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May 2023; 10 (3) Research ArticleOpen Access

Visually Evoked Potential as Prognostic Biomarker for Neuroaxonal Damage in Multiple Sclerosis From a Multicenter Longitudinal Cohort

View ORCID ProfileFrederike Cosima Oertel, Julia Krämer, Seyedamirhosein Motamedi, Azeen Keihani, Hanna G. Zimmermann, Nikolaos G. Dimitriou, View ORCID ProfileShivany Condor-Montes, Charlotte Bereuter, View ORCID ProfileChristian Cordano, View ORCID ProfileAhmed Abdelhak, Anand Trip, View ORCID ProfileOrhan Aktas, Sven G. Meuth, View ORCID ProfileHeinz Wiendl, Klemens Ruprecht, View ORCID ProfileJudith Bellmann-Strobl, Friedemann Paul, View ORCID ProfileAxel Petzold, View ORCID ProfileAlexander U. Brandt, View ORCID ProfilePhilipp Albrecht, Ari J. Green
First published March 6, 2023, DOI: https://doi.org/10.1212/NXI.0000000000200092
Frederike Cosima Oertel
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Julia Krämer
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Seyedamirhosein Motamedi
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Azeen Keihani
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Hanna G. Zimmermann
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Nikolaos G. Dimitriou
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Shivany Condor-Montes
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Charlotte Bereuter
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Christian Cordano
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Ahmed Abdelhak
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Anand Trip
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Orhan Aktas
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Sven G. Meuth
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Heinz Wiendl
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Klemens Ruprecht
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Judith Bellmann-Strobl
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Friedemann Paul
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Axel Petzold
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Alexander U. Brandt
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Philipp Albrecht
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Ari J. Green
From the Weill Institute for Neurosciences (F.C.C.O., A.K., S.C.-M., C.C., A.A., A.J.G.), Department of Neurology, University of California San Francisco (UCSF); Experimental and Clinical Research Center (F.C.C.O., S.M., H.G.Z., C.B., J.B.-S., F.P., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Neurology with Institute of Translational Neurology (J.K., H.W.), University Hospital Münster, Germany; University of California Berkeley (A.K.); Department of Neurology (N.G.D., O.A., S.G.M., P.A.), Medical Faculty, Heinrich-Heine University and University Hospital Düsseldorf, Germany; Department of Neurology (P.A.), Maria Hilf Clinic Moenchengladbach, Germany; Queen Square MS Centre (A.T., A.P.), University College London, UK; Department of Neurology (K.R., F.P.),–Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Moorfield's Eye Hospital & The National Hospital for Neurology and Neurosurgery (A.P.); Queen Square Institute of Neurology, University College London, UK; Dutch Neuro-ophthalmology Expertise Centre, Amsterdam, NL; Department of Neurology (A.U.B.), University of California Irvine (UCI); and Department of Ophthalmology (A.J.G.), University of California San Francisco (UCSF).
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Full PDF
Citation
Visually Evoked Potential as Prognostic Biomarker for Neuroaxonal Damage in Multiple Sclerosis From a Multicenter Longitudinal Cohort
Frederike Cosima Oertel, Julia Krämer, Seyedamirhosein Motamedi, Azeen Keihani, Hanna G. Zimmermann, Nikolaos G. Dimitriou, Shivany Condor-Montes, Charlotte Bereuter, Christian Cordano, Ahmed Abdelhak, Anand Trip, Orhan Aktas, Sven G. Meuth, Heinz Wiendl, Klemens Ruprecht, Judith Bellmann-Strobl, Friedemann Paul, Axel Petzold, Alexander U. Brandt, Philipp Albrecht, Ari J. Green
Neurol Neuroimmunol Neuroinflamm May 2023, 10 (3) e200092; DOI: 10.1212/NXI.0000000000200092

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Abstract

Background and Objectives With the increasing use of visually evoked potentials (VEPs) as quantitative outcome parameters for myelin in clinical trials, an in-depth understanding of longitudinal VEP latency changes and their prognostic potential for subsequent neuronal loss will be required. In this longitudinal multicenter study, we evaluated the association and prognostic potential of VEP latency for retinal neurodegeneration, measured by optical coherence tomography (OCT), in relapsing-remitting MS (RRMS).

Methods We included 293 eyes of 147 patients with RRMS (age [years, median ± SD] 36 ± 10, male sex 35%, F/U [years, median {IQR} 2.1 {1.5–3.9}]): 41 eyes had a history of optic neuritis (ON) ≥6 months before baseline (CHRONIC-ON), and 252 eyes had no history of ON (CHRONIC-NON). P100 latency (VEP), macular combined ganglion cell and inner plexiform layer volume (GCIPL), and peripapillary retinal nerve fiber layer thickness (pRNFL) (OCT) were quantified.

Results P100 latency change over the first year predicted subsequent GCIPL loss (36 months) across the entire chronic cohort (p = 0.001) and in (and driven by) the CHRONIC-NON subset (p = 0.019) but not in the CHRONIC-ON subset (p = 0.680). P100 latency and pRNFL were correlated at baseline (CHRONIC-NON p = 0.004, CHRONIC-ON p < 0.001), but change in P100 latency and pRNFL were not correlated. P100 latency did not differ longitudinally between protocols or centers.

Discussion VEP in non-ON eyes seems to be a promising marker of demyelination in RRMS and of potential prognostic value for subsequent retinal ganglion cell loss. This study also provides evidence that VEP may be a useful and reliable biomarker for multicenter studies.

Glossary

CHRONIC-NON=
eyes without a history of optic neuritis;
CHRONIC-ON=
eyes with a history of optic neuritis;
DMTs=
disease-modifying treatments;
F/U=
follow-up;
GCIPL=
ganglion cell and inner plexiform layer thickness;
ISCEV=
International Society for Clinical Electrophysiology of Vision;
MS=
multiple sclerosis;
OCT=
optical coherence tomography;
ON=
optic neuritis;
pRNFL=
peripapillary retinal nerve fiber layer thickness;
RRMS=
relapsing-remitting MS;
SE=
standard error;
VEPs=
visual evoked potentials

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by the authors.

  • Submitted and externally peer reviewed. The handling editor was Editor Josep O. Dalmau, MD, PhD, FAAN.

  • Received July 11, 2022.
  • Accepted in final form December 13, 2022.
  • Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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  • Multiple sclerosis
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  • Evoked Potentials/Visual
  • Retina

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