Abstract
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
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It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure.
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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.
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The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity.
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Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses.
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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.
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Change history
09 February 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41390-021-01736-8
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Acknowledgements
The work was funded by the Danish Council for Independent Research (grant no.r: 09-071546), Gangstedfonden, Ville Heises Legat, Hvidovre Hospital’s Research Fund and the Lundbeck Foundation, and the Centre of Excellence grant to The Centre for Integrated Molecular Brain Imaging. H.R.S. holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen, which is sponsored by the Lundbeck Foundation (grant no. R186-2015-2138).
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Conceived and designed the study: M.V., W.F.C.B., S.K.H., O.B.P., A.P.B., P.U., H.R.S. and K.S.M. Performed the experiments: M.V. and S.K.H. Evaluated the data: M.V., W.F.C.B., S.K.H., C.G.M. and K.S.M. Analysed the data: M.V., W.F.C.B. and K.S.M. Contributed to writing the paper: M.V., W.F.C.B., S.K.H., O.B.P., A.P.B., P.U., H.R.S. and K.S.M.
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H.R.S. has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark and as senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany. The other authors reported no competing interests.
Patient consent
Participants and their parents received thorough information regarding the project and written consent was obtained from all parents before study initiation. The study was approved by the Committee on Biomedical Research Ethics for the Capital Region of Denmark (protocol no. H-KF-01-131/03) and was conducted in accordance with the Declaration of Helsinki.
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Vestergaard, M., Baaré, W.F.C., Holm, S.K. et al. Glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with differences in uncinate fasciculus microstructure. Pediatr Res 91, 879–887 (2022). https://doi.org/10.1038/s41390-021-01394-w
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DOI: https://doi.org/10.1038/s41390-021-01394-w
