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Neurofilament light levels predict clinical progression and death in multiple system atrophy

dc.rights.licenseopenen_US
dc.contributor.authorCHELBAN, Viorica
dc.contributor.authorNIKRAM, Elham
dc.contributor.authorPEREZ-SORIANO, Alexandra
dc.contributor.authorWILKE, Carlo
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSAMIER FOUBERT, Alexandra
dc.contributor.authorVIJIARATNAM, Nirosen
dc.contributor.authorGUO, Tong
dc.contributor.authorJABBARI, Edwin
dc.contributor.authorOLUFODUN, Simisola
dc.contributor.authorGONZALEZ, Mariel
dc.contributor.authorSENKEVICH, Konstantin
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorLAURENS, Brice
dc.contributor.authorPERAN, Patrice
dc.contributor.authorRASCOL, Olivier
dc.contributor.authorLE TRAON, Anne Pavy
dc.contributor.authorTODD, Emily G.
dc.contributor.authorCOSTANTINI, Alyssa A.
dc.contributor.authorALIKHWAN, Sondos
dc.contributor.authorTARIQ, Ambreen
dc.contributor.authorLIN NG, Bai
dc.contributor.authorMUNOZ, Esteban
dc.contributor.authorPAINOUS, Celia
dc.contributor.authorCOMPTA, Yaroslau
dc.contributor.authorJUNQUE, Carme
dc.contributor.authorSEGURA, Barbara
dc.contributor.authorZHELCHESKA, Kristina
dc.contributor.authorWELLINGTON, Henny
dc.contributor.authorSCHOLS, Ludger
dc.contributor.authorJAUNMUKTANE, Zane
dc.contributor.authorKOBYLECKI, Christopher
dc.contributor.authorCHURCH, Alistair
dc.contributor.authorHU, Michele T. M.
dc.contributor.authorROWE, James B.
dc.contributor.authorLEIGH, P. Nigel
dc.contributor.authorMASSEY, Luke
dc.contributor.authorBURN, David J.
dc.contributor.authorPAVESE, Nicola
dc.contributor.authorFOLTYNIE, Tom
dc.contributor.authorPCHELINA, Sofya
dc.contributor.authorWOOD, Nicholas
dc.contributor.authorHESLEGRAVE, Amanda J.
dc.contributor.authorZETTERBERG, Henrik
dc.contributor.authorBOCCHETTA, Martina
dc.contributor.authorROHRER, Jonathan D.
dc.contributor.authorMARTI, Maria J.
dc.contributor.authorSYNOFZIK, Matthis
dc.contributor.authorMORRIS, Huw R.
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
dc.contributor.authorMEISSNER, Wassilios
IDREF: 113664761
dc.contributor.authorHOULDEN, Henry
dc.date.accessioned2022-10-17T10:32:33Z
dc.date.available2022-10-17T10:32:33Z
dc.date.issued2022-07-29
dc.identifier.issn1460-2156 (Electronic) 0006-8950 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/170033
dc.description.abstractEnDisease-modifying treatments are currently being trialed in multiple system atrophy (MSA). Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data in multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in MSA. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study we recruited cross-sectional and longitudinal cases in multicentre European set-up. Plasma and cerebrospinal fluid neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; ROC analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease NfL levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival, and degree of brain atrophy than the NfL rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression, and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enMultiple system atrophy
dc.subject.enMSA
dc.subject.enNfL
dc.title.enNeurofilament light levels predict clinical progression and death in multiple system atrophy
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/brain/awac253en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed35903017en_US
dc.description.sponsorshipEuropeEuropean Union’s Horizon 2020 research and innovation programmeen_US
bordeaux.journalBrain - A Journal of Neurologyen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.institutionCNRS
bordeaux.teamACTIVE_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDMedical Research Councilen_US
bordeaux.identifier.funderIDWellcome Trusten_US
bordeaux.identifier.funderIDMultiple System Atrophy Trusten_US
bordeaux.identifier.funderIDMultiple System Atrophy Coalitionen_US
bordeaux.identifier.funderIDGuarantors of Brainen_US
bordeaux.identifier.funderIDKing Baudouin Foundation United Statesen_US
bordeaux.identifier.funderIDEuropean Research Councilen_US
bordeaux.identifier.funderIDAlzheimer's Drug Discovery Foundationen_US
bordeaux.identifier.funderIDAlzheimer's Associationen_US
bordeaux.identifier.funderIDFamiljen Erling-Perssons Stiftelseen_US
bordeaux.identifier.funderIDStiftelsen för Gamla Tjänarinnoren_US
bordeaux.identifier.funderIDUK Dementia Research Instituteen_US
bordeaux.identifier.funderIDCanada First Research Excellence Funden_US
hal.identifierhal-03817584
hal.version1
hal.date.transferred2022-10-17T10:33:00Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Brain%20-%20A%20Journal%20of%20Neurology&rft.date=2022-07-29&rft.eissn=1460-2156%20(Electronic)%200006-8950%20(Linking)&rft.issn=1460-2156%20(Electronic)%200006-8950%20(Linking)&rft.au=CHELBAN,%20Viorica&NIKRAM,%20Elham&PEREZ-SORIANO,%20Alexandra&WILKE,%20Carlo&SAMIER%20FOUBERT,%20Alexandra&rft.genre=article


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