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Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study - PubMed

  • ️Mon Jan 01 2018

Review

. 2018 Sep 3:14:2241-2254.

doi: 10.2147/NDT.S173280. eCollection 2018.

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Review

Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study

Laisheng Cai et al. Neuropsychiatr Dis Treat. 2018.

Abstract

Purpose: There is a need for biomarkers in multiple sclerosis (MS) to make an early diagnosis and monitor its progression. This study was designed to evaluate the value of neurofilament light (NFL) chain levels as cerebrospinal fluid (CSF) or blood biomarker in patients with MS by using a quantitative meta-analysis.

Methods: The PubMed, Embase, and Web of Science databases were systematically searched for relevant studies. Articles in English that evaluated the utility of NFL in CSF and blood in the diagnosis of MS were included. Data were extracted by two independent researchers. Mean (± SD) NFL concentration for MS patients and control subjects were extracted. Review Manager version 5.3 software with a continuous-variable random-effects model was used to summarize the diagnostic indexes from eligible studies. The Newcastle-Ottawa Scale was used for assessing the quality and risk of bias of included studies. In addition, subgroup analysis and meta-regression were performed to assess potential heterogeneity sources.

Results: The meta-analysis included 13 articles containing results from 15 studies. A total of 10 studies measured NFL levels in CSF and five studies measured NFL levels in blood. Data were available on 795 participants in CSF and 1,856 participants in blood. Moreover, CSF NFL in MS patients was higher than that in healthy control groups (pooled standard mean difference [Std.MD]=0.88, 95% CI [0.50, 1.26], P<0.00001) and serum NFL in MS patients was higher than that in control subjects (pooled Std.MD=0.47, 95% CI [0.24, 0.71], P<0.0001).

Conclusion: NFL chain has significantly increased in MS patients, which substantially strengthens the clinical evidence of the NFL in MS. The NFL may be used as a prognostic biomarker to monitor disease progression, disease activity, and treatment efficacy in the future.

Keywords: meta-analysis; multiple sclerosis; neurofilament light chain.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1

Flowchart depicting literature search and study selection. Notes: Flow diagram of systematic search in the three databases. After removal of duplicates, reviews, and quality control, 13 articles were suitable for analysis. Abbreviations: NFH, neurofilament heavy; NFL, neurofilament light.

Figure 2
Figure 2

Meta-analysis of neurofilament light chain levels in CSF between MS patients and healthy controls. Notes: The random-effect model was used. Unit of CSF neurofilament light chain level was ng/L. There was a highly significant difference between the two groups (P<0.00001). Abbreviations: CSF, cerebrospinal fluid; IV, inverse variance; MS, multiple sclerosis.

Figure 3
Figure 3

Meta-analysis of neurofilament light chain levels in blood between MS patients and healthy controls. Notes: The random-effect model was applied. Unit of blood neurofilament light chain level was ng/L. There was a highly significant difference between the two groups (P<0.0001). Abbreviations: IV, inverse variance; MS, multiple sclerosis.

Figure 4
Figure 4

Subgroup analysis stratified by age for MS in CSF. Notes: The random-effect model was used. Unit of CSF neurofilament light chain level was ng/L. Abbreviations: CSF, cerebrospinal fluid; IV, inverse variance; MS, multiple sclerosis.

Figure 5
Figure 5

Subgroup analysis stratified by neurofilament light chain concentration for MS in CSF. Notes: The random-effect model was used. Unit of CSF neurofilament light chain level was ng/L. Abbreviations: CSF, cerebrospinal fluid; IV, inverse variance; MS, multiple sclerosis.

Figure 6
Figure 6

Subgroup analysis stratified by publication year for MS in CSF. Notes: The random-effect model was used. Unit of CSF neurofilament light chain level was ng/L. Abbreviations: CSF, cerebrospinal fluid; IV, inverse variance; MS, multiple sclerosis.

Figure 7
Figure 7

Subgroup analysis stratified by sample size for MS in blood. Notes: The random-effect model was used. Unit of blood neurofilament light chain level was ng/L. Abbreviations: IV, inverse variance; MS, multiple sclerosis.

Figure 8
Figure 8

Meta-regression of CSF NFL chain in MS patients relative to healthy controls. Notes: Separate meta-regressions of age (A), sample size (B), gender (C), and disease duration (D) between MS patients and HCs on SMDs comparing the CSF NFL chain levels in MS patients with those in HC. Abbreviations: CSF, cerebrospinal fluid; HC, healthy control; MS, multiple sclerosis; NFL, neurofilament light; SMD, standard mean difference.

Figure 9
Figure 9

The publication bias of included studies when comparing the CSF (A) and blood (B) neurofilament light chain levels in MS patients with healthy controls. Abbreviations: CSF, cerebrospinal fluid; MS, multiple sclerosis; SE, standard error; SMDs, standard mean differences.

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