title: NMDA receptor antibodies associated with distinct white matter syndromes.
abstract: OBJECTIVE
  To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders.
  
  
  METHODS
  Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody-positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated.
  
  
  RESULTS
  THREE DISTINCT CLINICORADIOLOGIC PHENOTYPES WERE RECOGNIZED: brainstem encephalitis (n = 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n = 2), and acquired demyelination syndromes (ADS) (n = 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers.
  
  
  CONCLUSIONS
  Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease.
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Yael
authors.initials: Y
authors.lastname: Hacohen
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Absoud
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hemingway
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Leslie
authors.initials: L
authors.lastname: Jacobson
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lin
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Pike
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Sunil
authors.initials: S
authors.lastname: Pullaperuma
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Ata
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Evangeline
authors.initials: E
authors.lastname: Wassmer
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Waters
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Sarosh R
authors.initials: SR
authors.lastname: Irani
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Camilla
authors.initials: C
authors.lastname: Buckley
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.affiliation: Nuffield Department of Clinical Neurosciences (Y.H., L.J., P.W., S.R.I., C.B., A.V., M.L.) and Department of Pediatric Neurology (M.P.), John Radcliffe Hospital, University of Oxford; Children's Neurosciences (M.A., J.-P.L., M.L.), Evelina Children's Hospital at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London; Department of Pediatric Neurology (C.H.), Great Ormond Street Hospital for Children, London; Department of Pediatrics (S.P.), St Mary's Hospital, Imperial College Academic Health Science Centre, London; Department of Neuroradiology (A.S.), Kings College Hospital, King's Health Partners Academic Health Science Centre, London; and Department of Pediatric Neurology (E.W.), Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Ming
authors.initials: M
authors.lastname: Lim