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 alt ered in the subcortical brain of HIV+ patients who are cognitively normal a nd clinically asymptomatic, and to determine whether these alterations are greater in the presence of cognitive impairments and clinical symptoms. Bac kground: Pathologic studies suggest that subcortical gray matter carries a heavy HIV load, and neuropsychological test results are consistent with inv olvement of subcortical and frontostriatal brain systems in HIV disease. No ninvasive proton magnetic resonance spectroscopy (H-1 MRS) suggests neurona l preservation and macrophage infiltration in the subcortical brain of clin ically 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-dimensiona l H-1 MRS imaging was performed on 30 HIV- control subjects and 70 HIV+ pat ients with varying severities of systemic disease and neuropsychological im pairments, but without cerebral opportunistic infections. Results: Subcorti cal Cho was elevated in HIV+ patients compared with control subjects regard less of the presence or absence of cognitive impairment or clinical symptom s. Subcortical NAA was lower than control NAA only in severely cognitively impaired HIV+ subjects. Subcortical NAA correlated with performance on a va riety of neuropsychological tests but not with Centers for Disease Control clinical stage, whereas high-thalamic Cho was associated with low CD4 lymph ocyte counts. Conclusions: H-1 MRS imaging detects higher Cho in subcortica l brain early in HIV disease, when individuals are clinically and neuropsyc hologically asymptomatic, whereas lower NAA is only found in subcortical br ain in individuals with severe neuropsychological impairments. Quantitative H-1 MRS imaging may play a role in the objective assessment of the presenc e, magnitude, and progression of brain involvement in HIV infection.