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Elevated Cerebrospinal Fluid Glutamate in Patients With HIV-related Dementia-Reply

Carlo Ferrarese, MD, PhD
JAMA. 1997;277(24):1931. doi:10.1001/jama.1997.03540480031024.
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In Reply.  —Drs Gurwitz and Kloog raise some points regarding possible alternative interpretations of our data. Human immunodeficiency virus—related encephalitis is present in all patients with AIDS-related dementia, and its severity is correlated with the extent of viral infection and degree of dementia.1 For this reason, we believe that an increased glutamate level in CSF can be directly explained by interaction of viral proteins or factors from virus-infected cells (cytokines, free radicals, and nitric oxide) with glutamate transporters within the central nervous system. The alternative explanation of increased CSF glutamate levels as a reflection of elevated plasma levels appears less likely, for several reasons. Plasma glutamate levels were similarly elevated in AIDS patients with and without dementia,2 and BBB disruption also may be present in nondemented HIV-positive patients who have normal CSF glutamate levels.3 Moreover, although glutamate levels are normally 10 times higher in blood than in CSF, in


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