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 phenotypeDiseaseDisordersDifferential 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
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 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-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 biologyTherapyA 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 immunophenotyping
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 ResearchConceptsCentral 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 ResearchConceptsNeuromyelitis 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 ResearchInfluence of menstrual cycle and hormonal contraceptive use on MS symptom fluctuations: A pilot study
Taylor H, Alhasan S, Saleem M, Poole S, Jiang F, Longbrake E, Bove R. Influence of menstrual cycle and hormonal contraceptive use on MS symptom fluctuations: A pilot study. Multiple Sclerosis And Related Disorders 2023, 77: 104864. PMID: 37480738, PMCID: PMC11090415, DOI: 10.1016/j.msard.2023.104864.Peer-Reviewed Original ResearchConceptsContinuous oral contraceptivesOral contraceptivesOC usersMenstrual cycleSymptom fluctuationsPilot studyTwo-centre pilot studyRegular menstrual cyclesHormonal contraceptive useIntrauterine device usersMenstrual cycle phaseFuture confirmatory studiesMedian EDSSMean ageGeneralized symptomsHormonal measurementsPerimenstrual periodSymptom SurveyContraceptive useLarge cohortLuteal periodClinical practiceContraceptive choicesParticipant retentionSymptom severityMicrofluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods 2023, 7: e2300594. PMID: 37312418, PMCID: PMC10592458, DOI: 10.1002/smtd.202300594.Peer-Reviewed Original ResearchConceptsB cell depletion therapyAcute COVID infectionAnti-spike IgGHigh-risk patientsCoronavirus disease-19COVID-19 pathologyDepletion therapyVaccine protectionAntibody responseCOVID infectionHematologic malignanciesImmune protectionDisease-19Healthy donorsMultiple time pointsSerology assaysBlood samplesSoluble markersB cellsImmunization strategiesPatientsFunctional deficiencySerological analysisTime pointsClonotype diversityMOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity
Yandamuri S, Filipek B, Obaid A, Lele N, Thurman J, Makhani N, Nowak R, Guo Y, Lucchinetti C, Flanagan E, Longbrake E, O'Connor K. MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity. JCI Insight 2023, 8: e165373. PMID: 37097758, PMCID: PMC10393237, DOI: 10.1172/jci.insight.165373.Peer-Reviewed Original ResearchConceptsMyelin oligodendrocyte glycoprotein antibody-associated diseaseAntibody-dependent cellular phagocytosisAntibody-dependent cellular cytotoxicityComplement-dependent cytotoxicityMOG autoantibodiesPatient seraCellular cytotoxicityEffector functionsComplement activityAntibody-associated diseaseMultiple mechanismsNK cellsPatient autoantibodiesCytotoxic capacityLesion histologyCellular phagocytosisFuture relapseIgG subclassesCerebrospinal fluidAutoantibodiesCNS conditionsMOGSerumRelapseCytotoxicityFuture of Neurology & Technology: Neuroimaging Made Accessible Using Low-Field, Portable MRI
Parasuram N, Crawford A, Mazurek M, Chavva I, Beekman R, Gilmore E, Petersen N, Payabvash S, Sze G, Eugenio Iglesias J, Omay S, Matouk C, Longbrake E, de Havenon A, Schiff S, Rosen M, Kimberly W, Sheth K. Future of Neurology & Technology: Neuroimaging Made Accessible Using Low-Field, Portable MRI. Neurology 2023, 100: 1067-1071. PMID: 36720639, PMCID: PMC10259275, DOI: 10.1212/wnl.0000000000207074.Peer-Reviewed Original Research
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 ResearchConceptsRelapsing-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 ResearchConceptsLong-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 MRI