Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study

Ingrid Anne Lie; Sezgi Kaçar; Kristin Wesnes; Iman Brouwer; Silje S Kvistad; Stig Wergeland; Trygve Holmøy; Rune Midgard; Alla Bru; Astrid Edland; Randi Eikeland; Sonia Gosal; Hanne F Harbo; Grethe Kleveland; Yvonne S Sørenes; Nina Øksendal; Kristin N Varhaug; Christian A Vedeler; Frederik Barkhof; Charlotte E Teunissen; Lars Bø; Øivind Torkildsen; Kjell-Morten Myhr; Hugo Vrenken

doi:10.1136/jnnp-2021-328568

Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study

J Neurol Neurosurg Psychiatry. 2022 Jun 1;93(8):849-857. doi: 10.1136/jnnp-2021-328568. Online ahead of print.

Authors

Ingrid Anne Lie^{1

2}, Sezgi Kaçar³, Kristin Wesnes^{2

4}, Iman Brouwer³, Silje S Kvistad^{2

5}, Stig Wergeland^{2

6}, Trygve Holmøy^{7

8}, Rune Midgard⁹, Alla Bru¹⁰, Astrid Edland¹¹, Randi Eikeland^{12

13}, Sonia Gosal¹⁴, Hanne F Harbo^{7

15}, Grethe Kleveland¹⁶, Yvonne S Sørenes¹⁷, Nina Øksendal¹⁸, Kristin N Varhaug^{19

2}, Christian A Vedeler^{19

2}, Frederik Barkhof^{3

20}, Charlotte E Teunissen²¹, Lars Bø^{19

22}, Øivind Torkildsen^{19

2}, Kjell-Morten Myhr^{19

2}, Hugo Vrenken³

Affiliations

¹ Department of Clinical Medicine, University of Bergen, Bergen, Norway ingrid.lie@uib.no.
² Neuro-SysMed, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
³ Department of Radiology and Nuclear Medicine, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
⁴ Department of Neurology, St. Olav's University Hospital, Trondheim, Norway.
⁵ Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.
⁶ Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁸ Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
⁹ Department of Neurology, Molde Hospital, Molde, Norway.
¹⁰ Department of Neurology, Stavanger University Hospital, Stavanger, Norway.
¹¹ Department of Neurology, Vestre Viken Hospital Trust, Drammen, Norway.
¹² Department of Research and Education, Sørlandet Hospital Trust, Kristiansand, Norway.
¹³ Faculty of Health and Sport Science, University of Agder, Grimstad, Norway.
¹⁴ Department of Neurology, Østfold Hospital Kalnes, Grålum, Norway.
¹⁵ Department of Neurology, Oslo University Hospital, Oslo, Norway.
¹⁶ Department of Neurology, Innlandet Hospital Trust, Lillehammer, Norway.
¹⁷ Department of Neurology, Haugesund Hospital, Haugesund, Norway.
¹⁸ Department of Neurology, Nordland Hospital Trust, Bodø, Norway.
¹⁹ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
²⁰ Institutes of Neurology and Healthcare Engineering, UCL, London, UK.
²¹ Neurochemistry Laboratory, Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centres, Amsterdam, The Netherlands.
²² Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway.

Abstract

Background: The predictive value of serum neurofilament light chain (sNfL) on long-term prognosis in multiple sclerosis (MS) is still unclear.

Objective: Investigate the relation between sNfL levels over a 2-year period in patients with relapsing-remitting MS, and clinical disability and grey matter (GM) atrophy after 10 years.

Methods: 85 patients, originally enrolled in a multicentre, randomised trial of ω-3 fatty acids, participated in a 10-year follow-up visit. sNfL levels were measured by Simoa quarterly until month 12, and then at month 24. The appearance of new gadolinium-enhancing (Gd+) lesions was assessed monthly between baseline and month 9, and then at months 12 and 24. At the 10-year follow-up visit, brain atrophy measures were obtained using FreeSurfer.

Results: Higher mean sNfL levels during early periods of active inflammation (Gd+ lesions present or recently present) predicted lower total (β=-0.399, p=0.040) and deep (β=-0.556, p=0.010) GM volume, lower mean cortical thickness (β=-0.581, p=0.010) and higher T2 lesion count (β=0.498, p=0.018). Of the clinical outcomes, higher inflammatory sNfL levels were associated with higher disability measured by the dominant hand Nine-Hole Peg Test (β=0.593, p=0.004). Mean sNfL levels during periods of remission (no Gd+ lesions present or recently present) did not predict GM atrophy or disability progression.

Conclusion: Higher sNfL levels during periods of active inflammation predicted more GM atrophy and specific aspects of clinical disability 10 years later. The findings suggest that subsequent long-term GM atrophy is mainly due to neuroaxonal degradation within new lesions.

Keywords: BIOCHEMISTRY; CLINICAL NEUROLOGY; MRI; MULTIPLE SCLEROSIS.