title: Isolated new onset 'atypical' optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up.
abstract: Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Ab(neg) patients. 37 AQP4-Ab positive (AQP4-Ab(pos)) and 32 AQP4-Ab negative (AQP4-Ab(neg)) patients (8 with MOG-Ab) were identified. The AQP4-Ab(neg) group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Ab(neg) patients, AQP4-Ab(pos) patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0, p = 0.010) and at last assessment (median VFSS 5 versus 2, p = 0.005). However, AQP4-Ab(neg) patients with RION also had poor visual outcome. Up to 35% of AQP4-Ab(neg) patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Ab(neg) patients (25%) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome [VFSS 4, range (0-6)]. In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Ab(neg) RION also had a poor visual outcome. Of those without AQP4-Ab, 25% had MOG-Ab and another 25% developed MS; thus, MOG-Ab is associated with AQP4-Ab(neg) non-MS ON.
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.|IRCCS C. Mondino, University of Pavia, Pavia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Piccolo
authors.affiliation: Neuroimmunology Group, Nuffield Department of Clinical Neurosciences, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
authors.forename: M
authors.initials: M
authors.lastname: Woodhall
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.
authors.forename: G
authors.initials: G
authors.lastname: Tackley
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.
authors.forename: M
authors.initials: M
authors.lastname: Juryńczyk
authors.affiliation: FMRIB Centre, John Radcliffe Hospital, Oxford University, Headington, Oxford, OX3 9DU, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.|Centro Hospitalar do Porto, Hospital de Santo António, Serviço de Neurologia, Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Domingos
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.
authors.forename: R
authors.initials: R
authors.lastname: Gore
authors.affiliation: Neuroimmunology Group, Nuffield Department of Clinical Neurosciences, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Neuroimmunology Group, Nuffield Department of Clinical Neurosciences, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.
authors.forename: P
authors.initials: P
authors.lastname: Waters
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK.
authors.forename: M I
authors.initials: MI
authors.lastname: Leite
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK. jacqueline.palace@ndcn.ox.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Palace
mesh_terms: D000293:Adolescent; D000328:Adult; D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D009471:Neuromyelitis Optica / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D009902:Optic Neuritis / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; C571326:MOG protein, human; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: AQP4-Ab; MOG-Ab; Neuromyelitis optica; Optic neuritis; Visual loss