title: Autoimmune N-methyl-D-aspartate receptor encephalitis is a differential diagnosis of infectious encephalitis.
abstract: BACKGROUND
  For 60% of acute febrile encephalitis cases, the cause is unknown. Autoantibodies directed against different synaptic proteins or receptors in patients with autoimmune encephalitis have recently been described and could indicate a differential diagnosis of infectious encephalitis.
  
  
  OBJECTIVE
  The aim of this study was to retrospectively investigate the presence of autoantibodies directed against synaptic proteins or receptors in patients with acute febrile encephalitis. Samples were collected in France in 2007 during a national prospective study.
  
  
  METHODS
  A total of 253 patients with acute febrile encephalitis were enrolled in 2007. Clinical data were collected with a standardized questionnaire. When possible, cerebrospinal fluid CSF was collected and stored at -80 °C. A total of 108 CSF samples were available for retrospective autoantibody screening. Among the 108 patients, infectious etiology had been detected in 38 cases (35%); of these 38 patients, 29 (27%) had viral encephalitis, and 9 (8%) had bacterial encephalitis. No specific diagnosis was indicated for the other 70 patients (65%). Autoantibodies were detected using a cell-based assay in which HEK293 cells were transfected with plasmids coding for different synaptic proteins or receptors.
  
  
  RESULTS
  Two patients had anti-NMDA receptor antibodies (NMDAR-Abs), and all patients were negative for anti-Lgi1, CASPR2, GABABR, AMPAR, and mGluR5 antibodies. The two patients with NMDAR-Abs presented neurological and psychiatric symptoms typical of NMDAR-Abs encephalitis.
  
  
  CONCLUSIONS
  Autoimmune etiology seems to be rare (less than 2%) in patients with acute febrile encephalitis. However, patients should be systematically screened for the presence of NMDAR-Abs, particularly patients presenting with psychiatric symptoms.
authors.affiliation: French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Neuro-oncology, F-69677 Bron, France. Electronic address: laure.thomas@chu-lyon.fr.
authors.forename: Laure
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Infectious Diseases Department, French Institute for Public Health Surveillance, F-94410 Saint Maurice, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mailles
authors.affiliation: Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, F-69372 Lyon, France; Lyon University - Université Claude Bernard Lyon 1, F-69372 Lyon, France; Hospices Civils de Lyon, Hôpital Neurologique, Neurology D, F-69677 Bron, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Desestret
authors.affiliation: French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Neuro-oncology, F-69677 Bron, France; Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, F-69372 Lyon, France; Lyon University - Université Claude Bernard Lyon 1, F-69372 Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ducray
authors.affiliation: French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Neuro-oncology, F-69677 Bron, France; Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, F-69372 Lyon, France; Lyon University - Université Claude Bernard Lyon 1, F-69372 Lyon, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Mathias
authors.affiliation: French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Neuro-oncology, F-69677 Bron, France; Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, F-69372 Lyon, France; Lyon University - Université Claude Bernard Lyon 1, F-69372 Lyon, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Rogemond
authors.affiliation: French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Neuro-oncology, F-69677 Bron, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Didelot
authors.affiliation: Pediatric Department, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, F-69677 Bron, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Marignier
authors.affiliation: Infectiology Department, CHU et Université 1, F-38041 Grenoble, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Stahl
authors.affiliation: French Reference Center on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Neuro-oncology, F-69677 Bron, France; Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, F-69372 Lyon, France; Lyon University - Université Claude Bernard Lyon 1, F-69372 Lyon, France. Electronic address: Jerome.honnorat@chu-lyon.fr.
authors.forename: Jerome
authors.initials: J
authors.lastname: Honnorat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000134:cerebrospinal fluid; D001927:Brain Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004660:Encephalitis; D004671:Encephalitis, Arbovirus / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology*; D016021:Epidemiologic Studies; D005260:Female; D005602:France / Q000453:epidemiology; D050031:Hashimoto Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Autoimmune encephalitis; Infectious encephalitis; NMDA receptor; Neuropsychiatric symptoms