2024
Early vigabatrin to augment GABAergic pathways in post-anoxic status epilepticus
Maciel C, Ahmad B, Jose Bruzzone Giraldez M, Eisenschenk S, Ramsay E, Maranchick N, Peloquin C, Hirsch L, Busl K. Early vigabatrin to augment GABAergic pathways in post-anoxic status epilepticus. Epilepsy & Behavior 2024, 160: 110082. PMID: 39393141, DOI: 10.1016/j.yebeh.2024.110082.Peer-Reviewed Original ResearchStatus epilepticusGamma-aminobutyric acidGABAergic pathwayHypoxic-ischemic brain injuryPost-cardiac arrest periodHypoxic-ischemic insultOutcomes of patientsEffective adjunctive therapyInhibition of gamma-aminobutyric acidLondon-Innsbruck ColloquiumAdjunctive therapyAcute seizuresEffective therapyPoor outcomeEpilepticusExclusion criteriaEarly inhibitionSynergistic augmentationGamma-aminobutyric acid catabolismArrest periodTherapeutic nihilismSeizuresClinal trialsAllosteric modulatorsVigabatrinOutpatient management of prolonged seizures and seizure clusters to prevent progression to a higher‐level emergency: Consensus recommendations of an expert working group
Pina‐Garza J, Chez M, Cloyd J, Hirsch L, Kälviäinen R, Klein P, Lagae L, Sankar R, Specchio N, Strzelczyk A, Toledo M, Trinka E. Outpatient management of prolonged seizures and seizure clusters to prevent progression to a higher‐level emergency: Consensus recommendations of an expert working group. Epileptic Disorders 2024, 26: 484-497. PMID: 38813941, DOI: 10.1002/epd2.20243.Peer-Reviewed Original ResearchConceptsExpert working groupDefinition of PSSeizure action planWorking GroupEvidence-based guidanceProlonged seizuresSeizure clustersManaging PSStatus epilepticusExpert recommendationsTreatment goalsConsensus recommendationsOutpatient managementConsensus definitionAction planMedicationManagement of acute seizuresRecommendationsIdeal medicationAcute seizuresPrevent progressionSevere seizuresSeizure activityGroup membersSeizure terminationTreatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs
Au Y, Kananeh M, Rahangdale R, Moore T, Panza G, Gaspard N, Hirsch L, Fernandez A, Shah S. Treatment of Refractory Status Epilepticus With Continuous Intravenous Anesthetic Drugs. JAMA Neurology 2024, 81: 534-548. PMID: 38466294, DOI: 10.1001/jamaneurol.2024.0108.Peer-Reviewed Original ResearchAssociated with mortalityRefractory status epilepticusTreatment of refractory status epilepticusOutcome variablesPreferred Reporting ItemsAssociated with lower mortalityRisk of biasCompare outcome measuresPeer-reviewed studiesNon-English articlesStatus epilepticusBinary logistic regressionWeb of ScienceRSE etiologyReporting ItemsOutcome measuresStudy selectionPredictors of mortalitySystematic reviewLogistic regressionManual searchIntravenous anesthetic drugsRefractory status epilepticus treatmentTreatment goalsIndependent extractionComparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection‐related epilepsy syndrome) versus without prior fever: An interim analysis
Jimenez A, Gopaul M, Asbell H, Aydemir S, Basha M, Batra A, Damien C, Day G, Eka O, Eschbach K, Fatima S, Fields M, Foreman B, Gerard E, Gofton T, Haider H, Hantus S, Hocker S, Jongeling A, Aparicio M, Kandula P, Kang P, Kazazian K, Kellogg M, Kim M, Lee J, Marcuse L, McGraw C, Mohamed W, Orozco J, Pimentel C, Punia V, Ramirez A, Steriade C, Struck A, Taraschenko O, Treister A, Yoo J, Zafar S, Zhou D, Zutshi D, Gaspard N, Hirsch L, Hanin A. Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection‐related epilepsy syndrome) versus without prior fever: An interim analysis. Epilepsia 2024, 65: e87-e96. PMID: 38625055, DOI: 10.1111/epi.17988.Peer-Reviewed Original ResearchFebrile infection-related epilepsy syndromeRefractory status epilepticusMacrophage inflammatory protein-1 alphaOnset refractory status epilepticusStatus epilepticusCerebrospinal fluidFIRES patientsCerebrospinal fluid interleukin-6Magnetic resonance imaging findingsComparative analysis of patientsAnalysis of patientsChemokine ligand 2Presenting symptomsFebrile infectionsClinical featuresGastrointestinal prodromeImaging findingsInflammatory biomarkersAntiseizure medicationsInterleukin-6Epilepsy syndromesInterim analysisPatientsEpilepticusFeverSecond‐line immunotherapy in new onset refractory status epilepticus
Hanin A, Muscal E, Hirsch L. Second‐line immunotherapy in new onset refractory status epilepticus. Epilepsia 2024, 65: 1203-1223. PMID: 38430119, DOI: 10.1111/epi.17933.Peer-Reviewed Original ResearchFebrile infection-related epilepsy syndromeSecond-line immunotherapyOnset refractory status epilepticusRefractory status epilepticusIntrathecal dexamethasoneStatus epilepticusCytokine levelsFunctional outcomesCerebrospinal fluid cytokine levelsInitiation of anakinraReduction of seizure frequencyLong-term functional outcomeResponse to treatmentSE onsetElevated serumFebrile infectionsImmune dysregulationLong-term disabilityTreatment initiationCase reportCytokine measurementsProspective studyAnakinraImmunotherapyTocilizumab
2022
Prevalence and Predictors of Seizure Clusters in Pediatric Patients With Epilepsy: The Harvard-Yale Pediatric Seizure Cluster Study
Jafarpour S, Fong MWK, Detyniecki K, Khan A, Jackson-Shaheed E, Wang X, Lewis S, Benjamin R, Gaínza-Lein M, O'Bryan J, Hirsch LJ, Loddenkemper T. Prevalence and Predictors of Seizure Clusters in Pediatric Patients With Epilepsy: The Harvard-Yale Pediatric Seizure Cluster Study. Pediatric Neurology 2022, 137: 22-29. PMID: 36208614, DOI: 10.1016/j.pediatrneurol.2022.08.014.Peer-Reviewed Original ResearchConceptsSeizure clustersRescue medicationPediatric patientsSeizure frequencyIntermediate-risk groupEmergency department visitsHigh seizure frequencyTwo-center studyEmergency room visitsHigh-risk groupActive seizuresMore seizuresDepartment visitsStatus epilepticusRoom visitsAdverse outcomesEpilepsy severityIsolated seizureSeizure diariesRisk factorsRisk groupsGreater oddsPatientsMedicationsSeizuresAssociation of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus
Rubinos C, Bruzzone MJ, Blodgett C, Tsai C, Patel P, Hianik R, Jadav R, Boudesseul J, Liu C, Zhu H, Wilson SE, Olm-Shipman C, Meeker R, Hirsch LJ. Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus. Neurocritical Care 2022, 38: 41-51. PMID: 36071331, DOI: 10.1007/s12028-022-01579-z.Peer-Reviewed Original ResearchConceptsStatus epilepticusPyridoxal phosphate levelsPLP levelsPyridoxine deficiencyHigh prevalenceControl groupMethodsThis retrospective cohort studyIntensive care unit patientsYale-New Haven HospitalCritical illness severitySerum PLP levelsRetrospective cohort studyCare unit patientsNon-ICU inpatientsPhosphate levelsHistory of epilepsyRole of pyridoxineNorth Carolina HospitalsNew Haven HospitalUnit patientsCohort studyMedian ageIllness severityPyridoxine supplementationProspective studyInternational consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection‐related epilepsy syndrome (FIRES): Summary and clinical tools
Wickström R, Taraschenko O, Dilena R, Payne ET, Specchio N, Nabbout R, Koh S, Gaspard N, Hirsch LJ, Group T, Auvin S, van Baalen A, Beghi E, Benseler S, Bergin P, Bleck T, Brunklaus A, Caraballo R, Cervenka M, Costello D, Drislane F, Farias‐Moeller R, Gallantine W, Gilmore E, Gofton T, Jimenez M, Hocker S, Kaliakatsos M, Kellogg M, Lee J, Loddenkemper T, Meletti S, Mizugushi M, Muscal E, Riviello J, Rosenthal E, Rossetti A, Ruegg S, Said R, Sculier C, Schmitt S, Schuele S, Stredny C, Trinka E, Wainwright M, VanHaerents S, Wells E, Wirrell E, Zuberi S. International consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection‐related epilepsy syndrome (FIRES): Summary and clinical tools. Epilepsia 2022, 63: 2827-2839. PMID: 35951466, PMCID: PMC9826478, DOI: 10.1111/epi.17391.Peer-Reviewed Original ResearchFebrile infection-related epilepsy syndromeNew-onset refractory status epilepticusAcute treatmentRecommendation statementMedian scoreRefractory status epilepticusManagement of adultsManagement of patientsPost-acute phaseConsensus-based recommendationsInternational consensus recommendationsBest available evidenceEvidence-based analysisPediatric patientsStatus epilepticusEpilepsy syndromesDisease characteristicsConsensus recommendationsDiagnostic testingClinical toolAvailable evidenceDiagnosisPatientsTreatmentDelphi methodologyElectroencephalogram in the intensive care unit: a focused look at acute brain injury
Alkhachroum A, Appavu B, Egawa S, Foreman B, Gaspard N, Gilmore EJ, Hirsch LJ, Kurtz P, Lambrecq V, Kromm J, Vespa P, Zafar SF, Rohaut B, Claassen J. Electroencephalogram in the intensive care unit: a focused look at acute brain injury. Intensive Care Medicine 2022, 48: 1443-1462. PMID: 35997792, PMCID: PMC10008537, DOI: 10.1007/s00134-022-06854-3.Peer-Reviewed Original ResearchConceptsAcute brain injuryNonconvulsive status epilepticusBrain injuryStatus epilepticusEEG monitoringIntensive care unit settingRefractory status epilepticusSecondary brain injuryIntensive care unitPossible clinical relevanceAssessment of consciousnessResource-limited settingsICU EEG monitoringFrequent seizuresAcute illnessCommon indicationCare unitWorse outcomesUnit settingClinical relevancePathophysiological eventsSeizure criteriaIschemia monitoringInjuryApplication of electroencephalographyEarly vigabatrin augmenting GABA-ergic pathways in post-anoxic status epilepticus (VIGAB-STAT) phase IIa clinical trial study protocol
Maciel CB, Teixeira FJP, Dickinson KJ, Spana JC, Merck LH, Rabinstein AA, Sergott R, Shan G, Miao G, Peloquin CA, Busl KM, Hirsch LJ. Early vigabatrin augmenting GABA-ergic pathways in post-anoxic status epilepticus (VIGAB-STAT) phase IIa clinical trial study protocol. Neurological Research And Practice 2022, 4: 4. PMID: 35067230, PMCID: PMC8785535, DOI: 10.1186/s42466-022-00168-x.Peer-Reviewed Original ResearchStatus epilepticusClinical trialsVigabatrin levelsClinical trial study protocolPost-cardiac arrest periodRefractory focal-onset seizuresDose-linear pharmacokineticsPrimary feasibility endpointBlinded outcome assessmentEffective adjunctive treatmentSingle loading doseTrial study protocolBrain GABA levelsCardiac arrest survivorsPilot clinical trialLast quantifiable concentrationFocal onset seizuresGABA-ergic pathwaysReports of survivorsConcentration-time curvePrimary pharmacokinetic endpointsFeasibility endpointsAggressive treatmentEligible subjectsNeuronal injury
2021
A systematic review of seizure clusters: Prevalence, risk factors, burden of disease and treatment patterns
Chung S, Szaflarski JP, Choi EJ, Wilson JC, Kharawala S, Kaur G, Hirsch LJ. A systematic review of seizure clusters: Prevalence, risk factors, burden of disease and treatment patterns. Epilepsy Research 2021, 177: 106748. PMID: 34521043, DOI: 10.1016/j.eplepsyres.2021.106748.Peer-Reviewed Original ResearchConceptsSeizure action planRescue medicationSeizure clustersStatus epilepticusTreatment patternsSeizure remissionTreatment resistanceHigh riskPoor physician-patient communicationSeizure-related hospitalizationHigh seizure frequencyBurden of diseaseProductivity of patientsPhysician-patient communicationNon-SC patientsQuality of lifeSystematic literature searchConsecutive seizuresSeizure frequencyTreatment guidelinesProspective studySC patientsCaregiver QOLDisease burdenRisk factorsPharmacotherapy for Nonconvulsive Seizures and Nonconvulsive Status Epilepticus
Bravo P, Vaddiparti A, Hirsch LJ. Pharmacotherapy for Nonconvulsive Seizures and Nonconvulsive Status Epilepticus. Drugs 2021, 81: 749-770. PMID: 33830480, DOI: 10.1007/s40265-021-01502-4.Peer-Reviewed Original ResearchConceptsNonconvulsive status epilepticusAntiseizure medicationsNonconvulsive seizuresStatus epilepticusIll patientsRefractory nonconvulsive status epilepticusFurther neurological injuryMultiple antiseizure medicationsAdverse neurological outcomesContinuous electroencephalogram monitoringLong-term outcomesHemodynamic labilityRecent neurosurgerySeizure burdenNeurological outcomePharmacological managementBrain infectionGlobal hypoxiaNeurological injuryEarly recognitionMost seizuresUnderlying conditionClinical trialsElectroencephalogram monitoringHepatic functionHow to Help Your Patients Enroll in the New-Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES) Family Registry, and Other Rare Epilepsy Registries
Kazazian K, Kellogg M, Wong N, Eschbach K, Moeller RF, Gaspard N, Hirsch LJ, Hocker S, Gofton T. How to Help Your Patients Enroll in the New-Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES) Family Registry, and Other Rare Epilepsy Registries. Epilepsy Currents 2021, 21: 382-384. PMID: 33769129, PMCID: PMC8655258, DOI: 10.1177/15357597211002869.Peer-Reviewed Original ResearchElectroencephalographic Abnormalities are Common in COVID‐19 and are Associated with Outcomes
Lin L, Al‐Faraj A, Ayub N, Bravo P, Das S, Ferlini L, Karakis I, Lee JW, Mukerji SS, Newey CR, Pathmanathan J, Abdennadher M, Casassa C, Gaspard N, Goldenholz DM, Gilmore EJ, Jing J, Kim JA, Kimchi EY, Ladha HS, Tobochnik S, Zafar S, Hirsch LJ, Westover MB, Shafi MM. Electroencephalographic Abnormalities are Common in COVID‐19 and are Associated with Outcomes. Annals Of Neurology 2021, 89: 872-883. PMID: 33704826, PMCID: PMC8104061, DOI: 10.1002/ana.26060.Peer-Reviewed Original ResearchConceptsNonconvulsive status epilepticusElectrographic seizuresClinical outcomesEpileptiform abnormalitiesRisk factorsPresence of NCSEMultivariate Cox proportional hazards analysisMulticenter retrospective cohort studyCox proportional hazards analysisCOVID-19Retrospective cohort studyClinical risk factorsContinuous electroencephalogram monitoringAdverse clinical outcomesProportional hazards analysisCoronavirus disease 2019Ann NeurolHospital mortalityHospital lengthClinical seizuresCohort studyIndependent predictorsStatus epilepticusEEG findingsElectroencephalographic abnormalitiesHow to Help Your Patients Enroll in the New-Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES) Family Registry, and Other Rare Epilepsy Registries.
Kazazian K, Kellogg M, Wong N, Eschbach K, Moeller RF, Gaspard N, Hirsch LJ, Hocker S, Gofton T. How to Help Your Patients Enroll in the New-Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES) Family Registry, and Other Rare Epilepsy Registries. Epilepsy Currents 2021, 1535759721998329. PMID: 33663265, DOI: 10.1177/1535759721998329.Peer-Reviewed Original ResearchFebrile infection-related epilepsy syndromeNew-onset refractory status epilepticusRefractory status epilepticusStatus epilepticusFamily RegistryRare clinical presentationPast medical historyQuality of lifeEpilepsy registryFebrile infectionsActive epilepsyDisease courseClinical outcomesClinical presentationEpilepsy syndromesMedical historyNeurologic disordersRigorous research studiesEpilepticusRegistryPatient enrollsFamily membersOutcomesMorbidityEpilepsyPearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist
Katz JB, Owusu K, Nussbaum I, Beekman R, DeFilippo NA, Gilmore EJ, Hirsch LJ, Cervenka MC, Maciel CB. Pearls and Pitfalls of Introducing Ketogenic Diet in Adult Status Epilepticus: A Practical Guide for the Intensivist. Journal Of Clinical Medicine 2021, 10: 881. PMID: 33671485, PMCID: PMC7926931, DOI: 10.3390/jcm10040881.Peer-Reviewed Original ResearchNew-onset refractory status epilepticusSuper-refractory status epilepticusMagnetic resonance imagingStatus epilepticusIntensive care unitKetogenic dietCryptogenic new-onset refractory status epilepticusCerebral spinal fluid (CSF) pleocytosisUse of KDDiffusion restrictionSerial magnetic resonance imagingAdult status epilepticusHospital day 28Non-ICU unitsSpinal fluid pleocytosisAggressive therapeutic approachRefractory status epilepticusSerum inflammatory markersResolution of edemaBeta-hydroxybutyrate levelsPoor nutritional stateTherapeutic comaBilateral oophorectomyInflammatory markersFebrile illness
2020
When and How to Treat Status Epilepticus: The Tortoise or the Hare?
Fong MWK, Hirsch LJ. When and How to Treat Status Epilepticus: The Tortoise or the Hare? Journal Of Clinical Neurophysiology 2020, 37: 393-398. PMID: 32890060, DOI: 10.1097/wnp.0000000000000656.Peer-Reviewed Original ResearchConceptsType of SEStatus epilepticusTreatment of SECessation of seizuresCurrent treatment guidelinesConvulsive status epilepticusTreatment guidelinesFull dosesNeuronal responsesVariety of subtypesPromising future approachUnnecessary harmEpilepticusPatientsTherapyTreatmentFuture approachesCollective termEvaluating the Clinical Impact of Rapid Response Electroencephalography: The DECIDE Multicenter Prospective Observational Clinical Study.
Vespa PM, Olson DM, John S, Hobbs KS, Gururangan K, Nie K, Desai MJ, Markert M, Parvizi J, Bleck TP, Hirsch LJ, Westover MB. Evaluating the Clinical Impact of Rapid Response Electroencephalography: The DECIDE Multicenter Prospective Observational Clinical Study. Critical Care Medicine 2020, 48: 1249-1257. PMID: 32618687, PMCID: PMC7735649, DOI: 10.1097/ccm.0000000000004428.Peer-Reviewed Original ResearchConceptsNonconvulsive seizuresSeizure diagnosisTreatment planProspective observational clinical studyDiagnostic assessmentObservational clinical studyAssessment of patientsCritical care settingSerious adverse effectsTherapeutic decision makingProspective multicenterSecondary outcomesICU patientsPrimary outcomeStatus epilepticusHigh suspicionElectroencephalography assessmentAcademic hospitalBedside assessmentClinical impactClinical studiesObservational studyCare settingsPhysician confidencePatientsChoosing Anticonvulsant Medications to Manage Status Epilepticus
Wu K, Hirsch LJ, Babl FE, Josephson SA. Choosing Anticonvulsant Medications to Manage Status Epilepticus. New England Journal Of Medicine 2020, 382: 2569-2572. PMID: 32579819, DOI: 10.1056/nejmclde2004317.Peer-Reviewed Original ResearchValidation of an algorithm of time-dependent electro-clinical risk stratification for electrographic seizures (TERSE) in critically ill patients
Cissé FA, Osman GM, Legros B, Depondt C, Hirsch LJ, Struck AF, Gaspard N. Validation of an algorithm of time-dependent electro-clinical risk stratification for electrographic seizures (TERSE) in critically ill patients. Clinical Neurophysiology 2020, 131: 1956-1961. PMID: 32622337, DOI: 10.1016/j.clinph.2020.05.031.Peer-Reviewed Original ResearchConceptsElectrographic seizuresRisk stratificationIll patientsAcute brain injuryContinuous electroencephalography monitoringElectrographic status epilepticusSubgroup of patientsDuration of EEGClinical seizuresConsecutive patientsStatus epilepticusElectroencephalography monitoringBrain injuryMedical recordsSubstantial burdenPatientsClinical practiceCEEGClinical neurophysiologistsSeizuresClinical implementationEEG recordingsTwo-thirdsFuture studiesEEG time