Bérengère Aubert-Broche1, Vladimir Fonov1, Sridar Narayanan1, Douglas L Arnold1, David Araujo1, Dumitru Fetco1, Christine Till1, John G Sled1, Brenda Banwell2, D Louis Collins1. 1. From the McConnell Brain Imaging Center (B.A.-B., V.F., S.N., D.L.A., D.A., D.F., D.L.C.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (C.T., J.G.S., B.B.), University of Toronto; York University (C.T.), Toronto, Canada; and Children's Hospital of Philadelphia (B.B.), University of Pennsylvania. 2. From the McConnell Brain Imaging Center (B.A.-B., V.F., S.N., D.L.A., D.A., D.F., D.L.C.), Montreal Neurological Institute, McGill University; The Hospital for Sick Children (C.T., J.G.S., B.B.), University of Toronto; York University (C.T.), Toronto, Canada; and Children's Hospital of Philadelphia (B.B.), University of Pennsylvania. banwellb@email.chop.edu.
Abstract
OBJECTIVE: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. METHODS: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2-11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. RESULTS: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10(-4)). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. CONCLUSIONS: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS.
OBJECTIVE: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. METHODS: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2-11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. RESULTS: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10(-4)). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. CONCLUSIONS: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS.
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Authors: Pierrick Coupé; José V Manjón; Elias Gedamu; Douglas Arnold; Montserrat Robles; D Louis Collins Journal: Med Image Anal Date: 2010-03-20 Impact factor: 8.545
Authors: B Aubert-Broche; V S Fonov; D García-Lorenzo; A Mouiha; N Guizard; P Coupé; S F Eskildsen; D L Collins Journal: Neuroimage Date: 2013-05-26 Impact factor: 6.556
Authors: A Kerbrat; B Aubert-Broche; V Fonov; S Narayanan; J G Sled; D A Arnold; B Banwell; D L Collins Journal: Neurology Date: 2012-01-04 Impact factor: 9.910
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Authors: James F Sumowski; Maria A Rocca; Victoria M Leavitt; Gianna Riccitelli; Alessandro Meani; Giancarlo Comi; Massimo Filippi Journal: Mult Scler Date: 2016-02-26 Impact factor: 6.312
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Authors: E J Mallack; G Askin; S van de Stadt; P A Caruso; P L Musolino; M Engelen; S N Niogi; F S Eichler Journal: AJNR Am J Neuroradiol Date: 2021-09-09 Impact factor: 4.966