Journal
EPILEPSIA
Volume 62, Issue 6, Pages E88-E97Publisher
WILEY
DOI: 10.1111/epi.16920
Keywords
ictogenesis; metabolism; microdialysis; neurochemistry; seizure prediction
Categories
Funding
- National Institute of Neurological Disorders and Stroke [NS058674, NS070824, NS109062, NS109734]
- Citizens United for Research in Epilepsy
- National Center for Advancing Translational Sciences [RR024139]
- Doris Duke Charitable Foundation
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This study monitored extracellular brain chemistry dynamics in patients with refractory epilepsy and found that branched-chain amino acids (BCAAs) and glutamate were chronically elevated in brain regions of seizure onset and propagation. Interestingly, isoleucine increased significantly above baseline as early as 3 hours before a spontaneous seizure, suggesting a potential role of BCAAs in the pathogenesis of spontaneous seizures.
The objective of this study was to monitor the extracellular brain chemistry dynamics at baseline and in relation to spontaneous seizures in human patients with refractory epilepsy. Thirty patients with drug-resistant focal epilepsy underwent intracranial electroencephalography and concurrent brain microdialysis for up to 8 continuous days. Extracellular brain glutamate, glutamine, and the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine were quantified in the dialysis samples by liquid chromatography-tandem mass spectrometry. Extracellular BCAAs and glutamate were chronically elevated at baseline by approximately 1.5-3-fold in brain regions of seizure onset and propagation versus regions not involved by seizures. Moreover, isoleucine increased significantly above baseline as early as 3 h before a spontaneous seizure. BCAAs play important roles in glutamatergic neurotransmission, mitochondrial function, neurodegeneration, and mammalian target of rapamycin signaling. Because all of these processes have been implicated in epilepsy, the results suggest a novel role of BCAAs in the pathogenesis of spontaneous seizures.
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