Central nervous system involvement has proven to be both an early and common manifestation of HIV infection. The presence of neurological complications of HIV infection is well established late in the disease; for symptomatic and AIDS patients. Neuropsychological testing has been widely used to identify and characterize cognitive abnormalities. However, the sensitivity of neuropsychological (NP) testing to the presence of cognitive dysfunction in asymptomatic patients has been controversial. Our preliminary data indicate that magnetic resonance spectroscopy (MRS) may play two different roles in the study of HIV. The major abnormality observed in the MR spectra of asymptomatic patients (with normal MRI and NP tests) is the elevation of peaks in the region of the spectra where amino acids (AA) resonate. Moreover, the levels of these amino acid peaks correlate with the CD4 counts in this group. For these reasons we suggest that alterations in the amino acid region of the MRS spectrum will provide the earliest metabolic indicators of the migration of the virus into the CNS. In these asymptomatic patients with elevated, amino acid peaks, the ratio of N-acetyl aspartate(NAA) to choline (Cho) is normal. Patients with atrophy on MRI demonstrate diminished ratios of NAA/Cho. This observation is consistent with widely held view that the level of NAA is an index of neuronal integrity. On this basis we suggest that longitudinal studies will provide a means of tracking the time course of alterations in these metabolic measures in individual patients and provide a metabolic basis for """"""""staging"""""""" their degree of CNS involvement (early stages characterized by elevated AA peaks; intermediate stages characterized by lower NAA/Cho). In order to test these two hypotheses we will employ localized proton MRS to obtain metabolic indices from regions located primarily in white matter and gray matter of patients who are seropositive for HIV and asymptomatic at the time of enrollment in the study (n=90; n=30 with CD4 counts greater than 400; n=30 with CD4 counts between 250 and 400; n=30 with CD4 counts between 100 and 250). These parameters will be compared with similar measurements made on normal controls (n=30). These spectral measures will be compared with neuropsychological evaluations, clinical status, qualitative and quantitative analysis of MR images. All of these tests will be repeated every six months.
