scholarly journals Correlation between CSF and blood neurofilament light chain protein: a systematic review and meta-analysis

2021 ◽  
Vol 3 (1) ◽  
pp. e000143
Author(s):  
Jasmini Alagaratnam ◽  
Sophia von Widekind ◽  
Davide De Francesco ◽  
Jonathan Underwood ◽  
Paul Edison ◽  
...  
Keyword(s):  
Correlation Coefficient ◽  
Single Molecule ◽  
Meta Analysis ◽  
Protein A ◽  
Sensitivity Analyses ◽  
Correlation Technique ◽  
Analytical Sensitivity ◽  
Coefficient Estimate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

ObjectiveTo assess the overall pooled correlation coefficient estimate between cerebrospinal fluid (CSF) and blood neurofilament light (NfL) protein.MethodsWe searched Medline, Embase and Web of Science for published articles, from their inception to 9 July 2019, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies reporting the correlation between CSF and blood NfL in humans were included. We conducted a random-effects meta-analysis to calculate the overall pooled correlation coefficient estimate, accounting for correlation technique and assay used. Heterogeneity was assessed using the I2 statistic test. In sensitivity analyses, we calculated the pooled correlation coefficient estimate according to blood NfL assay: single-molecule array digital immunoassay (Simoa), electrochemiluminescence (ECL) assay or ELISA.ResultsData were extracted from 36 articles, including 3961 paired CSF and blood NfL samples. Overall, 26/36 studies measured blood NfL using Simoa, 8/36 ECL, 1/36 ELISA and 1 study reported all three assay results. The overall meta-analysis demonstrated that the pooled correlation coefficient estimate for CSF and blood NfL was r=0.72. Heterogeneity was significant: I2=83%, p<0.01. In sensitivity analyses, the pooled correlation coefficient was similar for studies measuring blood NfL using Simoa and ECL (r=0.69 and r=0.68, respectively) but weaker for ELISA (r=0.35).ConclusionModerate correlations are demonstrated between CSF and blood NfL, especially when blood NfL was measured using Simoa and ECL. Given its high analytical sensitivity, Simoa is the preferred assay for measuring NfL, especially at low or physiological concentrations, and this meta-analysis supports its use as the current most advanced surrogate measure of CSF NfL.PROSPERO registration numberCRD42019140469

scholarly journals Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa

2016 ◽  
Vol 54 (10) ◽  
Author(s):  
Jens Kuhle ◽  
Christian Barro ◽  
Ulf Andreasson ◽  
Tobias Derfuss ◽  
Raija Lindberg ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Neuronal Damage ◽  
Neurological Diseases ◽  
Cytoskeletal Proteins ◽  
Response To Treatment ◽  
Analytical Sensitivity ◽  
Serum Samples ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

AbstractBackground:Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are specific cytoskeletal proteins of neurons and their quantification has shown encouraging results as a biomarker for axonal injury.Methods:We aimed at comparing a widely used conventional ELISA for Nf light chain (NfL) with an electrochemiluminescence-based method (ECL assay) and a newly developed single-molecule array (Simoa) method in clinically relevant cerebrospinal fluid (CSF) and serum samples.Results:Analytical sensitivity was 0.62 pg/mL for Simoa, 15.6 pg/mL for the ECL assay, and 78.0 pg/mL for the ELISA. Correlations between paired CSF and serum samples were strongest for Simoa (r=0.88, p<0.001) and the ECL assay (r=0.78, p<0.001) and weaker for ELISA measurements (r=0.38, p=0.030). CSF NfL measurements between the platforms were highly correlated (r=1.0, p<0.001). Serum NfL levels were highly related between ECL assay and Simoa (r=0.86, p<0.001), and this was less visible between ELISA-ECL assay (r=0.41, p=0.018) and ELISA-Simoa (r=0.43, p=0.013). Multiple sclerosis (MS) patients had significantly higher serum NfL levels than controls when measured with Simoa (p=0.001) but not with the other platforms.Conclusions:We found Simoa to be more sensitive than ELISA or the ECL assay. Our results support the feasibility of quantifying NfL in serum; the results correlate with the more-established CSF NfL test. The highly sensitive Simoa technology deserves further studies in larger patient cohorts to clarify whether serum NfL could be used in the future to measure disease severity and determine prognosis or response to treatment interventions in neurological diseases.

scholarly journals Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications

2021 ◽  
pp. jnnp-2021-326914
Author(s):  
Dario Saracino ◽  
Karim Dorgham ◽  
Agnès Camuzat ◽  
Daisy Rinaldi ◽  
Armelle Rametti-Lacroux ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Rate Of Change ◽  
Longitudinal Change ◽  
Youden Index ◽  
Clinical Genetic ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Link Type ◽  
Therapeutic Trials

ObjectiveNeurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages.MethodsWe analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical–genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index.ResultspNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. GRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades.ConclusionsThis study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression.Trial registration numbersNCT02590276 and NCT04014673.

scholarly journals Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19

2021 ◽  
Author(s):  
Anne Hege Aamodt ◽  
Einar August Høgestøl ◽  
Trine Haug Popperud ◽  
Jan Cato Holter ◽  
Anne Ma Dyrhol-Riise ◽  
...  
Keyword(s):  
Nervous System ◽  
Single Molecule ◽  
Linear Models ◽  
Clinical Signs ◽  
Repeated Measurements ◽  
Cns Injury ◽  
Serum Concentrations ◽  
Blood Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 × 10–7) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.

CSF chitinase 3-like 1 is associated with iron rims in patients with a first demyelinating event

2021 ◽  
pp. 135245852110100
Author(s):  
Manuel Comabella ◽  
Margareta A Clarke ◽  
Sabine Schaedelin ◽  
Mar Tintoré ◽  
Deborah Pareto ◽  
...  
Keyword(s):  
Single Molecule ◽  
Multivariable Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lesion Volume ◽  
Univariable Analysis ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Multivariable Analyses ◽  
Prognostic Implications ◽  
The Relationship

Background: Chronic active lesions with iron rims have prognostic implications in patients with multiple sclerosis. Objective: To assess the relationship between iron rims and levels of chitinase 3-like 1 (CHI3L1), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with a first demyelinating event. Methods: Iron rims were identified using 3T susceptibility-weighted imaging. Serum NfL and GFAP levels were measured by single-molecule array assays. CSF (cerebrospinal fluid) CHI3L1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Sixty-one patients were included in the study. The presence of iron rims was associated with higher T2 lesion volume and higher number of gadolinium-enhancing lesions. In univariable analysis, having ⩾2 iron rims (vs 0) was associated with increased CSF CHI3L1 levels (β = 1.41; 95% confidence interval (CI) = 1.10–1.79; p < 0.01) and serum NfL levels (β = 2.30; 95% CI = 1.47–3.60; p < 0.01). In multivariable analysis, however, only CSF CHI3L1 levels remained significantly associated with the presence of iron rim lesions (β = 1.45; 95% CI = 1.11–1.90; p < 0.01). The presence of ⩾2 iron rims was not associated with increased serum GFAP levels in univariable or multivariable analyses. Conclusion: These findings support an important contribution of activated microglia/macrophages to the pathophysiology of chronic active lesions with iron rims in patients with a first demyelinating event.

scholarly journals Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies

2019 ◽  
Vol 90 (9) ◽  
pp. 1059-1067 ◽  
Author(s):  
Sarah-Jane Martin ◽  
Sarah McGlasson ◽  
David Hunt ◽  
James Overell
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Meta Analysis ◽  
Grey Literature ◽  
Case Control ◽  
Disease Stage ◽  
Case Control Studies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

ObjectiveNeurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.MethodsGuidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.ResultsCSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).ConclusionsCSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.

scholarly journals Role of Blood Neurofilaments in the Prognosis of Amyotrophic Lateral Sclerosis: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan-ni Zhou ◽  
You-hong Chen ◽  
Si-qi Dong ◽  
Wen-bo Yang ◽  
Ting Qian ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Meta Analysis ◽  
Progression Rate ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Risk Of Death ◽  
Disease Progression Rate ◽  
Als Patients ◽  
Lateral Sclerosis

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 &lt; 0.01; high vs. low NfL level: HR = 4.51, 95% CI (2.45–8.32), p &lt; 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 &lt; 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 &lt; 0.01; pNfH: summary r = 0.51, 95% CI (0.24–0.71), p &lt; 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.

Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing–remitting MS

2021 ◽  
pp. 135245852110323
Author(s):  
Jens Kuhle ◽  
Nadia Daizadeh ◽  
Pascal Benkert ◽  
Aleksandra Maceski ◽  
Christian Barro ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Interferon Beta ◽  
Efficacy And Safety ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Active ◽  
Sustained Reduction ◽  
Relapsing Remitting ◽  
Healthy Control

Background: Alemtuzumab efficacy and safety was demonstrated in CARE-MS I and extension studies (CAMMS03409; TOPAZ). Objective: Evaluate serum neurofilament light chain (sNfL) in CARE-MS I patients and highly active disease (HAD) subgroup, over 7 and 2 years for alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), respectively. Methods: Patients received SC IFNB-1a 44 µg 3×/week or alemtuzumab 12 mg/day at baseline and month 12, with further as-needed 3-day courses. sNfL was measured using single-molecule array (Simoa™). HAD definition was ⩾2 relapses in year before randomization and ⩾1 baseline gadolinium-enhancing lesion. Results: Baseline median sNfL levels were similar in alemtuzumab ( n = 354) and SC IFNB-1a–treated ( n = 159) patients (31.7 vs 31.4 pg/mL), but decreased with alemtuzumab versus SC IFNB-1a until year 2 (Y2; 13.2 vs 18.7 pg/mL; p < 0.0001); 12.7 pg/mL for alemtuzumab at Y7. Alemtuzumab-treated patients had sNfL at/below healthy control median at Y2 (72% vs 47%; p < 0.0001); 73% for alemtuzumab at Y7. HAD patients ( n = 102) had higher baseline sNfL (49.4 pg/mL) versus overall population; alemtuzumab HAD patients attained similar levels (Y2, 12.8 pg/mL; Y7, 12.7 pg/mL; 75% were at/below control median at Y7). Conclusion: Alemtuzumab was superior to SC IFNB-1a in reducing sNfL, with levels in alemtuzumab patients remaining stable through Y7. ClinicalTrials.gov identifier: NCT00530348, NCT00930553, NCT02255656

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