Elevated subcortical choline metabolites in cognitively and clinically asymptomatic HIV+ patients

Objective: To determine whether the concentrations of the neuronal marker N-acetylaspartate (NAA) and the choline-containing metabolites (Cho) are altered in the subcortical brain of HIV+ patients who are cognitively normal and clinically asymptomatic, and to determine whether these alterations are greater in the presence of cognitive impairments and clinical symptoms. Background: Pathologic studies suggest that subcortical gray matter carries a heavy HIV load, and neuropsychological test results are consistent with involvement of subcortical and frontostriatal brain systems in HIV disease. Noninvasive proton magnetic resonance spectroscopy (H-1 MRS) suggests neuronal preservation and macrophage infiltration in the subcortical brain of clinically symptomatic and cognitively impaired HIV+ individuals. Improved H-1 MRS methods may allow the early detection of metabolite alterations in the subcortical brain of asymptomatic HIV+ individuals. Methods: Two-dimensional H-1 MRS imaging was performed on 30 HIV- control subjects and 70 HIV+ patients with varying severities of systemic disease and neuropsychological impairments, but without cerebral opportunistic infections. Results: Subcortical Cho was elevated in HIV+ patients compared with control subjects regardless of the presence or absence of cognitive impairment or clinical symptoms. Subcortical NAA was lower than control NAA only in severely cognitively impaired HIV+ subjects. Subcortical NAA correlated with performance on a variety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymphocyte counts. Conclusions: H-1 MRS imaging detects higher Cho in subcortical brain early in HIV disease, when individuals are clinically and neuropsychologically asymptomatic, whereas lower NAA is only found in subcortical brain in individuals with severe neuropsychological impairments. Quantitative H-1 MRS imaging may play a role in the objective assessment of the presence, magnitude, and progression of brain involvement in HIV infection.