Diagnostic Performance of Neurofilaments in Chinese Patients With Amyotrophic Lateral Sclerosis: A Prospective Study.

Da-Wei Li,Mingsheng Liu,Haitao Ren,Xiaoguang Li,Dongshao Shen,Andreas Jeromin,Qingyun Ding,Liying Cui,Hongfei Tai

doi:10.3389/fneur.2018.00726

Abstract

Several studies have attempted to reduce diagnostic delay and identify biomarkers for drug development in amyotrophic lateral sclerosis (ALS). In this study, we aimed to evaluate the diagnostic accuracy for ALS of cerebrospinal fluid (CSF) neurofilament (Nf), Tau protein, and inflammatory factors such as interleukin (IL)-2, IL-6, IL-10, IL-15, and granulocyte-macrophage colony-stimulating factor (GMCSF) in Chinese patients. Our prospective study measured the concentration of phosphorylated Nf heavy chain (pNfH), Nf light chain (NfL), Tau, pTau, and inflammatory factors in the CSF of 85 patients. Detailed clinical data and laboratory, neuroimaging, and neurophysiological findings were recorded. The concentrations of pNfH and NfL were higher in the ALS group than in the control group. At the 1104 pg/mL pNfH cutoff, the specificity was 68.8%, the sensitivity 100%, and the area under the curve (AUC) 0.907. At the 1,139 pg/mL NfL cutoff, the specificity was 56.3%, the sensitivity 96.2%, and the AUC 0.775. There was no significant difference in the concentrations of Tau, pTau, IL-2, IL-6, IL-10, IL-15, and GMCSF between the ALS and control groups (p > 0.05). In the ALS group, the concentration of pNfH in the CSF was correlated with disease duration (r = −0.475, p < 0.001). This is the first prospective study to confirm the diagnostic value of Nf for ALS in Chinese patients.

Highlights

Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease characterized by degeneration of upper and lower motor neurons [1].Diagnosis of ALS can be challenging at the early disease stage; the time from symptom presentation to diagnosis is approximately 12 months in most patients, by which time the patient may be beyond the window of therapeutic opportunity [2, 3]
The objectives of this study were to evaluate the diagnostic performance of phosphorylated neurofilament heavy chain (pNfH), neurofilament light chain (NfL), phosphorylated tau (pTau), Tau IL-2, IL-6, IL-10, IL-15, and granulocyte-macrophage colony-stimulating factor (GMCSF) in Chinese patients with ALS, at the early diagnostic stage, when the neurologist is in doubt of the diagnosis of ALS
We did not observe any significant differences in the concentrations of cerebrospinal fluid (CSF) Tau, pTau, IL-2, IL-6, IL-10, IL-15, and GMCSF between the ALS and control groups

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease characterized by degeneration of upper and lower motor neurons [1].Diagnosis of ALS can be challenging at the early disease stage; the time from symptom presentation to diagnosis is approximately 12 months in most patients, by which time the patient may be beyond the window of therapeutic opportunity [2, 3]. Validated biomarkers to detect ALS at the early disease stage are urgently needed to shorten diagnostic delay and facilitate differential diagnosis [3, 4]. Several studies and meta-analyses have provided evidence of significantly increased concentrations of pNfH and NfL in the cerebrospinal fluid (CSF) of patients with ALS compared with those in the CSF of healthy and disease controls [5,6,7,8,9,10,11,12,13,14]. The diagnostic utility of pNfH and NfL should be evaluated in the Chinese population because there is some heterogeneity in the age of disease onset, genetic basis, and median survival time of ALS between Chinese and Western patients [14, 15]

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