TY - JOUR
T1 - Clinical and MRI measures to identify non-acute MOG-antibody disease in adults
AU - Cortese, Rosa
AU - Battaglini, Marco
AU - Prados, Ferran
AU - Bianchi, Alessia
AU - Haider, Lukas
AU - Jacob, Anu
AU - Palace, Jacqueline
AU - Messina, Silvia
AU - Paul, Friedemann
AU - Wuerfel, Jens
AU - Marignier, Romain
AU - Durand-Dubief, Françoise
AU - de Medeiros Rimkus, Carolina
AU - Callegaro, Dagoberto
AU - Sato, Douglas Kazutoshi
AU - Filippi, Massimo
AU - Rocca, Maria Assunta
AU - Cacciaguerra, Laura
AU - Rovira, Alex
AU - Sastre-Garriga, Jaume
AU - Arrambide, Georgina
AU - Liu, Yaou
AU - Duan, Yunyun
AU - Gasperini, Claudio
AU - Tortorella, Carla
AU - Ruggieri, Serena
AU - Amato, Maria Pia
AU - Ulivelli, Monica
AU - Groppa, Sergiu
AU - Grothe, Matthias
AU - Llufriu, Sara
AU - Sepulveda, Maria
AU - Lukas, Carsten
AU - Bellenberg, Barbara
AU - Schneider, Ruth
AU - Sowa, Piotr
AU - Celius, Elisabeth G.
AU - Proebstel, Anne-Katrin
AU - Yaldizli, Özgür
AU - Müller, Jannis
AU - Stankoff, Bruno
AU - Bodini, Benedetta
AU - Carmisciano, Luca
AU - Sormani, Maria Pia
AU - Barkhof, Frederik
AU - de Stefano, Nicola
AU - Ciccarelli, Olga
AU - the MAGNIMS Study Group
AU - Enzinger, C.
AU - Kappos, L.
AU - Vrenken, H.
N1 - Funding Information: The present research was conducted thanks to the 2019 ECTRIMS-MAGNIMS fellowship (awarded to R.C.). Publisher Copyright: © The Author(s) 2022.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T 2 lesions, T 1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice.
AB - MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T 2 lesions, T 1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice.
KW - aquaporin 4-antibody positive neuromyelitis optica spectrum disorder
KW - differential diagnosis
KW - imaging
KW - multiple sclerosis
KW - myelin oligodendrocyte glycoprotein antibody-associated disease
UR - http://www.scopus.com/inward/record.url?scp=85150074894&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/brain/awac480
DO - https://doi.org/10.1093/brain/awac480
M3 - Article
C2 - 36515653
SN - 0006-8950
VL - 146
SP - 2489
EP - 2501
JO - Brain
JF - Brain
IS - 6
ER -