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01-06-2020 | Amyotrophic Lateral Sclerosis | Original Communication

Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis

Authors: Samir Abu-Rumeileh, Veria Vacchiano, Corrado Zenesini, Barbara Polischi, Silvia de Pasqua, Enrico Fileccia, Angela Mammana, Vitantonio Di Stasi, Sabina Capellari, Fabrizio Salvi, Rocco Liguori, Piero Parchi, BoReALS

Published in: Journal of Neurology | Issue 6/2020

Abstract

Neurofilament light chain protein (NfL) is currently the most accurate cerebrospinal fluid (CSF) biomarker in amyotrophic lateral sclerosis (ALS) in terms of both diagnostic and prognostic value, but the mechanism underlying its increase is still a matter of debate. Similarly, emerging CSF biomarkers of neurodegeneration and neuroinflammation showed promising results, although further studies are needed to clarify their clinical and pathophysiological roles. In the present study we compared the diagnostic accuracy of CSF NfL, phosphorylated (p)-tau/total (t)-tau ratio, chitinase-3-like protein 1 (YKL-40) and chitotriosidase 1 (CHIT1), in healthy controls (n = 43) and subjects with ALS (n = 80) or ALS mimics (n = 46). In ALS cases, we also investigated the association between biomarker levels and clinical variables, the extent of upper motor neuron (UMN) and lower motor neuron (LMN) degeneration, and denervation activity through electromyography (EMG). ALS patients showed higher levels of CSF NfL, YKL-40, CHIT1, and lower values of p-tau/t-tau ratio compared to both controls and ALS mimics. Among all biomarkers, NfL yielded the highest diagnostic performance (> 90% sensitivity and specificity) and was the best predictor of disease progression rate and survival in ALS. NfL levels showed a significant correlation with the extent of LMN involvement, whereas YKL-40 levels increased together with the number of areas showing both UMN and LMN damage. EMG denervation activity did not correlate with any CSF biomarker change. These findings confirm the highest value of NfL among currently available CSF biomarkers for the diagnostic and prognostic assessment of ALS and contribute to the understanding of the pathophysiological and electrophysiological correlates of biomarker changes.

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Title: Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis
Authors: Samir Abu-Rumeileh
Veria Vacchiano
Corrado Zenesini
Barbara Polischi
Silvia de Pasqua
Enrico Fileccia
Angela Mammana
Vitantonio Di Stasi
Sabina Capellari
Fabrizio Salvi
Rocco Liguori
Piero Parchi
BoReALS
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keywords: Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Neurotomy
Frontotemporal Dementia
Biomarkers
Published in: Journal of Neurology / Issue 6/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-09761-z

At a glance: The STEP trials

Springer Medicine

Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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