Evidence map›Paper›PMID 35903017›Full record

ArticleBrain : a journal of neurology2022

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

Viorica Chelban, Elham Nikram, Alexandra Perez-Soriano, Carlo Wilke, Alexandra Foubert-Samier, Nirosen Vijiaratnam, Tong Guo, Edwin Jabbari, Simisola Olufodun, Mariel Gonzalez and 39 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Review
  3. Multiple System Atrophy Combined Outcome Assessment (MuSyCA): process, format, and validation plan.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Cognitive profiles at presentation and subsequent cognitive decline and quality of life in Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Increase of Plasma Biomarkers in Friedreich's Ataxia: Potential Insights into Disease Pathology.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  15. Article
  16. Article
  17. Fluid biomarkers in atypical Parkinsonism: current state and future perspectives.Journal of neural transmission (Vienna, Austria : 1996) · 2025
    Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

49 authors at 20 institutions in 9 countries.

Viorica ChelbanDepartment of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0002-7797-0756
Elham NikramPeninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter EX 2LU, UK.
Alexandra Perez-SorianoMovement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona 08036, Spain.
Carlo WilkeDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, 72074 Tübingen, Germany.ORCID 0000-0002-7250-8597
Alexandra Foubert-SamierCRMR AMS, Service de Neurologie - Maladies Neurodégénératives, CHU de Bordeaux, F-33000 Bordeaux, France.
Nirosen VijiaratnamDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0002-9671-0212
Tong GuoDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Edwin JabbariDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0001-6844-882X
Simisola OlufodunDepartment of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Mariel GonzalezDepartment of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Konstantin SenkevichNeurogenomics and Precision Medicine (NAP-Med) Laboratory, The Neuro (Montreal Neurological Institute-Hospital), Montreal, QC H3A 2B4, Canada.
Brice LaurensCRMR AMS, Service de Neurologie - Maladies Neurodégénératives, CHU de Bordeaux, F-33000 Bordeaux, France.
Patrice PéranToNIC, Toulouse NeuroImaging Center, UMR 1214, Université de Toulouse, 31024 Toulouse, France.ORCID 0000-0001-7200-0139
Olivier RascolCRMR AMS, CHU de Toulouse, 31300 Toulouse, France.
Anne Pavy Le TraonCRMR AMS, CHU de Toulouse, 31300 Toulouse, France.
Emily G ToddDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, WC1N 3BG London, UK.ORCID 0000-0003-1551-5691
Alyssa A CostantiniDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Sondos AlikhwanDepartment of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Ambreen TariqDepartment of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Bai Lin NgDepartment of Economics, University College London, London WC1N 3BG, UK.
Esteban MuñozMovement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona 08036, Spain.
Celia PainousMovement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona 08036, Spain.
Yaroslau ComptaMovement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona 08036, Spain.
Carme JunqueParkinson's Disease and Movement Disorders Unit, Neurology Department, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain.
Barbara SeguraParkinson's Disease and Movement Disorders Unit, Neurology Department, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona 08036, Spain.
Kristina ZhelcheskaDepartment of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Henny WellingtonBiomarkers Factory Laboratory, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Ludger SchölsDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, 72074 Tübingen, Germany.
Zane JaunmuktaneQueen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, WC1N 3BG London, UK.
Christopher KobyleckiDepartment of Neurology, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK.
Alistair ChurchDepartment of Neurology, Royal Gwent Hospital, Newport NP20 2UB, UK.
Michele T M HuDivision of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
James B RoweDepartment of Clinical Neurosciences, Cambridge University, Cambridge CB3 0SZ, UK.
P Nigel LeighDepartment of Neuroscience, Brighton and Sussex Medical School, Brighton BN1 9PX, UK.
Luke MasseyNeurology Department, University Hospitals Dorset, Poole BH15 2JB, UK.
David J BurnFaculty of Medical Sciences, Clinical Ageing Research Unit, Newcastle University, NE4 5PL Newcastle, UK.
Nicola PaveseDepartment of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, WC1N 3BG London, UK.ORCID 0000-0002-6801-6194
Tom FoltynieDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0003-0752-1813
Sofya PchelinaLaboratory of Human Genetics, Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre 'Kurchatov Institute', Gatchina 188300, Russia.
Nicholas WoodDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Amanda J HeslegraveBiomarkers Factory Laboratory, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Henrik ZetterbergBiomarkers Factory Laboratory, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Martina BocchettaDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, WC1N 3BG London, UK.ORCID 0000-0003-1814-5024
Jonathan D RohrerDementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, WC1N 3BG London, UK.
Maria J MartiMovement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Barcelona 08036, Spain.
Matthis SynofzikDivision Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, 72074 Tübingen, Germany.ORCID 0000-0002-2280-7273
Huw R MorrisDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0002-5473-3774
Wassilios G MeissnerCRMR AMS, Service de Neurologie - Maladies Neurodégénératives, CHU de Bordeaux, F-33000 Bordeaux, France.
Henry HouldenDepartment of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0002-2866-7777
National Hospital for Neurology and Neurosurgery · GBCentro de Investigación Biomédica en Red · ESUK Dementia Research Institute · GBCentre National de la Recherche Scientifique · FRGerman Center for Neurodegenerative Diseases · DEInserm · FRBrighton and Sussex Medical School · GBFirst Pavlov State Medical University of St. Petersburg · RUManchester Academic Health Science Centre · GBMontreal Neurological Institute and Hospital · CAMRC Cognition and Brain Sciences Unit · GBNewcastle University · GBNicolae Testemițanu State University of Medicine and Pharmacy · MDPoole Hospital · GBRoyal Gwent Hospital · GBSahlgrenska University Hospital · SEUniversité Fédérale de Toulouse Midi-Pyrénées · FRUniversity College London · GBUniversity of Exeter · GBUniversity of Oxford · GB

Funding

Medical Research Council G0802760Medical Research Council G1001253Medical Research Council MR/J004758/1Medical Research Council MR/M008525/1Medical Research Council MR/M023664/1Medical Research Council MR/S01165X/1Medical Research Council MR/T046015/1Medical Research Council MR/V034758/1Parkinson's UK J-0901Wellcome Trust WT104033/Z/14/Z
6 · The paper itself

Abstract

Disease-modifying treatments are currently being trialled in multiple system atrophy. 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 on multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in multiple system atrophy. 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 a multicentre European set-up. Plasma and CSF 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; receiver operating characteristic 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 neurofilament light chain 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 neurofilament light chain 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.

Indexed as

Multiple System AtrophyBiomarkersCohort StudiesCross-Sectional StudiesDisease ProgressionHumansIntermediate FilamentsNeurofilament ProteinsBiomarkersNeurofilament ProteinsMSAmultiple system atrophyNfL

Identifiers

PMID35903017
PMCPMC9762941
OpenAlexW4288424534

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.