DYNAMIC NEUROCHEMICAL ALTERATIONS IN HUMAN TEMPORAL-LOBE EPILEPSY

Recent advances in neurochemical methods, particularly the development of intracerebral microdialysis for human use, have enabled in situ measurements of neurotransmitters, metabolites, and drugs in defined regions of the human brain. The microdialysis technique has been coupled with intracranial electrode recording as a means of monitoring neurochemical changes in patients with medically intractable epileptic seizures. Specifically, this combination of techniques is used to monitor transmitter release during the generation and arrest of spontaneous unilateral-onset hippocampal seizures. In the epileptogenic hippocampus, but not in the contralateral ''control'' hippocampus of patients with such seizures, interictal levels of glutamate are elevated and GABA levels are diminished. Immediately before the onset of a seizure, glutamate levels rise; during the ictal period, they rise further. In secondarily generalized seizures, glutamate levels remain elevated postictally in the epileptogenic hippocampus but fail in the contralateral hippocampus immediately after seizure arrest. This imbalance in excitatory transmission is exacerbated by an attenuated ictal increase in extracellular levels of GABA, the brain's major inhibitory neurotransmitter, in the epileptogenic hippocampus, but not in the contralateral hippocampus. In addition to changes in these amino acid transmitters, adenosine increases markedly during seizures, to levels that suppress epileptiform discharges in vitro. Furthermore, lactate increases significantly during seizures and, like adenosine, remains elevated during the postictal period. These data suggest that there is an underlying abnormalilty in the regulation of extracellular glutamate and GABA that favors excitation in the human epileptogenic hippocampus. Moreover, a preictal rise in glutamate release may trigger spontaneous seizures. The extracellular generation of adenosine and lactate may be responsible, in part, for seizure arrest and postictal refractoriness. (C) 1994 Wiley-Liss, Inc.