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@ARTICLE{Chelban:164974,
      author       = {Chelban, Viorica and Nikram, Elham and Perez-Soriano,
                      Alexandra and Wilke, Carlo and Foubert-Samier, Alexandra and
                      Vijiaratnam, Nirosen and Guo, Tong and Jabbari, Edwin and
                      Olufodun, Simisola and Gonzalez, Mariel and Senkevich,
                      Konstantin and Laurens, Brice and Péran, Patrice and
                      Rascol, Olivier and Le Traon, Anne Pavy and Todd, Emily G
                      and Costantini, Alyssa A and Alikhwan, Sondos and Tariq,
                      Ambreen and Lin Ng, Bai and Muñoz, Esteban and Painous,
                      Celia and Compta, Yaroslau and Junque, Carme and Segura,
                      Barbara and Zhelcheska, Kristina and Wellington, Henny and
                      Schöls, Ludger and Jaunmuktane, Zane and Kobylecki,
                      Christopher and Church, Alistair and Hu, Michele T M and
                      Rowe, James B and Leigh, P Nigel and Massey, Luke and Burn,
                      David J and Pavese, Nicola and Foltynie, Tom and Pchelina,
                      Sofya and Wood, Nicholas and Heslegrave, Amanda J and
                      Zetterberg, Henrik and Bocchetta, Martina and Rohrer,
                      Jonathan D and Marti, Maria J and Synofzik, Matthis and
                      Morris, Huw R and Meissner, Wassilios G and Houlden, Henry},
      title        = {{N}eurofilament light levels predict clinical progression
                      and death in multiple system atrophy.},
      journal      = {Brain},
      volume       = {145},
      number       = {12},
      issn         = {0006-8950},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2022-01378},
      pages        = {4398-4408},
      year         = {2022},
      abstract     = {Disease-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.},
      keywords     = {Humans / Cohort Studies / Multiple System Atrophy /
                      Cross-Sectional Studies / Intermediate Filaments /
                      Neurofilament Proteins / Biomarkers / Disease Progression /
                      MSA (Other) / NfL (Other) / multiple system atrophy (Other)},
      cin          = {AG Gasser 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9762941},
      pubmed       = {pmid:35903017},
      doi          = {10.1093/brain/awac253},
      url          = {https://pub.dzne.de/record/164974},
}