For a study, the researchers examined the relationship between sNfL levels throughout a 2-year period and clinical disability and gray matter (GM) atrophy after 10 years in early relapsing-remitting MS (RRMS) patients. A total of 85 patients (92%) from the multicenter trial of omega-3 fatty acids in MS (the OFAMS-study) participated in a 10-year follow-up visit (mean age 49.7 years, 55 females). sNfL levels were monitored quarterly until month 12 and then at month 24 in the OFAMS investigation, using an ultrasensitive immunoassay (Simoa). Between baseline and month 9, the emergence of new gadolinium (Gd)-enhancing brain lesions was monitored monthly and then again at months 12 and 24. During the 10-year follow-up visit, all tests were performed, and brain atrophy measurements were collected using FreeSurfer. The linear mixed model and linear regression analysis were used to look into the relationships. Higher mean overall sNfL levels in the first 2 years were linked to higher disability scores on the dominant hand 9-hole peg test (β=0.359, p=0.010) and a more significant increase in that score over time (β=0.301, p=0.038) 10 years later. After accounting for MRI activity, mean sNFL did not predict long-term GM atrophy. Greater mean sNfL levels during initial stages of energetic inflammation (Gd-enhancing lesions present or recently present) predicted lower total (β=-0.399, p=0.024) and depth (β=-0.556, p=0.003) GM volume, left thalamus volume (β=-0.411, p=0.046), mean cortical thickness in the left (β=-0.579, p=0.002) and right (β=-0.572, p=0.003) hemispheres and T2 lesion count (β=0.485, p=0.009), as well as an elevated score on the dominant hand 9-hole peg test (β=0.631, p=0.003) 10 years later, and more considerable elevation in that score over time (β=0.402, p=0.042). Higher mean sNfL levels during remission (no Gd-enhancing lesions present or recently present) were linked to a higher symbol digit modality test (SDMT) score (more excellent attention score) (β=0.473, p=0.003). Still, they did not foresee GM atrophy or disability progression. GM atrophy and particular characteristics of clinical impairment were predicted by higher sNfL levels during periods of active inflammation 10 years later. The data show that neuroaxonal deterioration within new lesions was the primary cause of long-term GM atrophy.