Association of Gray Matter Atrophy Patterns With Clinical Phenotype and Progression in Multiple Sclerosis

Maria A Rocca; Paola Valsasina; Alessandro Meani; Claudio Gobbi; Chiara Zecca; Alex Rovira; Jaume Sastre-Garriga; Hugh Kearney; Olga Ciccarelli; Lucy Matthews; Jacqueline Palace; Antonio Gallo; Alvino Bisecco; Carsten Lukas; Barbara Bellenberg; Frederik Barkhof; Hugo Vrenken; Paolo Preziosa; Massimo Filippi; MAGNIMS Study Group

doi:10.1212/WNL.0000000000011494

Association of Gray Matter Atrophy Patterns With Clinical Phenotype and Progression in Multiple Sclerosis

Neurology. 2021 Mar 16;96(11):e1561-e1573. doi: 10.1212/WNL.0000000000011494. Epub 2021 Jan 13.

Authors

Maria A Rocca¹, Paola Valsasina², Alessandro Meani², Claudio Gobbi², Chiara Zecca², Alex Rovira², Jaume Sastre-Garriga², Hugh Kearney², Olga Ciccarelli², Lucy Matthews², Jacqueline Palace², Antonio Gallo², Alvino Bisecco², Carsten Lukas², Barbara Bellenberg², Frederik Barkhof², Hugo Vrenken², Paolo Preziosa², Massimo Filippi²; MAGNIMS Study Group

Collaborators

MAGNIMS Study Group:
Nicola De Stefano, Christian Enzinger, Claudio Gasperini, Ludwig Kappos, Tarek Yousry

Affiliations

¹ From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.), Division of Neuroscience, Neurology Unit (M.A.R., P.P., M.F.), Neurorehabilitation Unit, and Neurophysiology Service (M.F.), IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University (M.A.R., M.F.), Milan, Italy; Multiple Sclerosis Center (C.G., C.Z.), Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital; Faculty of Biomedical Sciences Università della Svizzera Italiana (C.G., C.Z.), Lugano, Switzerland; Section of Neuroradiology (A.R.), Department of Radiology, and Department of Neurology/Neuroimmunology (J.S.-G.), Multiple Sclerosis Center 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 (A.G., A.B.) and 3T MRI-Center (A.G., A.B.), University of Campania Luigi Vanvitelli, Naples, Italy; Institute of Neuroradiology at the Department of Radiology and Nuclear Medicine (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; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK. rocca.mara@hsr.it.
² From the Neuroimaging Research Unit (M.A.R., P.V., A.M., P.P., M.F.), Division of Neuroscience, Neurology Unit (M.A.R., P.P., M.F.), Neurorehabilitation Unit, and Neurophysiology Service (M.F.), IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University (M.A.R., M.F.), Milan, Italy; Multiple Sclerosis Center (C.G., C.Z.), Department of Neurology, Neurocenter of Southern Switzerland, Civic Hospital; Faculty of Biomedical Sciences Università della Svizzera Italiana (C.G., C.Z.), Lugano, Switzerland; Section of Neuroradiology (A.R.), Department of Radiology, and Department of Neurology/Neuroimmunology (J.S.-G.), Multiple Sclerosis Center 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 (A.G., A.B.) and 3T MRI-Center (A.G., A.B.), University of Campania Luigi Vanvitelli, Naples, Italy; Institute of Neuroradiology at the Department of Radiology and Nuclear Medicine (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; and Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK.

PMID: 33441452
DOI: 10.1212/WNL.0000000000011494

Abstract

Objectives: Gay matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes.

Methods: Clinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 patients with MS (34 with clinically isolated syndrome [CIS], 226 with relapsing-remitting MS [RRMS], 95 with secondary progressive MS [SPMS], and 43 with primary progressive MS [PPMS]). Fifty-seven HCs and 144 with MS underwent 1-year follow-up. Baseline GM loss, atrophy progression, and correlations with disability and 1-year clinical worsening were assessed.

Results: SBM identified 26 cerebellar, subcortical, sensory, motor, and cognitive GM components. GM atrophy was found in patients with MS vs HCs in almost all components (p range <0.001-0.04). Compared to HCs, patients with CIS showed circumscribed subcortical, cerebellar, temporal, and salience GM atrophy, while patients with RRMS exhibited widespread GM atrophy. Cerebellar, subcortical, sensorimotor, salience, and frontoparietal GM atrophy was found in patients with PPMS vs HCs and in patients with SPMS vs those with RRMS. At 1 year, 21 (15%) patients had clinically worsened. GM atrophy progressed in MS in subcortical, cerebellar, sensorimotor, and fronto-temporo-parietal components. Baseline higher disability was associated (R ² = 0.65) with baseline lower normalized brain volume (β = -0.13, p = 0.001), greater sensorimotor GM atrophy (β = -0.12, p = 0.002), and longer disease duration (β = 0.09, p = 0.04). Baseline normalized GM volume (odds ratio 0.98, p = 0.008) and cerebellar GM atrophy (odds ratio 0.40, p = 0.01) independently predicted clinical worsening (area under the curve 0.83).

Conclusion: GM atrophy differed across disease phenotypes and progressed at 1 year in MS. In addition to global atrophy measures, sensorimotor and cerebellar GM atrophy explained baseline disability and clinical worsening.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Atrophy / pathology
Brain / pathology*
Disease Progression
Female
Gray Matter / pathology*
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis / pathology*
Phenotype

Grants and funding

DH_/Department of Health/United Kingdom