Brain Morphometric Changes Associated With Childhood‐Onset Systemic Lupus Erythematosus and Neurocognitive Deficit

Abstract

ObjectiveTo use structural magnetic resonance imaging (MRI) to characterize changes in gray matter and white matter volumes between patients with childhood-onset systemic lupus erythematosus (SLE) and matched controls, between patients with childhood-onset SLE with and those without neurocognitive deficit, and in relation to disease duration and treatment with steroids.MethodsTwenty-two patients with childhood-onset SLE and 19 healthy controls underwent high-resolution structural MRI. Probability density maps for gray matter and white matter were compared between groups.ResultsNeuropsychological testing confirmed the presence of neurocognitive deficit in 8 patients with childhood-onset SLE. Multiple brain regions had reduced gray matter volume in the patients with childhood- onset SLE with neurocognitive deficit versus controls or patients with childhood-onset SLE without neurocognitive deficit. Neither disease duration nor cumulative oral or intravenous steroid doses accounted for decreases in gray matter. White matter volume was also reduced in patients with childhood-onset SLE with neurocognitive deficit, and the reduction was positively associated with both disease duration and cumulative oral steroid dose. Conversely, higher cumulative intravenous steroid doses were associated with higher white matter volumes.ConclusionNeurocognitive deficit in patients with childhood-onset SLE is associated with multifocal decreases in both gray and white matter volumes. Since only white matter volume changes are related to disease duration and cumulative oral steroid use, this may suggest that gray and white matter alterations relate to different underlying mechanisms. Further work is needed to understand the relationship between gray and white matter alterations in childhood-onset SLE, whether the underlying mechanisms relate to immunologic, vascular, or other causes, and whether the changes are reversible or preventable. Likewise, the protective properties of intravenous steroids in maintaining white matter volumes require confirmation in larger cohorts.

Childhood-onset lupus with clinical neurocognitive dysfunction shows lower streamline density and pairwise connectivity on diffusion tensor imaging

“…These observations are in line with previous reports of functional and volumetric alterations with cSLE-associated neurocognitive dysfunction 14, 15 . Taken together this may suggest that cSLE-associated neurocognitive dysfunction is linked to measurable microstructure changes in both the gray and white brain matter.…”

“…Interestingly, the decrease in degree of pairwise connectivity with neurocognitive dysfunction in cSLE may not be uniform among all brain regions. Increases in pairwise connectivity between some ventral regions (right fusiform gyrus and temporal poles) and other brain regions might suggest a compensatory mechanism as these brain structures have also shown changes in functional connectivity 14 and gray matter volume 15 .…”

Proof of principle: Transformation approach alters caudate nucleus volume and structure-function associations

“…It has yet to be agreed upon, however, if degree of transformation should be a major consideration for brain-behavior based analyses and brain structural volumetric comparisons. It is unclear which transformation approach is most preferred; some studies report on 6 DOF alignment approaches (e.g., Allen, Damasio, & Grabowski, 2002; Hefkemeijer et al, 2012; Moller et al, 2013; Singh et al, 2012), while others report 12 DOF setting (e.g., Gitelman et al, 2013). Still, some publications do not report any degree of transformation (e.g., Jiji, Smitha, Gupta, Pillai, & Jayasree, 2013; Lee et al, 2013; Lubin et al, 2013; Martinot et al, 2013; Serra-Blasco et al, 2013; Winston et al, 2013).…”

Biomarkers for Childhood-Onset Systemic Lupus Erythematosus

“…Furthermore, using structural magnetic resonance imaging, there was volumetric loss in the gray matter morphology in children with cSLE compared to healthy children, especially when decreased cognitive ability was present (Fig. 2) [52•]…”