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Glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with differences in
Martin Vestergaard1,2, William F C Baaré1, Sara K Holm1,3
1Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.
Insights
Childhood glucocorticoid treatment alters white matter microstructure, specifically the uncinate fasciculus. Higher cumulative doses correlated with more significant microstructural changes in this brain pathway.
Area of Science:
- Neuroscience
- Pediatric Endocrinology
- Radiology
Background:
- Fronto-limbic brain regions and white matter tracts show hemispheric asymmetry in glucocorticoid sensitivity.
- The long-term effects of childhood glucocorticoid treatment on fronto-limbic white matter microstructure remain largely unknown.
- The uncinate fasciculus and cingulum bundle connect crucial fronto-limbic regions.
Purpose of the Study:
- To investigate if prior glucocorticoid treatment in children is associated with microstructural differences in the uncinate fasciculus and cingulum bundle.
- To test the hypothesis of altered fractional anisotropy (FA) asymmetry in these white matter tracts following glucocorticoid exposure.
Main Methods:
- Diffusion-weighted imaging was used to assess white matter microstructure.
- 28 children and adolescents (7-16 years) with prior glucocorticoid treatment were compared to 28 healthy controls.
- Fractional anisotropy (FA) and axial diffusivity were measured in the uncinate fasciculus and cingulum bundle.
Main Results:
- Glucocorticoid-treated patients showed significantly different uncinate fasciculus asymmetry, with higher left FA and axial diffusivity compared to controls.
- No significant differences were found in the cingulum bundle microstructure.
- Higher cumulative glucocorticoid doses were proportionally associated with increased bilateral uncinate fasciculus FA and axial diffusivity.
Conclusions:
- Previous glucocorticoid treatment for non-cerebral diseases in youth is linked to lasting changes in uncinate fasciculi microstructure.
- The cumulative dose of glucocorticoids directly impacts the degree of microstructural alteration.
- These findings highlight potential long-term neurological consequences of childhood corticosteroid therapy.
Background:
Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle.
Methods:
We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls.
Results:
Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally.
Conclusions:
Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure.
Impact:
It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.
