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Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease
To investigate the prognostic role and the major determinants of serum phosphorylated neurofilament heavy -chain (pNfH) concentration across a large cohort of motor neuron disease (MND) phenotypes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum pNfH concentration in 219 MND pati...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166001/ https://www.ncbi.nlm.nih.gov/pubmed/32306171 http://dx.doi.org/10.1007/s00415-020-09838-9 |
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author | Falzone, Yuri Matteo Domi, Teuta Agosta, Federica Pozzi, Laura Schito, Paride Fazio, Raffaella Del Carro, Ubaldo Barbieri, Alessandra Comola, Mauro Leocani, Letizia Comi, Giancarlo Carrera, Paola Filippi, Massimo Quattrini, Angelo Riva, Nilo |
author_facet | Falzone, Yuri Matteo Domi, Teuta Agosta, Federica Pozzi, Laura Schito, Paride Fazio, Raffaella Del Carro, Ubaldo Barbieri, Alessandra Comola, Mauro Leocani, Letizia Comi, Giancarlo Carrera, Paola Filippi, Massimo Quattrini, Angelo Riva, Nilo |
author_sort | Falzone, Yuri Matteo |
collection | PubMed |
description | To investigate the prognostic role and the major determinants of serum phosphorylated neurofilament heavy -chain (pNfH) concentration across a large cohort of motor neuron disease (MND) phenotypes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum pNfH concentration in 219 MND patients consecutively enrolled in our tertiary MND clinic. A multifactorial analysis was carried out to investigate the major clinical determinants of serum pNfH. Kaplan–Meier survival curves and Cox regression analysis were performed to explore the prognostic value of serum pNfH. Serum pNfH levels were not homogenous among MND phenotypes; higher concentrations in pyramidal, bulbar, and classic phenotypes were observed. C9orf72-MND exhibited higher pNfH concentrations compared to non-C9orf72 MND. Multiple linear regression analysis revealed mean MEP/cMAP and disease progression rate as the two major predictors of serum pNfH levels (R(2) = 0.188; p ≤ 0.001). Kaplan–Meier curves showed a significant difference of survival among MND subgroups when divided into quartiles based on pNfH concentrations, log-rank X(2) = 53.0, p ≤ 0.0001. Our study evidenced that higher serum pNfH concentration is a negative independent prognostic factor for survival. In Cox multivariate model, pNfH concentration showed the highest hazard ratio compared to the other factors influencing survival included in the analysis. pNfH differs among the MND phenotypes and is an independent prognostic factor for survival. This study provides supporting evidence of the role of pNfH as useful prognostic biomarker for MND patients. Neurofilament measurements should be considered in the future prognostic models and in clinical trials for biomarker-based stratification, and to evaluate treatment response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09838-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7166001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-71660012020-04-20 Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease Falzone, Yuri Matteo Domi, Teuta Agosta, Federica Pozzi, Laura Schito, Paride Fazio, Raffaella Del Carro, Ubaldo Barbieri, Alessandra Comola, Mauro Leocani, Letizia Comi, Giancarlo Carrera, Paola Filippi, Massimo Quattrini, Angelo Riva, Nilo J Neurol Original Communication To investigate the prognostic role and the major determinants of serum phosphorylated neurofilament heavy -chain (pNfH) concentration across a large cohort of motor neuron disease (MND) phenotypes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum pNfH concentration in 219 MND patients consecutively enrolled in our tertiary MND clinic. A multifactorial analysis was carried out to investigate the major clinical determinants of serum pNfH. Kaplan–Meier survival curves and Cox regression analysis were performed to explore the prognostic value of serum pNfH. Serum pNfH levels were not homogenous among MND phenotypes; higher concentrations in pyramidal, bulbar, and classic phenotypes were observed. C9orf72-MND exhibited higher pNfH concentrations compared to non-C9orf72 MND. Multiple linear regression analysis revealed mean MEP/cMAP and disease progression rate as the two major predictors of serum pNfH levels (R(2) = 0.188; p ≤ 0.001). Kaplan–Meier curves showed a significant difference of survival among MND subgroups when divided into quartiles based on pNfH concentrations, log-rank X(2) = 53.0, p ≤ 0.0001. Our study evidenced that higher serum pNfH concentration is a negative independent prognostic factor for survival. In Cox multivariate model, pNfH concentration showed the highest hazard ratio compared to the other factors influencing survival included in the analysis. pNfH differs among the MND phenotypes and is an independent prognostic factor for survival. This study provides supporting evidence of the role of pNfH as useful prognostic biomarker for MND patients. Neurofilament measurements should be considered in the future prognostic models and in clinical trials for biomarker-based stratification, and to evaluate treatment response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09838-9) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-04-18 2020 /pmc/articles/PMC7166001/ /pubmed/32306171 http://dx.doi.org/10.1007/s00415-020-09838-9 Text en © Springer-Verlag GmbH Germany, part of Springer Nature 2020 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Communication Falzone, Yuri Matteo Domi, Teuta Agosta, Federica Pozzi, Laura Schito, Paride Fazio, Raffaella Del Carro, Ubaldo Barbieri, Alessandra Comola, Mauro Leocani, Letizia Comi, Giancarlo Carrera, Paola Filippi, Massimo Quattrini, Angelo Riva, Nilo Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease |
title | Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease |
title_full | Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease |
title_fullStr | Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease |
title_full_unstemmed | Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease |
title_short | Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease |
title_sort | serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease |
topic | Original Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166001/ https://www.ncbi.nlm.nih.gov/pubmed/32306171 http://dx.doi.org/10.1007/s00415-020-09838-9 |
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