Clinical phenotypes, radiological characterisation, therapeutic responses, and outcomes in myelin oligodendrocyte glycoprotein antibody-associated demyelination

Abstract

Background: Myelin oligodendrocyte glycoprotein (MOG) is a putative candidate antigen in demyelination. Aims: We sought to identify the clinical phenotypes, radiological characteristics, treatment responses, and outcomes in MOG antibody-associated demyelination. Methods: We performed a flow cytometry live cell based assay to detect MOG antibodies in adults with demyelination; undertook blinded neuroradiological assessment on 50 patients with first episode optic neuritis (ON) due to multiple sclerosis (MS), MOG, or aquaporin-4 (AQP4) antibodies; and evaluated treatment responses and outcomes in 33 children and 26 adults with relapsing MOG antibody-associated demyelination. Results: MOG antibodies were strongly associated with recurrent and bilateral ON (BON) with optic disc swelling [9/23 adults with AQP4 antibody-negative neuromyelitis optica spectrum disorder v.0/52 controls (p<0.001)]. There were low rates of MOG antibody-positivity in Australian MS (1/76) and Japanese opticospinal MS (2/50). Radiologically, bilateral longitudinally extensive optic nerve involvement was more common in MOG and AQP4-ON than MS-ON. MOG-ON exhibited anterior and AQP4-ON exhibited posterior visual pathway involvement. ON was dominant at initial presentation [BON 32%, unilateral (UON) 22%] and throughout the clinical course (BON 19%, UON 34%) in relapsing MOG antibody-associated demyelination. Patients were steroid responsive but 70% of episodes relapsed, especially at prednisone doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab, and mycophenolate, all reduced annualised relapse rates. 59% of patients experienced residual disability, particularly with increasing relapses. Conclusions: MOG antibodies are strongly associated with ON. Relapsing disease is steroid responsive but vulnerable to relapse, responds to immunosuppression, and has the potential to result in sustained disability.