title: Myasthenia gravis-associated neuromyelitis optica-like disease: an immunological link between the central nervous system and muscle?
abstract: BACKGROUND
  Although overt involvement of the central nervous system (CNS) in myasthenia gravis (MG) is considered rare, hyperreflexia is a common and yet unexplained finding. Aquaporin 4 (AQP4), the target autoantigen in neuromyelitis optica, is expressed both in the CNS and in the neuromuscular junction.
  
  
  OBJECTIVE
  To evaluate the prevalence of even mild CNS involvement in patients with MG and to identify features indicative of neuromyelitis optica-like disease.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Outpatient clinic.
  
  
  METHODS
  A cohort of 164 patients with MG.
  
  
  METHODS
  In 24 patients with MG, signs of CNS involvement were detected; 15 of these patients had at least 1 additional paraclinical indication of neuromyelitis optica-like disease (presence of antibodies against AQP4, pathological visual evoked potentials, or white matter lesions detected on brain and/or spinal magnetic resonance imaging scans) and fulfilled the inclusion and exclusion criteria for our study.
  
  
  RESULTS
  Of the 15 patients who had at least 1 additional paraclinical indication of neuromyelitis optica-like disease, 14 had abnormal visual evoked potentials, and in 6 of 9 patients in whom magnetic resonance imaging was performed, there was evidence of lesions in the white matter of the brain and/or spinal cord. Anti-AQP4 antibodies were detected in 7 patients (out of the 14 tested). Thymic enlargement (hyperplasia or thymoma) was more frequent in patients with MG who had signs of CNS involvement than in patients with MG who did not.
  
  
  CONCLUSIONS
  The incidence of CNS involvement in MG is higher than previously reported and is expressed predominantly as a pyramidal syndrome accompanied by optical tract involvement (frequently subclinical). These features bear some resemblance to neuromyelitis optica spectrum disease, supported also by the presence of anti-AQP4 antibodies in 7 of the 14 patients tested. This association may represent a new nosological entity or may indicate that an autoimmune process targeting AQP4 is an integral part of the immunopathogenetic mechanisms in MG.
authors.affiliation: Department of Neurology, Multiple Sclerosis Center and Immunobiology Research Laboratory, Hadassah University Hospital, Ein Kerem, PO Box 12000, Jerusalem 91120, Israel. adembinsky@yahoo.com
authors.forename: Adi
authors.initials: A
authors.lastname: Vaknin-Dembinsky
authors.forename: Oded
authors.initials: O
authors.lastname: Abramsky
authors.forename: Panayiota
authors.initials: P
authors.lastname: Petrou
authors.forename: Tamir
authors.initials: T
authors.lastname: Ben-Hur
authors.forename: Marc
authors.initials: M
authors.lastname: Gotkine
authors.forename: Livnat
authors.initials: L
authors.lastname: Brill
authors.forename: Talma
authors.initials: T
authors.lastname: Brenner
authors.forename: Zohar
authors.initials: Z
authors.lastname: Argov
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karussis
mesh_terms: D000328:Adult; D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies; D015331:Cohort Studies; D005074:Evoked Potentials, Visual / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000175:diagnosis / Q000276:immunology*; D013945:Thymoma / Q000175:diagnosis / Q000276:immunology; D013953:Thymus Neoplasms / Q000175:diagnosis / Q000276:immunology; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies