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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
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.
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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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