Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity
Farina MG, Sandhu MRS, Parent M, Sanganahalli BG, Derbin M, Dhaher R, Wang H, Zaveri HP, Zhou Y, Danbolt NC, Hyder F, Eid T. Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity. Epilepsia 2021, 62: 2858-2870. PMID: 34536233, PMCID: PMC9006438, DOI: 10.1111/epi.17072.Peer-Reviewed Original ResearchConceptsPostnatal brainFunctional connectivityContinuous video-electroencephalographic recordingSpontaneous recurrent seizuresPathogenesis of epilepsyGlutamine synthetase deficiencyVideo-electroencephalographic recordingsSpecific animal modelsEx vivo studySeizure thresholdAdult patientsRecurrent seizuresFocal epilepsyAdeno-associated virusHippocampal formationAnimal modelsFocal mannerEpileptic seizuresGS deficiencySmall lociSynthetase deficiencyEpilepsyGradual returnVivo studiesBrainIncreased branched‐chain amino acids at baseline and hours before a spontaneous seizure in the human epileptic brain
Ong C, Damisah EC, Gruenbaum SE, Dhaher R, Deng Y, Sandhu MRS, Zaveri HP, Spencer DD, Eid T. Increased branched‐chain amino acids at baseline and hours before a spontaneous seizure in the human epileptic brain. Epilepsia 2021, 62: e88-e97. PMID: 33949690, PMCID: PMC11259155, DOI: 10.1111/epi.16920.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acids, Branched-ChainBrain ChemistryChildChild, PreschoolChromatography, High Pressure LiquidDrug Resistant EpilepsyElectrocorticographyElectroencephalographyEpilepsies, PartialExtracellular SpaceFemaleGlutamic AcidHumansIsoleucineMaleMicrodialysisMiddle AgedSeizuresTandem Mass SpectrometryYoung AdultConceptsSpontaneous seizuresDrug-resistant focal epilepsyExtracellular brain glutamateHuman epileptic brainBranched-chain amino acidsBranched chain amino acids valineRefractory epilepsyBrain microdialysisGlutamatergic neurotransmissionFocal epilepsySeizure onsetBrain glutamateEpileptic brainHuman patientsSeizuresBrain regionsDialysis samplesMammalian targetEpilepsyLiquid chromatography-tandem mass spectrometryBaselineBCAAIntracranial electroencephalographyChromatography-tandem mass spectrometryPatients