Abstract
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.
Highlights
Amyotrophic lateral sclerosis (ALS), which selectively affects upper and lower motor neurons (MNs), is a fatal neurodegenerative disorder for which an efficacious therapy is urgently needed [1]
The serum neurofilament light chain (NfL) levels of patients with ALS were highly correlated with the extent of axonal degeneration of limb lower motor neurons (LMNs) as assessed by the decrease in compound muscle action potentials (CMAPs)
The study added direct and solid evidence to blood NfL concentrations that could mirror the extent of axonal damage of limb LMNs among ALS patients [12, 21]
Summary
Amyotrophic lateral sclerosis (ALS), which selectively affects upper and lower motor neurons (MNs), is a fatal neurodegenerative disorder for which an efficacious therapy is urgently needed [1]. NFL and LMN correlated a higher cerebrospinal fluid (CSF) NfL level with subtypes of MN disorders, revealing that patients with upper motor neuron-dominant (UMND) ALS presented with high CSF levels of NfL, despite the well-known superior prognosis associated with this subtype [6, 7]. This puzzling finding that UMND ALS patients have longer survival despite their higher CSF NfL levels indicates that in patients with UMND ALS, NfL levels are probably not a reliable and effective prognostic predictor. This further suggests the hypothesis that the measurement of NfL levels would be more likely to have prognostic value in patients with predominant LMNrelated symptoms
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