Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.
OBJECTIVE
To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE).


METHODS
In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients.


RESULTS
Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all).


CONCLUSIONS
There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study.
University of Cincinnati College of Medicine, Cincinnati, Ohio.
Gaurav
G
Gulati
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Jordan T
JT
Jones
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
Gregory
G
Lee
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
Mekibib
M
Altaye
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
Dean W
DW
Beebe
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Jamie
J
Meyers-Eaton
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Kasha
K
Wiley
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
Hermine I
HI
Brunner
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio.
Mark W
MW
DiFrancesco
D001812:Blood-Brain Barrier / Q000473:pathology*; D002199:Capillary Permeability; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008180:Lupus Erythematosus, Systemic / Q000000981:diagnostic imaging* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D010865:Pilot Projects; D055815:Young Adult