Evidence map›Paper›PMID 36443488›Full record

ArticleJournal of neurology2023

Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study.

Agnès Pérez-Millan, Sergi Borrego-Écija, John C van Swieten, Lize Jiskoot, Fermin Moreno, Robert Laforce, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B Rowe and 22 more

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Article in Journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

1 citing paper in PubMed.

  1. 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

32 authors.

Agnès Pérez-Millan *Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
Sergi Borrego-Écija *Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain.
John C van SwietenDepartment of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Lize JiskootDepartment of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Fermin MorenoCognitive Disorders Unit, Department of Neurology, Donostia University Hospital, San Sebastian, Gipuzkoa, Spain.
Robert LaforceDépartement des Sciences Neurologiques, Clinique Interdisciplinaire de Mémoire, CHU de Québec, and Faculté de Médecine, Université Laval, Quebec City, QC, Canada.
Caroline GraffDivision of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Bioclinicum, Center for Alzheimer Research, Karolinska Institutet, Solna, Sweden.
Mario MasellisSunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.
Maria Carmela TartagliaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Canada.
James B RoweDepartment of Clinical Neurosciences and Cambridge University Hospitals NHS Trust and Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Barbara BorroniDepartment of Clinical and Experimental Sciences, Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy.
Elizabeth FingerDepartment of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada.
Matthis SynofzikDepartment of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.
Daniela GalimbertiDepartment of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
Rik VandenbergheLaboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Alexandre de MendonçaFaculty of Medicine, University of Lisbon, Lisbon, Portugal.
Chris R ButlerNuffield Department of Clinical Neurosciences, Medical Sciences Division, University of Oxford, Oxford, UK.
Alexander GerhardDivision of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.
Simon DucharmeDepartment of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
Isabelle Le BerSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière (DMU Neurosciences Paris 6), Paris, France.
Isabel SantanaNeurology Service, Faculty of Medicine, University Hospital of Coimbra (HUC), University of Coimbra, Coimbra, Portugal.
Florence PasquierUniv Lille, Lille, France.
Johannes LevinNeurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Munich, Germany.
Markus OttoDepartment of Neurology, University of Ulm, Ulm, Germany.
Sandro SorbiDepartment of Neurofarba, University of Florence, Florence, Italy.
Pietro TiraboschiFondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Harro SeelaarDepartment of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Tobias LangheinrichDivision of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.
Jonathan D RohrerDepartment of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, UK.
Roser Sala-Llonch *Department of Biomedicine, Faculty of Medicine, Institute of Neurosciences, University of Barcelona, 08036, Barcelona, Spain.
Raquel Sánchez-Valle *Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain. rsanchez@clinic.cat.ORCID http://orcid.org/0000-0001-7750-896X
Genetic FTD Initiative, GENFI

Funding

CIHR MOP- 371851CIHR PJT-175242Fundació la Marató de TV3 20143810German Research Foundation 390857198Instituto de Salud Carlos III PI20/00448JPND GENFI-PROX 2019-02248JPND-Prefrontals 2015-02926JPND-Prefrontals 2018-02754Medical Research Council MR/K010395/1Medical Research Council MR/M008525/1Medical Research Council MR/M023664/1Medical Research Council MR/T046015/1MRC Clinician Scientist MR/M008525/1MRC UK GENFI MR/M023664/1MRF SUAG/092 G116768NIHR Cambridge Biomedical Research Centre BRC-1215-20014NIHR Rare Disease Translational Research Collaboration BRC149/NS/MHWellcome Trust 103838Wellcome Trust 220258
6 · The paper itself

Abstract

BACKGROUND AND

objectivesThe C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD) and/or motor neuron disease (MND). Corticospinal degeneration has been described in post-mortem neuropathological studies in these patients, especially in those with MND. We used MRI to analyze white matter (WM) volumes in presymptomatic and symptomatic C9orf72 expansion carriers and investigated whether its measure may be helpful in predicting the onset of symptoms.

methodsWe studied 102 presymptomatic C9orf72 mutation carriers, 52 symptomatic carriers: 42 suffering from FTD and 11 from MND, and 75 non-carriers from the Genetic Frontotemporal dementia Initiative (GENFI). All subjects underwent T1-MRI acquisition. We used FreeSurfer to estimate the volume proportion of WM in the brainstem regions (midbrain, pons, and medulla oblongata). We calculated group differences with ANOVA tests and performed linear and non-linear regressions to assess group-by-age interactions.

resultsA reduced WM ratio was found in all brainstem subregions in symptomatic carriers compared to both noncarriers and pre-symptomatic carriers. Within symptomatic carriers, MND patients presented a lower ratio in pons and medulla oblongata compared with FTD patients. No differences were found between presymptomatic carriers and non-carriers. Clinical severity was negatively associated with the WM ratio. C9orf72 carriers presented greater age-related WM loss than non-carriers, with MND patients showing significantly more atrophy in pons and medulla oblongata. DISCUSSION: We find consistent brainstem WM loss in C9orf72 symptomatic carriers with differences related to the clinical phenotype supporting the use of brainstem measures as neuroimaging biomarkers for disease tracking.

Indexed as

Frontotemporal DementiaMotor Neuron DiseaseWhite MatterBrain StemC9orf72 ProteinHumansMotor NeuronsMutationC9orf72 ProteinC9orf72 protein, humanBrainstemC9orf72Frontotemporal dementiaGENFI

Identifiers

PMID36443488

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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.