Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis.
| Title: | Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis. |
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| Authors: | Abu-Rumeileh S; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40139, Bologna, Italy.; Vacchiano V; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40139, Bologna, Italy.; Zenesini C; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy.; Polischi B; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy.; de Pasqua S; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40139, Bologna, Italy.; Fileccia E; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40139, Bologna, Italy.; Mammana A; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy.; Di Stasi V; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy.; Capellari S; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40139, Bologna, Italy.; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy.; Salvi F; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy.; Liguori R; Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40139, Bologna, Italy.; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy.; Parchi P; IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Ospedale Bellaria, 40139, Bologna, Italy. piero.parchi@unibo.it.; Department of Experimental Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138, Bologna, Italy. piero.parchi@unibo.it. |
| Corporate Authors: | BoReALS |
| Source: | Journal of neurology [J Neurol] 2020 Jun; Vol. 267 (6), pp. 1699-1708. Date of Electronic Publication: 2020 Feb 25. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0423161 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1459 (Electronic) Linking ISSN: 03405354 NLM ISO Abbreviation: J Neurol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin ; New York, Springer-Verlag |
| MeSH Terms: | Amyotrophic Lateral Sclerosis/*cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/*diagnosis ; Amyotrophic Lateral Sclerosis/*physiopathology ; Chitinase-3-Like Protein 1/*cerebrospinal fluid ; Hexosaminidases/*cerebrospinal fluid ; Neurofilament Proteins/*cerebrospinal fluid ; tau Proteins/*cerebrospinal fluid; Biomarkers/cerebrospinal fluid ; Aged ; Disease Progression ; Electromyography ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Sensitivity and Specificity |
| 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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| Grant Information: | "Ricerca Corrente" Ministero della Salute |
| Contributed Indexing: | Investigator: I Bartolomei; R Plasmati; F Pastorelli; CC Quarta; V Reale; V Mariano; D Milletti; R Nasca; F Rizzi; A Cherici; D Rusolo; L Valeriani; F Anzolin; E Fantoni; A Fiorito; L Andrini; P Avoni; V Donadio; S Capellari; S de Pasqua; G Rizzo; V Vacchiano; E Fileccia; L Morandi; F Marliani; L Albini-Riccioli; P Parchi; MP Foschini; A Pession; S Battaglia; R Poda; D Valenti; S Asioli; L Vignatelli; F Oppi; M Stanzani-Maserati; A Bartoletti-Stella; C Colombo; S Maselli; MP Giannoccaro; M Moresco; F Salvi; R Liguori; Keywords: Amyotrophic lateral sclerosis; Glial markers; Neurofilament light chain; Phosphorylated tau; Prognosis |
| Substance Nomenclature: | 0 (Biomarkers); 0 (CHI3L1 protein, human); 0 (Chitinase-3-Like Protein 1); 0 (MAPT protein, human); 0 (Neurofilament Proteins); 0 (neurofilament protein L); 0 (tau Proteins); EC 3.2.1.- (Hexosaminidases); EC 3.2.1.- (chitotriosidase) |
| Entry Date(s): | Date Created: 20200227 Date Completed: 20210317 Latest Revision: 20211115 |
| Update Code: | 20260130 |
| DOI: | 10.1007/s00415-020-09761-z |
| PMID: | 32100123 |
| Database: | MEDLINE |
Journal Article