Increased glutamate in CSF and plasma of patients with HIV dementia

Background: Experimental evidence suggests that excitotoxicity might play a major role in HIV-induced neurodegeneration. However, few studies have investigated the role of endogenous glutamate in patients with HIV dementia. Objective: To analyze CSF and plasma glutamate levels in 30 patients with AIDS with different dementia severity compared with 10 patients with other neurologic disorders, 11 healthy control subjects, and 10 patients with Alzheimer-type dementia. Methods: CSF and plasma glutamate levels were measured by reverse-phase high-performance liquid chromatography followed by fluorometric analysis. Results: Glutamate CSF levels were increased fivefold in the patients with HIV vs normal control subjects (p = 0.001), patients with Alzheimer-type dementia (p < 0.0001), and patients with other neurologic disorders (p < 0.01). CSF glutamate levels were also related to the degree of dementia (p < 0.02) and brain atrophy (p < 0.002). Plasma levels were also higher in the patients with HIV (p < 0.0001) but did not correlate with either clinical or imaging features. Conclusion: Increased CSF glutamate may originate within the CNS and may play a pathogenetic role in HIV dementia, thus supporting the treatment of these patients with glutamate receptor antagonists.