Clinically relevant cranio-caudal patterns of cervical cord atrophy evolution in MS.


Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
12 11 2019
Historique:
received: 07 11 2018
accepted: 04 06 2019
pubmed: 16 10 2019
medline: 6 2 2020
entrez: 16 10 2019
Statut: ppublish

Résumé

To characterize the distribution and regional evolution of cervical cord atrophy in patients with multiple sclerosis (MS) in a multicenter dataset. MRI and clinical evaluations were acquired from 179 controls and 435 patients (35 clinically isolated syndromes [CIS], 259 relapsing-remitting multiple sclerosis [RRMS], 99 secondary progressive multiple sclerosis [SPMS], and 42 primary progressive multiple sclerosis [PPMS]). Sixty-nine controls and 178 patients underwent a 1-year MRI and clinical follow-up. Patients were classified as clinically stable/worsened according to their disability change. Longitudinal changes of cord atrophy were investigated with linear mixed-effect models. Sample size calculations were performed using age-, sex- and site-adjusted annualized percentage normalized cord cross-sectional area (CSAn) changes. Baseline CSAn was lower in patients with MS vs controls ( Cord atrophy increased in MS during 1 year, except for CIS. Faster atrophy contributed to explain clinical worsening.

Identifiants

pubmed: 31611336
pii: WNL.0000000000008466
doi: 10.1212/WNL.0000000000008466
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1852-e1866

Investigateurs

Nicola De Stefano (N)
Christian Enzinger (C)
Jette L. Frederiksen (JL)
Claudio Gasperini (C)
Ludwig Kappos (L)
Jaume Sastre- Garriga (J)
Tarek Yousry (T)

Informations de copyright

© 2019 American Academy of Neurology.

Auteurs

Maria A Rocca (MA)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy. rocca.mara@hsr.it.

Paola Valsasina (P)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Alessandro Meani (A)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Claudio Gobbi (C)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Chiara Zecca (C)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Àlex Rovira (À)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Xavier Montalban (X)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Hugh Kearney (H)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Olga Ciccarelli (O)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Lucy Matthews (L)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Jacqueline Palace (J)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Antonio Gallo (A)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Alvino Bisecco (A)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Achim Gass (A)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Philipp Eisele (P)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Carsten Lukas (C)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Barbara Bellenberg (B)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Frederik Barkhof (F)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Hugo Vrenken (H)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Paolo Preziosa (P)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Giancarlo Comi (G)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

Massimo Filippi (M)

From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.) and Neurology Unit (M.A.R., P.P., G.C., M.F.), Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Neurology (C.G., C.Z.), Neurocenter of Southern Switzerland, Regional Hospital Lugano (EOC), Lugano; Faculty of Biomedical Sciences (C.G., C.Z.), Università della Svizzera Italiana, Lugano, Switzerland; Section of Neuroradiology and MRI Unit, Department of Radiology (A.R.), and Department of Neurology/Neuroimmunology (X.M.), Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; NMR Research Unit (H.K., O.C.), Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London; Nuffield Department of Clinical Neurosciences (L.M., J.P.), University of Oxford, UK; Department of Advanced Medical and Surgical Sciences, and 3T MRI Center, (A.G., A.B.), University of Campania "Luigi Vanvitelli," Naples, Italy; Department of Neurology (A.G., P.E.), Universitätsmedizin Mannheim, University of Heidelberg, Germany; Department of Radiology and Nuclear Medicine (C.L., B.B.) and Institute of Neuroradiology (C.L., B.B.), St. Josef Hospital, Ruhr-University Bochum, Germany; Department of Radiology and Nuclear Medicine (F.B., H.V.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; and Vita-Salute San Raffaele University (P.P., G.C., M.F.), Milan, Italy.

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