, Norway/Department of Neurology, Oslo University Hospital, University of Oslo, Oslo, Norway

2. Institute of Clinical Medicine, University of Oslo, Oslo, Norway/Department of Neurology, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway

3. Department of Ophthalmology, Oslo University Hospital, Oslo, Norway

4. Department of Neurology, Oslo University Hospital, Oslo, Norway

5. Institute of Clinical Medicine, University of Oslo, Oslo, Norway/Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway

6. Department of Neurology, Oslo University Hospital, Oslo, Norway/Department of Research, Innovation and Education, Oslo University Hospital, Oslo, Norway

7. Institute of Clinical Medicine, University of Oslo, Oslo, Norway/Department of Neurology, Oslo University Hospital, Oslo, Norway

8. Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway

9. Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway

10. Institut d’Investigacions Biomediques August Pi Sunyer, Barcelona, Spain

11. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitaetsmedizin Berlin, Berlin, Germany

12. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitaetsmedizin Berlin, Berlin, Germany/NeuroCure Clinical Research Center, Charité-Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

13. NeuroCure Clinical Research Center, Charité-Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany/Department of Neuroradiology, Charité-Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

14. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden

15. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden/Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden/Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK/UK Dementia Research Institute at UCL, London, UK/Hong Kong Center for Neurodegenerative Diseases, Shatin, Hong Kong, China

16. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy

17. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy/Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy/IRCCS Ospedale Policlinico San Martino, Genoa, Italy

18. Department of Research, Innovation and Education, Oslo University Hospital, Oslo, Norway/Department of Mechanical, Electronic and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway

Abstract

Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. Methods: MS patients ( n = 309) were prospectively enrolled at four centres and re-examined after 2 years ( n = 226). NfL concentration was measured by single molecule array assay in serum. The patients’ phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. Results: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5–5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

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