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000164974 1001_ $$00000-0002-7797-0756$$aChelban, Viorica$$b0
000164974 245__ $$aNeurofilament light levels predict clinical progression and death in multiple system atrophy.
000164974 260__ $$aOxford$$bOxford Univ. Press$$c2022
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000164974 520__ $$aDisease-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.
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000164974 650_7 $$2Other$$aMSA
000164974 650_7 $$2Other$$aNfL
000164974 650_7 $$2Other$$amultiple system atrophy
000164974 650_2 $$2MeSH$$aHumans
000164974 650_2 $$2MeSH$$aCohort Studies
000164974 650_2 $$2MeSH$$aMultiple System Atrophy
000164974 650_2 $$2MeSH$$aCross-Sectional Studies
000164974 650_2 $$2MeSH$$aIntermediate Filaments
000164974 650_2 $$2MeSH$$aNeurofilament Proteins
000164974 650_2 $$2MeSH$$aBiomarkers
000164974 650_2 $$2MeSH$$aDisease Progression
000164974 7001_ $$aNikram, Elham$$b1
000164974 7001_ $$aPerez-Soriano, Alexandra$$b2
000164974 7001_ $$0P:(DE-2719)2814101$$aWilke, Carlo$$b3$$udzne
000164974 7001_ $$aFoubert-Samier, Alexandra$$b4
000164974 7001_ $$00000-0002-9671-0212$$aVijiaratnam, Nirosen$$b5
000164974 7001_ $$aGuo, Tong$$b6
000164974 7001_ $$00000-0001-6844-882X$$aJabbari, Edwin$$b7
000164974 7001_ $$aOlufodun, Simisola$$b8
000164974 7001_ $$aGonzalez, Mariel$$b9
000164974 7001_ $$aSenkevich, Konstantin$$b10
000164974 7001_ $$aLaurens, Brice$$b11
000164974 7001_ $$00000-0001-7200-0139$$aPéran, Patrice$$b12
000164974 7001_ $$aRascol, Olivier$$b13
000164974 7001_ $$aLe Traon, Anne Pavy$$b14
000164974 7001_ $$00000-0003-1551-5691$$aTodd, Emily G$$b15
000164974 7001_ $$aCostantini, Alyssa A$$b16
000164974 7001_ $$aAlikhwan, Sondos$$b17
000164974 7001_ $$aTariq, Ambreen$$b18
000164974 7001_ $$aLin Ng, Bai$$b19
000164974 7001_ $$aMuñoz, Esteban$$b20
000164974 7001_ $$aPainous, Celia$$b21
000164974 7001_ $$aCompta, Yaroslau$$b22
000164974 7001_ $$aJunque, Carme$$b23
000164974 7001_ $$aSegura, Barbara$$b24
000164974 7001_ $$aZhelcheska, Kristina$$b25
000164974 7001_ $$aWellington, Henny$$b26
000164974 7001_ $$0P:(DE-2719)2810795$$aSchöls, Ludger$$b27$$udzne
000164974 7001_ $$aJaunmuktane, Zane$$b28
000164974 7001_ $$aKobylecki, Christopher$$b29
000164974 7001_ $$aChurch, Alistair$$b30
000164974 7001_ $$aHu, Michele T M$$b31
000164974 7001_ $$aRowe, James B$$b32
000164974 7001_ $$aLeigh, P Nigel$$b33
000164974 7001_ $$aMassey, Luke$$b34
000164974 7001_ $$aBurn, David J$$b35
000164974 7001_ $$00000-0002-6801-6194$$aPavese, Nicola$$b36
000164974 7001_ $$00000-0003-0752-1813$$aFoltynie, Tom$$b37
000164974 7001_ $$aPchelina, Sofya$$b38
000164974 7001_ $$aWood, Nicholas$$b39
000164974 7001_ $$aHeslegrave, Amanda J$$b40
000164974 7001_ $$aZetterberg, Henrik$$b41
000164974 7001_ $$00000-0003-1814-5024$$aBocchetta, Martina$$b42
000164974 7001_ $$aRohrer, Jonathan D$$b43
000164974 7001_ $$aMarti, Maria J$$b44
000164974 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b45$$udzne
000164974 7001_ $$00000-0002-5473-3774$$aMorris, Huw R$$b46
000164974 7001_ $$aMeissner, Wassilios G$$b47
000164974 7001_ $$00000-0002-2866-7777$$aHoulden, Henry$$b48
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