Abstract

BackgroundGray matter (GM) pathology is closely associated with physical and cognitive impairment in persons with multiple sclerosis (PwMS). Similarly, serum neurofilament light chain (sNfL) levels are related to MS disease activity and progression.ObjectivesTo assess the cross–sectional and longitudinal associations between sNfL and MRI–derived lesion and brain volume outcomes in PwMS and age–matched healthy controls (HCs).Materials and MethodsForty‐seven HCs and 120 PwMS were followed over 5 years. All subjects underwent baseline and follow–up 3T MRI and sNfL examinations. Lesion volumes (LV) and global, tissue–specific and regional brain volumes were assessed. sNfL levels were analyzed using single molecule array (Simoa) assay and quantified in pg/mL. The associations between sNfL levels and MRI outcomes were investigated using regression analyses adjusted for age, sex, baseline disease modifying treatment (DMT) use and change in DMT over the follow‐up. False discovery rate (FDR)–adjusted q‐values <0.05 were considered significant.ResultsIn PwMS, baseline sNfL was associated with baseline T1‐, T2‐ and gadolinium‐LV (q = 0.002, q = 0.001 and q < 0.001, respectively), but not with their longitudinal changes. Higher baseline sNfL levels were associated with lower baseline deep GM (β = −0.257, q = 0.017), thalamus (β = −0.216, q = 0.0017), caudate (β = −0.263, q = 0.014) and hippocampus (β = −0.267, q = 0.015) volumes. Baseline sNfL was associated with longitudinal decline of deep GM (β = −0.386, q < 0.001), putamen (β = −0.395, q < 0.001), whole brain (β = −0.356, q = 0.002), thalamus (β = −0.272, q = 0.049), globus pallidus (β = −0.284, q = 0.017), and GM (β = −0.264, q = 0.042) volumes. No associations between sNfL and MRI–derived measures were seen in the HCs.ConclusionHigher sNfL levels were associated with baseline LVs and greater development of GM atrophy in PwMS.

Highlights

  • Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system which presents with reoccurring and transient neurological deficits followed frequently by insidious accumulation of physical and cognitive disability.[1]

  • Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association

  • Within the MS phenotype, the progressive MS (PMS) group was older and had longer disease duration when compared to the RRMS population (56.5 vs. 44.6 years, t-test P < 0.001 and 22.6 vs. 13.4 years, t-test P < 0.001)

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Summary

Introduction

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system which presents with reoccurring and transient neurological deficits followed frequently by insidious accumulation of physical and cognitive disability.[1]. Objectives: To assess the cross–sectional and longitudinal associations between sNfL and MRI–derived lesion and brain volume outcomes in PwMS and age–matched healthy controls (HCs). The associations between sNfL levels and MRI outcomes were investigated using regression analyses adjusted for age, sex, baseline disease modifying treatment (DMT) use and change in DMT over the follow-up. Baseline sNfL was associated with longitudinal decline of deep GM (b = À0.386, q < 0.001), putamen (b = À0.395, q < 0.001), whole brain (b = À0.356, q = 0.002), thalamus (b = À0.272, q = 0.049), globus pallidus (b = À0.284, q = 0.017), and GM (b = À0.264, q = 0.042) volumes. No associations between sNfL and MRI– derived measures were seen in the HCs. Conclusion: Higher sNfL levels were associated with baseline LVs and greater development of GM atrophy in PwMS

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