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01-08-2020 | Amyotrophic Lateral Sclerosis | Original Communication

Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease

Authors: Yuri Matteo Falzone, Teuta Domi, Federica Agosta, Laura Pozzi, Paride Schito, Raffaella Fazio, Ubaldo Del Carro, Alessandra Barbieri, Mauro Comola, Letizia Leocani, Giancarlo Comi, Paola Carrera, Massimo Filippi, Angelo Quattrini, Nilo Riva

Published in: Journal of Neurology | Issue 8/2020

Abstract

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 (R² = 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 X² = 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.

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Title: Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease
Authors: Yuri Matteo Falzone
Teuta Domi
Federica Agosta
Laura Pozzi
Paride Schito
Raffaella Fazio
Ubaldo Del Carro
Alessandra Barbieri
Mauro Comola
Letizia Leocani
Giancarlo Comi
Paola Carrera
Massimo Filippi
Angelo Quattrini
Nilo Riva
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Motor Evoked Potential
Frontotemporal Dementia
Motor Evoked Potential
Biomarkers
Published in: Journal of Neurology / Issue 8/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-09838-9

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Serum phosphorylated neurofilament heavy-chain levels reflect phenotypic heterogeneity and are an independent predictor of survival in motor neuron disease

Abstract

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