Clinical and MRI measures to identify non-acute MOG-antibody disease in adults
Authors: Cortese Rosa , Battaglini Marco , Prados Ferran , Bianchi Alessia , Haider Lukas , Jacob Anu , Palace Jacqueline , Messina Silvia , Paul Friedemann , Wuerfel Jens , Marignier Romain , Durand-Dubief Françoise , de Medeiros Rimkus Carolina , Callegaro Dagoberto , Sato Douglas Kazutoshi , Filippi Massimo , Rocca Maria Assunta , Cacciaguerra Laura , Rovira Alex , Sastre-Garriga Jaume , Arrambide Georgina , Liu Yaou , Duan Yunyun , Gasperini Claudio , Tortorella Carla , Ruggieri Serena , Amato Maria Pia , Ulivelli Monica , Groppa Sergiu , Grothe Matthias , Llufriu Sara , Sepulveda Maria , Lukas Carsten , Bellenberg Barbara , Schneider Ruth , Sowa Piotr , Celius Elisabeth G , Proebstel Anne-Katrin , Yaldizli Özgür , Müller Jannis , Stankoff Bruno , Bodini Benedetta , Carmisciano Luca , Sormani Maria Pia , Barkhof Frederik , De Stefano Nicola , Ciccarelli Olga ,   for the MAGNIMS Study Group, Barkhof F , de Stefano N , Sastre-Garriga J , Ciccarelli O , Enzinger C , Filippi M , Gasperini C , Kappos L , Palace J , Vrenken H , Rovira À , Rocca M A , Yousry T 
Published: December 2022

Abstract
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 T2 lesions, T1-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 (&lt;34 years), with low disability (EDSS &lt; 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 &lt; 0.001). In these non-acute patients, the number of brain lesions &lt; 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P &lt; 0.001). An EDSS &lt; 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 &lt; 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.