title: Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens.
abstract: OBJECTIVE
  To report the clinical and investigative features of children with a clinical diagnosis of probable autoimmune encephalopathy, both with and without antibodies to central nervous system antigens.
  
  
  METHODS
  Patients with encephalopathy plus one or more of neuropsychiatric symptoms, seizures, movement disorder or cognitive dysfunction, were identified from 111 paediatric serum samples referred from five tertiary paediatric neurology centres to Oxford for antibody testing in 2007-2010. A blinded clinical review panel identified 48 patients with a diagnosis of probable autoimmune encephalitis whose features are described. All samples were tested/retested for antibodies to N-methyl-D-aspartate receptor (NMDAR), VGKC-complex, LGI1, CASPR2 and contactin-2, GlyR, D1R, D2R, AMPAR, GABA(B)R and glutamic acid decarboxylase.
  
  
  RESULTS
  Seizures (83%), behavioural change (63%), confusion (50%), movement disorder (38%) and hallucinations (25%) were common. 52% required intensive care support for seizure control or profound encephalopathy. An acute infective organism (15%) or abnormal cerebrospinal fluid (32%), EEG (70%) or MRI (37%) abnormalities were found. One 14-year-old girl had an ovarian teratoma. Serum antibodies were detected in 21/48 (44%) patients: NMDAR 13/48 (27%), VGKC-complex 7/48(15%) and GlyR 1/48(2%). Antibody negative patients shared similar clinical features to those who had specific antibodies detected. 18/34 patients (52%) who received immunotherapy made a complete recovery compared to 4/14 (28%) who were not treated; reductions in modified Rankin Scale for children scores were more common following immunotherapies. Antibody status did not appear to influence the treatment effect.
  
  
  CONCLUSIONS
  Our study outlines the common clinical and paraclinical features of children and adolescents with probable autoimmune encephalopathies. These patients, irrespective of positivity for the known antibody targets, appeared to benefit from immunotherapies and further antibody targets may be defined in the future.
authors.affiliation: Paediatric Neurosciences, Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Sciences Centre, London SE1 7EH. angela.vincent@ndcn.ox.ac.uk
authors.forename: Yael
authors.initials: Y
authors.lastname: Hacohen
authors.forename: Sukhvir
authors.initials: S
authors.lastname: Wright
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.forename: Shakti
authors.initials: S
authors.lastname: Agrawal
authors.forename: Lucinda
authors.initials: L
authors.lastname: Carr
authors.forename: Helen
authors.initials: H
authors.lastname: Cross
authors.forename: Carlos
authors.initials: C
authors.lastname: De Sousa
authors.forename: Catherine
authors.initials: C
authors.lastname: Devile
authors.forename: Penny
authors.initials: P
authors.lastname: Fallon
authors.forename: Rajat
authors.initials: R
authors.lastname: Gupta
authors.forename: Tammy
authors.initials: T
authors.lastname: Hedderly
authors.forename: Elaine
authors.initials: E
authors.lastname: Hughes
authors.forename: Tim
authors.initials: T
authors.lastname: Kerr
authors.forename: Karine
authors.initials: K
authors.lastname: Lascelles
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lin
authors.forename: Sunny
authors.initials: S
authors.lastname: Philip
authors.forename: Keith
authors.initials: K
authors.lastname: Pohl
authors.forename: Prab
authors.initials: P
authors.lastname: Prabahkar
authors.forename: Martin
authors.initials: M
authors.lastname: Smith
authors.forename: Ruth
authors.initials: R
authors.lastname: Williams
authors.forename: Antonia
authors.initials: A
authors.lastname: Clarke
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hemingway
authors.forename: Evangeline
authors.initials: E
authors.lastname: Wassmer
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.forename: Ming J
authors.initials: MJ
authors.lastname: Lim
mesh_terms: D000293:Adolescent; D044466:Asian People; D001324:Autoantigens / Q000032:analysis*; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D044383:Black People; D001927:Brain Diseases / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D002490:Central Nervous System / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000523:psychology; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D016896:Treatment Outcome; D044465:White People
chemical_list: D001324:Autoantigens; D024642:Potassium Channels, Voltage-Gated; D016194:Receptors, N-Methyl-D-Aspartate