Background: Experimental evidence suggests that excitotoxicity might play a
major role in HIV-induced neurodegeneration. However, few studies have inv
estigated the role of endogenous glutamate in patients with HIV dementia. O
bjective: To analyze CSF and plasma glutamate levels in 30 patients with AI
DS with different dementia severity compared with 10 patients with other ne
urologic disorders, 11 healthy control subjects, and 10 patients with Alzhe
imer-type dementia. Methods: CSF and plasma glutamate levels were measured
by reverse-phase high-performance liquid chromatography followed by fluorom
etric analysis. Results: Glutamate CSF levels were increased fivefold in th
e patients with HIV vs normal control subjects (p = 0.001), patients with A
lzheimer-type dementia (p < 0.0001), and patients with other neurologic dis
orders (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 eit
her clinical or imaging features. Conclusion: Increased CSF glutamate may o
riginate within the CNS and may play a pathogenetic role in HIV dementia, t
hus supporting the treatment of these patients with glutamate receptor anta
gonists.