Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis

Rosa Cortese; Marco Battaglini; Ferran Prados; Giordano Gentile; Ludovico Luchetti; Alessia Bianchi; Lukas Haider; Anu Jacob; Jacqueline Palace; Silvia Messina; Friedemann Paul; Romain Marignier; Françoise Durand-Dubief; Carolina de Medeiros Rimkus; Samira Luisa Apostolos Pereira; Douglas Kazutoshi Sato; Massimo Filippi; Maria Assunta Rocca; Laura Cacciaguerra; Àlex Rovira; Jaume Sastre-Garriga; Georgina Arrambide; Yaou Liu; Yunyun Duan; Claudio Gasperini; Carla Tortorella; Serena Ruggieri; Maria Pia Amato; Monica Ulivelli; Sergiu Groppa; Matthias Grothe; Sara Llufriu; Maria Sepulveda; Carsten Lukas; Barbara Bellenberg; Ruth Schneider; Piotr Sowa; Elisabeth G Celius; Anne-Katrin Pröbstel; Cristina Granziera; Özgür Yaldizli; Jannis Müller; Bruno Stankoff; Benedetta Bodini; Frederik Barkhof; Olga Ciccarelli; Nicola De Stefano; MAGNIMS Study Group

doi:10.1002/ana.26951

Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis

Ann Neurol. 2024 Aug;96(2):276-288. doi: 10.1002/ana.26951. Epub 2024 May 23.

Authors

Rosa Cortese^{1

2}, Marco Battaglini^{1

3}, Ferran Prados^{2

4

5}, Giordano Gentile^{1

3}, Ludovico Luchetti^{1

3}, Alessia Bianchi², Lukas Haider², Anu Jacob^{6

7}, Jacqueline Palace⁸, Silvia Messina⁸, Friedemann Paul⁹, Romain Marignier¹⁰, Françoise Durand-Dubief¹⁰, Carolina de Medeiros Rimkus¹¹, Samira Luisa Apostolos Pereira¹², Douglas Kazutoshi Sato¹³, Massimo Filippi^{14

15

16

17

18}, Maria Assunta Rocca^{14

15

18}, Laura Cacciaguerra^{14

15}, Àlex Rovira¹⁹, Jaume Sastre-Garriga²⁰, Georgina Arrambide²⁰, Yaou Liu²¹, Yunyun Duan²¹, Claudio Gasperini²², Carla Tortorella²², Serena Ruggieri^{23

24}, Maria Pia Amato^{25

26}, Monica Ulivelli¹, Sergiu Groppa²⁷, Matthias Grothe²⁸, Sara Llufriu²⁹, Maria Sepulveda²⁹, Carsten Lukas^{30

31}, Barbara Bellenberg³⁰, Ruth Schneider^{30

31}, Piotr Sowa³², Elisabeth G Celius³³, Anne-Katrin Pröbstel³⁴, Cristina Granziera^{34

35}, Özgür Yaldizli³⁴, Jannis Müller^{34

35}, Bruno Stankoff³⁶, Benedetta Bodini³⁶, Frederik Barkhof^{4

37}, Olga Ciccarelli^{2

38}, Nicola De Stefano¹; MAGNIMS Study Group

Collaborators

MAGNIMS Study Group:
F Barkhof, N de Stefano, J Sastre-Garriga, O Ciccarelli, C Enzinger, M Filippi, Claudio Gasperini, L Kappos, J Palace, H Vrenken, À Rovira, M A Rocca, T Yousry

Affiliations

¹ Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
² Queen Square MS Center, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
³ SIENA imaging SRL, Siena, Italy.
⁴ Center for Medical Imaging Computing, Medical Physics, and Biomedical Engineering, UCL, London, UK.
⁵ E-Health Center University Oberta de Catalunya, Barcelona, Spain.
⁶ NMO Clinical Service at the Walton Centre, Liverpool, UK.
⁷ Department of Neurology, Cleveland Clinic, Abu Dhabi, UAE.
⁸ Department of Clinical Neurology, John Radcliffe Hospital, Oxford, UK.
⁹ Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitaetsmedizin Berlin, Berlin, Germany.
¹⁰ Department of Neurology, Multiple Sclerosis, Myelin Disorders, and Neuro-inflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Lyon, France.
¹¹ Department of Radiology and Oncology, Faculty of Medicine, University of São Paulo (FMUSP), São Paulo, Brazil.
¹² Department of Neurology, Faculty of Medicine, University of São Paulo (FMUSP), São Paulo, Brazil.
¹³ Pontifical Catholic University of Rio Grande do Sul (PUCRS), School of Medicine, Porto Alegre, Brazil.
¹⁴ Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁵ Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁶ Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁷ Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁸ Vita-Salute San Raffaele University, Milan, Italy.
¹⁹ Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
²⁰ Multiple Sclerosis Centre of Catalonia (Cemcat), Department of Neurology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
²¹ Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
²² Department of Neurosciences, S. Camillo-Forlanini Hospital, Rome, Italy.
²³ Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy.
²⁴ Neuroimmunology Unit, IRCSS Fondazione Santa Lucia, Rome, Italy.
²⁵ Department Neurofarba, University of Florence, Florence, Italy.
²⁶ IRCCS Don Carlo Gnocchi Foundation, Florence, Italy.
²⁷ Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
²⁸ Department of Neurology, University Medicine of Greifswald, Greifswald, Germany.
²⁹ Service of Neurology, Laboratory of Advanced Imaging in Neuroimmunological Diseases, Center of Neuroimmunology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), and Universitat de Barcelona, Barcelona, Spain.
³⁰ Institute of Neuroradiology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
³¹ Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
³² Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
³³ Department of Neurology, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway.
³⁴ Department of Neurology, Biomedicine and Clinical Research, and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital and University of Basel, Basel, Switzerland.
³⁵ Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
³⁶ Sorbonne University, Paris Brain Institute, ICM, Pitié Salpêtrière Hospital, Paris, France.
³⁷ Radiology & Nuclear medicine, VU University Medical Center, Amsterdam, The Netherlands.
³⁸ National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Center, London, UK.

PMID: 38780377
DOI: 10.1002/ana.26951

Abstract

Objective: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease.

Methods: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p < 0.05), volumes of atrophic areas are reported.

Results: We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm³); AQP4+NMOSD in the occipital cortex (32.83 cm³); and RRMS diffusely in the GM (260.61 cm³). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm³), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm³). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm³) and AQP4+NMOSD (47.04 cm³). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation.

Interpretation: GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024;96:276-288.

Publication types

Multicenter Study

MeSH terms

Adult
Aquaporin 4* / immunology
Atrophy* / pathology
Autoantibodies* / blood
Female
Gray Matter* / diagnostic imaging
Gray Matter* / pathology
Humans
Magnetic Resonance Imaging*
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
Multiple Sclerosis, Relapsing-Remitting / immunology
Multiple Sclerosis, Relapsing-Remitting / pathology
Myelin-Oligodendrocyte Glycoprotein* / immunology
Neuromyelitis Optica* / diagnostic imaging
Neuromyelitis Optica* / immunology
Neuromyelitis Optica* / pathology
Retrospective Studies
White Matter* / diagnostic imaging
White Matter* / immunology
White Matter* / pathology
Young Adult

Substances

Aquaporin 4
Myelin-Oligodendrocyte Glycoprotein
Autoantibodies
AQP4 protein, human