Simon Rinaldi1, Alexander Davies1, Janev Fehmi1, Heidi N Beadnall1, Justine Wang1, Todd A Hardy1, Michael H Barnett1, Simon A Broadley1, Patrick Waters1, Stephen W Reddel1, Sarosh R Irani1, Fabienne Brilot1, Russell C Dale1, Sudarshini Ramanathan2. 1. From the Inflammatory Neuropathy Group (S. Rinaldi, A.D., J.F.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital; University of Oxford; Department of Neurology (S. Rinaldi, S.R.I.), Oxford University Hospitals NHS Foundation Trust, UK; Department of Neurology (H.N.B., M.H.B.), Royal Prince Alfred Hospital, Sydney; Brain and Mind Centre (H.N.B., T.A.H., M.H.B., S.W.R., F.B., R.C.D.), University of Sydney; Department of Neurology (J.W.), St George Hospital, Sydney; Department of Neurology (T.A.H., S.W.R., S. Ramanathan), Concord Repatriation General Hospital, Sydney; Menzies Institute of Health Queensland (S.A.B.), Griffith University; Department of Neurology (S.A.B.), Gold Coast University Hospital, Australia; Autoimmune Neurology Group (P.W., S.R.I., S. Ramanathan), Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital; University of Oxford, UK; Brain Autoimmunity and Clinical Neuroimmunology Groups (F.B., R.C.D., S. Ramanathan), Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney; Faculty of Medicine and Health (F.B., R.C.D., S. Ramanathan), University of Sydney; School of Medical Sciences (F.B.), Discipline of Applied Medical Science, Faculty of Medicine and Health, University of Sydney, Australia; and TY Nelson Department of Paediatric Neurology (R.C.D.), Children's Hospital at Westmead, Sydney, Australia. 2. From the Inflammatory Neuropathy Group (S. Rinaldi, A.D., J.F.), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital; University of Oxford; Department of Neurology (S. Rinaldi, S.R.I.), Oxford University Hospitals NHS Foundation Trust, UK; Department of Neurology (H.N.B., M.H.B.), Royal Prince Alfred Hospital, Sydney; Brain and Mind Centre (H.N.B., T.A.H., M.H.B., S.W.R., F.B., R.C.D.), University of Sydney; Department of Neurology (J.W.), St George Hospital, Sydney; Department of Neurology (T.A.H., S.W.R., S. Ramanathan), Concord Repatriation General Hospital, Sydney; Menzies Institute of Health Queensland (S.A.B.), Griffith University; Department of Neurology (S.A.B.), Gold Coast University Hospital, Australia; Autoimmune Neurology Group (P.W., S.R.I., S. Ramanathan), Nuffield Department of Clinical Neuroscience, John Radcliffe Hospital; University of Oxford, UK; Brain Autoimmunity and Clinical Neuroimmunology Groups (F.B., R.C.D., S. Ramanathan), Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney; Faculty of Medicine and Health (F.B., R.C.D., S. Ramanathan), University of Sydney; School of Medical Sciences (F.B.), Discipline of Applied Medical Science, Faculty of Medicine and Health, University of Sydney, Australia; and TY Nelson Department of Paediatric Neurology (R.C.D.), Children's Hospital at Westmead, Sydney, Australia. sudarshini.ramanathan@sydney.edu.au.
Abstract
OBJECTIVE: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody-associated disorders (MOGAD), we performed detailed characterization of an Australasian MOGAD cohort. METHODS: Using a live cell-based assay, we diagnosed 271 adults with MOGAD (2013-2018) and performed detailed clinical and immunologic characterization on those with likely PNS involvement. RESULTS: We identified 19 adults with MOGAD and PNS involvement without prior TM. All patients had CNS involvement including ON (bilateral [n = 3], unilateral [n = 3], and recurrent [n = 7]), a cortical lesion (n = 1), meningoencephalitis (n = 1), and subsequent TM (n = 4). Clinical phenotyping and neurophysiology were consistent with acute inflammatory demyelinating polyneuropathy (n = 1), myeloradiculitis (n = 3), multifocal motor neuropathy (n = 1), brachial neuritis (n = 2), migrant sensory neuritis (n = 3), and paresthesia and/or radicular limb pain (n = 10). Onset MRI spine was consistent with myeloradiculitis with nerve root enhancement in 3/19 and normal in 16/19. Immunotherapy resulted in partial/complete PNS symptom resolution in 12/15 (80%) (steroids and/or IV immunoglobulin n = 9, rituximab n = 2, and plasmapheresis n = 1). We identified serum antibodies targeting neurofascin 155, contactin-associated protein 2, or GM1 in 4/16 patients with MOGAD PNS compared with 0/30 controls (p = 0.01). There was no binding to novel cell surface antigens using an in vitro myelinating sensory neuronal coculture model. CONCLUSIONS: Myeloradiculitis, combined central and peripheral demyelination syndromes, and inflammatory neuropathies may be associated with MOGAD and may be immunotherapy responsive. We identified a subgroup who may have pathology mediated by coexistent autoantibodies.
OBJECTIVE: Antibodies to myelin oligodendrocyte glycoprotein (MOG) are associated with CNS demyelination inclusive of optic neuritis (ON) and transverse myelitis (TM). To examine whether peripheral nervous system (PNS) involvement is associated with MOG antibody-associated disorders (MOGAD), we performed detailed characterization of an Australasian MOGAD cohort. METHODS: Using a live cell-based assay, we diagnosed 271 adults with MOGAD (2013-2018) and performed detailed clinical and immunologic characterization on those with likely PNS involvement. RESULTS: We identified 19 adults with MOGAD and PNS involvement without prior TM. All patients had CNS involvement including ON (bilateral [n = 3], unilateral [n = 3], and recurrent [n = 7]), a cortical lesion (n = 1), meningoencephalitis (n = 1), and subsequent TM (n = 4). Clinical phenotyping and neurophysiology were consistent with acute inflammatory demyelinating polyneuropathy (n = 1), myeloradiculitis (n = 3), multifocal motor neuropathy (n = 1), brachial neuritis (n = 2), migrant sensory neuritis (n = 3), and paresthesia and/or radicular limb pain (n = 10). Onset MRI spine was consistent with myeloradiculitis with nerve root enhancement in 3/19 and normal in 16/19. Immunotherapy resulted in partial/complete PNS symptom resolution in 12/15 (80%) (steroids and/or IV immunoglobulin n = 9, rituximab n = 2, and plasmapheresis n = 1). We identified serum antibodies targeting neurofascin 155, contactin-associated protein 2, or GM1 in 4/16 patients with MOGAD PNS compared with 0/30 controls (p = 0.01). There was no binding to novel cell surface antigens using an in vitro myelinating sensory neuronal coculture model. CONCLUSIONS: Myeloradiculitis, combined central and peripheral demyelination syndromes, and inflammatory neuropathies may be associated with MOGAD and may be immunotherapy responsive. We identified a subgroup who may have pathology mediated by coexistent autoantibodies.
Authors: Elia Sechi; Laura Cacciaguerra; John J Chen; Sara Mariotto; Giulia Fadda; Alessandro Dinoto; A Sebastian Lopez-Chiriboga; Sean J Pittock; Eoin P Flanagan Journal: Front Neurol Date: 2022-06-17 Impact factor: 4.086
Authors: Giulia Fadda; Cesar A Alves; Julia O'Mahony; Denise A Castro; E Ann Yeh; Ruth Ann Marrie; Douglas L Arnold; Patrick Waters; Amit Bar-Or; Arastoo Vossough; Brenda Banwell Journal: JAMA Netw Open Date: 2021-10-01
Authors: David L Bennett; Sarosh R Irani; Sudarshini Ramanathan; Mandy Tseng; Alexander J Davies; Christopher E Uy; Sofija Paneva; Victor C Mgbachi; Sophia Michael; James A Varley; Sophie Binks; Andreas C Themistocleous; Janev Fehmi; Yaacov Anziska; Anushka Soni; Monika Hofer; Patrick Waters; Fabienne Brilot; Russell C Dale; John Dawes; Simon Rinaldi Journal: Ann Neurol Date: 2021-08-30 Impact factor: 11.274