Alterations in Blood-Brain Barrier Permeability in Patients with Systemic Lupus Erythematosus

Abstract

Background and purpose: Neuropsychiatric systemic lupus erythematosus refers to central and peripheral nervous system involvement, which may occur secondary to antineuronal antibodies crossing the blood-brain barrier that preferentially target cells in the hippocampus leading to abnormal hypermetabolism and atrophy. Thus, we hypothesized that alterations in BBB permeability, detected on dynamic contrast-enhanced MR imaging, occur in the hippocampus in patients with systemic lupus erythematosus before development of neuropsychiatric systemic lupus erythematosus.

Materials and methods: Six patients with systemic lupus erythematosus without neuropsychiatric systemic lupus erythematosus and 5 healthy controls underwent dynamic contrast-enhanced MR imaging with postprocessing into BBB permeability parameters (K ^trans and Ve) and CBF. Standardized methods selected ROI sampling of the abnormal brain regions detected on FDG-PET. The mean and SD of K ^trans, Ve, and CBF were calculated. Linear regression and nonparametric Spearman rank correlation analyses of K ^trans and Ve with CBF were performed. Dynamic contrast-enhanced curves and the area under the curve were generated for each brain region. Student t test comparisons were performed.

Results: Quantitative data revealed that patients with systemic lupus erythematosus have statistically increased K ^trans (P < .001) and Ve (P < .001) compared with controls. In patients with systemic lupus erythematosus, statistically significant positive correlations were seen between K ^trans (P < .001) and Ve (P < .001) with CBF. Furthermore, the mean area under the curve revealed statistically increased BBB permeability in the hippocampus (P = .02) compared with other brain regions in patients with systemic lupus erythematosus compared with controls.

Conclusions: These initial findings are proof-of-concept to support the hypothesis that patients with systemic lupus erythematosus have increased BBB permeability, specifically in the hippocampus, compared with other brain regions. These findings may advance our understanding of the underlying pathophysiology affecting the brain in autoimmune diseases.

Fig 1.

DCE-MR imaging data acquisition methods. Mirror ROIs were placed for sampling the abnormal regions described on FDG-PET: hippocampus, orbitofrontal, anterior putamen/caudate, posterior putamen/globus pallidus/thalamus, and prefrontal regions. Ant Put indicates anterior putamen; Post Put, posterior putamen; GP, globus pallidus.

Fig 2.

Linear regression analyses of the correlation of the BBBP factors (K^trans and Ve) with CBF using all brain regions for patients with SLE. Patients with SLE have a statistically significant moderate positive correlation between K^trans and Ve with CBF separately. Higher variance seen in patients with SLE compared with controls may be attributed to disease- and/or treatment-related variability. Healthy controls demonstrate strong consistency in the quantitative data for both K^trans and Ve (not shown).

Fig 3.

Dynamic contrast-enhancement curves for patients with SLE (blue) and healthy controls (red) according to the brain regions sampled. Signal intensity is represented on the y-axis, and the cine phase is represented on the x-axis. The hippocampus is the only brain region that demonstrates statistically significant increased BBB permeability (P = .02) in the patients with SLE compared with the healthy controls. GP indicates globus pallidus.