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      Magnetization transfer ratio recovery in new lesions decreases during adolescence in pediatric-onset multiple sclerosis patients

      research-article
      a , * , a , b , a , on behalf of the Canadian Pediatric Demyelinating Disease Network
      NeuroImage : Clinical
      Elsevier
      MRI, Multiple sclerosis, Remyelination, Pediatric multiple sclerosis

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          Abstract

          Children and adolescents diagnosed with multiple sclerosis rarely accrue physical disability early in their disease. This could be explained by greater remyelination in children, a capacity that may be lost in adolescence or early adulthood. Magnetization transfer ratio (MTR) MRI can be used to quantify changes in myelin in MS. We used serial MTR imaging and longitudinal random effects analysis to quantify recovery of MTR in acute lesions and to evaluate MTR changes in normal-appearing tissue in 19 adolescent MS patients. Our objective was to determine whether younger adolescents have a greater capacity for remyelination and whether this decreases as patients approach adulthood. We detected a significant decrease in MTR recovery between ages 16 and 20 years ( p = 0.023), with older subjects approaching typical recovery levels for adult-onset MS. MTR recovery in acute MS lesions decreases with age in adolescents, suggesting loss of remyelination capacity. This may be related to the conclusion of primary myelination or other developmental factors.

          Highlights

          • Decrease and recovery of MTR in multiple sclerosis suggest demyelination and remyelination.

          • We quantified MTR recovery in lesions in adolescents and modeled age related changes.

          • Recovery decreased ( p = 0.023) between ages 16 and 20.

          • Older subjects approached adult-typical recovery values.

          • This suggests a loss of remyelination capacity during adolescence.

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          Most cited references44

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          R: a language and environment for statistic computing

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            Sexual dimorphism of brain developmental trajectories during childhood and adolescence.

            Human total brain size is consistently reported to be approximately 8-10% larger in males, although consensus on regionally specific differences is weak. Here, in the largest longitudinal pediatric neuroimaging study reported to date (829 scans from 387 subjects, ages 3 to 27 years), we demonstrate the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism. Using magnetic resonance imaging (MRI) we found robust male/female differences in the shapes of trajectories with total cerebral volume peaking at age 10.5 in females and 14.5 in males. White matter increases throughout this 24-year period with males having a steeper rate of increase during adolescence. Both cortical and subcortical gray matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years earlier in females. These sexually dimorphic trajectories confirm the importance of longitudinal data in studies of brain development and underline the need to consider sex matching in studies of brain development.
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              Rejuvenation of regeneration in the aging central nervous system.

              Remyelination is a regenerative process in the central nervous system (CNS) that produces new myelin sheaths from adult stem cells. The decline in remyelination that occurs with advancing age poses a significant barrier to therapy in the CNS, particularly for long-term demyelinating diseases such as multiple sclerosis (MS). Here we show that remyelination of experimentally induced demyelination is enhanced in old mice exposed to a youthful systemic milieu through heterochronic parabiosis. Restored remyelination in old animals involves recruitment to the repairing lesions of blood-derived monocytes from the young parabiotic partner, and preventing this recruitment partially inhibits rejuvenation of remyelination. These data suggest that enhanced remyelinating activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                10 September 2014
                10 September 2014
                2014
                : 6
                : 237-242
                Affiliations
                [a ]McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital 3801 Rue University, Montreal H3A 2B4, Canada
                [b ]Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, USA
                Author notes
                [* ]Corresponding author. robert.brown@ 123456mcgill.ca
                Article
                S2213-1582(14)00139-9
                10.1016/j.nicl.2014.09.003
                4215523
                a504eeb0-1df8-4a2a-a47d-15ba4754089b
                © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 11 June 2014
                : 25 August 2014
                : 5 September 2014
                Categories
                Article

                mri,multiple sclerosis,remyelination,pediatric multiple sclerosis

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