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 ResearchConceptsCentral 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 causeMyelin Oligodendrocyte Glycoprotein–Associated Disorders
Longbrake E. Myelin Oligodendrocyte Glycoprotein–Associated Disorders. CONTINUUM Lifelong Learning In Neurology 2022, 28: 1171-1193. PMID: 35938661, PMCID: PMC9523511, DOI: 10.1212/con.0000000000001127.Peer-Reviewed Original ResearchConceptsAcute disseminated encephalomyelitisClinical spectrumCentral nervous system autoimmune diseaseNatural historyFuture therapeutic trialsLarge cohort studyRecent case reportsDistinct clinical phenotypesDisseminated encephalomyelitisGlycoprotein autoantibodiesOptic neuritisCohort studyMost patientsRelapse patternsNeuromyelitis opticaTherapeutic trialsMultiple sclerosisAutoimmune diseasesCNS diseaseCase reportCNS diseasesAccurate diagnosisClinical phenotypeDiseaseDisordersConsensus Curriculum for Fellowship Training in Multiple Sclerosis and Neuroimmunology
Hua LH, Obeidat AZ, Amezcua L, Cohen JA, Costello K, Dunn J, Gelfand JM, Goldman MD, Hopkins S, Jeffery D, Krieger S, Newsome SD, Shah S, Sicotte NL, Yadav V, Longbrake EE. Consensus Curriculum for Fellowship Training in Multiple Sclerosis and Neuroimmunology. Neurology Clinical Practice 2021, 11: 352-357. PMID: 34484933, PMCID: PMC8382436, DOI: 10.1212/cpj.0000000000001040.Peer-Reviewed Original ResearchMultiple sclerosisNeuroimmunologic disordersFellowship trainingNeuroimmune disordersTherapeutic optionsMore subspecialistsSubspecialty workforceSclerosisFellowship curriculumDisordersConsensus curriculumFellowship programsFuture training programsTraining programPatientsNeuroimmunologySubspecialistsCareDifferential 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 ResearchConceptsEarly 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 cascadePrior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre N, Lutz R, Cruz I, Raddassi K, Ruff W, Racke M, Wilson J, Givens T, Grifoni A, Weiskopf D, Sette A, Kleinstein S, Montgomery R, Shaw A, Li F, Fan R, Hafler D, Tomayko M, Longbrake E. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023, 8: e168102. PMID: 37606046, PMCID: PMC10543713, DOI: 10.1172/jci.insight.168102.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinationB-cell-depleted patientsB-cell depletionAntibody responseMRNA vaccinationThird doseCell depletionT cellsClaude D. Pepper Older Americans Independence CenterB cellsNational Multiple Sclerosis SocietyAnti-CD20 antibodySpike-specific antibodiesMultiple Sclerosis SocietyLow cumulative exposureLogistic regression modelsImportant clinical needCD20 therapyCD20 treatmentMost patientsThird vaccineSerologic responseVaccine dosesMRNA vaccinesVaccination strategies
2024
Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients
Mao-Draayer Y, Bar-Or A, Balashov K, Foley J, Smoot K, Longbrake E, Robertson D, Mendoza J, Lewin J, Everage N, Božin I, Lyons J, Mokliatchouk O, Bame E, Giuliani F. Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients. Advances In Therapy 2024, 1-18. PMID: 39570545, DOI: 10.1007/s12325-024-03047-w.Peer-Reviewed Original ResearchAbsolute lymphocyte countRelapsing-remitting MSEffect of dimethyl fumarateAnnualized relapse rateDisease-modifying therapiesAdverse eventsDimethyl fumarateCD8+ T cell compartmentMultiple sclerosisOlder patientsMedian absolute lymphocyte countOral disease-modifying therapyTreated with dimethyl fumarateSafety outcomesTreating relapsing MST cell compartmentPhase 3 studyResponse to disease-modifying therapiesIncidence of SAEsLymphocyte subset changesReal-world safetyTreatment discontinuationCD4+Immunophenotypic changesRelapse rateIncorporation of the Central Vein Sign into the McDonald Criteria
Amin M, Nakamura K, Daboul L, O'Donnell C, Cao Q, 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, Prčkovska V, Raza P, Ramos M, Samudralwar R, Schindler M, Sotirchos E, Sicotte N, Solomon A, Shinohara R, Reich D, Sati P, Ontaneda D. Incorporation of the Central Vein Sign into the McDonald Criteria. Multiple Sclerosis And Related Disorders 2024, 106182. DOI: 10.1016/j.msard.2024.106182.Peer-Reviewed Original ResearchCentral vein signDIS criteriaDiagnostic performanceMultiple sclerosisDeep white matter lesionsDiagnosis of multiple sclerosisMulti-center studyInternational multi-center studyWhite matter lesionsNorth American ImagingMcDonald CriteriaProspective studyDiagnostic accuracyMRI disseminationDemyelinating diseaseBackground DiagnosisMS diagnosisDiagnostic biomarkersCompare sensitivityLesionsBrain locationsMethods DataBrain imagingBrainSignsMulticenter validation of automated detection of paramagnetic rim lesions on brain MRI in multiple sclerosis
Chen L, Ren Z, Clark K, Lou C, Liu F, Cao Q, Manning A, Martin M, Luskin E, O'Donnell C, Azevedo C, Calabresi P, Freeman L, Henry R, Longbrake E, Oh J, Papinutto N, Bilello M, Song J, Kaisey M, Sicotte N, Reich D, Solomon A, Ontaneda D, Sati P, Absinta M, Schindler M, Shinohara R, Cooperative T. Multicenter validation of automated detection of paramagnetic rim lesions on brain MRI in multiple sclerosis. Journal Of Neuroimaging 2024, 34: 750-757. PMID: 39410780, DOI: 10.1111/jon.13242.Peer-Reviewed Original ResearchParamagnetic rim lesionsArea under the curveRim lesionsMultiple sclerosisPrognosis of MSBiomarkers of chronic inflammationWhite matter lesionsMulticenter settingMulticenter studyMulticenter validationChronic inflammationBrain MRIClinical trialsIdentified lesionsMulticenterMS diagnosisLesionsParamagnetic rimAutomated segmentation methodMRIMRI biomarkersMulticenter datasetDiagnosisSclerosisTeam of trained ratersMulticenter automated central vein sign detection performs as well as manual assessment for the diagnosis of multiple sclerosis.
Manning A, Letchuman V, Martin M, Gombos E, Roberts-Fitzgerald T, Cao Q, Raza P, O'Donnell C, Renner B, Daboul L, Rodrigues P, Ramos M, 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, Suthiphosuwan S, Schindler M, Bilello M, Song J, Sotirchos E, Sicotte N, Al-Louzi O, Solomon A, Reich D, Ontaneda D, Sati P, Shinohara R. Multicenter automated central vein sign detection performs as well as manual assessment for the diagnosis of multiple sclerosis. American Journal Of Neuroradiology 2024 PMID: 39332906, DOI: 10.3174/ajnr.a8510.Peer-Reviewed Original ResearchCentral vein signCVS+ lesionsWhite matter lesionsMultiple sclerosisMulticenter studyProportions of white matter lesionsSuspicion of MSReceiver-operating characteristic curveFluid-attenuated inversion recoveryDiagnosis of multiple sclerosisDiagnosis of MSMagnetic resonance imagingAtypical clinical syndromeRadiological mimicsClinical syndromeDiagnostic imaging biomarkersManual assessmentT MRIClinical implementationImaging biomarkersLesionsInversion recoveryResonance imagingCharacteristic curveInter-rater reliabilityDiagnostic 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 3Gut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles
Chang D, Gupta V, Hur B, Cobo-López S, Cunningham K, Han N, Lee I, Kronzer V, Teigen L, Karnatovskaia L, Longbrake E, Davis J, Nelson H, Sung J. Gut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles. Nature Communications 2024, 15: 7447. PMID: 39198444, PMCID: PMC11358288, DOI: 10.1038/s41467-024-51651-9.Peer-Reviewed Original ResearchConceptsMicrobiome taxonomic profilingTaxonomic profilesOpen-source command-line toolGut microbiome researchGut microbial compositionGut microbiome signaturesFecal microbiota transplantationCommand-line toolShotgun metagenomicsTaxonomic signalMicrobiome researchMicrobial compositionMicrobiome signaturesGut healthMicrobiota transplantationGutPublished datasetsMultiple diseasesAntibiotic exposureEffects of dietMetagenomicsHigh confidencePhenotypeCross-validated balanced accuracyMeta-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 ResearchConceptsRRNA 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-analysisPhenotypes of B Cells Producing Autoantibodies in MOGAD Patients (N1.002)
Filipek B, Yandamuri S, Obaid A, Thurman J, Makhani N, Nowak R, Guo Y, Lucchinetti C, Flanagan E, Longbrake E, O’Connor K. Phenotypes of B Cells Producing Autoantibodies in MOGAD Patients (N1.002). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000208259.Peer-Reviewed Original ResearchPost-COVID Conditions in People with Multiple Sclerosis: A Cross-sectional Multicenter Study (P1-6.002)
Son J, Hu C, McAlpine L, Bar-Or A, Dahl M, Brito S, Kavak K, Onomichi K, Perrone C, Riley C, Song E, Walker E, Weinstock-Guttman B, De Jager P, Longbrake E, Xia Z. Post-COVID Conditions in People with Multiple Sclerosis: A Cross-sectional Multicenter Study (P1-6.002). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205595.Peer-Reviewed Original ResearchShifting 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 biologyTherapyChoroid plexus volume differentiates MS from its mimics
Levit E, Ren Z, Gonzenbach V, Azevedo C, Calabresi P, Cree B, Freeman L, Longbrake E, Oh J, Schindler M, Sicotte N, Reich D, Ontaneda D, Sati P, Cao Q, Shinohara R, Solomon A. Choroid plexus volume differentiates MS from its mimics. Multiple Sclerosis Journal 2024, 30: 1072-1076. PMID: 38481081, PMCID: PMC11288781, DOI: 10.1177/13524585241238094.Peer-Reviewed Original ResearchEmerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis
Cross A, Gelfand J, Thebault S, Bennett J, von Büdingen H, Cameron B, Carruthers R, Edwards K, Fallis R, Gerstein R, Giacomini P, Greenberg B, Hafler D, Ionete C, Kaunzner U, Kodama L, Lock C, Longbrake E, Musch B, Pardo G, Piehl F, Weber M, Yuen S, Ziemssen T, Bose G, Freedman M, Anania V, Ramesh A, Winger R, Jia X, Herman A, Harp C, Bar-Or A. Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis. JAMA Neurology 2024, 81: 373-383. PMID: 38466277, PMCID: PMC10928543, DOI: 10.1001/jamaneurol.2024.0017.Peer-Reviewed Original ResearchPrimary progressive MSGlial fibrillary acidic proteinNeurofilament heavy chainRelapsing MSCerebrospinal fluidTest cohortMultiple sclerosisDisease-modifying MS therapyMulticenter study of patientsBiomarkers of disease activityAnti-CD20 treatmentCentral nervous system biologyClinical follow-upConfirmation cohortT2 lesion volumeStudy of patientsHeavy chainCSF-GFAP levelsMS disease progressionMagnetic resonance imaging measuresNeurofilament light chainActivated glial markersStudy assessed dataFibrillary acidic proteinAnti-CD20Impact of the COVID-19 Pandemic on the Personal Networks and Neurological Outcomes of People With Multiple Sclerosis: Cross-Sectional and Longitudinal Case-Control Study
Riley C, Venkatesh S, Dhand A, Doshi N, Kavak K, Levit E, Perrone C, Weinstock-Guttman B, Longbrake E, De Jager P, Xia Z. Impact of the COVID-19 Pandemic on the Personal Networks and Neurological Outcomes of People With Multiple Sclerosis: Cross-Sectional and Longitudinal Case-Control Study. JMIR Public Health And Surveillance 2024, 10: e45429. PMID: 38319703, PMCID: PMC10879979, DOI: 10.2196/45429.Peer-Reviewed Original ResearchA Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases.
Yandamuri S, Filipek B, Lele N, Cohen I, Bennett J, Nowak R, Sotirchos E, Longbrake E, Mace E, O'Connor K. A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases. The Journal Of Immunology 2024, 212: 785-800. PMID: 38251887, PMCID: PMC10932911, DOI: 10.4049/jimmunol.2300015.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderAb-dependent cellular cytotoxicityNK cellsMyasthenia gravisMG patientsInduced Ab-dependent cellular cytotoxicityNK cell-mediated effector functionsPeripheral blood immune cell populationsCell-mediated effector functionsNeuromyelitis optica spectrum disorder patientsBlood immune cell populationsAb-dependent cellular cytotoxicity activityNK marker CD56NK cell markersHLA-DR expressionNK cell subsetsExpression of perforinImmune cell populationsAutoimmune myasthenia gravisElevated disease burdenHLA-DRCell subsetsCellular cytotoxicityChemokine receptorsMultiparameter immunophenotypingP841: Recruitment, consent and DNA sample acquisition in a US precision health cohort during the COVID-19 pandemic
Derry A, Strong Y, Schioppo D, Cotter J, Wilkins G, Siqueiros L, Ouyang A, Hulseman K, Petrosino J, Liang L, Stevenson M, Aguilera T, Soto A, Meurer K, Herman A, Cohen I, Falcone G, Longbrake E, Chaar C, Anastasio K, Murray M. P841: Recruitment, consent and DNA sample acquisition in a US precision health cohort during the COVID-19 pandemic. Genetics In Medicine Open 2024, 2: 101752. DOI: 10.1016/j.gimo.2024.101752.Peer-Reviewed Original Research