Serum neurofilament as a predictor of 10-year grey matter atrophy and clinical disability in multiple sclerosis: a longitudinal study
Lie, Ingrid Anne; Kacar, Sezgi; Wesnes, Kristin; Brouwer, Iman; Kvistad, Silje S.; Wergeland, Stig; Holmøy, Trygve; Midgard, Rune; Bru, Alla Nikolajevna S; Edland, Astrid; Eikeland, Randi; Gosal, Sonia; Harbo, Hanne-Cathrin Flinstad; Kleveland, Grethe; Sørenes, Yvonne; Øksendal, Nina; Varhaug, Kristin Nielsen; Vedeler, Christian Alexander; Barkhof, Frederik; Teunissen, Charlotte E.; Bø, Lars; Torkildsen, Øivind Fredvik Grytten; Myhr, Kjell-Morten; Vrenken, Hugo
Peer reviewed, Journal article
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Date
2022Metadata
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Original version
Journal of Neurology, Neurosurgery and Psychiatry. 2022, 93 (8), 1-9. 10.1136/jnnp-2021-328568Abstract
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.