To investigate the association between serum levels of neurofilament light chain (sNfL) and atrophied T2 lesion volume (LV) and other MRI measures indicative of inflammation and neurodegeneration, and disability progression (DP) in multiple sclerosis (MS).

Recently, high sNfL and atrophied T2-LV have been proposed as novel markers associated with progression of clinical disability in MS. Atrophied T2-LV reflects disappearance of T2 lesions into cerebrospinal fluid spaces.

127 MS (85 relapsing remitting-RRMS, 42 progressive MS-PMS) and 20 clinically isolated syndromes patients were enrolled. Of those, 37 developed DP over the follow-up. There was a significant association at baseline between sNfL and T2-LV (β=0.294, p=0.001), and T1-LV (β=0.22, p=0.018) in MS patients. Baseline sNfL predicted atrophied T2-LV (β=0.357, p<0.001), the percentage brain volume change (PBVC, β=-0.335, p<0.001), and absolute change in T1-LV (β=0.274, p=0.005). Furthermore, over 5 years, MS patients with baseline sNfL ≥30 pg/ml showed significantly higher atrophied T2-LV (p<0.001) and PBVC (p<0.001) than patients with sNfL <30 pg/ml. Atrophied T2-LV was the only measure associated with DP over the follow-up (p=0.006).

sNfL was significantly associated with MRI measures indicative of both inflammation and neurodegeneration in MS patients. Atrophied T2-LV is a promising new MRI biomarker of disease progression that showed the strongest association with sNfL and DP, compared to conventional lesion burden and global brain atrophy measures.