The effect of clinical, spontaneous-onset
seizures on extracellular fluid
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 utilization and is dependent on the activity of neurons under physiological conditions. Patients with medically refractory
complex partial epilepsy underwent stereotactic implantation of combination depth
electrode/microdialysis probes into both hippocampi for 7-16 days. During spontaneous
complex partial seizures with secondary generalization, extracellular
lactate levels rose by 91 +/- 32%. Moreover, this increase persisted for 60-90 min. During a unilateral hippocampal seizure that did not propagate to the contralateral hippocampus, the increase in
lactate content was restricted to the side of seizure activity. Between
seizures, extracellular
lactate levels correlated with the frequency of interictal spikes. In summary, these data suggest that brief clinical
seizures increase nonoxidative
glucose metabolism significantly as measured by the generation of extracellular
lactate. Furthermore, the increase in extracellular
lactate levels is limited to the site of seizure activity.
Lactate is transported extracellularly via a
lactate/
proton cotransporter, therefore, the rise in extracellular
lactate level may mediate the drop in pH0 associated with seizure activity. As acidification of the extracellular compartment has an inhibitory effect on neuronal excitability, the rise in extracellular
lactate content may be a mechanism of seizure arrest and postictal refractoriness. Moreover, extracellular
lactate may also mediate the decreased seizure susceptibility associated with frequent interictal spikes.