2024
Early Disease-Modifying Treatments for Presymptomatic Multiple Sclerosis
Zeydan B, Azevedo C, Makhani N, Cohen M, Tutuncu M, Thouvenot E, Siva A, Okuda D, Kantarci O, Lebrun-Frenay C. Early Disease-Modifying Treatments for Presymptomatic Multiple Sclerosis. CNS Drugs 2024, 38: 973-983. PMID: 39285136, PMCID: PMC11560559, DOI: 10.1007/s40263-024-01117-9.Peer-Reviewed Original ResearchRadiologically isolated syndromeRisk factorsLaboratory biomarkersMultiple sclerosisDisease-modifying treatmentsSpinal cordGadolinium-enhancing lesionsEfficacy of disease-modifying treatmentsRandomized clinical trialsIncrease diagnostic accuracyLack of clinical guidelinesSymptomatic MSNeurofilament-light chainCSF abnormalitiesPresymptomatic individualsAdverse eventsMale sexMS criteriaClinical eventsDiagnostic accuracyClinical trialsDisease outcomeClinical guidelinesYounger ageLesionsThe diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex
Makhani N, Lebrun-Frenay C, Siva A, Shabanova V, Wassmer E, Santoro J, Narula S, Brenton J, Mar S, Durand-Dubief F, Zephir H, Mathey G, Rojas J, de Seze J, Tenembaum S, Stone R, Casez O, Carra-Dallière C, Neuteboom R, Ahsan N, Arroyo H, Cabre P, Gombolay G, Inglese M, Louapre C, Margoni M, Palavra F, Pohl D, Reich D, Ruet A, Thouvenot E, Timby N, Tintore M, Uygunoglu U, Vargas W, Venkateswaran S, Verhelst H, Wickstrom R, Azevedo C, Kantarci O, Shapiro E, Okuda D, Pelletier D. The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex. Journal Of Neurology 2024, 271: 4019-4027. PMID: 38564056, PMCID: PMC11323224, DOI: 10.1007/s00415-024-12289-1.Peer-Reviewed Original ResearchRadiologically isolated syndromeSpinal MRIDiagnostic workup of childrenMultiple sclerosisWorkup of childrenFisher's exact testMultivariate logistic regressionInternational longitudinal studyDiagnostic workupConsensus guidelinesExact testMS riskLogistic regressionConclusionsYoung childrenCSFBackgroundCerebrospinal fluidMRIPre-2017Longitudinal studySyndromeRadiologyChildrenAgeSexRiskThe diagnostic value of the central vein sign in radiologically isolated syndrome
Landes‐Chateau C, Levraut M, Okuda D, Themelin A, Cohen M, Kantarci O, Siva A, Pelletier D, Mondot L, Lebrun‐Frenay C, Lebrun‐Frenay C, Kantarci O, Siva A, Pelletier D, Azevedo C, Makhani N, Okuda D. The diagnostic value of the central vein sign in radiologically isolated syndrome. Annals Of Clinical And Translational Neurology 2024, 11: 662-672. PMID: 38186317, PMCID: PMC10963291, DOI: 10.1002/acn3.51986.Peer-Reviewed Original ResearchConceptsRadiologically isolated syndromeCentral vein signCVS+ lesionsNon-MSMultiple sclerosisControl group of sex-RIS diagnosisAge-matched subjectsDetectable preclinical phaseProportion of lesionsWhite matter lesionsGroup of sex-Effective imaging biomarkerMagnetic resonance imagingDiagnostic performanceDiagnostic accuracyDiagnostic valueLesion criteriaImaging biomarkersLesionsResonance imagingLesion-specificAbsolute numberControl groupROC comparisons
2023
The radiologically isolated syndrome: revised diagnostic criteria
Lebrun-Frénay C, Okuda D, Siva A, Landes-Chateau C, Azevedo C, Mondot L, Carra-Dallière C, Zephir H, Louapre C, Durand-Dubief F, Le Page E, Bensa C, Ruet A, Ciron J, Laplaud D, Casez O, Mathey G, de Seze J, Zeydan B, Makhani N, Tutuncu M, Levraut M, Cohen M, Thouvenot E, Pelletier D, Kantarci O. The radiologically isolated syndrome: revised diagnostic criteria. Brain 2023, 146: 3431-3443. PMID: 36864688, PMCID: PMC11004931, DOI: 10.1093/brain/awad073.Peer-Reviewed Original ResearchConceptsRadiologically isolated syndromeClinical eventsGroup 1Risk factorsDIS criteriaPresence of spinal cord lesionsClinical follow-up timeCSF-restricted oligoclonal bandsMultivariate Cox regression modelDiagnostic criteriaFocal T2 hyperintensitiesGadolinium-enhancing lesionsMultiple sclerosisNegative predictive valueFollow-up scansFollow-up timeArea under the curveClass I evidenceSpinal cord lesionsCox regression modelsRisk of developmentWhite matter lesionsProspective databaseSymptomatic MST2 lesions
2022
From the prodromal stage of multiple sclerosis to disease prevention
Marrie R, Allegretta M, Barcellos L, Bebo B, Calabresi P, Correale J, Davis B, De Jager P, Gasperi C, Greenbaum C, Helme A, Hemmer B, Kanellis P, Kostich W, Landsman D, Lebrun-Frenay C, Makhani N, Munger K, Okuda D, Ontaneda D, Postuma R, Quandt J, Roman S, Saidha S, Sormani M, Strum J, Valentine P, Walton C, Zackowski K, Zhao Y, Tremlett H. From the prodromal stage of multiple sclerosis to disease prevention. Nature Reviews Neurology 2022, 18: 559-572. PMID: 35840705, DOI: 10.1038/s41582-022-00686-x.Peer-Reviewed Original ResearchConceptsMultiple sclerosisTrials of interventionsType 1 diabetes mellitusImmune-mediated diseasesStandard criteriaDiagnosis of MSStages of MSDisease frameworkIdentification of individualsProdromal stageMS prodromeDisease preventionProdromal MSStop progressionRheumatoid arthritisProdromeDiseaseDisease markersConfirming a Historical Diagnosis of Multiple Sclerosis
Solomon AJ, Arrambide G, Brownlee W, Cross AH, Gaitan MI, Lublin FD, Makhani N, Mowry EM, Reich DS, Rovira À, Weinshenker BG, Cohen JA. Confirming a Historical Diagnosis of Multiple Sclerosis. Neurology Clinical Practice 2022, 12: 263-269. PMID: 35747540, PMCID: PMC9208427, DOI: 10.1212/cpj.0000000000001149.Peer-Reviewed Original ResearchMultiple sclerosisHistorical diagnosisSubsequent disease activityEvaluation of patientsTime of diagnosisDiagnosis of MSEarly MS diagnosisPrior clinical examinationDisease activityMcDonald criteriaNeurologic examinationTherapeutic challengeClinical progressionMS diagnosisMS attacksClinical examinationPatient recollectionTherapeutic decisionsDiagnostic confirmationMRI scansClinical practiceClinical approachPatientsDiagnosisSclerosisThe Multiple Sclerosis Prodrome: Evidence to Action
Tremlett H, Munger KL, Makhani N. The Multiple Sclerosis Prodrome: Evidence to Action. Frontiers In Neurology 2022, 12: 761408. PMID: 35173664, PMCID: PMC8841819, DOI: 10.3389/fneur.2021.761408.Peer-Reviewed Original ResearchMultiple sclerosisProdromal phaseEarly recognitionImproved disease courseProdromal multiple sclerosisImmune-mediated diseasesMultiple sclerosis prodromeEarly disease managementDisease courseProdromal featuresDefinitive diagnosisClassical diseaseGeneral populationMS prodromeDisease preventionProdromeMajor long-term implicationsDisease managementPrognosisDiseaseLong-term implicationsPreventionSclerosisEvidenceSymptoms
2021
Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome
Lebrun-Frénay C, Rollot F, Mondot L, Zephir H, Louapre C, Le Page E, Durand-Dubief F, Labauge P, Bensa C, Thouvenot E, Laplaud D, de Seze J, Ciron J, Bourre B, Cabre P, Casez O, Ruet A, Mathey G, Berger E, Moreau T, Al Khedr A, Derache N, Clavelou P, Guennoc AM, Créange A, Neau JP, Tourbah A, Camdessanché JP, Maarouf A, Callier C, Vermersch P, Kantarci O, Siva A, Azevedo C, Makhani N, Cohen M, Pelletier D, Okuda D, Vukusic S, Kantarci O, Siva A, Pelletier D, Okuda D, Azevedo C, Makhani N, Radji F, Morel N, Grosset-Jeannin D, Ungureanu A, Boyer L, Suchet L, Elias Z, Lebrun-Frénay C, Cohen M, Mondot L, Thouvenot E, Ciron J, Durand-Dubief F, Brochet B, Ruet A, Ouallet J, Defer G, Branger P, Derache N, Clavelou P, Taithe F, Alkhedr A, Fromont A, Moreau T, Tourbah A, Casez O, Berger E, Zephir H, Outteryck O, Vermersch P, Hautecoeur P, Androdias G, Ionescu I, Pelletier J, Audoin B, Maarouf A, Ayrignac X, Carra-Dalliere C, Labauge P, Debouverie M, Mathey G, Cabre P, Laplaud D, Wiertlevski S, Bresch S, Castelnovo G, Papeix C, Louapre C, Maillart E, Lubetzki C, Stankoff B, Fontaine B, Giannesini C, Heinzleff O, Créange A, Bourre B, Gout O, Guegen A, Bensa C, Le Page E, Michel L, Magy L, De Seze J, Collongues N, Leray E, Guennoc A, Biotti D, Camdessanché J, De Broucker T, Sehaki S, Devys-Meyer N, Bereau M, Cappe C, Kounkou K, Dumont E, Lescieux E, Protin A, Kane M, Boucher J, Petit J, Tabellah Kasonde I, De Vilmarrest A, Nicol M, Malbezin M, Olaiz J, Rigaud-Bully C, Casey R, Rollot F, Vukusic I, Debard N, Cotton F, Abdelalli A, Di Lelio B, Pinna F, Guillemin F, Ziegler A, Callier C, Zehrouni K, Hodel J, Wahab A, Zedet M, Fagniez O, Laage C, Pottier C, Slesari I, Sampaio M, Neau J, Rabois E, Castex C, Hebant B, Guillaume M, Vimont C, Muraz R, Le Port D, Henry C, Berthe C, Freitas N, Visneux V, Forestier M, Beltran S, Meunier G, Servan J, Pico F, Chatagner V. Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome. JAMA Network Open 2021, 4: e2128271. PMID: 34633424, PMCID: PMC8506228, DOI: 10.1001/jamanetworkopen.2021.28271.Peer-Reviewed Original ResearchConceptsGadolinium-enhancing lesionsSpinal cord lesionsClinical eventsMultiple sclerosisRisk of conversionCord lesionsRisk factorsMRI scansPhase III clinical trialsMagnetic resonance imaging (MRI) scansEarly clinical diseaseFirst clinical eventDisease-modifying therapiesEarly clinical eventsSpinal cord involvementAge 37 yearsResonance imaging scansPotential treatment effectsMS careCohort studyCord involvementStudy entryTertiary centerClinical symptomsOligoclonal bandsThe multiple sclerosis prodrome
Makhani N, Tremlett H. The multiple sclerosis prodrome. Nature Reviews Neurology 2021, 17: 515-521. PMID: 34155379, PMCID: PMC8324569, DOI: 10.1038/s41582-021-00519-3.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMS prodromeProdromal phaseCause of MSLong-term disabilityMultiple sclerosis prodromePutative risk factorsProfound clinical implicationsRelapse rateClinical featuresEarly recognitionInflammatory diseasesRisk factorsEarly initiationProdromePotential biomarkersClinical implicationsTypical symptomsDiseaseSymptomsFuture initiativesSclerosisMajor knowledge gapsBiomarkersPossible durationGuideline for the Assessment and Treatment of Pain in Children with Multiple Sclerosis (MS): A Delphi Panel (4328)
Stratton C, Bartels A, Brenton J, Odonkor C, Potter K, Rumm H, Stoll S, Vargas W, Yeh E, Zempsky W, Makhani N, Bailey M. Guideline for the Assessment and Treatment of Pain in Children with Multiple Sclerosis (MS): A Delphi Panel (4328). Neurology 2021, 96 DOI: 10.1212/wnl.96.15_supplement.4328.Peer-Reviewed Original Research
2020
Radiologically Isolated Syndrome: 10‐Year Risk Estimate of a Clinical Event
Lebrun‐Frenay C, Kantarci O, Siva A, Sormani M, Pelletier D, Okuda D, Azevedo C, Amato M, Bensa C, Berger E, Brochet B, Ciron J, Cohen M, Inglese M, Keegan B, Labauge P, Laplaud D, Le Page E, Louapre C, Makhani N, Mathey G, Mondot L, Montalban X, Pelletier J, Seze J, deStefano N, Thouvenot E, Tintore M, Tutuncuoglu M, Uygunoglu U, Vermersch P, Weinshenker B, Zeydan B. Radiologically Isolated Syndrome: 10‐Year Risk Estimate of a Clinical Event. Annals Of Neurology 2020, 88: 407-417. PMID: 32500558, DOI: 10.1002/ana.25799.Peer-Reviewed Original ResearchConceptsFirst clinical eventSubsequent clinical eventsGadolinium-enhancing lesionsSpinal cord lesionsClinical eventsRIS subjectsCord lesionsIndependent predictorsMultivariate Cox regression modelMagnetic resonance imaging (MRI) characteristicsBaseline independent predictorsWorldwide cohort studiesPositive cerebrospinal fluidCox regression modelAnn NeurolIsolated SyndromeRIS diagnosisCohort studySymptom onsetMale sexMultiple sclerosisOligoclonal bandsInfratentorial lesionsMean ageClinical managementMultiple Sclerosis in Children: Current and Emerging Concepts
Brenton JN, Kammeyer R, Gluck L, Schreiner T, Makhani N. Multiple Sclerosis in Children: Current and Emerging Concepts. Seminars In Neurology 2020, 40: 192-200. PMID: 32294785, PMCID: PMC8514113, DOI: 10.1055/s-0040-1703000.Peer-Reviewed Original ResearchTreatment Considerations in the Radiologically Isolated Syndrome
Makhani N. Treatment Considerations in the Radiologically Isolated Syndrome. Current Treatment Options In Neurology 2020, 22: 3. PMID: 32009206, DOI: 10.1007/s11940-020-0608-8.Peer-Reviewed Original ResearchClinical intervention trialsMultiple sclerosisIntervention trialsClinical neurological symptomsFirst clinical eventDisease-modifying therapiesDisease-modifying treatmentsIsolated SyndromeNeurological eventsNeurological symptomsClinical eventsClinical trialsRecent FindingsIndividualsTreatment considerationsTherapeutic interventionsAccurate diagnosisBeneficial effectsTrialsSclerosisSuch interventionsSyndromeSubsequent developmentDiagnosisInterventionTherapy
2019
Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome
Makhani N, Lebrun C, Siva A, Narula S, Wassmer E, Brassat D, Brenton JN, Cabre P, Carra Dallière C, de Seze J, Durand Dubief F, Inglese M, Langille M, Mathey G, Neuteboom RF, Pelletier J, Pohl D, Reich DS, Ignacio Rojas J, Shabanova V, Shapiro ED, Stone RT, Tenembaum S, Tintoré M, Uygunoglu U, Vargas W, Venkateswaren S, Vermersch P, Kantarci O, Okuda DT, Pelletier D, . Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome. Multiple Sclerosis Journal - Experimental Translational And Clinical 2019, 5: 2055217319836664. PMID: 30915227, PMCID: PMC6429663, DOI: 10.1177/2055217319836664.Peer-Reviewed Original ResearchOligoclonal bandsMultiple sclerosisCerebrospinal fluidDiagnostic criteriaCentral nervous system demyelinationMagnetic resonance imaging criteriaFirst clinical eventCerebrospinal fluid analysisNervous system demyelinationOptimal diagnostic criteriaDiagnostic indexMagnetic resonanceSpecificity 72.7Historical cohortProspective studyClinical eventsMRI criteriaSensitivity 66.7Imaging criteriaDiagnostic certaintySpecificity 83.3SyndromeFluid analysisSensitivity 76.5Demyelination
2018
Acquisition of Early Developmental Milestones and Need for Special Education Services in Pediatric Multiple Sclerosis
Aaen G, Waltz M, Vargas W, Makhani N, Ness J, Harris Y, Casper TC, Benson L, Candee M, Chitnis T, Gorman M, Graves J, Greenberg B, Lotze T, Mar S, Tillema JM, Rensel M, Rodriguez M, Rose J, Rubin J, Schreiner T, Waldman A, Weinstock-Guttman B, Belman A, Waubant E, Krupp L. Acquisition of Early Developmental Milestones and Need for Special Education Services in Pediatric Multiple Sclerosis. Journal Of Child Neurology 2018, 34: 148-152. PMID: 30556452, PMCID: PMC6579723, DOI: 10.1177/0883073818815041.Peer-Reviewed Original ResearchConceptsPediatric multiple sclerosisMultiple sclerosisEarly developmental milestonesPediatric Multiple Sclerosis CentersPediatric-onset multiple sclerosisMultiple sclerosis onsetMultiple Sclerosis CenterDevelopmental milestonesPediatric controlsDisease onsetHealthy controlsSclerosisAge 18Age 11ChildrenOnsetIndividualized education planFurther researchControl
2017
Radiologically Isolated Syndrome
DeStefano K, Makhani N. Radiologically Isolated Syndrome. 2017, 61-65. DOI: 10.1007/978-3-319-61407-6_8.ChaptersGenetic and Environmental Risk Factors for Pediatric Multiple Sclerosis
Makhani N, George I. Genetic and Environmental Risk Factors for Pediatric Multiple Sclerosis. Journal Of Pediatric Neurology 2017, 16: 141-147. DOI: 10.1055/s-0037-1604339.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsEnvironmental risk factorsMultiple sclerosisRisk factorsLow serum vitamin D levelsSerum vitamin D levelsNon-HLA single nucleotide polymorphismsVitamin D levelsPediatric multiple sclerosisEpstein-Barr virusHuman leukocyte antigenDifferent risk factorsGenetic risk factorsD levelsLeukocyte antigenParental smokingPrior exposureSingle nucleotide polymorphismsSclerosisCurrent literatureNucleotide polymorphismsChildrenFactorsSmokingAntigenDisease
2016
Pediatric multiple sclerosis
Ghezzi A, Amato MP, Makhani N, Shreiner T, Gärtner J, Tenembaum S. Pediatric multiple sclerosis. Neurology 2016, 87: s97-s102. PMID: 27572869, DOI: 10.1212/wnl.0000000000002823.Peer-Reviewed Original ResearchConceptsFirst-line treatmentPediatric multiple sclerosisMultiple sclerosisObservational studyRandomized placebo-controlled trialStandard first-line treatmentFirst-line treatment optionRelapsing-remitting multiple sclerosisPlacebo-controlled trialAcceptable safety profilePediatric age groupDisease-modifying therapiesPediatric MSGlatiramer acetateRelapse rateUnblinded trialSafety profileTreatment optionsDisease progressionExpert guidelinesAge groupsSclerosisTrialsCurrent knowledgeTreatmentInternational Pediatric MS Study Group Global Members Symposium report
Wassmer E, Chitnis T, Pohl D, Amato MP, Banwell B, Ghezzi A, Hintzen RQ, Krupp LB, Makhani N, Rostásy K, Tardieu M, Tenembaum S, Waldman A, Waubant E, Kornberg AJ. International Pediatric MS Study Group Global Members Symposium report. Neurology 2016, 87: s110-s116. PMID: 27572855, PMCID: PMC10688073, DOI: 10.1212/wnl.0000000000002880.Peer-Reviewed Original ResearchConceptsPediatric multiple sclerosisMultiple sclerosisInternational Pediatric Multiple Sclerosis Study GroupMultiple Sclerosis Study GroupOptimal vitamin D intakeEarly-onset multiple sclerosisNewer MS agentsAcute disseminated encephalomyelitisVitamin D intakeVitamin D deficiencyChildhood multiple sclerosisLong-term outcomesDrug treatment optionsDiverse patient samplesDifferentiation of MSEffective cognitive rehabilitationD intakeDisseminated encephalomyelitisD deficiencyNeuroinflammatory disordersNeuromyelitis opticaMS riskTreatment optionsMS outcomesClinical trialsOral Dimethyl Fumarate in Children With Multiple Sclerosis: A Dual-Center Study
Makhani N, Schreiner T. Oral Dimethyl Fumarate in Children With Multiple Sclerosis: A Dual-Center Study. Pediatric Neurology 2016, 57: 101-104. PMID: 26996405, DOI: 10.1016/j.pediatrneurol.2016.01.010.Peer-Reviewed Original ResearchConceptsOral dimethyl fumarateMultiple sclerosisDimethyl fumarateSide effectsFirst-line injectable therapiesBrain magnetic resonance imagingAbnormal liver transaminasesDual-Center ExperienceUsual adult doseMonths of therapyNew T2 lesionsFirst-line therapyCommon side effectsMagnetic resonance imaging (MRI) parametersPediatric multiple sclerosisDual-center studyChildren 18 yearsFormal clinical trialsMagnetic resonance imagingLiver transaminasesDisability scoresLaboratory abnormalitiesOral medicationsRelapse rateRetrospective review