title: Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature.
abstract: BACKGROUND
  Neuromyelitis optica (NMO, Devic syndrome) and myasthenia gravis (MG) are rare antibody-mediated autoimmune disorders. Concurrent incidence has been reported in only few patients, mostly non-Caucasians.
  
  
  OBJECTIVE
  To report on ten Caucasian patients with NMO spectrum disorders (NMOSD) and MG and to provide a comprehensive review of the literature.
  
  
  METHODS
  Retrospective study.
  
  
  RESULTS
  In total, 26 patients (m:f = 1:12; Caucasian in 12) with MG (generalized in 17) and NMOSD (NMO in 21, longitudinally extensive transverse myelitis in five) were identified from the authors' own files (n = 10) and the previous literature (n = 16). MG preceded NMOSD in 24/25 cases (96%). AQP4-Ab were tested in 20 patients and were positive in 17 (85%). Twenty out of 25 patients (80%) had been treated with thymectomy or thymic irradiation, which preceded NMOSD in all cases (median latency, 12 years; range, 0.3-32). At last follow-up, complete remission of MG was reported in 15/22 (68%), and MG was well controlled with pyridostigmine in three. Co-existing autoimmune disorders or autoimmune antibodies were reported in 17 patients.
  
  
  CONCLUSIONS
  Our study demonstrates that i) AQP4-Ab-positive NMOSD are more commonly associated with MG in Caucasians than previously thought; ii) MG precedes NMOSD in most cases, often by more than a decade; iii) NMOSD almost exclusively occur in females with juvenile or early-onset MG; and iv) MG frequently takes an unusually mild course in patients with NMOSD. A history of thymectomy could be a possible risk factor for the later development of NMOSD. We recommend testing for AQP4-Ab in MG patients presenting with atypical motor or optic symptoms.
authors.affiliation: Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jarius
authors.forename: F
authors.initials: F
authors.lastname: Paul
authors.forename: D
authors.initials: D
authors.lastname: Franciotta
authors.forename: J
authors.initials: J
authors.lastname: de Seze
authors.forename: C
authors.initials: C
authors.lastname: Münch
authors.forename: M
authors.initials: M
authors.lastname: Salvetti
authors.forename: K
authors.initials: K
authors.lastname: Ruprecht
authors.forename: M
authors.initials: M
authors.lastname: Liebetrau
authors.forename: K P
authors.initials: KP
authors.lastname: Wandinger
authors.forename: G
authors.initials: G
authors.lastname: Akman-Demir
authors.forename: A
authors.initials: A
authors.lastname: Melms
authors.forename: W
authors.initials: W
authors.lastname: Kristoferitsch
authors.forename: B
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000293:Adolescent; D000328:Adult; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications* / Q000175:diagnosis / Q000208:ethnology / Q000276:immunology / Q000628:therapy; D009471:Neuromyelitis Optica / Q000150:complications* / Q000175:diagnosis / Q000208:ethnology / Q000276:immunology; D043025:Oligoclonal Bands / Q000097:blood / Q000134:cerebrospinal fluid; D011729:Pyridostigmine Bromide / Q000627:therapeutic use; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013934:Thymectomy; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D002800:Cholinesterase Inhibitors; D043025:Oligoclonal Bands; D011729:Pyridostigmine Bromide