title: Psychiatric phenomena as initial manifestation of encephalitis by anti-NMDAR antibodies.
abstract: OBJECTIVE
  Autoimmune encephalitis associated with autoantibodies against the N-methyl-d-aspartate receptor (NMDAR) often presents with behavioural change. Our objective was to describe in detail the psychiatric presentation and pathways to care in order to aid the early diagnosis of NMDAR encephalitis.
  
  
  METHODS
  Sera and cerebrospinal fluid (CSF) from patients with suspected NMDAR encephalitis were tested on HEK 293 cells transfected with the NR1 subunit of the NMDAR. Clinical information was obtained from the referring psychiatrists and neurologists and by review of the clinical records.
  
  
  RESULTS
  Samples from 15 patients (13 female, 2 male, mean age 24 years, range 5-56 years) tested anti-NMDAR positive. Twelve of the 15 patients (80%) presented with prominent psychiatric symptoms and 8 were initially referred to a psychiatric service. The most prominent initial psychiatric symptoms were anxiety in seven (47%), behavioural change (often bizarre) in six (40%) and agitation in five (33%). All patients developed psychiatric symptoms in the first 6 weeks of illness. Thirteen patients received psychotropic medications: antipsychotics in 12 and benzodiazepines in 11. Treating physicians considered the psychotropic medication not effective in 11 patients resulting in many drug switches. At nadir, all patients were in a very poor condition. However, eight patients (53%) recovered (almost) completely. Outcome tended to be better in patients who had received early immunotherapy or tumour removal.
  
  
  CONCLUSIONS
  Autoimmune encephalitis and anti-NMDAR testing in serum and CSF should be considered in patients, especially young females, presenting with atypical psychiatric phenomena. Early diagnosis and treatment will likely improve the prognosis of NMDAR encephalitis.
authors.affiliation: 1 Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Maat
authors.affiliation: 1 Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: de Graaff
authors.affiliation: 3 Department of Psychiatry, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Nico M
authors.initials: NM
authors.lastname: van Beveren
authors.affiliation: 1 Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Hulsenboom
authors.affiliation: 4 Department of Pathology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Verdijk
authors.affiliation: 3 Department of Psychiatry, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Koorengevel
authors.affiliation: 1 Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: van Duijn
authors.affiliation: 5 Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Herbert
authors.initials: H
authors.lastname: Hooijkaas
authors.affiliation: 2 Department of Neurosciences, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Casper
authors.initials: C
authors.lastname: Hoogenraad
authors.affiliation: 1 Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sillevis Smitt