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Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal
Antonio Giorgio1, Jian Zhang1, Maria Laura Stromillo1
1Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Insights
Pediatric-onset multiple sclerosis (POMS) shows early brain alterations and connectivity disruptions. These changes in young adults with POMS may predict long-term disability, even with minimal symptoms.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Pediatric-onset multiple sclerosis (POMS) affects the maturing brain, leading to irreversible disability at a younger age than adult-onset MS (AOMS).
- Understanding early brain changes in POMS is crucial for predicting long-term outcomes.
Purpose of the Study:
- To investigate early adult brain alterations in POMS patients with minimal disability.
- To compare structural and functional brain connectivity in POMS, AOMS, and normal controls (NC).
Main Methods:
- Utilized a multimodal MRI approach with FSL software.
- Analyzed voxelwise microstructural integrity of white matter tracts and gray matter volumes.
- Modeled intra- and internetwork functional connectivity (FC) using resting-state fMRI.
Main Results:
- POMS patients exhibited altered diffusion tensor imaging measures (reduced fractional anisotropy, increased diffusivities) compared to NC and AOMS.
- POMS showed increased lesion probability in the posterior corona radiata, a key region for physical disability.
- Reduced long-range FC was observed between the default mode network and secondary visual network in POMS patients.
Conclusions:
- Early structural damage and disrupted brain connectivity in POMS patients with minimal disability may underlie their unfavorable long-term prognosis.
- These findings highlight the vulnerability of the developing brain in POMS and its long-term consequences.
Abstract:
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.
