title: Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes.
abstract: Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (p o = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (p o = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3, West Wing, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford, OX3 9DU, UK. maciej.jurynczyk@ndcn.ox.ac.uk.|Department of Neurology, Medical University of Lodz, Lodz, Poland. maciej.jurynczyk@ndcn.ox.ac.uk.
authors.forename: Maciej
authors.initials: M
authors.lastname: Juryńczyk
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, 55905, MN, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Weinshenker
authors.affiliation: Department of Neurology, School of Medicine, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Gulsen
authors.initials: G
authors.lastname: Akman-Demir
authors.affiliation: Department of Neurology, Vejle Hospital and Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Asgari
authors.affiliation: Department of Neurology, Atkinson Morley's Wing, St George's Hospital, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Barnes
authors.affiliation: The Townsville Hospital, 100 Angus Smith Drive, Douglas Qld 4814, Douglas, Townsville, Australia.
authors.forename: Mike
authors.initials: M
authors.lastname: Boggild
authors.affiliation: Department of Neurology, Queens Hospital Rom Valley Way, Romford, RM7 0AG, UK.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chaudhuri
authors.affiliation: Department of Neurology, University Hospital Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: D'hooghe
authors.affiliation: Division of Clinical Neuroscience, Queens Medical Center, University of Nottingham, Derby Road, Nottingham, NG7 2UH, UK.
authors.forename: Nikos
authors.initials: N
authors.lastname: Evangelou
authors.affiliation: Neuroscience Department, Santa Maria Hospital, University of Lisbon, Lisbon, Portugal.
authors.forename: Ruth
authors.initials: R
authors.lastname: Geraldes
authors.affiliation: Department of Neurology, Institute of Clinical Research, Odense, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
authors.affiliation: NMO Clinical Service, The Walton Centre, Liverpool, UK.
authors.forename: Anu
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Department of Neurology, National Cancer Center, Seoul, South Korea.
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kleiter
authors.affiliation: Neuromyelitis Optica Clinic, John Hopkins University, 1800 E. Orleans St., Baltimore, MD, 21287, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Levy
authors.affiliation: Service de Neurologie A, Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677, Lyon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Marignier
authors.affiliation: University College Dublin, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
authors.affiliation: Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Chancellor's Building, Edinburgh, EH16 4SB, UK.
authors.forename: Katy
authors.initials: K
authors.lastname: Murray
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, 980-8574, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.affiliation: Nitte University, Mangalore, 575018, Karnataka, India.
authors.forename: Lekha
authors.initials: L
authors.lastname: Pandit
authors.affiliation: Department of Neurology, NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Department of Neurology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Pittock
authors.affiliation: Department of Neurology, Medical University of Lodz, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: Neurology Service, University Hospital of Strasbourg, Strasbourg, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: de Sèze
authors.affiliation: Department of Neurology, Cerrahpasa School of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Aksel
authors.initials: A
authors.lastname: Siva
authors.affiliation: Division of Clinical Neuroscience, Queens Medical Center, University of Nottingham, Derby Road, Nottingham, NG7 2UH, UK.|Department of Neurology, Neurosurgery and Psychiatry, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
authors.forename: Radu
authors.initials: R
authors.lastname: Tanasescu
authors.affiliation: Service de Neurologie A, Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677, Lyon, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Vukusic
authors.affiliation: Mayo Clinic Division of Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, 13400 E Shea BLVD, Scottsdale, 85259, AZ, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Wingerchuk
authors.affiliation: Department of Neurology, Atkinson Morley's Wing, St George's Hospital, London, UK.
authors.forename: Damian
authors.initials: D
authors.lastname: Wren
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3, West Wing, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford, OX3 9DU, UK.
authors.forename: Isabel
authors.initials: I
authors.lastname: Leite
authors.affiliation: Nuffield Department of Clinical Neurosciences, Level 3, West Wing, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford, OX3 9DU, UK. jacqueline.palace@ndcn.ox.ac.uk.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
mesh_terms: D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D004673:Encephalomyelitis, Acute Disseminated / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D009471:Neuromyelitis Optica / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D013577:Syndrome
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D007074:Immunoglobulin G
keywords: All demyelinating disease (CNS); Devic’s syndrome; Multiple sclerosis; Optic neuritis; Transverse myelitis