Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab.


Journal

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

Informations de publication

Date de publication:
07 2021
Historique:
received: 23 11 2020
accepted: 03 03 2021
entrez: 27 4 2021
pubmed: 28 4 2021
medline: 22 1 2022
Statut: epublish

Résumé

The study aimed to assess the potential for serum neurofilament light chain (NFL) levels to predict the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab (NTZ)-treated patients with multiple sclerosis (MS) and to discriminate PML from MS relapses. NFL levels were measured with single molecule array (Simoa) in 4 cohorts: (1) a prospective cohort of patients with MS who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr); (2) a cohort of patients whose blood was collected during PML; (3) an independent cohort of non-PML NTZ-treated patients with serum NFL determinations at 2 years (replication cohort); and (4) a cohort of patients whose blood was collected during exacerbations. Serum NFL levels were significantly increased after 2 years of NTZ treatment in pre-PML patients compared with NTZ-ctr. The prognostic performance of serum NFL levels to predict PML development at 2 years was similar in the NTZ-ctr group and replication cohort. Serum NFL levels also distinguished PML from MS relapses and were 8-fold higher during PML compared with relapses. These results support the use of serum NFL levels in clinical practice to identify patients with relapsing-remitting MS at higher PML risk and to differentiate PML from clinical relapses in NTZ-treated patients. This study provides Class I evidence that serum NFL levels can identify NTZ-treated patients with MS who will develop PML with a sensitivity of 67% and specificity of 80%.

Identifiants

pubmed: 33903203
pii: 8/4/e1003
doi: 10.1212/NXI.0000000000001003
pmc: PMC8105883
pii:
doi:

Substances chimiques

Immunologic Factors 0
Natalizumab 0
Neurofilament Proteins 0
neurofilament protein L 0

Types de publication

Clinical Trial Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

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

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Auteurs

Nicolás Fissolo (N)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Beatrice Pignolet (B)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Jordi Rio (J)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Patrick Vermersch (P)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Aurélie Ruet (A)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Jerome deSèze (J)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Pierre Labauge (P)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Sandra Vukusic (S)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Caroline Papeix (C)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Laurent Martinez-Almoyna (L)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Ayman Tourbah (A)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Pierre Clavelou (P)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Thibault Moreau (T)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Jean Pelletier (J)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Christine Lebrun-Frenay (C)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Bertrand Bourre (B)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Gilles Defer (G)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Xavier Montalban (X)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

David Brassat (D)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.

Manuel Comabella (M)

From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France. nicolas.fissolo@vhir.org.

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