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, 1-11. PMID: 39285136, 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 ageLesionsPhenotypes 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 ResearchThe 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
Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications
Hayes LH, Hopkins SE, Liu S, Pardo CA, Garcia-Dominguez MA, Oleszek J, Yea C, Ciftci-Kavaklioglu B, Yeh EA, Dean J, Sadowsky CL, Desai J, Wiegand S, Farias-Moeller R, Nash K, Thakur KT, Vargas WS, Hong-Routson SJ, Yeshokumar A, Zhou MS, Makhani N, Wilson-Murphy M, Bove R, Zhang B, Benson LA. Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications. The Journal Of Pediatrics 2022, 253: 55-62.e4. PMID: 36115622, DOI: 10.1016/j.jpeds.2022.09.012.Peer-Reviewed Original ResearchConceptsAcute flaccid myelitisInitial diagnosisCase definitionRetrospective multicenter studyPrevention case definitionInitial differential diagnosisNew treatment optionsInitial clinical encounterIntensive care monitoringRespiratory decompensationImmunomodulatory treatmentIntravenous immunoglobulinVentilatory supportPediatric patientsClinical featuresAcute careMulticenter studyTreatment optionsClinical recognitionTreatment paradigmClinical impactDifferential diagnosisPatientsDisease controlClinical encountersFrom 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 is just unspecific symptoms in radiologically isolated syndrome patients – Commentary
Makhani N. The multiple sclerosis prodrome is just unspecific symptoms in radiologically isolated syndrome patients – Commentary. Multiple Sclerosis Journal 2021, 27: 1827-1828. PMID: 34494919, PMCID: PMC8740898, DOI: 10.1177/13524585211044951.Peer-Reviewed Original ResearchThe 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
Acute flaccid myelitis: cause, diagnosis, and management
Murphy O, Messacar K, Benson L, Bove R, Carpenter J, Crawford T, Dean J, DeBiasi R, Desai J, Elrick M, Farias-Moeller R, Gombolay G, Greenberg B, Harmelink M, Hong S, Hopkins S, Oleszek J, Otten C, Sadowsky C, Schreiner T, Thakur K, Van Haren K, Carballo C, Chong P, Fall A, Gowda V, Helfferich J, Kira R, Lim M, Lopez E, Wells E, Yeh E, Pardo C, group A, Salazar-Camelo A, Mithal D, Wilson-Murphy M, Bauer A, Watkins C, Abzug M, Dominguez S, Press C, Yang M, Ahsan N, Ramos-Platt L, Tiongson E, Seruya M, Tilton A, Katz E, Kirschen M, Shah A, Ulloa E, Yum S, Mondok L, Blaufuss M, Rosenfeld A, Vargas W, Zucker J, Yeshokumar A, Navis A, Chao K, Hagen K, Melicosta M, Porter C, Tunney M, Scheuermann R, Duggal P, Pekosz A, Bayliss A, Moore M, Belzberg A, Bembea M, O'Brien C, Riggs R, Nance J, Milstone A, Rice J, Garcia-Dominguez M, Flanagan E, Tillema J, Bosques G, Bhatia S, Gordon-Lipkin E, Deike D, Revivo G, Zlotolow D, deFiebre G, Lazerow P, Lotze T, Bitnun A, Davidge K, Vajsar J, Moore A, Konersman C, Nash K, Strober J, Gupta N, Chiu C, Sweeney M, Jackson W, Simon D, Thakkar K, Cheng J, Luce J, Das S, Vogt M, Vu N, Gofshteyn J, Makhani N, Patel P. Acute flaccid myelitis: cause, diagnosis, and management. The Lancet 2020, 397: 334-346. PMID: 33357469, PMCID: PMC7909727, DOI: 10.1016/s0140-6736(20)32723-9.Peer-Reviewed Original ResearchConceptsAcute flaccid myelitisNon-polio enterovirus infectionMajor public health challengeAcute neurological illnessCerebrospinal fluid characteristicsPolio-like illnessSubstantial residual disabilityProfound muscle weaknessLong-term outcomesTargeted therapeutic approachesPublic health challengeLong-term rehabilitationResidual disabilityAcute phaseClinical featuresClinical presentationEnterovirus infectionImmunological featuresMuscle weaknessNeurological illnessTherapeutic approachesHost-virus interactionsPathogen factorsHealth challengesDiagnosisRadiologically 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 ResearchClinical Reasoning: A 16-year-old girl with ataxia, oscillopsia, and behavioral changes
Silverman A, Selvadurai C, Picard J, Gluck L, Fisayo A, Makhani N, Benitez V. Clinical Reasoning: A 16-year-old girl with ataxia, oscillopsia, and behavioral changes. Neurology 2020, 94: 10.1212/wnl.0000000000009297. PMID: 32234821, PMCID: PMC7282879, DOI: 10.1212/wnl.0000000000009297.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
Clinical trials of disease-modifying agents in pediatric MS: Opportunities, challenges, and recommendations from the IPMSSG
Waubant E, Banwell B, Wassmer E, Sormani M, Amato M, Hintzen R, Krupp L, Rostásy K, Tenembaum S, Chitnis T, Aaen G, Ben Adou E, Al-Roughani R, Alvarez V, Anagnostouli M, Anlar B, Armangue T, Arrambide G, Baroncini D, Bembeeva R, Benson L, Bizjak N, Blaschek A, Boyko A, Brenton J, Brück W, Klein da Costa B, Dive D, Elpers C, Filippi M, de Oliveira Fragomeni M, Havrdova E, Hemingway C, Kornek B, Deiva K, Lacy A, Liba Z, Lim M, Lotze T, Mah J, Makhani N, Mar S, McKay K, Menascu S, Moiola L, Mulero P, Ndiaye M, Neuteboom R, Ness J, Lobato de Oliveira E, Otallah S, Patti F, Albino da Paz J, Perez C, Pohl D, Ponsonby A, Rensel M, Rocca M, Rijke N, Rodriguez M, Rossman I, Sakuma H, Schreiner T, Schteinschnaider A, Sikes E, Simone I, Sweeney M, Tillema J, Troxell R, Verhelst H, Vilchez L, De Waele L, Weinstock-Guttman B, Wilbur C, Yann M, Yeh E, Zafeiriou D. Clinical trials of disease-modifying agents in pediatric MS: Opportunities, challenges, and recommendations from the IPMSSG. Neurology 2019, 92: 10.1212/wnl.0000000000007572. PMID: 31043474, PMCID: PMC6556085, DOI: 10.1212/wnl.0000000000007572.Peer-Reviewed Original ResearchOligoclonal 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