Cerebral metabolite abnormalities correlate with clinical severity of HIV-1 cognitive motor complex

Objective: To investigate the relation between biochemical alterations and disease severity in HIV-cognitive motor complex (HIV-CMC). Background: HIV- CMC encompasses both the milder form (HN-minor cognitive motor disorder [HI V-MCMD]) and the more severe form (HIV-dementia). There is no validated mar ker to monitor disease severity noninvasively. Methods: A total of 54 patie nts with HIV-CMC (20 with HIV-MCMD, 34 with HIV-dementia) and 29 seronegati ve healthy volunteers were evaluated for cerebral metabolite abnormalities using proton (H-1) MRS in the frontal cortex, frontal white matter, and bas al ganglia. Results: The three subject groups showed different concentratio ns of myoinositol (MI; p = 0.0005) and choline-containing compounds (CHO; p = 0.004) in the frontal white matter. HIV-dementia patients had metabolite changes in all three brain regions whereas HIV-MCMD patients had abnormali ties in the frontal white matter only. HIV-CMC patients had elevated MI (p < 0.0001) and CHO (p = 0.004) levels with increasing AIDS dementia complex stage, and N-acetyl compounds (NA) were decreased only in moderate to sever e stages of dementia. Furthermore, CD4 count and CSF viral load, but not pl asma viral load, showed significant effects on cerebral metabolite concentr ations, which in turn showed significant effects on the HIV-dementia scale. Conclusions: In early stages of HIV-CMC, frontal white matter showed evide nce of glial proliferation (with elevated MI and CHO levels) and cell membr ane injury (with increased CHO levels), but no significant neuronal injury (with normal NA concentrations). HIV-MCMD and HIV-dementia patients have di fferent neurochemical abnormalities. Because these biochemical alterations are related to clinical disease severity, they may be useful surrogate mark ers for noninvasive quantitative assessment of brain injury in patients wit h HIV-CMC.