Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis: Neurofilament Light Chain Levels in Definite Subtypes of Disease.
Alessandra Gaiani,Ilaria Martinelli,Luca Bello,Giorgia Querin,Marco Puthenparampil,S. Ruggero,Elisabetta Toffanin,Annachiara Cagnin,Chiara Briani,Elena Pegoraro,Gianni Sorarù +10 more
TLDR
The role of NFL as a biomarker in ALS is confirmed, and Elevation in NFL levels in patients with upper motor neuron involvement and FTD might reflect the corticospinal tract degeneration.Abstract:
Importance A clearer definition of the role of neurofilament light chain (NFL) as a biomarker in amyotrophic lateral sclerosis (ALS) is needed. Objectives To assess the ability of NFL to serve as a diagnostic biomarker in ALS and the prognostic value of cerebrospinal fluid NFL in patients with ALS. Design, Setting, and Participants In this single-center, retrospective, longitudinal study, disease progression was assessed by the ALS Functional Rating Score–Revised and the ALS Milano-Torino Staging system at baseline and 6, 12, 24, and 36 months. Cerebrospinal fluid samples were obtained from 176 patients admitted to the Department of Neurosciences of the University of Padua, Padova, Italy, from January 1, 2010, through February 29, 2016. Patients with ALS underwent ambulatory follow-up at the same department. Main Outcomes and Measures Levels of NFL. Results The study included 94 patients with ALS (64 men [36.4%] and 30 women [17.0%]; median age, 62.5 years), 20 patients with frontotemporal dementia (FTD) (8 men [4.5%] and 12 women [6.8%]; median age, 65 years), 18 patients with motor neuropathies (14 men [8.0%] and 4 women [2.3%]; median age, 63 years), and 44 controls (24 men [13.6%] and 20 women [11.4%]; median age, 54 years). Log-transformed NFL (log[NFL]) concentrations were higher in the ALS and FTD groups compared with the motor neuropathies and control groups (hazard ratio [HR], 2.45; 95% CI, 1.66-3.61; P P = .41), and upper motor neuron dominant ALS (HR, 0.12; 95% CI, 0.02-0.61; P = .01) had higher levels of NFL than did those with flail arm or leg syndrome (HR, 0.28; 95% CI, 0.08-0.10; P = .049) and progressive muscular atrophy (HR, 0.17; 95% CI, 0.22-1.36; P = .10). There was an inverse correlation between log[NFL] concentration and overall survival (HR, 2.45; 95% CI, 1.66-3.61; P Conclusions and Relevance This study confirms the role of NFL as a biomarker in ALS. Elevation in NFL levels in patients with upper motor neuron involvement and FTD might reflect the corticospinal tract degeneration. Low NFL levels in patients with lower motor neuron signs might be a prognostic indicator of milder phenotypes of disease.read more
Citations
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Journal ArticleDOI
Amyotrophic lateral sclerosis
Eva L. Feldman,Stephen A. Goutman,Susanne Petri,Letizia Mazzini,Masha G. Savelieff,Pamela J. Shaw,Gen Sobue +6 more
TL;DR: Two possible disease-modifying therapies that can slow disease progression are available for ALS, but patient management is largely mediated by symptomatic therapies, such as the use of muscle relaxants for spasticity and speech therapy for dysarthria.
Journal ArticleDOI
Neurofilament light chain as a biomarker in neurological disorders
Lorenzo Gaetani,Kaj Blennow,Paolo Calabresi,Massimiliano Di Filippo,Lucilla Parnetti,Henrik Zetterberg +5 more
TL;DR: Evidence that both CSF and blood NfL may serve as diagnostic, prognostic and monitoring biomarkers in neurological diseases is progressively increasing, and N fL is one of the most promising biomarkers to be used in clinical and research setting in the next future.
Journal ArticleDOI
The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta-analysis.
TL;DR: A systematic review and meta‐analysis was performed regarding the diagnostic performance of neurofilament light chain (NfL) in CSF and blood.
Journal ArticleDOI
A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis
David Devos,Caroline Moreau,Maeva Kyheng,Guillaume Garçon,Anne Sophie Rolland,Hélène Blasco,Patrick Gelé,Timothée Lenglet,Charlotte Veyrat-Durebex,Philippe Corcia,Mary Dutheil,Peter Bede,Peter Bede,Andreas Jeromin,Patrick Oeckl,Markus Otto,Vincent Meininger,Véronique Danel-Brunaud,Jean-Christophe Devedjian,James A. Duce,James A. Duce,Pierre-François Pradat,Pierre-François Pradat +22 more
TL;DR: Blood-based prognostic indicators linked to ‘ferroptosis’, a recently discovered form of programmed cell death with promising therapeutic targets, may offer superior patient stratification for future trials, individualised patient care and resource allocation.
Journal ArticleDOI
Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS
Michael Benatar,Lanyu Zhang,Lily Wang,Volkan Granit,Jeffrey Statland,Richard J. Barohn,Andrea Swenson,John Ravits,Carlayne E. Jackson,Ted M. Burns,Jaya Trivedi,Erik P. Pioro,James B. Caress,Jonathan S. Katz,Jacob L. McCauley,Rosa Rademakers,Andrea Malaspina,Lyle W. Ostrow,Joanne Wuu +18 more
TL;DR: Serum NfL may be considered a clinically validated prognostic biomarker for ALS and has potential utility as a pharmacodynamic biomarker of treatment effect, depending on the method used to estimate effect size.
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