Brain perfusion and blood-brain barrier permeability in systemic lupus erythematosus patients: Associations with disease activity, cognitive dysfunction, fatigue and pain

Abstract

High disease activity, cognitive dysfunction (CD), fatigue and pain negatively affect the quality of life in patients with systemic lupus erythematosus (SLE). However, the impact on brain perfusion and blood-brain barrier (BBB) permeability remains incompletely understood. Therefore, we utilized 3 T dynamic susceptibility contrast magnetic resonance imaging to investigate these factors in a cohort of 66 female SLE patients. Normalized leakage corrected cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and the BBB leakage parameter K_2, were compared within the cohort by splitting the group into patients with and without each symptom respectively. Fourteen regions of interest were chosen, and the results were adjusted for age, disease duration, smoking and glucocorticoids. We found regional significant alterations in the different SLE subgroups compared to patients without each corresponding symptom, with patterns as follows: moderate to high disease activity (n = 17, decreased MTT, increased K₂), CD in ≥1 domain (n = 36, decreased MTT, increased K₂), CD in ≥2 domains (n = 20, increased CBF, CBV and K₂), fatigue (n = 44, increased CBV and MTT), pain (n = 9, increased CBF and CBV, decreased MTT). Additionally, inverse correlations were found between cognitive scores and K₂ in multiple areas, indicating increased BBB permeability with worse cognitive performance. To elucidate the underlying mechanisms, longitudinal studies should be conducted in a larger variation of patients, using different measurements of BBB disruption.