A study of glutamate excitotoxicity in seizures related to tuberculous meningitis

Glutamate is a neurotransmitter that regulates approximately half of the nervous system, along with the sensory system. Glutamate excitotoxicity is related to seizures but its role in TBM-related seizure has not been reported to our best knowledge. It is proposed to report plasma glutamate level and its receptors in TBM patients with seizures and correlate with the type of seizures, Magnetic Resonance Imaging (MRI) findings, and outcome.

TBM was diagnosed clinically with MRI as well as cerebrospinal fluid examination. TBM-related seizures have been categorized into early (< 1 month) or late (> 1 month) seizures. Six months outcome was defined using modified Rankin Scale as good (mRS ≤ 2) or poor (mRS > 2). Plasma glutamate was measured by ELISA, along with NR1, NR2A, and NR2B receptors using Real Time Polymerase Chain Reaction (RT-PCR) and have been correlated with seizure, MRI abnormalities, and outcome.

A total of 29 (53.7%) patients developed seizures (early-09, late-20). Glutamate (P < 0.0001), NR1 (p ≤ 0.0001), NR2A (p ≤ 0.0001), and NR2B (p ≤ 0.0001) were higher than the controls. In TBM patients with seizures, plasma glutamate (p = 0.01), NR1 (p = 0.03) and NR2A (p = 0.001) were significantly higher than those without seizures. Plasma glutamate level and all three receptor genes expression were higher during seizures and improved on cessation of seizure compared to the baseline. These markers correlated well with MRI findings and determined the outcome. ROC curve was used to estimate the diagnostic accuracy of the markers. The result indicated that NR2A gene was the best predictor followed by glutamate and NR1 gene.

Our results highlight the role of glutamate and its receptors in TBM-related seizures and outcomes.