EBioMedicine (Jun 2020)
Clinical implications of serum neurofilament in newly diagnosed MS patients: A longitudinal multicentre cohort study
- Stefan Bittner,
- Falk Steffen,
- Timo Uphaus,
- Muthuraman Muthuraman,
- Vinzenz Fleischer,
- Anke Salmen,
- Felix Luessi,
- Achim Berthele,
- Luisa Klotz,
- Sven G. Meuth,
- Antonios Bayas,
- Friedemann Paul,
- Hans-Peter Hartung,
- Ralf Linker,
- Christoph Heesen,
- Martin Stangel,
- Brigitte Wildemann,
- Florian Then Bergh,
- Björn Tackenberg,
- Tania Kuempfel,
- Frank Weber,
- Uwe K. Zettl,
- Ulf Ziemann,
- Hayrettin Tumani,
- Sergiu Groppa,
- Mark Mühlau,
- Carsten Lukas,
- Bernhard Hemmer,
- Heinz Wiendl,
- Ralf Gold,
- Frauke Zipp
Affiliations
- Stefan Bittner
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany
- Falk Steffen
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany
- Timo Uphaus
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany
- Muthuraman Muthuraman
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany
- Vinzenz Fleischer
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany
- Anke Salmen
- Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany; Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
- Felix Luessi
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany
- Achim Berthele
- Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- Luisa Klotz
- Department of Neurology, University Hospital Münster, Westfälische-Wilhelms-University Münster, Münster, Germany
- Sven G. Meuth
- Department of Neurology, University Hospital Münster, Westfälische-Wilhelms-University Münster, Münster, Germany
- Antonios Bayas
- Department of Neurology, Universitätsklinikum Augsburg, Augsburg, Germany
- Friedemann Paul
- NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charité, Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany
- Hans-Peter Hartung
- Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- Ralf Linker
- Department of Neurology, University of Regensburg, Regensburg, Germany
- Christoph Heesen
- Institute for Neuroimmunology and Multiple Sclerosis, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
- Martin Stangel
- Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany
- Brigitte Wildemann
- Department of Neurology, University of Heidelberg, Heidelberg, Germany
- Florian Then Bergh
- Department of Neurology, University of Leipzig, Leipzig, Germany
- Björn Tackenberg
- Center of Neuroimmunology, Philipps-University Marburg, Marburg, Germany
- Tania Kuempfel
- Institute of Clinical Neuroimmunology, Ludwig Maximilian University of Munich, Munich, Germany
- Frank Weber
- Max-Planck Institute of Psychiatry, Munich, Germany; Neurological Clinic, Sana Kliniken des Landkreises Cham, Cham, Germany
- Uwe K. Zettl
- Department of Neurology, Neuroimmunological Section, University of Rostock, Rostock, Germany
- Ulf Ziemann
- Department of Neurology, University of Tuebingen, Tuebingen, Germany
- Hayrettin Tumani
- Department of Neurology, University of Ulm, Ulm, Germany; Clinic of Neurology Dietenbronn, Schwendi, Germany
- Sergiu Groppa
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany
- Mark Mühlau
- Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- Carsten Lukas
- Department of Radiology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
- Bernhard Hemmer
- Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- Heinz Wiendl
- Department of Neurology, University Hospital Münster, Westfälische-Wilhelms-University Münster, Münster, Germany
- Ralf Gold
- Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
- Frauke Zipp
- Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz 55131, Germany; Corresponding author: Stefan Bittner or Frauke Zipp, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, Mainz, 55131, Germany. Phone: +49(0)6131-17-2805 or +49(0)6131-17-7156.
- Journal volume & issue
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Vol. 56
p. 102807
Abstract
Background: We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. Methods: In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers. Clinical parameters, MRI, and sNfL levels (measured by single molecule array) were assessed at baseline and up to four-year follow-up. Findings: Of 814 patients, 54.7% (445) were diagnosed with RRMS and 45.3% (369) with CIS when applying 2010 McDonald criteria (RRMS[2010] and CIS[2010]). After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2–13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4–20.1 pg/ml, n = 213; p = 0.036). sNfL levels correlated with number of T2 and Gd+ lesions at baseline and future clinical relapses. Patients receiving disease-modifying therapy (DMT) during the first four years had higher baseline sNfL levels than DMT-naïve patients (11.8 pg/ml, IQR 7.5-20.7 pg/ml, n = 726; 9.7 pg/ml, IQR 6.4–15.3 pg/ml, n = 88). Therapy escalation decisions within this period were reflected by longitudinal changes in sNfL levels. Interpretation: Assessment of sNfL increases diagnostic accuracy, is associated with disease course prognosis and may, particularly when measured longitudinally, facilitate therapeutic decisions. Funding: Supported the German Federal Ministry for Education and Research, the German Research Council, and Hertie-Stiftung.
