Correlational Analysis of ALS Progression and Serum NfL Measured by Simoa Assay in Chinese Patients.

Kazuo Sugimoto,Yuebo Song,Ying Gao,Yi Han

doi:10.3389/fneur.2020.579094

Abstract

Background: Neurofilament light chain (NFL) was believed to be a promising biomarker for the diagnosis of Amyotrophic lateral sclerosis (ALS) and disease burden evaluation.Objective: To determine the serum NFL level and its clinical relevance, including its association with disease severity [evaluated by the ALS Functional Rating Scale–revised (ALSFRS-r) score and King's College staging system] and progression (evaluated by the disease progression rate (DPR) and diagnostic delay), in ALS patients in China.Method: Serum NFL levels were detected using the Single Molecule Array (Simoa) technology in 30 ALS patients and 20 healthy controls (HCs).Results: There were significantly elevated levels of serum NFL in patients with ALS than in the HCs (P < 0.001). The serum NFL levels were significantly higher in rapidly progressive ALS and patients in Stage 3 than in slowly progressive ALS and patients in Stage 2 (PDPR < 0.001, PDiagnosticdelay = 0.019; Pstage= 0.033). Furthermore, the serum NFL levels negatively correlated with the diagnostic delay (R2 = 0.23, P = 0.016), the ALSFRS-r score (R2 = 0.15, P = 0.047) and disease duration (R2 = 0.15, P = 0.034), and positively correlated with the DPR (R2 = 0.42, P < 0.001).Conclusions: The present study preliminarily investigated the diagnostic value of serum NFL and its clinical relevance in the Chinese ALS population using the ultrasensitive Simoa technology. The results demonstrated that the level of serum NFL may become a potential biomarker for ALS diagnosis and indicate disease severity and progression.

Highlights

Amyotrophic lateral sclerosis (ALS) is a rare, disabling, and fatal neurodegenerative disease involving upper motor neurons that comprise the corticospinal tract and lower motor neurons that originate in the brain stem nuclei and ventral roots of the spinal cord [1,2,3]
The serum Neurofilament light chain (NFL) levels negatively correlated with the diagnostic delay (R2 = 0.23, P = 0.016), ALSFRS-r score (R2 = 0.15, P = 0.047), and disease duration (R2 = 0.15, P = 0.034), and positively correlated with the disease progression rate (DPR) (R2 = 0.42, P < 0.001), but did not correlate with the disease stage (P = 0.320)
The serum NFL levels negatively correlated with the diagnostic delay, the ALSFRS-r score, and disease duration, and positively correlated with the DPR

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a rare, disabling, and fatal neurodegenerative disease involving upper motor neurons that comprise the corticospinal tract and lower motor neurons that originate in the brain stem nuclei and ventral roots of the spinal cord [1,2,3]. After the diagnosis of ALS has been made, an efficient evaluation of the neurodegenerative burden, such as the disease severity and progression, are crucial for an appropriate medical plan that would be beneficial for improving the patient’s quality of life and prolonging their survival. The King’s College staging system evaluates the anatomical extension of the disease. These have both been widely used in clinical practice for disease severity appraisals, and the disease progression rate (DPR) and diagnostic delay have been used as disease progression indicators [8,9,10]. Neurofilament light chain (NFL) was believed to be a promising biomarker for the diagnosis of Amyotrophic lateral sclerosis (ALS) and disease burden evaluation

Methods

Results

Discussion

Conclusion