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January 2023; 10 (1) ReviewOpen Access

Secondary Progressive Multiple Sclerosis

A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies

View ORCID ProfileTjalf Ziemssen, Virender Bhan, Jeremy Chataway, Tanuja Chitnis, View ORCID ProfileBruce Anthony Campbell Cree, Eva Kubala Havrdova, Ludwig Kappos, Pierre Labauge, Aaron Miller, Jin Nakahara, View ORCID ProfileCelia Oreja-Guevara, Jacqueline Palace, Barry Singer, Maria Trojano, Ashwini Patil, Benedict Rauser, View ORCID ProfileThomas Hach
First published November 22, 2022, DOI: https://doi.org/10.1212/NXI.0000000000200064
Tjalf Ziemssen
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Virender Bhan
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Jeremy Chataway
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Tanuja Chitnis
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Bruce Anthony Campbell Cree
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Eva Kubala Havrdova
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Ludwig Kappos
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Pierre Labauge
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Aaron Miller
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Jin Nakahara
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Celia Oreja-Guevara
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Jacqueline Palace
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Barry Singer
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Maria Trojano
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Ashwini Patil
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Benedict Rauser
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Thomas Hach
From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
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Full PDF
Citation
Secondary Progressive Multiple Sclerosis
A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies
Tjalf Ziemssen, Virender Bhan, Jeremy Chataway, Tanuja Chitnis, Bruce Anthony Campbell Cree, Eva Kubala Havrdova, Ludwig Kappos, Pierre Labauge, Aaron Miller, Jin Nakahara, Celia Oreja-Guevara, Jacqueline Palace, Barry Singer, Maria Trojano, Ashwini Patil, Benedict Rauser, Thomas Hach
Neurol Neuroimmunol Neuroinflamm Jan 2023, 10 (1) e200064; DOI: 10.1212/NXI.0000000000200064

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Article Information

vol. 10 no. 1 e200064
DOI: 
https://doi.org/10.1212/NXI.0000000000200064
PubMed: 
36414428

Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received April 5, 2022
  • Accepted in final form September 30, 2022
  • First Published November 22, 2022.

Copyright & Usage: 
Copyright © 2022 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-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Author Disclosures

    1. Tjalf Ziemssen, MD,
    2. Virender Bhan, MD,
    3. Jeremy Chataway, PhD,
    4. Tanuja Chitnis, MD,
    5. Bruce Anthony Campbell Cree, MD, PhD,
    6. Eva Kubala Havrdova, MD,
    7. Ludwig Kappos, MD,
    8. Pierre Labauge, PhD,
    9. Aaron Miller, MD,
    10. Jin Nakahara, MD, PhD,
    11. Celia Oreja-Guevara, MD, PhD,
    12. Jacqueline Palace, MD, PhD,
    13. Barry Singer, MD,
    14. Maria Trojano, MD,
    15. Ashwini Patil, MS,
    16. Benedict Rauser, PhD and
    17. Thomas Hach, MD
  1. Tjalf Ziemssen, MD,
  2. Scientific Advisory Boards:
    1. (1) Biogen (2) Novartis (3) Teva (4) Roche (5) BMS (6) <br>Viatris<br>all commercial

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. Speaker honorarium for all commercial entities (1) Biogen <br>(2) Sanofi (3) BMS (4) Roche (5) Novartis (6) Teva

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. 1) Biogen (2) Sanofi (3) Novartis (4) Teva (5) Roche

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. (1) Bayer (2) Roche

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  3. Virender Bhan, MD,
  4. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. 1. Novartis<br>2. EMD Serono<br>3. Roche<br>4. Sanofi

    Speakers' Bureaus:
    1. 1. Novartis

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  5. Jeremy Chataway, PhD,
  6. Scientific Advisory Boards:
    1. 1)Scientific advisory Board - commercial<br>Azadyne, Janssen, MedDay, Merck, NervGen, <br>Novartis and Roche.<br>2)Data safety monitoring Board - non-profit/academic<br>DexEnceph trial in Herpes Encephalitis (International Data <br>Monitoring and Safety Committee, IDMSC); PD-STAT trial in <br>Parkinson's disease (Trial Steering Committtee,TSC)

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. Chief Investigator:<br>2021-2028: UK MS Society &#x00A3;12.98M: OCTOPUS Trial Platform<br>2017-2022: UCL. National Institute for Health Research <br>(NIHR) Health Technology Assessment (HTA); &#x00A3;3.8M: MS-STAT2 <br>Trial. Grant reference 15/57/143.<br>2017-2022: UCL. UK and US MS (NMSS) societies. MS-STAT2-MRI <br>study 2017-2022; &#x00A3;0.9M; Rosetrees Trust &#x00A3;0.1M

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  7. Tanuja Chitnis, MD,
  8. Scientific Advisory Boards:
    1. Dr. Chitnis has served on clinical trial advisory boards <br>for Novartis Pharmaceuticals, Roche-Genentech and Sanofi-Genzyme.

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. Dr. Chitnis has served as a one-time consultant for Biogen, Genentech-Roche, <br>Novartis and Sanofi-Genzyme, Tiziana Life Sciences

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. Dr. Chitnis receives research support from (1) Sanofi-Genzyme (2) Novartis in <br>the form of Independent Investigator Awards.

    Research Support, Government Entities:
    1. NIH, Department of Defense

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. Dr. Chitnis has received research support from the National<br>Multiple Sclerosis Society, the Peabody Foundation, the <br>Sumaira Foundation and the Guthy-Jackson Charitable Foundation.

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  9. Bruce Anthony Campbell Cree, MD, PhD,
  10. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, <br>Gossamer Bio, Hexal/Sandoz, Horizon, Neuron23, Novartis, Sanofi, Siemens, TG <br>Therapeutics and Therini

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. Genentech

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  11. Eva Kubala Havrdova, MD,
  12. Scientific Advisory Boards:
    1. 1. Biogen 2. Novartis 3. Genzyme 4. Actelion 5. Celgene

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. 1. Biogen 2. Novartis 3. Celgene 4. Genzyme 5. Actelion <br>6. Roche 7. Merck Serono 8. Janssen

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. 1. Biogen 2. Novartis 3. Celgene 4. Genzyme 5. <br>Actelion 6. Roche 7. Merck Serono

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. 1. European Commission Grant: ABIRISK - IMI (2012-2016), <br>investigator

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. Biogen - Expert witness, 2019

  13. Ludwig Kappos, MD,
  14. Scientific Advisory Boards:
    1. (1) Abbvie <br>(2) Actelion<br>(3) AurigaVision AG <br>(4) Biogen<br>(5) Janssen<br>(6) Celgene<br>(7) Merck<br>(8) Minoryx<br>(9) Novartis <br>(10) Sanofi Genzym<br>(11) Santhera Pharmaceuticals<br><br>All payments to my institution (University Hospital Basel, <br>RC2NB) not to my own financial benefit

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. (1) Clinical and Translational Neuroscience, member of the <br>Editorial Board, (2) Neurology and Clinical Neuroscience, <br>member of <br>the Editorial Board, (3) Multiple Sclerosis and Related <br>Disorders

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. (1) Actelion, (2), AurigaVision AG, (3) Biogen, (4) Celgene, <br>(5) Desitin, (6) Eli Lilly, (7) EMD Serono, (8) Genentech, <br>(9) <br>Genzym, (10) GlaxoSmithKline, (11) Janssen, (12) Japan <br>Tobacco <br>Inc., (13) Merck, (14) Minoryx Therapeutics S.L., (15) <br>Novartis, (16) Roche, (17) Sanofi, (18) Santhera <br>Pharmaceuticals, (19) Senda Biosciences, (20) <br>Shionogi BV, (21) Teva, (22) Wellmera AG<br><br>All payments to my institution (University Hospital Basel, <br>RC2NB) not to my own financial benefit

    Research Support, Government Entities:
    1. (1)the Swiss National Research Foundation, (2)the European <br>Union, (3) InnoSuisse<br><br>All payments to my institution (University Hospital Basel, <br>RC2NB) not to my own financial benefit

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. (1)the Swiss MS Society

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. (1) license fees for Neurostatus products paid directly to<br>University Hospital Basel and used for research support

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  15. Pierre Labauge, PhD,
  16. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  17. Aaron Miller, MD,
  18. Scientific Advisory Boards:
    1. Viatris (Mylan); Janssen

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. Speakers honoraria from Biogen (for <br>non-branded programs only) and for Alexion (for non-branded <br>programs only)

    Editorial Boards:
    1. Continuum Audio (AAN) received fees as editor 2012-12/21

    Patents:
    1. NONE

    Publishing Royalties:
    1. Neuroimmunology; Oxford University Press, 2018

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. Caremark (Accordant <br>Health <br>Services); Mapi-Pharma; CorEvitas; Verana Health, Viatris <br>(Mylan)

    Speakers' Bureaus:
    1. Biogen Idec (only for an unbranded disease awareness <br>program)<br>Genentech/Roche (only for an unbranded program)<br>EMD Serono (unbranded journal clubs)

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. Novartis, Roche/Genentech, <br>Genzyme/Sanofi-aventis <br>Biogen Idec<br>MedDay, Corevitas

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. I have occasionally reviewed medico-legal cases as a <br>defense expert; the <br>cases are not in the public domain and remain <br>confidential.<br><br>I have served as an expert witness for a lawyer <br>representing Chubb Insurance Company in which I assessed <br>the MS status of the plaintiff who brought suit against <br>Chubb.

  19. Jin Nakahara, MD, PhD,
  20. Scientific Advisory Boards:
    1. (1) Novartis<br>(2) Biogen<br>(3) Alexion<br>(4) Mitsubishi-Tanabe<br>(5) Chugai

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. (1) Novartis, speaker honoraria<br>(2) Biogen, speaker honoraria<br>(3) Alexion, speaker honoraria<br>(4) Mitsubishi-Tanabe, speaker honoraria<br>(5) Chugai, speaker honoraria<br>(6) Takeda, speaker honoraria<br>(7) Daiichi-Sankyo, speaker honoraria<br>(8) Teijin, speaker honoraria<br>(9) Otsuka, speaker honoraria<br>(10) Abbvie, speaker honoraria<br>(11) Amgen, speaker honoraria<br>(12) CSL Behring, speaker honoraria<br>(13) Asahi-Kasei, speaker honoraria<br>(14) Eisai, speaker honoraria<br>(15) Bristol Myers, speaker honoraria<br>(16) Kyorin, speaker honoraria<br>(17) Roche, speaker honoraria

    Editorial Boards:
    1. (1) Neurology and Clinical Neuroscience, Associate editor, 2021-2<br>(2) Neuroscience Research, Associate editor, 2021-2<br>(3) Keio Journal of Medicine, Associate editor, 2022<br>(4) Nihon Naika Gakkai Zasshi, Associate editor, 2021-2<br>(5) No Shinkei Naika, Associate editor, 2021-2<br>Patents: <br>(1) Antibodies for remyelination<br>(2) Methods for CNS drug delivery

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. (1) Novartis<br>(2) Biogen<br>(3) Alexion

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. (1) JB<br>(2) Otsuka<br>(3) Boehringer Ingelheim<br>(4) Chugai<br>(5) Daiichi-Sankyo<br>(6) Teijin<br>(7) Biogen<br>(8) Sumitomo Pharma<br>(9) EA Pharma<br>(10) Shionogi<br>(11) Mitsubishi-Tanabe<br>(12) Eisai<br>(13) Takeda

    Research Support, Government Entities:
    1. (1) MEXT Japan, Kakenhi, 18K07508, PI, 2021-2

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  21. Celia Oreja-Guevara, MD, PhD,
  22. Scientific Advisory Boards:
    1. Biogen Idec (1), Sanofi-Genzyme(1), Merck-Serono (1), Roche<br>(1), Celgene-BMS(1) and<br>Novartis(1) and Janssen (1)

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. (1) Speaker honoraria by Sanofi-Genzyme (1),<br>Merck-Serono (1),Celgene-BMS (1), Biogen (1),Teva<br>(1),Roche(1) and Novartis(1)

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  23. Jacqueline Palace, MD, PhD,
  24. Scientific Advisory Boards:
    1. 1) Merck Serono <br>2) Roche <br>3) ARGENX <br>4) Novartis <br>5) UCB <br>6) Alexion <br>7)Janssen<br>8) Sanofi

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. All commercial (speakers/meetings honorarium last two <br>years)<br>1) Roche <br>2) Alexion <br>3) Chugai

    Editorial Boards:
    1. Lancet Neurology editorial advisorry committee member

    Patents:
    1. ISIS Innovation Ltd. To protect for the use of<br>metabolomics as a method to diagnose and stage disease in<br>multiple sclerosis. Patent ref P37347WO and licence <br>agreement Numares multimarker MS diagnostics

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. Amplo

    Speakers' Bureaus:
    1. Please see 3 (speaker/meetings)

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. All commercial (support for research)<br>1) Amplo <br>2) UCB<br>3) Alexion<br>4)Medimmune

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. Grant for research:<br>1) Multiple Sclerosis Society<br>4) SPARKS Great Ormond Street

    Stock/Stock Options/Board of Directors Compensation:
    1. Astra Zenica shares

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. Patent ref P37347WO and licence agreement Numares <br>multimarker MS diagnostics

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  25. Barry Singer, MD,
  26. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Janssen, <br>Genentech, Horizon, Novartis, Roche and Sanofi for <br>speaker/travel honoraria.

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. AbbVie, Biogen, Bristol Myers Squibb, Cigna, EMD Serono, <br>Janssen, Genentech, Greenwich Biosciences, Novartis, Octave <br>Bioscience, Sanofi and TG Therapeutics.

    Speakers' Bureaus:
    1. Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Janssen, <br>Genentech, Horizon, Novartis, Roche, Sanofi and TG <br>Therapeutics.

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. AbbVie, Biogen, Bristol Myers Squibb, Greenwich Biosciences, <br>Novartis and Sanofi: research grant support.

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  27. Maria Trojano, MD,
  28. Scientific Advisory Boards:
    1. MT has served on scientific Advisory Boards for Biogen, <br>Novartis, Merck, BMS, Roche and Genzyme

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. M.T. received honoraria for travel, consultancy or <br>speaking from Biogen, Roche, Sanofi, Merck, Genzyme, <br>Janssen and Novartis

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. M Trojano received research support for her Institution <br>by Novartis, Biogen, Roche, and Merck

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  29. Ashwini Patil, MS,
  30. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. Employee of Novartis Healthcare Pvt. Ltd., India

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  31. Benedict Rauser, PhD and
  32. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. Novartis Pharma GmbH, Medical Advisor, 5 years

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  33. Thomas Hach, MD
  34. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. Novartis Pharma AG, Executive Director, 7

    Consultancies:
    1. NONE

    Speakers' Bureaus:
    1. NONE

    Other Activities:
    1. NONE

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. NONE

    Research Support, Government Entities:
    1. NONE

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. None

    Stock/Stock Options/Board of Directors Compensation:
    1. NONE

    License Fee Payments, Technology or Inventions:
    1. NONE

    Royalty Payments, Technology or Inventions:
    1. NONE

    Stock/Stock Options, Research Sponsor:
    1. Novartis Pharma AG, 7

    Stock/Stock Options, Medical Equipment & Materials:
    1. NONE

    Legal Proceedings:
    1. NONE

  1. From the Center of Clinical Neuroscience (T.Z.), Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Germany; Division of Neurology (Medicine) (V.B.), University of British Columbia, Vancouver, Canada; Queen Square Multiple Sclerosis Centre (J.C.), UCL Queen Square Institute of Neurology, London, United Kingdom; Partners Pediatric Multiple Sclerosis Centre (T.C.), Massachusetts General Hospital, Boston; Department of Neurology (B.A.C.C.), Weill Institute for Neurosciences, UCSF, San Francisco, CA; Department of Neurology and Center of Clinical Neuroscience (E.K.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; Neurologic Clinic and Policlinic (L.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Multiple Sclerosis Clinic (P.L.), Department of Neurology, Montpellier University Hospital, France; Department of Neurology (A.M.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.N.), Keio University School of Medicine, Tokyo, Japan; Department of Neurology (C.O.-G.), Hospital Clinico San Carlos, IdISSC, Departametno de medicina, Universidad Complutense de Madrid, Spain; Nuffield Department of Clinical Neurosciences (J.P.), John Radcliffe Hospital, University of Oxford, United Kingdom; The MS Center for Innovations in Care (B.S.), Missouri Baptist Medical Center, St Louis, MO; Department of Basic Medical Sciences (M.T.), Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy; Novartis Healthcare Pvt. Ltd. (A.P.), Hyderabad, India; Novartis Pharma GmbH (B.R.), Nuremberg, Germany; and Novartis Pharma AG (T.H.), Basel, Switzerland.
  1. Correspondence
    Dr. Ziemssen tjalf.ziemssen{at}uniklinikum-dresden.de
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