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The Association Between Elevated Hippocampal Glutamate Levels and Cognitive Deficits in Epilepsy

The purpose of this study was to investigate the association between extracellular basal hippocampal glutamate levels and cognitive function in epileptic patients. We used the zero-flow microdialysis method to measure the extracellular concentrations of glutamate in the epileptogenic and non-epileptogenic hippocampus of 23 awake epileptic patients during the interictal period. All patients underwent extensive neuropsychological testing to assess cognitive functioning prior to probe implantation. Basal glutamate levels in the epileptogenic hippocampus were significantly higher than the non-epileptogenic hippocampus (mean, 11.96 micromolar (µM) versus 2.92 µM, respectively). Elevated basal glutamate levels in the epileptogenic hippocampus correlated with decreased scores on the Verbal Selective Reminding Test (V-SRT) (R[exponent]2 = 0.36, p = 0.0244). When controlling for MRI-detected hippocampal atrophy within epileptogenic regions, elevated basal glutamate levels within atrophic hippocampus correlated with decreased cognitive functioning measured by both the V-SRT (R[exponent]2 = 0.7764, p = 0.0204) and Performance Intelligence Quotient (PIQ) (R[exponent]2 = 0.7324, p = 0.0297), but not within non-atrophic hippocampus (V-SRT: R2 = 0.1013, p = 0.4424; PIQ: R[exponent]2 = 0.2303, p = 0.2288). These data suggest that elevated basal glutamate levels in the epileptogenic hippocampus may be implicated in the pathogenesis of hippocampal atrophy and may contribute to impaired cognitive functioning involving verbal memory and visual-spatial skills in patients with temporal lobe epilepsy.

Identiferoai:union.ndltd.org:YALE_med/oai:ymtdl.med.yale.edu:etd-06262006-125510
Date03 November 2006
CreatorsBuragas, Michele Sophia
ContributorsIdil Cavus
PublisherYale University
Source SetsYale Medical student MD Thesis
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://ymtdl.med.yale.edu/theses/available/etd-06262006-125510/
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