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Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study.
Rise, Henning H; Brune, Synne; Chien, Claudia; Berge, Tone; Bos, Steffan D; Andorrà, Magí; Valdeolivas, Irene Pulido; Beyer, Mona K; Sowa, Piotr; Scheel, Michael; Brandt, Alexander U; Asseyer, Susanna; Blennow, Kaj; Pedersen, Mads L; Zetterberg, Henrik; de Schotten, Michel Thiebaut; Cellerino, Maria; Uccelli, Antonio; Paul, Friedemann; Villoslada, Pablo; Harbo, Hanne F; Westlye, Lars T; Høgestøl, Einar A.
Affiliation
  • Rise HH; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
  • Brune S; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
  • Chien C; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Membe
  • Berge T; Department of Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, Oslo, Norway; Department of Research, Innovation and Education, Oslo University Hospital, Oslo, Norway.
  • Bos SD; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
  • Andorrà M; Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
  • Valdeolivas IP; Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
  • Beyer MK; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
  • Sowa P; Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
  • Scheel M; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, NeuroCure Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Neurorad
  • Brandt AU; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Membe
  • Asseyer S; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany.
  • Blennow K; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
  • Pedersen ML; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
  • Zetterberg H; Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, United Kingdo
  • de Schotten MT; Brain Connectivity and Behaviour Laboratory, Sorbonne Universities, Paris, France; Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives- UMR 5293, CNRS, CEA University of Bordeaux, Bordeaux, France.
  • Cellerino M; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
  • Uccelli A; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  • Paul F; Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin & Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Experimental and Clinical Research Center, Germany; Charité -Universitätsmedizin Berlin, Corporate Membe
  • Villoslada P; Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
  • Harbo HF; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway.
  • Westlye LT; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway; KG Jebsen, Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.
  • Høgestøl EA; Department of Psychology, University of Oslo, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital, Oslo, Norway. Electronic address: einar.august@gmail.com.
Neuroimage Clin ; 35: 103099, 2022.
Article in En | MEDLINE | ID: mdl-35772194
BACKGROUND AND OBJECTIVES: Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative imaging-based brain network aberrations and levels of serum neurofilament light chain (NfL) as a neuroaxonal injury biomarker. METHODS: MS patients (n = 312, mean age 42.9 years, 71 % female) and healthy controls (HC) (n = 59, mean age 39.9 years, 78 % female) were prospectively enrolled at four European MS centres, and reassessed after two years (MS, n = 242; HC, n = 30). Post-processing of 3 Tesla (3 T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient's white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient as a random factor, serum NfL, age, sex, timepoint for visit, diagnosis, treatment, and center as fixed factors were run. RESULTS: rLMM revealed significant associations between GD and serum NfL (t = 2.94, p = 0.003), age (t = 4.21, p = 2.5 × 10-5), and longitudinal changes in NfL (t = -2.29, p = 0.02), but not for sex (t = 0.63, p = 0.53) or treatments (t = 0.80-0.83, p = 0.41-0.42). Voxel-wise analyses revealed significant associations between dysconnectivity in cerebellar and brainstem regions and serum NfL (t = 7.03, p < 0.001). DISCUSSION: In our prospective multi-site MS cohort, rLMMs demonstrated that the extent of global and regional brain disconnectivity is sensitive to a systemic biomarker of axonal damage, serum NfL, in patients with MS. These findings provide a neuroaxonal correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and potential clinical relevance of brain disconnectome mapping in patients with brain disorders.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: White Matter / Multiple Sclerosis Type of study: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: Neuroimage Clin Year: 2022 Document type: Article Affiliation country: Norway Country of publication: Netherlands
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: White Matter / Multiple Sclerosis Type of study: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: Neuroimage Clin Year: 2022 Document type: Article Affiliation country: Norway Country of publication: Netherlands