title: Monophasic demyelination reduces brain growth in children.
abstract: OBJECTIVE
  To investigate how monophasic acquired demyelinating syndromes (ADS) affect age-expected brain growth over time.
  
  
  METHODS
  We analyzed 83 pediatric patients imaged serially from initial demyelinating attack: 18 with acute disseminated encephalomyelitis (ADEM) and 65 with other monophasic ADS presentations (monoADS). We further subdivided the monoADS group by the presence (n = 33; monoADSlesion) or absence (n = 32; monoADSnolesion) of T2 lesions involving the brain at onset. We used normative data to compare brain volumes and calculate age- and sex-specificzscores, and used mixed-effect models to investigate their relationship with time from demyelinating illness.
  
  
  RESULTS
  Children with monophasic demyelination (ADEM, non-ADEM with brain lesions, and those without brain involvement) demonstrated reduced age-expected brain growth on serial images, driven by reduced age-expected white matter growth. Cortical gray matter volumes were not reduced at onset but demonstrated reduced age-expected growth afterwards in all groups. Brain volumes differed from age- and sex-expected values to the greatest extent in children with ADEM. All patient groups failed to recover age-expected brain growth trajectories.
  
  
  CONCLUSIONS
  Brain volume, and more importantly age-expected brain growth, is negatively affected by acquired demyelination, even in the absence of chronicity, implicating factors other than active inflammation as operative in this process.
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania. broche@bic.mni.mcgill.ca.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Aubert-Broche
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Katrin
authors.initials: K
authors.lastname: Weier
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Giulia
authors.initials: G
authors.lastname: Longoni
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Fonov
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Marrie
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: E Ann
authors.initials: EA
authors.lastname: Yeh
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Sridar
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Verhey
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: Brenda
authors.initials: B
authors.lastname: Banwell
authors.affiliation: From the McConnell Brain Imaging Center (B.A.-B., K.W., V.S.F., S.N., D.L.A., D.L.C.) and Department of Neurology and Neurosurgery and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (G.L., E.A.Y., L.H.V.), University of Toronto; Departments of Internal Medicine and Community Health Sciences (R.A.M.), University of Manitoba, Winnipeg, Canada; and Children's Hospital of Philadelphia (B.B.), Perelman School of Medicine, University of Pennsylvania.
authors.forename: D Louis
authors.initials: DL
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging* / Q000254:growth & development*; D002648:Child; D002675:Child, Preschool; D020278:Demyelinating Autoimmune Diseases, CNS / Q000000981:diagnostic imaging*; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000254:growth & development; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D011446:Prospective Studies; D055815:Young Adult