Serum neurofilament light chain levels associations with gray matter pathology: a 5-year longitudinal study

Abstract

Background: Gray 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.

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).

Materials and methods: Forty-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.

Results: In 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.

Conclusion: Higher sNfL levels were associated with baseline LVs and greater development of GM atrophy in PwMS.

Figure 1

Box plot representation of baseline (A) and follow‐up (B) sNfL levels between the study populations. PwMS, persons with multiple sclerosis; HCs, healthy controls; RRMS, relapsing–remitting multiple sclerosis; PMS, progressive multiple sclerosis; sNfL, serum neurofilament light chain. Median and interquartile range are shown.

Figure 2

Scatter plot representation of the PwMS associations between baseline sNfL and MRI–derived DGM volume at baseline and the 5‐year longitudinal change. PwMS, persons with multiple sclerosis; DGM, deep gray matter; sNfL, serum neurofilament light chain levels. Due to the data distribution of the baseline sNfL, the value was logarithmically transformed and plotted as such on the x‐axis.

Figure 3

Visual representation of the differences in 5‐year atrophy rate between PwMS with sNfL <30 and ≥30 pg/mL. PwMS, persons with multiple sclerosis; sNfL, serum neurofilament light chain; WBV, whole brain volume; GMV, gray matter volume; CV, cortical volume; DGM, deep gray matter.