Abstract
Background: Neurofilaments in cerebrospinal fluid (CSF) and in blood are considered promising biomarkers of amyotrophic lateral sclerosis (ALS) because their levels can be significantly increased in patients with ALS. However, the roles of neurofilaments, especially blood neurofilaments, in the prognosis of ALS are inconsistent. We performed a meta-analysis to explore the prognostic roles of blood neurofilaments in ALS patients.Methods: We searched all relevant studies on the relationship between blood neurofilament levels and the prognosis of ALS patients in PubMed, Embase, Scopus, and Web of Science before February 2, 2021. The quality of the included articles was assessed using the Quality in Prognosis Studies (QUIPS) scale, and R (version 4.02) was used for statistical analysis.Results: Fourteen articles were selected, covering 1,619 ALS patients. The results showed that higher blood neurofilament light chain (NfL) levels in ALS patients were associated with a higher risk of death [medium vs. low NfL level: HR = 2.43, 95% CI (1.34–4.39), p < 0.01; high vs. low NfL level: HR = 4.51, 95% CI (2.45–8.32), p < 0.01]. There was a positive correlation between blood phosphorylated neurofilament heavy chain (pNfH) levels and risk of death in ALS patients [HR = 1.87, 95% CI (1.35–2.59), p < 0.01]. The levels of NfL and pNfH in blood positively correlated with disease progression rate (DPR) of ALS patients [NfL: summary r = 0.53, 95% CI (0.45–0.60), p < 0.01; pNfH: summary r = 0.51, 95% CI (0.24–0.71), p < 0.01].Conclusion: The blood neurofilament levels can predict the prognosis of ALS patients; specifically, higher levels of blood neurofilaments are associated with a greater risk of death.
Highlights
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that selectively causes the degeneration of upper and lower motor neurons, resulting in progressive muscle wasting and weakness [1]
In the process of data extraction, we found that only four articles exploring the relationship between serum neurofilament light chain (NfL) and survival were qualified
The results showed that ALS patients had higher blood neurofilament heavy chain (NfH) levels and a higher risk of death compared with the control group [HR = 1.87, 95% CI (1.35–2.59), p < 0.01]
Summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that selectively causes the degeneration of upper and lower motor neurons, resulting in progressive muscle wasting and weakness [1]. Neurofilaments are potential biomarkers in ALS; they are considered promising and useful biomarkers for the diagnosis of ALS [7]. Their prognostic roles in ALS are still not clear. It has been shown that patients with ALS have elevated neurofilament levels compared to control groups, both in cerebrospinal fluid (CSF) and in blood [11,12,13,14]. Neurofilaments in cerebrospinal fluid (CSF) and in blood are considered promising biomarkers of amyotrophic lateral sclerosis (ALS) because their levels can be significantly increased in patients with ALS. We performed a meta-analysis to explore the prognostic roles of blood neurofilaments in ALS patients
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