title: The growing spectrum of antibody-associated inflammatory brain diseases in children.
abstract: OBJECTIVE
  To describe the clinical spectrum, diagnostic evaluation, current management, and neurologic outcome of pediatric antibody-associated inflammatory brain diseases (AB-associated IBrainD).
  
  
  METHODS
  We performed a single-center retrospective cohort study of consecutive patients aged ≤18 years diagnosed with an AB-associated IBrainD at The Hospital for Sick Children, Toronto, Ontario, Canada, between January 2005 and June 2013. Standardized clinical data, laboratory test results, neuroimaging features, and treatment regimens were captured.
  
  
  RESULTS
  Of 169 children (93 female, 55%) diagnosed with an IBrainD, 16 (10%) had an AB-associated IBrainD. Median age at presentation was 13.3 years (range 3.1-17.9); 11 (69%) were female. Nine patients (56%) had anti-NMDA receptor encephalitis, 4 (25%) had aquaporin-4 autoimmunity, 2 (13%) had Hashimoto encephalitis, and 1 (6%) had anti-glutamic acid decarboxylase 65 (GAD65) encephalitis. The key presenting features in children with anti-NMDA receptor encephalitis, Hashimoto encephalopathy, and anti-GAD65 encephalitis included encephalopathy, behavioral symptoms, and seizures; patients with aquaporin-4 autoimmunity showed characteristic focal neurologic deficits. Six patients (38%) required intensive care unit admission at presentation. Median time from symptom onset to diagnosis was 55 days (range 6-358). All but 1 patient received immunosuppressive therapy. One child with anti-NMDA receptor encephalitis died due to multiorgan failure. At last follow-up, after a median follow-up time of 1.7 years (range 0.8-3.7), 27% of the children had function-limiting neurologic sequelae.
  
  
  CONCLUSIONS
  Children with AB-associated IBrainD represent an increasing subgroup among IBrainD; 1 in 4 children has function-limiting residual neurologic deficits. Awareness of the different clinical patterns is important in order to facilitate timely diagnosis and initiate immunosuppressive treatment.
authors.affiliation: Department of Pediatrics (S.B.), Division of Neurology; Department of Pediatrics (M.H.), Division of Rheumatology; and Department of Emergency Medicine and Research Institute (S.M.B.), The Hospital for Sick Children, University of Toronto, Ontario, Canada; Department of Pediatrics (S.B.), Division of Child Neurology, University Children's Hospital, Berne, Switzerland; Department of Pediatric Rheumatology (M.T.), Aarhus University Hospital, Aarhus, Denmark; Catalan Institution of Research and Advanced Studies (ICREA) and Biomedical Research Institute August Pi i Sunyer (IDIBAPS) (J.D.), Hospital Clinic, University of Barcelona, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Section of Rheumatology (S.M.B.), Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bigi
authors.affiliation: Department of Pediatrics (S.B.), Division of Neurology; Department of Pediatrics (M.H.), Division of Rheumatology; and Department of Emergency Medicine and Research Institute (S.M.B.), The Hospital for Sick Children, University of Toronto, Ontario, Canada; Department of Pediatrics (S.B.), Division of Child Neurology, University Children's Hospital, Berne, Switzerland; Department of Pediatric Rheumatology (M.T.), Aarhus University Hospital, Aarhus, Denmark; Catalan Institution of Research and Advanced Studies (ICREA) and Biomedical Research Institute August Pi i Sunyer (IDIBAPS) (J.D.), Hospital Clinic, University of Barcelona, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Section of Rheumatology (S.M.B.), Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Manisha
authors.initials: M
authors.lastname: Hladio
authors.affiliation: Department of Pediatrics (S.B.), Division of Neurology; Department of Pediatrics (M.H.), Division of Rheumatology; and Department of Emergency Medicine and Research Institute (S.M.B.), The Hospital for Sick Children, University of Toronto, Ontario, Canada; Department of Pediatrics (S.B.), Division of Child Neurology, University Children's Hospital, Berne, Switzerland; Department of Pediatric Rheumatology (M.T.), Aarhus University Hospital, Aarhus, Denmark; Catalan Institution of Research and Advanced Studies (ICREA) and Biomedical Research Institute August Pi i Sunyer (IDIBAPS) (J.D.), Hospital Clinic, University of Barcelona, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Section of Rheumatology (S.M.B.), Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Marinka
authors.initials: M
authors.lastname: Twilt
authors.affiliation: Department of Pediatrics (S.B.), Division of Neurology; Department of Pediatrics (M.H.), Division of Rheumatology; and Department of Emergency Medicine and Research Institute (S.M.B.), The Hospital for Sick Children, University of Toronto, Ontario, Canada; Department of Pediatrics (S.B.), Division of Child Neurology, University Children's Hospital, Berne, Switzerland; Department of Pediatric Rheumatology (M.T.), Aarhus University Hospital, Aarhus, Denmark; Catalan Institution of Research and Advanced Studies (ICREA) and Biomedical Research Institute August Pi i Sunyer (IDIBAPS) (J.D.), Hospital Clinic, University of Barcelona, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Section of Rheumatology (S.M.B.), Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: Department of Pediatrics (S.B.), Division of Neurology; Department of Pediatrics (M.H.), Division of Rheumatology; and Department of Emergency Medicine and Research Institute (S.M.B.), The Hospital for Sick Children, University of Toronto, Ontario, Canada; Department of Pediatrics (S.B.), Division of Child Neurology, University Children's Hospital, Berne, Switzerland; Department of Pediatric Rheumatology (M.T.), Aarhus University Hospital, Aarhus, Denmark; Catalan Institution of Research and Advanced Studies (ICREA) and Biomedical Research Institute August Pi i Sunyer (IDIBAPS) (J.D.), Hospital Clinic, University of Barcelona, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Section of Rheumatology (S.M.B.), Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Benseler