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.

Chitinase 3–like 1 and neurofilament light chain in CSF and CNS atrophy in MS

“…Our findings of associations between NfL levels and baseline reduction of BGM are corroborated by recent findings based on serum NfL. 26 Other studies reported relations between NfL in CSF or serum with longitudinal brain volume changes. 7 , 8 …”

Serum Neurofilament Light Chain Levels are Associated with Lower Thalamic Perfusion in Multiple Sclerosis

“…However, sNfL levels are generally considered to be biomarkers with a relatively short temporal window in which changes relate to the acute state of axonal damage [5]. Conversely to our hypoperfusion association, these acute MS changes, commonly seen as contrast-enhancing MS lesions, are accompanied by inflammation-induced hyperperfusion [7]. Regardless of the proposed directionality in the casual relationship between hypoperfusion and sNfL levels, we demonstrated that both changes in perfusion and neurodegeneration may describe overlapping MS pathophysiological mechanisms.…”

“…However, with the development of fourth-generation single-cell array assays, such as Simoa, it is possible to measure concentrations in serum (sNfL). As such, sNfL has been utilized in various MS studies and successfully verified as a reliable proxy of axonal neuroinflammatory and neurodegenerative pathology [7].…”

Association of Serum Neurofilament Light Levels With Long-term Brain Atrophy in Patients With a First Multiple Sclerosis Episode

“…10 In MS, elevated levels of serum neurofilament light have been shown to correlate with disease activity 11 and worse long-term clinical and paraclinical outcomes. 7,[11][12][13][14][15][16][17][18][19][20][21] Although these studies demonstrate utility for serum neurofilament light level as a potential biomarker associated with disease activity and shorter-term prognosis, information is scarce on the association of serum neurofilament light level at first MS presentation with long-term disease outcomes.…”