Increased Serum Neurofilament Light and Thin Ganglion Cell-Inner Plexiform Layer Are Additive Risk Factors for Disease Activity in Early Multiple Sclerosis.


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
09 2021
Historique:
received: 10 02 2021
accepted: 10 05 2021
entrez: 5 8 2021
pubmed: 6 8 2021
medline: 1 3 2022
Statut: epublish

Résumé

To investigate the association of combined serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements with future disease activity in patients with early multiple sclerosis (MS). We analyzed sNfL by single molecule array technology and performed OCT measurements in a prospective cohort of 78 patients with clinically isolated syndrome and early relapsing-remitting MS with a median (interquartile range) follow-up of 23.9 (23.3-24.7) months. Patients were grouped into those with abnormal or normal sNfL levels, defined as sNfL ≥/<80th percentile of age-corrected reference values. Likewise, patients were grouped by a median split into those with thin or thick ganglion cell and inner plexiform layer (GCIP), peripapillary retinal nerve fiber layer, and inner nuclear layer in nonoptic neuritis eyes. Outcome parameters were violation of no evidence of disease activity (NEDA-3) criteria or its components. Patients with abnormal baseline sNfL had a higher risk of violating NEDA-3 (hazard ratio [HR] 2.28, 95% CI 1.27-4.09, In patients with early MS, the presence of both abnormal sNfL and thin GCIP is a stronger risk factor for future disease activity than the presence of each parameter alone.

Identifiants

pubmed: 34348969
pii: 8/5/e1051
doi: 10.1212/NXI.0000000000001051
pmc: PMC8362351
pii:
doi:

Substances chimiques

Neurofilament Proteins 0
neurofilament protein L 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Ting-Yi Lin (TY)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Viktoriya Vitkova (V)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Susanna Asseyer (S)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Ivette Martorell Serra (I)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Seyedamirhosein Motamedi (S)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Claudia Chien (C)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Marc Ditzhaus (M)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Athina Papadopoulou (A)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Pascal Benkert (P)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Jens Kuhle (J)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Judith Bellmann-Strobl (J)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Klemens Ruprecht (K)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Friedemann Paul (F)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Alexander U Brandt (AU)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine.

Hanna G Zimmermann (HG)

From the Experimental and Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; NeuroCure Clinical Research Center (T.-Y.L., V.V., S.A., I.M.S., S.M., C.C., A.P., J.B.-S., F.P., A.U.B., H.G.Z.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Psychiatry and Psychotherapy (C.C.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Statistics (M.D.), TU Dortmund University, Germany; Neurology Clinic and Policlinic (A.P., J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland; Department of Neurology (K.R., F.P.), Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; and Department of Neurology (A.U.B.), University of California, Irvine. hanna.zimmermann@charite.de.

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