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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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vol. 10 no. 1 e200064
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History:
- Received April 5, 2022
- Accepted in final form September 30, 2022
- First Published November 22, 2022.
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Author Disclosures
- Tjalf Ziemssen, MD,
- Virender Bhan, MD,
- Jeremy Chataway, PhD,
- Tanuja Chitnis, MD,
- Bruce Anthony Campbell Cree, MD, PhD,
- Eva Kubala Havrdova, MD,
- Ludwig Kappos, MD,
- Pierre Labauge, PhD,
- Aaron Miller, MD,
- Jin Nakahara, MD, PhD,
- Celia Oreja-Guevara, MD, PhD,
- Jacqueline Palace, MD, PhD,
- Barry Singer, MD,
- Maria Trojano, MD,
- Ashwini Patil, MS,
- Benedict Rauser, PhD and
- Thomas Hach, MD
- Tjalf Ziemssen, MD,
(1) Biogen (2) Novartis (3) Teva (4) Roche (5) BMS (6) <br>Viatris<br>all commercial
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Speaker honorarium for all commercial entities (1) Biogen <br>(2) Sanofi (3) BMS (4) Roche (5) Novartis (6) Teva
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1) Biogen (2) Sanofi (3) Novartis (4) Teva (5) Roche
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(1) Bayer (2) Roche
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- Virender Bhan, MD,
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1. Novartis<br>2. EMD Serono<br>3. Roche<br>4. Sanofi
1. Novartis
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- Jeremy Chataway, PhD,
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)
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Chief Investigator:<br>2021-2028: UK MS Society £12.98M: OCTOPUS Trial Platform<br>2017-2022: UCL. National Institute for Health Research <br>(NIHR) Health Technology Assessment (HTA); £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; £0.9M; Rosetrees Trust £0.1M
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- Tanuja Chitnis, MD,
Dr. Chitnis has served on clinical trial advisory boards <br>for Novartis Pharmaceuticals, Roche-Genentech and Sanofi-Genzyme.
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Dr. Chitnis has served as a one-time consultant for Biogen, Genentech-Roche, <br>Novartis and Sanofi-Genzyme, Tiziana Life Sciences
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Dr. Chitnis receives research support from (1) Sanofi-Genzyme (2) Novartis in <br>the form of Independent Investigator Awards.
NIH, Department of Defense
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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.
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- Bruce Anthony Campbell Cree, MD, PhD,
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Atara, Autobahn, Avotres, Biogen, Boston Pharma, EMD Serono, <br>Gossamer Bio, Hexal/Sandoz, Horizon, Neuron23, Novartis, Sanofi, Siemens, TG <br>Therapeutics and Therini
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Genentech
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- Eva Kubala Havrdova, MD,
1. Biogen 2. Novartis 3. Genzyme 4. Actelion 5. Celgene
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1. Biogen 2. Novartis 3. Celgene 4. Genzyme 5. Actelion <br>6. Roche 7. Merck Serono 8. Janssen
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1. Biogen 2. Novartis 3. Celgene 4. Genzyme 5. <br>Actelion 6. Roche 7. Merck Serono
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1. European Commission Grant: ABIRISK - IMI (2012-2016), <br>investigator
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Biogen - Expert witness, 2019
- Ludwig Kappos, MD,
(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
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(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
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(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
(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
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(1)the Swiss MS Society
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(1) license fees for Neurostatus products paid directly to<br>University Hospital Basel and used for research support
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- Pierre Labauge, PhD,
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- Aaron Miller, MD,
Viatris (Mylan); Janssen
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Speakers honoraria from Biogen (for <br>non-branded programs only) and for Alexion (for non-branded <br>programs only)
Continuum Audio (AAN) received fees as editor 2012-12/21
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Neuroimmunology; Oxford University Press, 2018
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Caremark (Accordant <br>Health <br>Services); Mapi-Pharma; CorEvitas; Verana Health, Viatris <br>(Mylan)
Biogen Idec (only for an unbranded disease awareness <br>program)<br>Genentech/Roche (only for an unbranded program)<br>EMD Serono (unbranded journal clubs)
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Novartis, Roche/Genentech, <br>Genzyme/Sanofi-aventis <br>Biogen Idec<br>MedDay, Corevitas
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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.
- Jin Nakahara, MD, PhD,
(1) Novartis<br>(2) Biogen<br>(3) Alexion<br>(4) Mitsubishi-Tanabe<br>(5) Chugai
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(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
(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
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(1) Novartis<br>(2) Biogen<br>(3) Alexion
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(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
(1) MEXT Japan, Kakenhi, 18K07508, PI, 2021-2
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- Celia Oreja-Guevara, MD, PhD,
Biogen Idec (1), Sanofi-Genzyme(1), Merck-Serono (1), Roche<br>(1), Celgene-BMS(1) and<br>Novartis(1) and Janssen (1)
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(1) Speaker honoraria by Sanofi-Genzyme (1),<br>Merck-Serono (1),Celgene-BMS (1), Biogen (1),Teva<br>(1),Roche(1) and Novartis(1)
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- Jacqueline Palace, MD, PhD,
1) Merck Serono <br>2) Roche <br>3) ARGENX <br>4) Novartis <br>5) UCB <br>6) Alexion <br>7)Janssen<br>8) Sanofi
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All commercial (speakers/meetings honorarium last two <br>years)<br>1) Roche <br>2) Alexion <br>3) Chugai
Lancet Neurology editorial advisorry committee member
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
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Amplo
Please see 3 (speaker/meetings)
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All commercial (support for research)<br>1) Amplo <br>2) UCB<br>3) Alexion<br>4)Medimmune
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Grant for research:<br>1) Multiple Sclerosis Society<br>4) SPARKS Great Ormond Street
Astra Zenica shares
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Patent ref P37347WO and licence agreement Numares <br>multimarker MS diagnostics
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- Barry Singer, MD,
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Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Janssen, <br>Genentech, Horizon, Novartis, Roche and Sanofi for <br>speaker/travel honoraria.
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AbbVie, Biogen, Bristol Myers Squibb, Cigna, EMD Serono, <br>Janssen, Genentech, Greenwich Biosciences, Novartis, Octave <br>Bioscience, Sanofi and TG Therapeutics.
Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Janssen, <br>Genentech, Horizon, Novartis, Roche, Sanofi and TG <br>Therapeutics.
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AbbVie, Biogen, Bristol Myers Squibb, Greenwich Biosciences, <br>Novartis and Sanofi: research grant support.
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- Maria Trojano, MD,
MT has served on scientific Advisory Boards for Biogen, <br>Novartis, Merck, BMS, Roche and Genzyme
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M.T. received honoraria for travel, consultancy or <br>speaking from Biogen, Roche, Sanofi, Merck, Genzyme, <br>Janssen and Novartis
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M Trojano received research support for her Institution <br>by Novartis, Biogen, Roche, and Merck
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- Ashwini Patil, MS,
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Employee of Novartis Healthcare Pvt. Ltd., India
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- Benedict Rauser, PhD and
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Novartis Pharma GmbH, Medical Advisor, 5 years
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- Thomas Hach, MD
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Novartis Pharma AG, Executive Director, 7
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Novartis Pharma AG, 7
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- 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.
- Correspondence
Dr. Ziemssen tjalf.ziemssen{at}uniklinikum-dresden.de
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