2025
A Modern Design for a Phase 2/3 Randomized, Double-blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BHV-7000 in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures (P8-9.016)
Lerner J, Stock D, Bozik M, Suarez V, Jensen C, Donahue L, DeGrosky M, Kozauer N, Coric V, Qureshi I, Kerr W, French J. A Modern Design for a Phase 2/3 Randomized, Double-blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BHV-7000 in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures (P8-9.016). Neurology 2025, 104 DOI: 10.1212/wnl.0000000000211240.Peer-Reviewed Original Research
2023
Isradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities
Stölting G, Dinh H, Volkert M, Hellmig N, Schewe J, Hennicke L, Seidel E, Oberacher H, Zhang J, Lifton R, Urban I, Long M, Rivalan M, Nottoli T, Scholl U. Isradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities. JCI Insight 2023, 8: e162468. PMID: 37698934, PMCID: PMC10619505, DOI: 10.1172/jci.insight.162468.Peer-Reviewed Original ResearchConceptsPrimary aldosteronismNeurologic abnormalitiesZona glomerulosaIntracellular calciumElevated aldosterone/renin ratioCalcium channel blocker isradipineAldosterone/renin ratioL-type calcium channel Cav1.3Aldosterone-producing lesionsAdrenal aldosterone-producing adenomaHigh-salt dietTonic-clonic seizuresChannel blocker isradipineReduced body weightAldosterone-producing adenomaTherapy of patientsElevated intracellular calciumFunction mutationsDe novo germline mutationsDays of ageIsradipine therapyAldosterone levelsRenin ratioSerum aldosteroneRotarod test
2022
Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures
Juan E, Górska U, Kozma C, Papantonatos C, Bugnon T, Denis C, Kremen V, Worrell G, Struck A, Bateman L, Merricks E, Blumenfeld H, Tononi G, Schevon C, Boly M. Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures. Brain 2022, 146: 109-123. PMID: 36383415, PMCID: PMC10582624, DOI: 10.1093/brain/awac291.Peer-Reviewed Original ResearchConceptsBilateral tonic-clonic seizuresFocal impaired awarenessTonic-clonic seizuresLoss of consciousnessSeizure onset zoneSlow wave activityIntracranial EEG activityImpaired awarenessIctal recruitmentCortical activationOnset zoneHigh-gamma activityCross-frequency couplingFocal impaired awareness seizuresNegative prognostic consequencesSleep-like activityEEG activityCortical firing ratesParieto-occipital cortexPosterior brain regionsMulti-unit activityAwareness seizuresClinical outcomesPrognostic consequencesClinical signs
2021
Anti-seizure medications and efficacy against focal to bilateral tonic-clonic seizures: A systematic review with relevance for SUDEP prevention
Cutillo G, Tolba H, Hirsch LJ. Anti-seizure medications and efficacy against focal to bilateral tonic-clonic seizures: A systematic review with relevance for SUDEP prevention. Epilepsy & Behavior 2021, 117: 107815. PMID: 33640562, DOI: 10.1016/j.yebeh.2021.107815.Peer-Reviewed Original ResearchConceptsAnti-seizure medicationsBilateral tonic-clonic seizuresTonic-clonic seizuresSUDEP preventionSystematic reviewPlacebo-controlled clinical trialFocal impaired awareness seizuresRisk of SUDEPSudden unexpected deathMajor risk factorAwareness seizuresRisk factorsClinical trialsUnexpected deathFBTCSHigh dosesSeizuresStrong associationSUDEPPreventionMedicationsTiagabineEfficacyLamotrigineBrivaracetam
2020
The Sensitivity of Scalp EEG at Detecting Seizures—A Simultaneous Scalp and Stereo EEG Study
Casale M, Marcuse L, Young J, Jette N, Panov F, Bender H, Saad A, Ghotra R, Ghatan S, Singh A, Yoo J, Fields M. The Sensitivity of Scalp EEG at Detecting Seizures—A Simultaneous Scalp and Stereo EEG Study. Journal Of Clinical Neurophysiology 2020, 39: 78-84. PMID: 32925173, PMCID: PMC8290181, DOI: 10.1097/wnp.0000000000000739.Peer-Reviewed Original ResearchConceptsBilateral tonic-clonic seizuresTonic-clonic seizuresSEEG seizuresMRI lesionsSubclinical seizuresScalp EEGDrug-resistant epilepsy patientsStereo-EEG studyStereo-EEG recordingsSimultaneous scalp EEGDetection of FocalNonlesional patientsInterictal abnormalitiesIctal patternsEpilepsy patientsLong-term effectsSeizuresPatientsSimultaneous scalpEEG seizuresScalpAbnormalitiesLonger durationEEG studiesLesionsAntiepileptic drug withdrawal and seizure severity in the epilepsy monitoring unit
Duy PQ, Krauss GL, Crone NE, Ma M, Johnson EL. Antiepileptic drug withdrawal and seizure severity in the epilepsy monitoring unit. Epilepsy & Behavior 2020, 109: 107128. PMID: 32417383, DOI: 10.1016/j.yebeh.2020.107128.Peer-Reviewed Original ResearchConceptsEpilepsy monitoring unitBilateral tonic-clonic seizuresSevere seizure typeTonic-clonic seizuresFocal seizuresSeizure typesAED doseLorazepam administrationAntiepileptic drug reductionAntiepileptic drug withdrawalDrug withdrawal ratesReceiver-operating characteristic curveRisk of complicationsAED dosageAED withdrawalEMU stayConsecutive patientsSeizure clustersAED reductionDrug withdrawalSeizure severityPresurgical patientsDrug reductionSeizuresEffective dose
2017
Novel clinical manifestations in patients with KCNA2 mutations
Sachdev M, Gaínza-Lein M, Tchapyjnikov D, Jiang YH, Loddenkemper T, Mikati MA. Novel clinical manifestations in patients with KCNA2 mutations. Seizure 2017, 51: 74-76. PMID: 28806589, DOI: 10.1016/j.seizure.2017.07.018.Peer-Reviewed Original ResearchConceptsGeneralized tonic-clonic seizuresTonic-clonic seizuresElectrical status epilepticusNovel clinical manifestationYear old maleStatus epilepticusKCNA2 mutationsClonic seizuresClinical manifestationsMyoclonic-astatic seizuresStatus epilepticus episodesYear old femaleYears of ageAstatic seizuresSeizure typesEpileptic manifestationsFocal seizuresPatient 1Patient 2Patient 3Clinical criteriaSevere manifestationsEpileptic encephalopathyBlood samplesPatients
2016
Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement
Hsieh LS, Wen JH, Claycomb K, Huang Y, Harrsch FA, Naegele JR, Hyder F, Buchanan GF, Bordey A. Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement. Nature Communications 2016, 7: 11753. PMID: 27249187, PMCID: PMC4895394, DOI: 10.1038/ncomms11753.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCognitive DysfunctionDisease Models, AnimalFemaleGene Expression RegulationGenes, ReporterGreen Fluorescent ProteinsHumansMaleMalformations of Cortical DevelopmentMiceNeuronsPrefrontal CortexSeizuresSignal TransductionSirolimusTOR Serine-Threonine KinasesWhite MatterConceptsFocal cortical dysplasiaCortical dysplasiaType II focal cortical dysplasiaWhite matter heterotopiasLayer 2/3 neuronsLife-long treatmentTonic-clonic seizuresNormal survival rateMedial prefrontal cortexLocal malformationsConvulsive seizuresPharmacoresistant epilepsySeizure activitySeizure generationSeizure occurrenceCommon causeCortical developmentMurine modelNeurocognitive impairmentSurvival rateSeizuresRapamycin withdrawalPrefrontal cortexMTOR activityRapamycin treatmentCentral Nervous System Oxygen Toxicity and Hyperbaric Oxygen Seizures
Manning EP. Central Nervous System Oxygen Toxicity and Hyperbaric Oxygen Seizures. Aerospace Medicine And Human Performance 2016, 87: 477-486. PMID: 27099087, PMCID: PMC7092644, DOI: 10.3357/amhp.4463.2016.Peer-Reviewed Original ResearchConceptsCNS O2 toxicityO2 toxicityCentral nervous system O2 toxicityCentral nervous system oxygen toxicityHyperbaric O2 treatmentTonic-clonic seizuresOxygen seizuresMulticenter trialHyperbaric oxygenNumerous physiological changesTherapeutic agentsOxygen toxicityElevated PO2Scientific evidenceFurther studiesNumerous endpointsSeizuresProtective reactionsPhysiological changesToxicityChapter 16 Epilepsy and Consciousness
Blumenfeld H. Chapter 16 Epilepsy and Consciousness. 2016, 255-270. DOI: 10.1016/b978-0-12-800948-2.00016-9.Peer-Reviewed Original ResearchSeizure typesImpaired consciousnessNormal consciousnessDiverse seizure typesTemporal lobe seizuresTonic-clonic seizuresParietal association cortexMedial thalamusUpper brainstemAbsence seizuresNeuronal activityPatient injuryBehavioral testingAssociation cortexEpileptic seizuresSeizuresInterhemispheric regionSynchronous dischargesLateral frontalNeuroimaging signalsAbnormal increaseAnatomical regionsEpilepsySpecific anatomical structuresConsciousness system
2015
Late Postpartum Eclampsia with Postpartum Angiopathy: An Uncommon Diagnosis in the Emergency Department
Garg D, Rahaman B, Stein EG, Dickman E. Late Postpartum Eclampsia with Postpartum Angiopathy: An Uncommon Diagnosis in the Emergency Department. Journal Of Emergency Medicine 2015, 49: e187-e191. PMID: 26409671, DOI: 10.1016/j.jemermed.2015.07.019.Peer-Reviewed Original ResearchConceptsLate postpartum eclampsiaEmergency departmentPostpartum eclampsiaMedical intensive care unitGeneralized tonic-clonic seizuresFurther seizure activityPossibility of preeclampsiaBlood pressure controlControl of seizuresNormal vaginal deliveryRare clinical entityTonic-clonic seizuresPast medical historyIntensive care unitBeats/minOccurrence of eclampsiaPostpartum angiopathyUndifferentiated headacheEntire pregnancyNonspecific symptomsBlood pressureVaginal deliveryCare unitChief complaintBlurry visionLong-term treatment with responsive brain stimulation in adults with refractory partial seizures
Bergey GK, Morrell MJ, Mizrahi EM, Goldman A, King-Stephens D, Nair D, Srinivasan S, Jobst B, Gross RE, Shields DC, Barkley G, Salanova V, Olejniczak P, Cole A, Cash SS, Noe K, Wharen R, Worrell G, Murro AM, Edwards J, Duchowny M, Spencer D, Smith M, Geller E, Gwinn R, Skidmore C, Eisenschenk S, Berg M, Heck C, Van Ness P, Fountain N, Rutecki P, Massey A, O'Donovan C, Labar D, Duckrow RB, Hirsch LJ, Courtney T, Sun FT, Seale CG. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology 2015, 84: 810-817. PMID: 25616485, PMCID: PMC4339127, DOI: 10.1212/wnl.0000000000001280.Peer-Reviewed Original ResearchConceptsRefractory partial-onset seizuresPartial-onset seizuresRefractory partial seizuresOnset seizuresQuality of lifePartial seizuresResponsive neurostimulatorSerious device-related adverse eventsMedian percent seizure reductionGeneralized tonic-clonic seizuresOpen-label safety studyDevice-related adverse eventsImplant site infectionPercent seizure reductionResponsive brain stimulationClass IV evidenceTonic-clonic seizuresDirect cortical stimulationLong-term efficacyLong-term treatmentRNS SystemDirect neurostimulationSeizure reductionAdverse eventsSite infectionRhythmic 3–4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures
Youngblood MW, Chen WC, Mishra AM, Enamandram S, Sanganahalli BG, Motelow JE, Bai HX, Frohlich F, Gribizis A, Lighten A, Hyder F, Blumenfeld H. Rhythmic 3–4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures. NeuroImage 2015, 109: 368-377. PMID: 25562830, PMCID: PMC4340775, DOI: 10.1016/j.neuroimage.2014.12.066.Peer-Reviewed Original ResearchConceptsHz spike-wave dischargesSpike-wave dischargesFMRI decreasesSpike-wave seizuresAnimal modelsHuman patientsMagnetic resonance imaging studyTonic-clonic seizuresBlood oxygen level-dependent (BOLD) signalResonance imaging studyFunctional magnetic resonance imaging studyHuman functional magnetic resonance imaging (fMRI) studiesGeneralized seizuresFerret modelCortical decreasesAbsence seizuresCortical developmentAnesthetic regimeSeizuresTransient episodesHuman seizuresImaging studiesPatientsBOLD fMRISimultaneous electroencephalography
2014
Ictal spread of medial temporal lobe seizures with and without secondary generalization: An intracranial electroencephalography analysis
Yoo JY, Farooque P, Chen WC, Youngblood MW, Zaveri HP, Gerrard JL, Spencer DD, Hirsch LJ, Blumenfeld H. Ictal spread of medial temporal lobe seizures with and without secondary generalization: An intracranial electroencephalography analysis. Epilepsia 2014, 55: 289-295. PMID: 24417694, PMCID: PMC4103687, DOI: 10.1111/epi.12505.Peer-Reviewed Original ResearchConceptsSecondary generalizationTemporal lobe seizuresFocal seizuresTemporal cortexMedial temporal lobe seizuresCortical regionsLow-voltage fast activityProminent activationAnteromedial temporal lobe resectionTonic-clonic seizuresSeizure-onset patternsTemporal lobe resectionLateral temporal cortexQuality of lifePosterior lateral temporal cortexTemporal lobe areasIntracranial electroencephalography studyMedial temporal lobe areasMedial temporal lobePosterior lateral temporal regionsIctal spreadHippocampal sclerosisSeizure spreadLobe resectionTemporal lobe
2011
The Secret “Spice”: An Undetectable Toxic Cause of Seizure
de Havenon A, Chin B, Thomas KC, Afra P. The Secret “Spice”: An Undetectable Toxic Cause of Seizure. The Neurohospitalist 2011, 1: 182-186. PMID: 23983854, PMCID: PMC3726077, DOI: 10.1177/1941874411417977.Peer-Reviewed Original ResearchFirst generalized seizureEmergency department physiciansGeneralized seizuresDepartment physiciansSide effectsSynthetic cannabinoidsEmergency department visitsTonic-clonic seizuresCannabinoid receptors CB1US Drug Enforcement AdministrationToxic side effectsProconvulsant effectsProvoked seizuresDepartment visitsAntiepileptic drugsToxic causesUnnecessary treatmentDifferential diagnosisPrior historyDrug toxicityReceptors CB1Detailed historyNeurological diseasesSeizuresSynthetic cannabinoid products
2010
Four Novel SCN1A Mutations in Turkish Patients With Severe Myoclonic Epilepsy of Infancy (SMEI)
Arlier Z, Bayri Y, Kolb LE, Erturk O, Ozturk AK, Bayrakli F, Bilguvar K, Moliterno JA, Dervent A, Demirbilek V, Yalcinkaya C, Korkmaz B, Tuysuz B, Gunel M. Four Novel SCN1A Mutations in Turkish Patients With Severe Myoclonic Epilepsy of Infancy (SMEI). Journal Of Child Neurology 2010, 25: 1265-1268. PMID: 20110217, DOI: 10.1177/0883073809357241.Peer-Reviewed Original ResearchConceptsSevere myoclonic epilepsyDravet syndromeTurkish patientsMyoclonic epilepsySCN1A geneNovel SCN1A mutationTonic-clonic seizuresRare genetic disorderUnilateral clonicSCN1A mutationsType 1SyndromeSpectrum of mutationsDisease phenotypeGenetic disordersNovel mutationsPatientsEpilepsyNovo mutationsFirst yearResponsible geneInfancyMutationsBroad spectrumAllelic heterogeneity
2009
Cortical and subcortical networks in human secondarily generalized tonic–clonic seizures
Blumenfeld H, Varghese GI, Purcaro MJ, Motelow JE, Enev M, McNally KA, Levin AR, Hirsch LJ, Tikofsky R, Zubal IG, Paige AL, Spencer SS. Cortical and subcortical networks in human secondarily generalized tonic–clonic seizures. Brain 2009, 132: 999-1012. PMID: 19339252, PMCID: PMC2724910, DOI: 10.1093/brain/awp028.Peer-Reviewed Original ResearchConceptsGeneralized tonic-clonic seizuresTonic-clonic seizuresFocal CBF increasesCBF increaseAssociation cortexImpaired consciousnessBasal gangliaSubcortical structuresCerebral blood flow changesBlood flow changesPartial seizure onsetLateral cerebellar hemispheresSingle photon emissionStatistical parametric mappingSecondary generalizationCBF decreasePartial seizuresCerebral cortexMotor manifestationsUpper brainstemSeizure onsetCerebellar hemisphereIndividual patientsTemporal lobeSeizure phaseClinical use of ictal SPECT in secondarily generalized tonic–clonic seizures
Varghese GI, Purcaro MJ, Motelow JE, Enev M, McNally KA, Levin AR, Hirsch LJ, Tikofsky R, Paige AL, Zubal IG, Spencer SS, Blumenfeld H. Clinical use of ictal SPECT in secondarily generalized tonic–clonic seizures. Brain 2009, 132: 2102-2113. PMID: 19339251, PMCID: PMC2714057, DOI: 10.1093/brain/awp027.Peer-Reviewed Original ResearchConceptsCerebral blood flow increasesBlood flow increasesGeneralized tonic-clonic seizuresIctal SPECTTonic-clonic seizuresPartial seizuresPost-ictal periodSeizure onsetGeneralized seizuresSecondary generalizationCerebral blood flow decreasesRegional cerebral blood flow increasesPropagation of seizuresBlood flow decreaseCerebral blood flowEpilepsy surgery evaluationUseful clinical toolSingle photon emissionFlow increasesSeizure localizationSurgery evaluationBlood flowSeizuresClinical toolClinical use
1997
Sodium/Hydrogen Exchanger Gene Defect in Slow-Wave Epilepsy Mutant Mice
Cox G, Lutz C, Yang C, Biemesderfer D, Bronson R, Fu A, Aronson P, Noebels J, Frankel W. Sodium/Hydrogen Exchanger Gene Defect in Slow-Wave Epilepsy Mutant Mice. Cell 1997, 91: 139-148. PMID: 9335342, DOI: 10.1016/s0092-8674(01)80016-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxiaBrain ChemistryCell LineCerebellumCerebral CortexChromosome MappingCrosses, GeneticElectroencephalographyEpilepsyFibroblastsGenes, RecessiveIon TransportMiceMice, Inbred C57BLMice, Neurologic MutantsOrgan SpecificityPhenotypePoint MutationRNASodiumSodium-Hydrogen ExchangersConceptsSodium/hydrogen exchangerSpontaneous mouse mutantDisease-causing mutationsPlasma membraneChromosome 4Null allelesMouse mutantsCell survivalHydrogen exchangerNHE genesMutantsGene defectsMutant miceNHE1Growth factorTonic-clonic seizuresSelective neuronal deathNeuronal deathDelicate balanceNeurological syndromeEpilepsy phenotypeGenesNew toolCell volumeMutations
1994
Vigabatrin: Effects on Human Brain GABA Levels by Nuclear Magnetic Resonance Spectroscopy
Mattson R, Petroff O, Rothman D, Behar K. Vigabatrin: Effects on Human Brain GABA Levels by Nuclear Magnetic Resonance Spectroscopy. Epilepsia 1994, 35: s29-s32. PMID: 8039467, DOI: 10.1111/j.1528-1157.1994.tb05963.x.Peer-Reviewed Original ResearchConceptsBrain GABA levelsGABA levelsHuman brain GABA levelsGeneralized tonic-clonic seizuresTonic-clonic seizuresGamma-aminobutyric acid transaminaseNew antiepileptic drugsElevated brain GABA levelsTimes control valuesLong-term trialsDaily dosageAntiepileptic drugsClinical effectsGABA elevationCerebrospinal fluidSide effectsMagnetic resonance spectroscopyControl valuesIrreversible substrateResonance spectroscopyFirst studyDosageConcentrations 2VigabatrinSeizures
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