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Objectives The aims of this study were to investigate whether serum neurofilament light chain (NfL) levels were correlated with the severity of the axonal degeneration of lower motor neurons (LMNs) in the early symptomatic phase of amyotrophic lateral sclerosis (ALS). Methods In this prospective study, the serum samples used for NfL measurement were obtained from 103 sporadic ALS outpatients within 2 years of disease duration. The severity of axonal degeneration was assessed by assessing the decrease in the compound muscle action potentials (CMAPs) within a 1-month interval from serum sampling. Results The NfL levels showed a significant positive correlation with the relative score as a proxy for the axonal damage of LMNs in patients with ALS (coefficient: 0.264,  p  = 0.009). Furthermore, this correlation became stronger (coefficient: 0.582,  p  = 0.037) when estimated only among patients with disease subtypes that involve only LMNs, that is, patients with flail arm or leg syndrome (FAS or FLS). The levels of NfL increased with the severity of axonal damage of LMNs (F = 6.694,  P  = 0.0001). Conclusions Serum NfL levels mirrored the severity of the axonal degeneration of LMNs, particularly in patients with signs of predominant LMN involvement. These results may have a profound effect on the selection of patients and the monitoring of treatment efficacy in future disease-modifying clinical trials.

Serum Neurofilament Light Chain Levels May Be a Marker of Lower Motor Neuron Damage in Amyotrophic Lateral Sclerosis