Effects of valproate and other antiepileptic drugs on brain glutamate, glutamine, and GABA in patients with refractory complex partial seizures

Preclinical studies suggested valproate increased brain gamma-aminobutyric acid (GABA) with no major effects on brain glutamate or glutamine. Valproat e increased human cerebrospinal fluid GABA and glutamine in some studies; o thers reported no effect. In vivo measurements of glutamate, glutamine, and GABA were made of a 14 cm(3) volume in the occipital cortex using a H-1 sp ectroscopy with a 2.1 Tesla magnetic resonance spectrometer and an 8 cm sur face coil. Ten control subjects and 14 patients with refractory complex par tial seizures were examined. Brain glutamine concentrations were above norm al in three of five patients taking valproate and two of nine taking carbam azepine or phenytoin. Mean glutamine levels of patients taking valproate we re higher than control subjects and patients taking carbamazepine or phenyt oin. Brain glutamate concentrations were above normal in four of nine patie nts taking phenytoin or carbamazepine and two of five taking valproate. Bra in GABA levels were below normal in four of nine patients taking carbamazep ine or phenytoin and one of five taking valproate. Above normal glutamate o r below normal GABA was present in nine of 14 patients and may contribute t o their refractory epilepsy Increased brain glutamine associated with valpr oate therapy may reflect mild hyperammonemia.