Abstracts

Rationale: Many physiological processes and diseases exhibit intriguing rhythmic patterns such as cortisol secretion, body temperature, sleep/wakefulness, and epilepsy. Regarding epilepsy, it is well-known that seizures can occur in clusters, followed by long periods of seizure freedom. While many focal epilepsies exhibit circadian oscillations of seizure vulnerability, the mechanisms underlying periodicity in epilepsy are incompletely understood, and very little is known about circadian chemistry changes in human or animal brains. Investigating these mechanisms will significantly advance the fields of chronobiology and epilepsy and likely lead to more effective antiseizure therapies. Here, we present preliminary results from a study which explores dynamic changes in brain metabolites in epileptic human brain.

Methods: Thirty patients with drug-resistant focal epilepsy underwent intracranial electroencephalography and concurrent brain microdialysis continuously for 8 days. Extracellular brain fluid was collected in 1-hour aliquots. Glutamate, GABA, glutamine, and the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine were quantified in the dialysis samples by liquid chromatography-tandem mass spectrometry. JTK cycle analysis was used to detect circadian oscillations in these metabolites.

Results: In one patient, depth electrodes were implanted in the left hippocampus and left occipital lobe. Among several metabolomic ratios, glutamate/GABA showed significant oscillation in hippocampus (p < 0.001) and occipital lobe (p = 0.005). However, there was a phase difference noticed between the two regions. Therefore, indicating the regional influence on metabolomic periodicity in the epileptic brain. Similarly, for another patient, the depth electrodes were implanted in the left hippocampus (p = 0.02) and left lesion. Glutamate/GABA showed significant circadian oscillation in the left hippocampus, but not in the lesional region.