Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability
Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patie...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00608/full |
| _version_ | 1818264857139478528 |
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| author | Antonio Giorgio Jian Zhang Maria Laura Stromillo Francesca Rossi Marco Battaglini Lucia Nichelli Marzia Mortilla Emilio Portaccio Bahia Hakiki Maria Pia Amato Nicola De Stefano |
| author_facet | Antonio Giorgio Jian Zhang Maria Laura Stromillo Francesca Rossi Marco Battaglini Lucia Nichelli Marzia Mortilla Emilio Portaccio Bahia Hakiki Maria Pia Amato Nicola De Stefano |
| author_sort | Antonio Giorgio |
| collection | DOAJ |
| description | Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15) in comparison with age- and disability-matched AOMS patients (n = 14) and to normal controls (NC, n = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term. |
| first_indexed | 2024-12-12T19:41:34Z |
| format | Article |
| id | doaj.art-246a6e14189c4f08aafe1ee1361d422d |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-12T19:41:34Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-246a6e14189c4f08aafe1ee1361d422d2022-12-22T00:14:12ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-11-01810.3389/fneur.2017.00608297134Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical DisabilityAntonio Giorgio0Jian Zhang1Maria Laura Stromillo2Francesca Rossi3Marco Battaglini4Lucia Nichelli5Marzia Mortilla6Emilio Portaccio7Bahia Hakiki8Maria Pia Amato9Nicola De Stefano10Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, ItalyAnna Meyer Children’s University Hospital, Florence, ItalyIRCCS Don Gnocchi Foundation, Florence, ItalyDepartment of Neurology, University of Florence, Florence, ItalyDepartment of Neurology, University of Florence, Florence, ItalyDepartment of Medicine, Surgery and Neuroscience, University of Siena, Siena, ItalyPediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability (n = 15) in comparison with age- and disability-matched AOMS patients (n = 14) and to normal controls (NC, n = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.http://journal.frontiersin.org/article/10.3389/fneur.2017.00608/fullmultiple sclerosisMRIdisabilitydiffusion tensor imagingresting state networksconnectivity |
| spellingShingle | Antonio Giorgio Jian Zhang Maria Laura Stromillo Francesca Rossi Marco Battaglini Lucia Nichelli Marzia Mortilla Emilio Portaccio Bahia Hakiki Maria Pia Amato Nicola De Stefano Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability Frontiers in Neurology multiple sclerosis MRI disability diffusion tensor imaging resting state networks connectivity |
| title | Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability |
| title_full | Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability |
| title_fullStr | Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability |
| title_full_unstemmed | Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability |
| title_short | Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability |
| title_sort | pronounced structural and functional damage in early adult pediatric onset multiple sclerosis with no or minimal clinical disability |
| topic | multiple sclerosis MRI disability diffusion tensor imaging resting state networks connectivity |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2017.00608/full |
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