title: Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.
abstract: OBJECTIVE
  Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome.
  
  
  METHODS
  By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis).
  
  
  RESULTS
  An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission.
  
  
  CONCLUSIONS
  We have defined clinical and radiologic phenotypes of infectious and immune-mediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority.
authors: Neuroimmunology Group, Institute of Neuroscience and Muscle Research at the Kids Research Institute, Children's Hospital at Westmead, University of Sydney, Australia; TY Nelson Department of Neurology and Neurosurgery and.
authors: Sekhar C
authors: SC
authors: Pillai
authors: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, England;
authors: Yael
authors: Y
authors: Hacohen
authors: Neuroimmunology Group, Institute of Neuroscience and Muscle Research at the Kids Research Institute, Children's Hospital at Westmead, University of Sydney, Australia; TY Nelson Department of Neurology and Neurosurgery and.
authors: Esther
authors: E
authors: Tantsis
authors: Departments of Medical Imaging.
authors: Kristina
authors: K
authors: Prelog
authors: Neuroimmunology Group, Institute of Neuroscience and Muscle Research at the Kids Research Institute, Children's Hospital at Westmead, University of Sydney, Australia;
authors: Vera
authors: V
authors: Merheb
authors: Infectious Diseases and Microbiology, and.
authors: Alison
authors: A
authors: Kesson
authors: Statistics, the Children's Hospital at Westmead, Sydney, Australia; National Health Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, Australia;
authors: Elizabeth
authors: E
authors: Barnes
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Deepak
authors: D
authors: Gill
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Richard
authors: R
authors: Webster
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Manoj
authors: M
authors: Menezes
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Simone
authors: S
authors: Ardern-Holmes
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Sachin
authors: S
authors: Gupta
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Peter
authors: P
authors: Procopis
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Christopher
authors: C
authors: Troedson
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Jayne
authors: J
authors: Antony
authors: TY Nelson Department of Neurology and Neurosurgery and.
authors: Robert A
authors: RA
authors: Ouvrier
authors: Centre Hospitalier Territorial Magenta, Service Pediatric, Nouméa, New Caledonia;
authors: Yann
authors: Y
authors: Polfrit
authors: Chelsea & Westminster Hospital, Department of Neurology, Imperial College Healthcare National Health Service Trust, London, England; and.
authors: Nicholas W S
authors: NW
authors: Davies
authors: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, England;
authors: Patrick
authors: P
authors: Waters
authors: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, England;
authors: Bethan
authors: B
authors: Lang
authors: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, England; Evelina Children's Hospital, London, England.
authors: Ming J
authors: MJ
authors: Lim
authors: Neuroimmunology Group, Institute of Neuroscience and Muscle Research at the Kids Research Institute, Children's Hospital at Westmead, University of Sydney, Australia;
authors: Fabienne
authors: F
authors: Brilot
authors: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, England;
authors: Angela
authors: A
authors: Vincent
authors: Neuroimmunology Group, Institute of Neuroscience and Muscle Research at the Kids Research Institute, Children's Hospital at Westmead, University of Sydney, Australia; TY Nelson Department of Neurology and Neurosurgery and russell.dale@health.nsw.gov.au.
authors: Russell C
authors: RC
authors: Dale
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D004660:Encephalitis / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000276:immunology; D017063:Outcome Assessment, Health Care; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated; D016194:Receptors, N-Methyl-D-Aspartate
keywords: MRI; autoantibody; encephalitis; infection; outcome