Neuroimaging correlates of HIV-associated BBB compromise.
The mechanisms underlying blood-brain barrier (BBB) compromise in human immunodeficiency virus (HIV) infection and the ways in which BBB compromise might impair neurocognitive function remain poorly understood. This study had two aims: (1) to examine the relationship between BBB breakdown, measured using contrast-enhanced magnetic resonance imaging (CE-MRI), plasma viral load, and neurological status; and (2) to examine the influence of highly active antiretroviral therapy (HAART) on the relationship between neuroinflammation using myoinositol/creatine (mI/Cr), a surrogate marker of glial activation as measured by magnetic resonance spectroscopy (MRS), and BBB compromise determined by CE-MRI. In 25 HIV-infected patients, we found that: (1) the severity of neurocognitive impairment correlated with the degree of BBB breakdown in the basal ganglia; (2) for any given degree of BBB compromise, patients with high plasma viral load were more severely impaired; (3) BBB compromise correlated with mI/Cr in the basal ganglia; and (4) for any given level of mI/Cr, the severity of BBB compromise and the severity of neurocognitive impairment were significantly less in patients on HAART than in those who were HAART-naive. These results confirm a role for BBB compromise in the pathogenesis of HIV-associated neurocognitive impairment and suggest that elevated plasma viral load in the presence of BBB compromise may increase the risk for development of HIV-associated dementia (HAD). Additionally, they suggest a salutary effect of HAART on the incidence and severity of HAD, which may, in part, be due to protection of BBB integrity.
Avison
Malcolm J
MJ
Department of Neurology, University of Kentucky Medical Center,Lexington, KY, USA. calum.avison@vuiis.vanderbilt.edu
Nath
Avindra
A
Greene-Avison
Robin
R
Schmitt
Frederick A
FA
Greenberg
Richard N
RN
Berger
Joseph R
JR
D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology* / Q000821:virology; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy / Q000821:virology; D003287:Contrast Media / Q000493:pharmacokinetics; D003710:Demography; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D009460:Neurologic Examination / Q000379:methods; D009483:Neuropsychological Tests
D003287:Contrast Media