Featured Publications
Central vein sign: A diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial
Ontaneda D, Sati P, Raza P, Kilbane M, Gombos E, Alvarez E, Azevedo C, Calabresi P, Cohen JA, Freeman L, Henry RG, Longbrake EE, Mitra N, Illenberger N, Schindler M, Moreno-Dominguez D, Ramos M, Mowry E, Oh J, Rodrigues P, Chahin S, Kaisey M, Waubant E, Cutter G, Shinohara R, Reich DS, Solomon A, Sicotte NL, Cooperative N. Central vein sign: A diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial. NeuroImage Clinical 2021, 32: 102834. PMID: 34592690, PMCID: PMC8482479, DOI: 10.1016/j.nicl.2021.102834.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCross-Sectional StudiesHumansMagnetic Resonance ImagingMulticenter Studies as TopicMultiple SclerosisProspective StudiesConceptsCentral vein signDiagnosis of MSMultiple sclerosisDiagnostic biomarkersMcDonald criteriaVein signProspective multicenter trialCross-sectional studyNumerous cross-sectional studiesNorth American ImagingNeuroradiologist reviewMulticenter trialAtypical presentationMulticenter studyTypical presentationSectional studyStudy protocolClinical careMS lesionsCentral readersEcho-planar MRIDiagnostic criteriaMS misdiagnosisMRI biomarkersMajor causeDifferential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity
Shinoda K, Li R, Rezk A, Mexhitaj I, Patterson K, Kakara M, Zuroff L, Bennett J, von Büdingen H, Carruthers R, Edwards K, Fallis R, Giacomini P, Greenberg B, Hafler D, Ionete C, Kaunzner U, Lock C, Longbrake E, Pardo G, Piehl F, Weber M, Ziemssen T, Jacobs D, Gelfand J, Cross A, Cameron B, Musch B, Winger R, Jia X, Harp C, Herman A, Bar-Or A. Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2207291120. PMID: 36634138, PMCID: PMC9934304, DOI: 10.1073/pnas.2207291120.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CD20CD8-Positive T-LymphocytesFlow CytometryHumansLeukocytes, MononuclearMultiple SclerosisRecurrenceConceptsEarly disease activityDisease activityCD8 T cellsT cellsCD20 therapyPeripheral blood mononuclear cellsCellular immune profilesNew disease activityMS disease activityT cell poolMultiple sclerosis patientsAnti-inflammatory profileBlood mononuclear cellsTreatment-associated changesMultiparametric flow cytometryCentral nervous systemFurther dosingRepeat infusionsImmune profileMS patientsSclerosis patientsValidation cohortMononuclear cellsRelapse developmentImmune cascade
2024
Diagnostic performance of central vein sign versus oligoclonal bands for multiple sclerosis
Toljan K, Daboul L, Raza P, Martin M, Cao Q, O’Donnell C, Rodrigues P, Derbyshire J, Azevedo C, Bar-Or A, Caverzasi E, Calabresi P, Cree B, Freeman L, Henry R, Longbrake E, Oh J, Papinutto N, Pelletier D, Samudralwar R, Schindler M, Sotirchos E, Sicotte N, Solomon A, Shinohara R, Reich D, Sati P, Ontaneda D. Diagnostic performance of central vein sign versus oligoclonal bands for multiple sclerosis. Multiple Sclerosis Journal 2024, 30: 1268-1277. PMID: 39234802, PMCID: PMC11421977, DOI: 10.1177/13524585241271988.Peer-Reviewed Original ResearchConceptsCentral vein signPositive predictive valueOligoclonal bandsDiagnostic performanceMS diagnosisCerebrospinal fluidMultiple sclerosisPredictive valueNegative predictive valueCerebrospinal fluid testingRadiological suspicionDiagnostic accuracyImaging biomarkersDiagnosisDiagnostic biomarkersMonthsSclerosisBiomarkersPilot studyBaselineSelection 3Meta-analysis identifies common gut microbiota associated with multiple sclerosis
Lin Q, Dorsett Y, Mirza A, Tremlett H, Piccio L, Longbrake E, Choileain S, Hafler D, Cox L, Weiner H, Yamamura T, Chen K, Wu Y, Zhou Y. Meta-analysis identifies common gut microbiota associated with multiple sclerosis. Genome Medicine 2024, 16: 94. PMID: 39085949, PMCID: PMC11293023, DOI: 10.1186/s13073-024-01364-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBacteriaCase-Control StudiesFemaleGastrointestinal MicrobiomeHumansMaleMultiple SclerosisRNA, Ribosomal, 16SConceptsRRNA gene sequence dataGroups of microbial taxaGene sequence dataMicrobiome community structureAbundance of FaecalibacteriumAbundance of PrevotellaAbundance of ActinomycesSequence dataBeta diversityMicrobial taxaGut microbiotaMicrobial compositionCommunity structureNetwork analysisGutBacterial correlationsMicrobiotaAbundanceMultiple sclerosisDiverse groupMeta-analysisDiversityTaxaFaecalibacteriumConclusionsOur meta-analysisShifting our attention earlier in the multiple sclerosis disease course
Epstein S, Longbrake E. Shifting our attention earlier in the multiple sclerosis disease course. Current Opinion In Neurology 2024, 37: 212-219. PMID: 38546031, DOI: 10.1097/wco.0000000000001268.Peer-Reviewed Original ResearchConceptsRadiologically isolated syndromeDisease courseStages of MSPrompt initiation of therapyDiagnostic criteriaInitiation of therapyMultiple sclerosisHigh-risk patientsClinical diseaseDisease modifying therapy useMS disease courseRandomized controlled trialsImmunomodulatory therapyPrompt initiationClinical outcomesTherapy useDiagnosed patientsMultiple sclerosis disease courseClinical MSHigh riskPatientsControlled trialsPrevent onsetDisease biologyTherapy
2023
A multicenter pilot study evaluating simplified central vein assessment for the diagnosis of multiple sclerosis
Daboul L, O’Donnell C, Amin M, Rodrigues P, Derbyshire J, Azevedo C, Bar-Or A, Caverzasi E, Calabresi P, Cree B, Freeman L, Henry R, Longbrake E, Oh J, Papinutto N, Pelletier D, Prchkovska V, Raza P, Ramos M, Samudralwar R, Schindler M, Sotirchos E, Sicotte N, Solomon A, Shinohara R, Reich D, Sati P, Ontaneda D. A multicenter pilot study evaluating simplified central vein assessment for the diagnosis of multiple sclerosis. Multiple Sclerosis Journal 2023, 30: 25-34. PMID: 38088067, PMCID: PMC11037932, DOI: 10.1177/13524585231214360.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrainFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMultiple SclerosisPilot ProjectsReproducibility of ResultsVeinsYoung AdultConceptsCentral vein signMultiple sclerosisPositive lesionsInter-rater agreementDiagnosis of MSMagnetic resonance imaging (MRI) biomarkersDiagnostic performancePossible multiple sclerosisInter-rater reliability assessmentGood diagnostic performanceMcDonald criteriaMulticenter studyVein assessmentMean ageVein signImaging biomarkersLesionsMRI sequencesCharacteristic curveSclerosisPatientsDiagnosisAssessmentParticipantsOptimal methodSecondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management
Alvarez E, Longbrake E, Rammohan K, Stankiewicz J, Hersh C. Secondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management. Multiple Sclerosis And Related Disorders 2023, 79: 105009. PMID: 37783194, DOI: 10.1016/j.msard.2023.105009.Peer-Reviewed Original ResearchConceptsRisk of infectionCD20 therapySecondary hypogammaglobulinemiaMultiple sclerosisAnti-CD20 therapySerum immunoglobulin levelsB cell levelsDisease managementImmunoglobulin levelsSerious infectionsTherapy clinical trialsPotential complicationsClinical trialsHypogammaglobulinemiaPatientsTreatment approachesTherapyInfectionSclerosisRiskPossible mechanismMedicationsBest practice approachComplicationsPathogenesisAnti‐CD20 monoclonal antibody therapy in postpartum women with neurological conditions
Anderson A, Rowles W, Poole S, Balan A, Bevan C, Brandstadter R, Ciplea A, Cooper J, Fabian M, Hale T, Jacobs D, Kakara M, Krysko K, Longbrake E, Marcus J, Repovic P, Riley C, Romeo A, Rutatangwa A, West T, Hellwig K, LaHue S, Bove R. Anti‐CD20 monoclonal antibody therapy in postpartum women with neurological conditions. Annals Of Clinical And Translational Neurology 2023, 10: 2053-2064. PMID: 37675826, PMCID: PMC10647007, DOI: 10.1002/acn3.51893.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsChildFemaleHumansImmunoglobulin GInfantMultiple SclerosisPostpartum PeriodPregnancyRituximabConceptsNeuromyelitis optica spectrum disorderDisease-modifying therapiesMultiple sclerosisAnti-CD20 monoclonal antibody therapyCD20 IgG1 monoclonal antibodyInfant development outcomesPatient questionnaire responsesRelative infant doseOptica spectrum disorderMonoclonal antibody therapyIgG1 monoclonal antibodyMature breastmilkClinical relapseDisease activityInfant doseMAb therapyInfant outcomesAntibody therapyPostpartum womenPostpartum periodMedical recordsInfant growthPostpartum treatmentNeurological conditionsBreastmilkEarly Treatment for Multiple Sclerosis
Longbrake E, Kalincik T. Early Treatment for Multiple Sclerosis. Neurology 2023, 101: 549-550. PMID: 37468283, DOI: 10.1212/wnl.0000000000207754.Peer-Reviewed Original ResearchMeSH KeywordsBrainHeadHumansMagnetic Resonance ImagingMultiple SclerosisMultiple Sclerosis, Relapsing-Remitting
2022
High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing–Remitting Multiple Sclerosis
Freeman L, Longbrake E, Coyle P, Hendin B, Vollmer T. High-Efficacy Therapies for Treatment-Naïve Individuals with Relapsing–Remitting Multiple Sclerosis. CNS Drugs 2022, 36: 1285-1299. PMID: 36350491, PMCID: PMC9645316, DOI: 10.1007/s40263-022-00965-7.Peer-Reviewed Original ResearchMeSH KeywordsAlemtuzumabHumansImmunologic FactorsMultiple SclerosisMultiple Sclerosis, Relapsing-RemittingNatalizumabConceptsRelapsing-remitting multiple sclerosisHigh-efficacy therapiesMultiple sclerosisClinical benefitEarly treatmentRecent international consensus guidelinesLong-term clinical outcomesAvailable treatment optionsInternational consensus guidelinesTreatment-naïve individualsMechanism of actionDMT optionsMS careDisease courseClinical outcomesConsensus guidelinesTherapy optionsTreatment optionsNeurological damageTreatment strategiesEscalation approachClinical practiceUS FoodDrug AdministrationPatientsInfection risk in a real-world cohort of patients treated with long-term B-cell depletion for autoimmune neurologic disease
Peters J, Longbrake E. Infection risk in a real-world cohort of patients treated with long-term B-cell depletion for autoimmune neurologic disease. Multiple Sclerosis And Related Disorders 2022, 68: 104400. PMID: 36544307, PMCID: PMC10075342, DOI: 10.1016/j.msard.2022.104400.Peer-Reviewed Original ResearchMeSH KeywordsAutoimmune Diseases of the Nervous SystemFemaleHumansInfectionsMultiple SclerosisRetrospective StudiesRituximabConceptsLong-term B-cell depletionB-cell depletionReal-world cohortSevere infectionsTotal infectionsSingle-center observational studyEffective disease-modifying therapiesInfectious adverse effectsFormer smoking statusRisk of hospitalizationAutoimmune neurologic diseasesAutoimmune neurologic disordersDisease-modifying therapiesYears of treatmentRate of infectionLong-term useImmunologic changesLaboratory abnormalitiesClinical factorsSmoking statusHigher BMIMultiple sclerosisSerious infectionsNeurologic disordersFemale genderImpaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis
Asashima H, Axisa PP, Pham THG, Longbrake EE, Ruff WE, Lele N, Cohen I, Raddassi K, Sumida TS, Hafler DA. Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis. Journal Of Clinical Investigation 2022, 132: e156254. PMID: 36250467, PMCID: PMC9566906, DOI: 10.1172/jci156254.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisMemory B cellsCTfh cellsB cellsTIGIT expressionMultiple sclerosisT cellsFollicular helper T cellsHealthy age-matched controlsB-cell depletionT cell expansionHelper T cellsAge-matched controlsB cell functionB-cell pathwayDifferential gene expression signaturesTfh cellsDisease activityGene expression signaturesCell depletionCD40 ligandTranscription factor TCF4Disease pathogenesisImmune systemNew MRIToward Precision Phenotyping of Multiple Sclerosis
Pitt D, Lo CH, Gauthier SA, Hickman RA, Longbrake E, Airas LM, Mao-Draayer Y, Riley C, De Jager PL, Wesley S, Boster A, Topalli I, Bagnato F, Mansoor M, Stuve O, Kister I, Pelletier D, Stathopoulos P, Dutta R, Lincoln MR. Toward Precision Phenotyping of Multiple Sclerosis. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e200025. PMID: 36041861, PMCID: PMC9427000, DOI: 10.1212/nxi.0000000000200025.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersDisease ProgressionHumansInflammationMultiple SclerosisMultiple Sclerosis, Chronic ProgressiveNervous System DiseasesConceptsMultiple sclerosisSecondary progressive multiple sclerosisPathological processesProgressive multiple sclerosisKey pathological processClinical trial designDevelopment of biomarkersPerilesional inflammationNeuroaxonal degenerationMS phenotypeTrial designClinical importancePersonalized careM phenotypeSclerosisPhenotypeRemyelinationInflammationSyndromePrognosticationDegenerationProgressionBiomarkersCareThe CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome
Longbrake EE, Hua LH, Mowry EM, Gauthier SA, Alvarez E, Cross AH, Pei J, Priest J, Raposo C, Hafler DA, Winger RC. The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome. Multiple Sclerosis And Related Disorders 2022, 68: 104143. PMID: 36031693, PMCID: PMC9772048, DOI: 10.1016/j.msard.2022.104143.Peer-Reviewed Original ResearchConceptsEfficacy of ocrelizumabMultiple sclerosisImmunologic biomarkersClinical trialsTransient B-cell depletionClinical multiple sclerosisCSF immune cellsEffects of ocrelizumabMS disease pathophysiologyNew brain lesionsOvert neurological symptomsB-cell depletionPlacebo-controlled studyPhase 4 studyLong-term outcomesPatient-reported outcomesPrimary progressive MSHumanized monoclonal antibodyFirst-degree relativesB cell biologySubtle cognitive impairmentEligible patientsImmune recoveryProgressive MSWeek 48Effect of GBCA Use on Detection and Diagnostic Performance of the Central Vein Sign: Evaluation Using a 3-T FLAIR* Sequence in Patients With Suspected Multiple Sclerosis.
Daboul L, O'Donnell CM, Cao Q, Amin M, Rodrigues P, Derbyshire J, Azevedo C, Bar-Or A, Caverzasi E, Calabresi P, Cree BAC, Freeman L, Henry RG, Longbrake EE, Nakamura K, Oh J, Papinutto N, Pelletier D, Samudralwar RD, Suthiphosuwan S, Schindler MK, Sotirchos ES, Sicotte NL, Solomon AJ, Shinohara RT, Reich DS, Ontaneda D, Sati P. Effect of GBCA Use on Detection and Diagnostic Performance of the Central Vein Sign: Evaluation Using a 3-T FLAIR* Sequence in Patients With Suspected Multiple Sclerosis. American Journal Of Roentgenology 2022, 220: 115-125. PMID: 35975888, PMCID: PMC10016223, DOI: 10.2214/ajr.22.27731.Peer-Reviewed Original ResearchConceptsWhite matter lesionsCentral vein signGBCA useMultiple sclerosisMS diagnosisVein signPostcontrast imagesGadolinium-based contrast agent administrationPilot study cohortDiagnostic performanceContrast agent administrationMcDonald criteriaInvestigational trialsStudy cohortMatter lesionsClinical dataClinical impactBrain MRIClinical practiceAgent administrationDiagnostic biomarkersMRI biomarkersPostcontrast FLAIRPrecontrast imagesSecondary analysis
2021
23Na imaging: Worth its salt for understanding multiple sclerosis
Longbrake EE, Hafler DA. 23Na imaging: Worth its salt for understanding multiple sclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2110799118. PMID: 34376559, PMCID: PMC8379906, DOI: 10.1073/pnas.2110799118.Commentaries, Editorials and LettersManifestations and impact of the COVID‐19 pandemic in neuroinflammatory diseases
Levin SN, Venkatesh S, Nelson KE, Li Y, Aguerre I, Zhu W, Masown K, Rimmer KT, Diaconu CI, Onomichi KB, Leavitt VM, Levine LL, Strauss‐Farber R, Vargas WS, Banwell B, Bar‐Or A, Berger JR, Goodman AD, Longbrake EE, Oh J, Weinstock‐Guttman B, Thakur KT, Edwards KR, Riley CS, Xia Z, De Jager PL, Collaborative M. Manifestations and impact of the COVID‐19 pandemic in neuroinflammatory diseases. Annals Of Clinical And Translational Neurology 2021, 8: 918-928. PMID: 33616290, PMCID: PMC8013889, DOI: 10.1002/acn3.51314.Peer-Reviewed Original ResearchConceptsNeuroinflammatory disordersMultiple sclerosisCOVID-19Year-long prospective studyPotential risk factorsPatient reported experienceTesting shortagesNeurological disabilityLiver diseaseNeuroinflammatory diseasesTelemedicine visitsProspective studyPotential confoundersMS casesRisk factorsNeurological careSevere casesTreatment changesSymptom criteriaEarly changesMore depressionReference groupCase prevalenceDisease managementGreater likelihood
2020
Outcomes and future directions for neuroimmunology/multiple sclerosis fellowship training: Survey of recent trainees
Hua LH, Obeidat AZ, Longbrake EE. Outcomes and future directions for neuroimmunology/multiple sclerosis fellowship training: Survey of recent trainees. Multiple Sclerosis And Related Disorders 2020, 44: 102296. PMID: 32585616, PMCID: PMC8023409, DOI: 10.1016/j.msard.2020.102296.Peer-Reviewed Original ResearchMeSH KeywordsCurriculumFellowships and ScholarshipsHumansMultiple SclerosisSpecializationSurveys and QuestionnairesConceptsNeuroimmune diseasesFellowship trainingRecent traineesTraditional clinic-based modelNeuromyelitis optica spectrum disorderOptica spectrum disorderDiagnosis of MSNational MS SocietyClinic-based modelFellowship training experienceMS SocietyMultiple sclerosisCurrent medical practiceBasic immunologyUS training programsTraining programNeuro-rehabilitationSubspecialty certificationOutcomesMedical practiceDiseasePractice outcomesCurrent traineesDidactic trainingFellowship experienceEducation Research: Multiple sclerosis and neuroimmunology fellowship training status in the United States
Obeidat AZ, Jassam YN, Hua LH, Cutter G, Ford CC, Halper J, Lisak RP, Sicotte NL, Longbrake EE. Education Research: Multiple sclerosis and neuroimmunology fellowship training status in the United States. Neurology 2020, 94: 10.1212/wnl.0000000000009096. PMID: 32107321, PMCID: PMC9246053, DOI: 10.1212/wnl.0000000000009096.Peer-Reviewed Original ResearchConceptsMS trainingMultiple sclerosisFellowship training statusProgram directorsDuration of trainingTraining statusMost programsSubspecialty certificationSclerosisUnited StatesNumber of fellowsTrainee educationFellowship programsQuestionnaireCurrent statusStatusCertification statusPostgraduate training
2019
Siponimod Chips Away at Progressive MS
Longbrake EE, Hafler DA. Siponimod Chips Away at Progressive MS. Cell 2019, 179: 1440. PMID: 31951523, PMCID: PMC8023412, DOI: 10.1016/j.cell.2019.11.034.Peer-Reviewed Original ResearchMeSH KeywordsAzetidinesBenzyl CompoundsClinical Trials as TopicHumansMultiple SclerosisUnited StatesUnited States Food and Drug AdministrationConceptsProgressive multiple sclerosisGadolinium-enhancing MRI lesionsInflammatory disease activityImmunomodulatory medicationsDisability progressionDisease activityMRI lesionsProgressive MSNeurologic disabilityPMS patientsMultiple sclerosisSiponimodMedicationsSclerosisPatientsLesionsBedsideProgression