TY - JOUR
T1 - Neuronal and glial CSF biomarkers in multiple sclerosis: A systematic review and meta-analysis
AU - Momtazmanesh, Sara
AU - Shobeiri, Parnian
AU - Saghazadeh, Amene
AU - Teunissen, Charlotte E.
AU - Burman, Joachim
AU - Szalardy, Levente
AU - Klivenyi, Peter
AU - Bartos, Ales
AU - Fernandes, Adelaide
AU - Rezaei, Nima
N1 - Funding Information: Research funding: This systematic review and meta-analysis was supported by a grant from Tehran University of Medical Sciences (No. 50866). LS was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences and the ÚNKP-20-5 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. AB was supported by PROGRES Q35, Charles University. Publisher Copyright: © 2021 Walter de Gruyter GmbH, Berlin/Boston 2021. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the leading factors of disability. We aimed to perform a meta-analysis to determine changes in CSF levels of neuronal and glial biomarkers, including neurofilament light chain (NFL), total tau (t-tau), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), and S100B in various groups of MS (MS versus controls, clinically isolated syndrome (CIS) versus controls, CIS versus MS, relapsing-remitting MS (RRMS) versus progressive MS (PMS), and MS in relapse versus remission. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 64 articles in the meta-analysis, including 4071 subjects. For investigation of sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. Meta-analyses were performed for comparisons including at least three individual datasets. NFL, GFAP, t-tau, CHI3L1, and S100B were higher in MS and NFL, t-tau, and CHI3L1 were also elevated in CIS patients than controls. CHI3L1 was the only marker with higher levels in MS than CIS. GFAP levels were higher in PMS versus RRMS, and NFL, t-tau, and CHI3L1 did not differ between different subtypes. Only levels of NFL were higher in patients in relapse than remission. Meta-regression showed influence of sex and disease severity on NFL and t-tau levels, respectively and disease duration on both. Added to the role of these biomarkers in determining prognosis and treatment response, to conclude, they may serve in diagnosis of MS and distinguishing different subtypes.
AB - Multiple sclerosis (MS) is a neurodegenerative disease associated with inflammatory demyelination and astroglial activation, with neuronal and axonal damage as the leading factors of disability. We aimed to perform a meta-analysis to determine changes in CSF levels of neuronal and glial biomarkers, including neurofilament light chain (NFL), total tau (t-tau), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), and S100B in various groups of MS (MS versus controls, clinically isolated syndrome (CIS) versus controls, CIS versus MS, relapsing-remitting MS (RRMS) versus progressive MS (PMS), and MS in relapse versus remission. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 64 articles in the meta-analysis, including 4071 subjects. For investigation of sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. Meta-analyses were performed for comparisons including at least three individual datasets. NFL, GFAP, t-tau, CHI3L1, and S100B were higher in MS and NFL, t-tau, and CHI3L1 were also elevated in CIS patients than controls. CHI3L1 was the only marker with higher levels in MS than CIS. GFAP levels were higher in PMS versus RRMS, and NFL, t-tau, and CHI3L1 did not differ between different subtypes. Only levels of NFL were higher in patients in relapse than remission. Meta-regression showed influence of sex and disease severity on NFL and t-tau levels, respectively and disease duration on both. Added to the role of these biomarkers in determining prognosis and treatment response, to conclude, they may serve in diagnosis of MS and distinguishing different subtypes.
KW - chitinase-3-like protein 1
KW - diagnosis
KW - glial fibrillary acidic protein
KW - neurofilament protein light
KW - tau protein
UR - http://www.scopus.com/inward/record.url?scp=85101030060&partnerID=8YFLogxK
U2 - https://doi.org/10.1515/revneuro-2020-0145
DO - https://doi.org/10.1515/revneuro-2020-0145
M3 - Review article
C2 - 33594840
SN - 0334-1763
VL - 32
SP - 573
EP - 595
JO - Reviews in the Neurosciences
JF - Reviews in the Neurosciences
IS - 6
ER -