title: Clinical relevance of serum antibodies to extracellular N-methyl-D-aspartate receptor epitopes.
abstract: OBJECTIVE
  There are now a large number of requests for N-methyl-D-aspartate receptor autoantibody (NMDAR-Ab) tests, and it is important to assess the clinical relevance of all results, particularly when they are reported as 'Low Positive'.
  
  
  METHODS
  The clinical data of 56 patients found Positive or Low Positive by the Oxford live cell-based assay were reviewed. An autoimmune basis for the condition was assigned as 'Definite', 'Possible' or 'Unlikely'. The number of core features (encephalopathy, psychiatric, cognitive, epileptic, extrapyramidal and inflammatory cerebrospinal fluid (CSF)) was tabulated.
  
  
  RESULTS
  Twenty-five (44.6%) patients had a Definite NMDAR-Ab encephalitis (eight ovarian teratomas, one Hodgkin's lymphoma), 18 (32.1%) a Possible NMDAR-Ab encephalitis and 13 (23.2%) an Unlikely autoimmune syndrome. Serum NMDAR-Ab levels were higher in patients with tumours. Positive NMDAR-Abs were found not only in patients with three or more core features and a Definite syndrome, but also in five patients classified as Possible. Conversely, Low Positive NMDAR-Abs were present in 7 Definite cases as well as in 13 Possible cases. Unlikely patients had mainly Low Positive antibodies and fewer core features. CSF NMDAR-Abs, only available in 11 pairs and at varying time points, broadly related to serum levels and were Positive in 3/3 patients with tumours but in only 2/5 Definite patients, and none of the Possible or Unlikely cases.
  
  
  CONCLUSIONS
  Using live cell-based assays, Positive and Low Positive antibodies can be of clinical significance. The number of core clinical features should help to select those patients in whom an immunotherapy intervention might be considered, irrespective of the antibody level.
authors.affiliation: Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Zandi
authors.affiliation: National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.
authors.forename: Ross W
authors.initials: RW
authors.lastname: Paterson
authors.affiliation: Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ellul
authors.affiliation: Neurosciences Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
authors.forename: Leslie
authors.initials: L
authors.lastname: Jacobson
authors.affiliation: Neurosciences Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Al-Diwani
authors.affiliation: Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Jones
authors.affiliation: Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Cox
authors.affiliation: Department of Psychiatry, Warneford Hospital, Oxford, UK.
authors.forename: Belinda
authors.initials: B
authors.lastname: Lennox
authors.affiliation: National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Stamelou
authors.affiliation: National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.
authors.forename: Kailash P
authors.initials: KP
authors.lastname: Bhatia
authors.affiliation: National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.affiliation: Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Coles
authors.affiliation: National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK.
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Kullmann
authors.affiliation: National Hospital for Neurology and Neurosurgery, UCL Institute of Neurology, London, UK Neurosciences Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
mesh_terms: D000293:Adolescent; D000328:Adult; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009384:Paraneoplastic Endocrine Syndromes / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D016194:Receptors, N-Methyl-D-Aspartate
keywords: IMMUNOLOGY; NEUROIMMUNOLOGY; NMDA; PARANEOPLASTIC SYNDROME; PSYCHIATRY