title: Influence of female sex and fertile age on neuromyelitis optica spectrum disorders.
abstract: BACKGROUND
  Gender and age at onset are important epidemiological factors influencing prevalence, clinical presentation, and treatment response in autoimmune diseases.
  
  
  OBJECTIVE
  To evaluate the impact of female sex and fertile age on aquaporin-4-antibody (AQP4-ab) status, attack localization, and response to attack treatment in patients with neuromyelitis optica (NMO) and its spectrum disorders (neuromyelitis optica spectrum disorder (NMOSD)).
  
  
  METHODS
  Female-to-male ratios, diagnosis at last visit (NMO vs NMOSD), attack localization, attack treatment, and outcome were compared according to sex and age at disease or attack onset.
  
  
  RESULTS
  A total of 186 NMO/SD patients (82% female) were included. In AQP4-ab-positive patients, female predominance was most pronounced during fertile age (female-to-male ratio 23:1). Female patients were more likely to be positive for AQP4-abs (92% vs 55%; p < 0.001). Interval between onset and diagnosis of NMO/SD was longer in women than in men (mean 54 vs 27 months; p = 0.023). In women, attacks occurring ⩽40 years of age were more likely to show complete remission ( p = 0.003) and better response to high-dose intravenous steroids ( p = 0.005) compared to woman at >40 years.
  
  
  CONCLUSIONS
  Our data suggest an influence of sex and age on susceptibility to AQP4-ab-positive NMO/SD. Genetic and hormonal factors might contribute to pathophysiology of NMO/SD.
authors.affiliation: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Borisow
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kleiter
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Gahlen
authors.affiliation: Department of Neurology, Asklepios Fachklinikum Teupitz, Teupitz, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Fischer
authors.affiliation: CRO SOSTANA GmbH and Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.affiliation: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Florence
authors.initials: F
authors.lastname: Pache
authors.affiliation: Department of Neurology and Clinical and Experimental Multiple Sclerosis Research Center, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: Institute of Clinical Neuroimmunology, Medical Campus Grosshadern, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Havla
authors.affiliation: Institute of Clinical Neuroimmunology, Medical Campus Grosshadern, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Krumbholz
authors.affiliation: Institute of Clinical Neuroimmunology, Medical Campus Grosshadern, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ringelstein
authors.affiliation: Department of Neurology, University Hospital of Würzburg, Würzburg, Germany/Hans-Berger Department of Neurology and Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Geis
authors.affiliation: Department of Neurology, University Hospital Essen, Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Berthele
authors.affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany/Munich Cluster for Systems Neurology (SyNergy), Technische Universität München, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.affiliation: Department of Neurology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Angstwurm
authors.affiliation: Department of Neurology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Weissert
authors.affiliation: Institute of Neuroimmunology and MS (INIMS), University Medical Center Hamburg-Eppendorf, Hamburg, Germany/Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jan-Patrick
authors.initials: JP
authors.lastname: Stellmann
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schuster
authors.affiliation: Department of Clinical Neuroimmunology and Neurochemistry and Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lauda
authors.affiliation: Department of Neurology at RKU and Specialty Clinic of Neurology Dietenbronn, University of Ulm, Ulm, Germany.
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.affiliation: Department of Neurology, Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mayer
authors.affiliation: Department of Neurology and Stroke and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Zeltner
authors.affiliation: Department of Neurology and Stroke and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Ziemann
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nüremberg, Erlangen, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.affiliation: Hans-Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Department of Neurology, University of Münster, Münster, Germany/Department of Neurology and Neurological Intensive Care, Isar-Amper-Clinic, Munich-East, Haar, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Marziniak
authors.affiliation: Department of Neurology, Leipzig University, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Then Bergh
authors.affiliation: Department of Neurology, Klinikum Bayreuth, Bayreuth, Germany/Department of Neurology, Klinikum Westfalen, Dortmund, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hofstadt-van Oy
authors.affiliation: Department of Neurology, SRH Krankenhaus Sigmaringen, Sigmaringen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Neuhaus
authors.affiliation: Department of Neurology, University of Rostock, Rostock, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Winkelmann
authors.affiliation: Department of Neurology, HELIOS Hanseklinikum Stralsund, Stralsund, Germany.
authors.forename: Wael
authors.initials: W
authors.lastname: Marouf
authors.affiliation: Department of Neurology, MediClin Hedon Klinik, Lingen, Germany.
authors.forename: Lioba
authors.initials: L
authors.lastname: Rückriem
authors.affiliation: Department of Neurology, Asklepios Fachklinikum Teupitz, Teupitz, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Faiss
authors.affiliation: Department of Neurology, Heidelberg University, Heidelberg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
authors.affiliation: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Berlin, Germany/Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Department of Neurology, Heidelberg University, Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jarius
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Trebst
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hellwig
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D005260:Female; D005298:Fertility / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000235:genetics / Q000276:immunology*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies
keywords: Neuromyelitis optica; age factors; aquaporin 4; sex