DIRECT MEASUREMENT OF EXTRACELLULAR LACTATE IN THE HUMAN HIPPOCAMPUS DURING SPONTANEOUS SEIZURES

The effect of clinical, spontaneous-onset seizures on extracellular fl uid lactate was investigated by the method of lactography, the in vivo on-line measurement of lactate levels using microdialysis. Studies of experimental animals have suggested that generation of extracellular lactate as measured by microdialysis is an index of local glucose util ization and is dependent on the activity of neurons under physiologica l conditions. Patients with medically refractory complex partial epile psy underwent stereotactic implantation of combination depth electrode /microdialysis probes into both hippocampi for 7-16 days. During spont aneous complex partial seizures with secondary generalization, extrace llular lactate levels rose by 98 +/- 32%. Moreover, this increase pers isted for 60-90 min. During a unilateral hippocampal seizure that did not propagate to the contralateral hippocampus, the increase in lactat e content was restricted to the side of seizure activity. Between seiz ures, extracellular lactate levels correlated with the frequency of in terictal spikes. In summary, these data suggest that brief clinical se izures increase nonoxidative glucose metabolism significantly as measu red by the generation of extracellular lactate. Furthermore, the incre ase in extracellular lactate level is limited to the site of seizure a ctivity. Lactate is transported extracellularly via a lactate/proton c otransporter; therefore, the rise in extracellular lactate level may m ediate the drop in pH(0) associated with seizure activity. As acidific ation of the extracellular compartment has an inhibitory effect on neu ronal excitability, the rise in extracellular lactate content may be a mechanism of seizure arrest and postictal refractoriness. Moreover, e xtracellular lactate may also mediate the decreased seizure susceptibi lity associated with frequent interictal spikes.