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Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis

BACKGROUND AND PURPOSE: This study was undertaken to determine the diagnostic and prognostic value of a panel of serum biomarkers and to correlate their concentrations with several clinical parameters in a large cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: One hundred forty‐...

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Autores principales: Falzone, Yuri Matteo, Domi, Teuta, Mandelli, Alessandra, Pozzi, Laura, Schito, Paride, Russo, Tommaso, Barbieri, Alessandra, Fazio, Raffaella, Volontè, Maria Antonietta, Magnani, Giuseppe, Del Carro, Ubaldo, Carrera, Paola, Malaspina, Andrea, Agosta, Federica, Quattrini, Angelo, Furlan, Roberto, Filippi, Massimo, Riva, Nilo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314044/
https://www.ncbi.nlm.nih.gov/pubmed/35263489
http://dx.doi.org/10.1111/ene.15321
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author Falzone, Yuri Matteo
Domi, Teuta
Mandelli, Alessandra
Pozzi, Laura
Schito, Paride
Russo, Tommaso
Barbieri, Alessandra
Fazio, Raffaella
Volontè, Maria Antonietta
Magnani, Giuseppe
Del Carro, Ubaldo
Carrera, Paola
Malaspina, Andrea
Agosta, Federica
Quattrini, Angelo
Furlan, Roberto
Filippi, Massimo
Riva, Nilo
author_facet Falzone, Yuri Matteo
Domi, Teuta
Mandelli, Alessandra
Pozzi, Laura
Schito, Paride
Russo, Tommaso
Barbieri, Alessandra
Fazio, Raffaella
Volontè, Maria Antonietta
Magnani, Giuseppe
Del Carro, Ubaldo
Carrera, Paola
Malaspina, Andrea
Agosta, Federica
Quattrini, Angelo
Furlan, Roberto
Filippi, Massimo
Riva, Nilo
author_sort Falzone, Yuri Matteo
collection PubMed
description BACKGROUND AND PURPOSE: This study was undertaken to determine the diagnostic and prognostic value of a panel of serum biomarkers and to correlate their concentrations with several clinical parameters in a large cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: One hundred forty‐three consecutive patients with ALS and a control cohort consisting of 70 patients with other neurodegenerative disorders (DEG), 70 patients with ALS mimic disorders (ALSmd), and 45 healthy controls (HC) were included. Serum neurofilament light chain (NfL), ubiquitin carboxyl‐terminal hydrolase isozyme L1 (UCHL1), glial fibrillary acidic protein (GFAP), and total tau protein levels were measured using ultrasensitive single molecule array. RESULTS: NfL correlated with disease progression rate (p < 0.001) and with the measures of upper motor neuron burden (p < 0.001). NfL was higher in the ALS patients with classic and pyramidal phenotype. GFAP was raised in ALS with cognitive–behavioral impairment compared with ALS with normal cognition. NfL displayed the best diagnostic performance in discriminating ALS from HC (area under the curve [AUC] = 0.990), DEG (AUC = 0.946), and ALSmd (AUC = 0.850). UCHL1 performed well in distinguishing ALS from HC (AUC = 0.761), whereas it was not helpful in differentiating ALS from DEG and ALSmd. In multivariate analysis, NfL (p < 0.001) and UCHL1 (p = 0.038) were independent prognostic factors. Survival analysis combining NfL and UCHL1 effectively stratified patients with lower NfL levels (p < 0.001). CONCLUSIONS: NfL is a useful biomarker for the diagnosis of ALS and the strongest predictor of survival. UCHL1 is an independent prognostic factor helpful in stratifying survival in patients with low NfL levels, likely to have slowly progressive disease. GFAP reflects extramotor involvement, namely cognitive impairment or frontotemporal dementia.
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spelling pubmed-93140442022-07-30 Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis Falzone, Yuri Matteo Domi, Teuta Mandelli, Alessandra Pozzi, Laura Schito, Paride Russo, Tommaso Barbieri, Alessandra Fazio, Raffaella Volontè, Maria Antonietta Magnani, Giuseppe Del Carro, Ubaldo Carrera, Paola Malaspina, Andrea Agosta, Federica Quattrini, Angelo Furlan, Roberto Filippi, Massimo Riva, Nilo Eur J Neurol ALS and frontotemporal dementia BACKGROUND AND PURPOSE: This study was undertaken to determine the diagnostic and prognostic value of a panel of serum biomarkers and to correlate their concentrations with several clinical parameters in a large cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: One hundred forty‐three consecutive patients with ALS and a control cohort consisting of 70 patients with other neurodegenerative disorders (DEG), 70 patients with ALS mimic disorders (ALSmd), and 45 healthy controls (HC) were included. Serum neurofilament light chain (NfL), ubiquitin carboxyl‐terminal hydrolase isozyme L1 (UCHL1), glial fibrillary acidic protein (GFAP), and total tau protein levels were measured using ultrasensitive single molecule array. RESULTS: NfL correlated with disease progression rate (p < 0.001) and with the measures of upper motor neuron burden (p < 0.001). NfL was higher in the ALS patients with classic and pyramidal phenotype. GFAP was raised in ALS with cognitive–behavioral impairment compared with ALS with normal cognition. NfL displayed the best diagnostic performance in discriminating ALS from HC (area under the curve [AUC] = 0.990), DEG (AUC = 0.946), and ALSmd (AUC = 0.850). UCHL1 performed well in distinguishing ALS from HC (AUC = 0.761), whereas it was not helpful in differentiating ALS from DEG and ALSmd. In multivariate analysis, NfL (p < 0.001) and UCHL1 (p = 0.038) were independent prognostic factors. Survival analysis combining NfL and UCHL1 effectively stratified patients with lower NfL levels (p < 0.001). CONCLUSIONS: NfL is a useful biomarker for the diagnosis of ALS and the strongest predictor of survival. UCHL1 is an independent prognostic factor helpful in stratifying survival in patients with low NfL levels, likely to have slowly progressive disease. GFAP reflects extramotor involvement, namely cognitive impairment or frontotemporal dementia. John Wiley and Sons Inc. 2022-03-23 2022-07 /pmc/articles/PMC9314044/ /pubmed/35263489 http://dx.doi.org/10.1111/ene.15321 Text en © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle ALS and frontotemporal dementia
Falzone, Yuri Matteo
Domi, Teuta
Mandelli, Alessandra
Pozzi, Laura
Schito, Paride
Russo, Tommaso
Barbieri, Alessandra
Fazio, Raffaella
Volontè, Maria Antonietta
Magnani, Giuseppe
Del Carro, Ubaldo
Carrera, Paola
Malaspina, Andrea
Agosta, Federica
Quattrini, Angelo
Furlan, Roberto
Filippi, Massimo
Riva, Nilo
Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
title Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
title_full Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
title_fullStr Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
title_full_unstemmed Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
title_short Integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
title_sort integrated evaluation of a panel of neurochemical biomarkers to optimize diagnosis and prognosis in amyotrophic lateral sclerosis
topic ALS and frontotemporal dementia
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314044/
https://www.ncbi.nlm.nih.gov/pubmed/35263489
http://dx.doi.org/10.1111/ene.15321
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