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

Dejan Jakimovski,Bianca Weinstock-Guttman,Robert Zivadinov,Michael G Dwyer,Niels Bergsland,Deepa P Ramasamy,Murali Ramanathan

doi:10.3390/diagnostics10090685

Abstract

Both perfusion-weighted imaging (PWI) measures and serum neurofilament light (sNfL) chain levels have been independently associated with disability in multiple sclerosis (MS) patients. This study aimed to determine whether these measures are correlated to each other or independently describe different MS processes. For this purpose, 3T MRI dynamic susceptibility contrast (DSC)–PWI and single-molecule assay (Simoa)-based sNfL methods were utilized when investigating 86 MS patients. The perfusion measures of mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were derived for the normal-appearing whole brain (NAWB), the normal-appearing white matter (NAWM), the gray matter (GM), the deep GM (DGM), and the thalamus. The normalized CBV and CBF (nCBV and nCBV) were calculated by dividing by the corresponding NAWM measure. Age- and sex-adjusted linear regression models were used to determine associations between the DSC–PWI and sNfL results. False discovery rate (FDR)-adjusted p-values < 0.05 were considered statistically significant. A greater age and thalamic MTT were independently associated with higher sNfL levels (p < 0.001 and p = 0.011) and explained 36.9% of sNfL level variance. NAWM MTT association with sNfL levels did not survive the FDR correction. In similar models, a lower thalamic nCBF and nCBV were both associated with greater sNfL levels (p < 0.001 and p = 0.022), explaining 37.8% and 44.7% of the variance, respectively. In conclusion, higher sNfL levels were associated with lower thalamic perfusion.

Highlights

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that presents as variable levels of demyelination, neurodegeneration, and axonal loss [1]
Five patients were classified as having clinically isolated syndrome (CIS), 51 as having relapsing-remitting MS (RRMS), and 30 as having progressive MS (PMS) (25 secondary-progressive MS (SPMS) and 5 primary-progressive MS (PPMS))
In addition to the age and sex effects, this cross-sectional biomarker study demonstrated that lower thalamic perfusion explained the significantly greater serum neurofilament light (sNfL) level variance

Summary

Introduction

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that presents as variable levels of demyelination, neurodegeneration, and axonal loss [1]. To provide timely disease treatment, multiple methods for early detection have been proposed. They range from traditional magnetic resonance imaging (MRI) measures to emerging serum-derived disease markers and non-conventional MRI sequences. Given that each disease biomarker may describe different pathophysiological processes, it is important to determine their divergent or concurrent utility [3,4]. The measurement of neurofilament light chain (NfL) levels is emerging as a promising biomarker for the monitoring and management of neurodegenerative diseases, such as Alzheimer’s disease, MS, and Parkinson’s disease. Because of the analytical limitations of previous generation assays, NfL levels were originally measurable only in samples with high concentrations, e.g., cerebrospinal fluid (CSF) [6]. SNfL has been utilized in various MS studies and successfully verified as a reliable proxy of axonal neuroinflammatory and neurodegenerative pathology [7]

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