Gamma-amimo-butyric acid (GABA) is the major inhibitory neurotransmitter in human cortex and plays a pivotal role in suppressing the origin and spread of seizure activity. Nuclear magnetic resonance spectroscopy (NMRS) permits serial, non-invasive metabolite and macromolecule measurements without discomfort or known hazard for most people. Low CSF and tissue GABA concentrations in patients with epilepsy are associated with frequent seizures. Whether low GABA levels are the cause or the result of frequent seizures is unknown. The effectiveness of the class of antiepileptic drugs which target GABA metabolism , e.g., vigabitrin, gabapentin, tiagabine, depend on the elevation of GABA concentration. The focus of this proposal is the regulation of GABA and homocarnasine concentrations in patients with epilepsy.
Three aims propose to examine prospectively changes in occipital lobe GABA and homocarnazine induced by vigabatrin, gabapentin, and tiagabine. The purpose is to improve AED selection by developing guidelines based on GABA and homocarnosine levels. These NMRS measurements may provide a rational approach in selecting an appropriate drug. This proposal is the first attempt to provide estimates of """"""""therapeutic levels"""""""" for brain GABA and homocarnosine, similar to serum AED levels in widespread clinical use.
The fourth aim proposes to examine prospectively whether temporal lobectomy alters occipital lobe GABA and homocarnosine concentrations. The answer may impact both patient selection and the long-term post-surgical management. In the past decade, magnetic resonance methods have become standard of care in the evaluation of human epilepsy. NMRS based measurements of neurotransmitters and modulators should enter the clinical armamentarium in the next decade. This proposal will advance clinical care of seizure disorders.
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