2020
Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections
Chain JL, Alvarez K, Mascaro-Blanco A, Reim S, Bentley R, Hommer R, Grant P, Leckman JF, Kawikova I, Williams K, Stoner JA, Swedo SE, Cunningham MW. Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections. Frontiers In Psychiatry 2020, 11: 564. PMID: 32670106, PMCID: PMC7328706, DOI: 10.3389/fpsyt.2020.00564.Peer-Reviewed Original ResearchPediatric autoimmune neuropsychiatric disordersAnti-neuronal autoantibodiesSerum autoantibody titersAutoimmune neuropsychiatric disordersSydenham's choreaAutoantibody titersEnzyme-linked immunosorbent assayCerebrospinal fluidNeuronal autoantigensNeuropsychiatric disordersPANDAS patientsPANDAS subjectsStreptococcal infectionHealthy controlsAcute symptomatic phaseBasal ganglia encephalitisGroup of autoantibodiesHealthy control subjectsCaMKII activationAttention deficit hyperactivity disorderHuman neuronal cellsDeficit hyperactivity disorderGroup of childrenAutoantibody biomarkersObsessive-compulsive disorderAntibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types
2017
Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS)
Leon J, Hommer R, Grant P, Farmer C, D’Souza P, Kessler R, Williams K, Leckman JF, Swedo S. Longitudinal outcomes of children with pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). European Child & Adolescent Psychiatry 2017, 27: 637-643. PMID: 29119300, DOI: 10.1007/s00787-017-1077-9.Peer-Reviewed Original ResearchConceptsPediatric autoimmune neuropsychiatric disordersAutoimmune neuropsychiatric disordersIntravenous immunoglobulinStreptococcal infectionDose of IVIGNeuropsychiatric disordersPlacebo-controlled trialSignificant obsessive-compulsive symptomsPopulation of childrenCognitive behavioral therapySubacute illnessSydenham's choreaBlinded infusionChronic coursePsychiatric medicationsTreatment modalitiesSpecific symptomsChildhood-onset OCDLongitudinal courseNatural historyObsessive-compulsive symptomsBehavioral therapyExacerbationParents of participantsTelephone interviewsClinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I—Psychiatric and Behavioral Interventions
Thienemann M, Murphy T, Leckman J, Shaw R, Williams K, Kapphahn C, Frankovich J, Geller D, Bernstein G, Chang K, Elia J, Swedo S. Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I—Psychiatric and Behavioral Interventions. Journal Of Child And Adolescent Psychopharmacology 2017, 27: 566-573. PMID: 28722481, PMCID: PMC5610394, DOI: 10.1089/cap.2016.0145.Peer-Reviewed Original ResearchConceptsPediatric acute-onset neuropsychiatric syndromeNeuropsychiatric syndromeInitial treatment doseEvidence-based interventionsPANDAS patientsImmunomodulatory therapyStreptococcal infectionChronic stageSymptomatic treatmentPsychopharmacologic interventionsPsychopharmacologic treatmentSymptom improvementSyndrome AssociatedConsensus guidelinesPsychotropic medicationsClinical managementInflammatory processCurrent guidelinesGuideline SeriesTreatment doseClinical experienceBehavioral symptomsVaried symptomsTherapeutic interventionsBehavioral interventions
2016
Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
Williams KA, Swedo SE, Farmer CA, Grantz H, Grant PJ, D’Souza P, Hommer R, Katsovich L, King RA, Leckman JF. Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections. Journal Of The American Academy Of Child & Adolescent Psychiatry 2016, 55: 860-867.e2. PMID: 27663941, DOI: 10.1016/j.jaac.2016.06.017.Peer-Reviewed Original ResearchConceptsPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulinAutoimmune neuropsychiatric disordersYale-Brown Obsessive Compulsive ScaleChildren's Yale-Brown Obsessive Compulsive ScaleStreptococcal infectionIVIG groupPlacebo groupObsessive-compulsive disorderClinical Global Impression improvement ratingNeuropsychiatric disordersDouble-blind infusionDouble-blind phaseSustained symptom improvementDouble-blind comparisonOpen-label treatmentPrimary outcome measureSevere obsessive-compulsive disorderCY-BOCS total scoreCross-reactive antibodiesIdentification of biomarkersCY-BOCS scoresObsessive Compulsive ScaleImmunomodulatory therapyControlled Trials
2012
Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders
Brimberg L, Benhar I, Mascaro-Blanco A, Alvarez K, Lotan D, Winter C, Klein J, Moses AE, Somnier FE, Leckman JF, Swedo SE, Cunningham MW, Joel D. Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders. Neuropsychopharmacology 2012, 37: 2076-2087. PMID: 22534626, PMCID: PMC3398718, DOI: 10.1038/npp.2012.56.Peer-Reviewed Original ResearchConceptsSydenham's choreaNeuropsychiatric disordersStreptococcal exposureImmunological abnormalitiesMotor symptomsRat modelAnimal modelsSelective serotonin reuptake inhibitor paroxetineGroup A streptococcal infectionsSerotonin reuptake inhibitor paroxetineSK-N-SH neuronal cellsMale Lewis ratsNovel rat modelNew animal modelCalcium/calmodulin-dependent protein kinase IIRelated neuropsychiatric disordersStreptococcal infectionLewis ratsAntibody depositionBasal gangliaCalmodulin-dependent protein kinase IIDopamine D1GAS antigensGlutamate levelsD2 receptors
2010
Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study
Leckman JF, King RA, Gilbert DL, Coffey BJ, Singer HS, Dure LS, Grantz H, Katsovich L, Lin H, Lombroso PJ, Kawikova I, Johnson DR, Kurlan RM, Kaplan EL. Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study. Journal Of The American Academy Of Child & Adolescent Psychiatry 2010, 50: 108-118.e3. PMID: 21241948, PMCID: PMC3024577, DOI: 10.1016/j.jaac.2010.10.011.Peer-Reviewed Original ResearchConceptsExacerbation of ticsGABHS infectionStreptococcal infectionSymptom exacerbationStreptococcal upper respiratory tract infectionPediatric autoimmune neuropsychiatric disordersUpper respiratory tract infectionObsessive-compulsive symptomsAutoimmune neuropsychiatric disordersHemolytic streptococcal infectionRespiratory tract infectionsThroat swab cultureLongitudinal studyProspective longitudinal studyPANDAS subjectsClinical exacerbationStreptococcal antibodiesTract infectionsClinical symptomsGABHS infectionsGroup of childrenLaboratory valuesSwab culturesClinical conditionsClinical evaluatorsTourette Syndrome in Children: An Updated Review
Du JC, Chiu TF, Lee KM, Wu HL, Yang YC, Hsu SY, Sun CS, Hwang B, Leckman JF. Tourette Syndrome in Children: An Updated Review. Pediatrics & Neonatology 2010, 51: 255-264. PMID: 20951354, DOI: 10.1016/s1875-9572(10)60050-2.Peer-Reviewed Original ResearchConceptsTourette syndromeVocal ticsMovement disordersBasal ganglia-related circuitsRepetitive transcranial magnetic stimulationPathophysiology of TSA2-adrenergic agonistHabit reversal therapySocial functioningTranscranial magnetic stimulationCommon neuropsychiatric disorderPatients' social functioningAttention deficit hyperactivity disorderDeficit hyperactivity disorderCommon comorbiditiesNeurological examinationStreptococcal infectionReversal therapyObsessive-compulsive disorderAtypical neurolepticsDopaminergic innervationCorrect diagnosisSevere casesMagnetic stimulationSensory urge
2009
Streptococcal Upper Respiratory Tract Infections and Psychosocial Stress Predict Future Tic and Obsessive-Compulsive Symptom Severity in Children and Adolescents with Tourette Syndrome and Obsessive-Compulsive Disorder
Lin H, Williams KA, Katsovich L, Findley DB, Grantz H, Lombroso PJ, King RA, Bessen DE, Johnson D, Kaplan EL, Landeros-Weisenberger A, Zhang H, Leckman JF. Streptococcal Upper Respiratory Tract Infections and Psychosocial Stress Predict Future Tic and Obsessive-Compulsive Symptom Severity in Children and Adolescents with Tourette Syndrome and Obsessive-Compulsive Disorder. Biological Psychiatry 2009, 67: 684-691. PMID: 19833320, PMCID: PMC2843763, DOI: 10.1016/j.biopsych.2009.08.020.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnti-Bacterial AgentsAttention Deficit Disorder with HyperactivityChildDepressive DisorderFemaleForecastingHumansLife Change EventsMaleObsessive-Compulsive DisorderPredictive Value of TestsProspective StudiesPsychologyRespiratory Tract InfectionsSeverity of Illness IndexStreptococcal InfectionsTicsTourette SyndromeConceptsDepressive symptom severityObsessive-compulsive disorderGABHS infectionPsychosocial stressTourette syndromeSymptom severityControl subjectsStreptococcal upper respiratory tract infectionUpper respiratory tract infectionBeta-hemolytic streptococcal infectionCurrent psychosocial stressRespiratory tract infectionsHealthy control subjectsProspective longitudinal studyEarly-onset obsessive-compulsive disorderMinority of childrenOC symptom severityTract infectionsStreptococcal infectionGABHS infectionsObsessive-compulsive symptom severityClinical ratingsNew infectionsClinical ratersControl statusImmunopathogenic mechanisms in tourette syndrome: A critical review
Martino D, Dale RC, Gilbert DL, Giovannoni G, Leckman JF. Immunopathogenic mechanisms in tourette syndrome: A critical review. Movement Disorders 2009, 24: 1267-1279. PMID: 19353683, PMCID: PMC3972005, DOI: 10.1002/mds.22504.Peer-Reviewed Original ResearchConceptsTourette syndromeT cellsTS patientsBeta-haemolytic streptococcal infectionPathogenesis of TSPeripheral immune cellsRegulatory T cellsCell-mediated mechanismsPro-inflammatory cytokinesCourse of diseaseGeneration of ticsAdaptive immune systemImmune effector moleculesAntineuronal antibodiesImmunopathogenic mechanismsLymphocyte subpopulationsNatural killerStreptococcal infectionAutoimmune responseImmune activationPlasma levelsDisease onsetImmune cellsPathogenic roleImmune response
2008
Neuropsychiatric Disorders Associated With Streptococcal Infection: A Case-Control Study Among Privately Insured Children
Leslie DL, Kozma L, Martin A, Landeros A, Katsovich L, King RA, Leckman JF. Neuropsychiatric Disorders Associated With Streptococcal Infection: A Case-Control Study Among Privately Insured Children. Journal Of The American Academy Of Child & Adolescent Psychiatry 2008, 47: 1166-1172. PMID: 18724258, PMCID: PMC2783578, DOI: 10.1097/chi.0b013e3181825a3d.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAttention Deficit Disorder with HyperactivityCase-Control StudiesChildChild, PreschoolCross-Sectional StudiesDepressive Disorder, MajorFemaleHealth SurveysHumansIncidenceInsurance, HealthMaleMigraine DisordersNeurocognitive DisordersObsessive-Compulsive DisorderOdds RatioOtitis MediaRiskSinusitisStreptococcal InfectionsTic DisordersTourette SyndromeUnited StatesConceptsMajor depressive disorderAttention-deficit/hyperactivity disorderPrior streptococcal infectionStreptococcal infectionObsessive-compulsive disorderTic disordersTourette syndromeNeuropsychiatric disordersConditional logistic regression modelsStreptococcal sore throatDiagnosis of OCDCase-control studyLogistic regression modelsSore throatIncident diagnosisEpidemiologic evidenceDepressive disorderSubsequent diagnosisNoninfectious conditionsScarlet feverChildren ages 4Immune systemInfectious diseasesInfectionDiagnosis
2006
Identification of pyruvate kinase as an antigen associated with Tourette syndrome
Kansy JW, Katsovich L, McIver KS, Pick J, Zabriskie JB, Lombroso PJ, Leckman JF, Bibb JA. Identification of pyruvate kinase as an antigen associated with Tourette syndrome. Journal Of Neuroimmunology 2006, 181: 165-176. PMID: 17011640, PMCID: PMC1853370, DOI: 10.1016/j.jneuroim.2006.08.007.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsAntibodies, BacterialAntigensAutoantibodiesBrainChildCross ReactionsHumansImmunohistochemistryLongitudinal StudiesMaleMiceMice, Inbred C57BLMolecular Sequence DataProspective StudiesPyruvate KinaseRatsSeroepidemiologic StudiesStreptococcal InfectionsTicsTourette SyndromeConceptsStreptococcal infectionObsessive-compulsive disorderTourette syndromeAutoimmune targetExacerbated symptomsBeta-hemolytic streptococcal infectionEarly-onset obsessive-compulsive disorderStreptococcal M proteinPediatric populationTic disordersImmune responseSurface antigenInfectious strainsSyndromeInfectionDisordersPyruvate kinaseM proteinPatientsImmunoreactivitySymptomsAntigenAntibodiesGlycolytic enzymesM1 isoformDecreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study
Kawikova I, Leckman JF, Kronig H, Katsovich L, Bessen DE, Ghebremichael M, Bothwell AL. Decreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study. Biological Psychiatry 2006, 61: 273-278. PMID: 16996487, DOI: 10.1016/j.biopsych.2006.06.012.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAge of OnsetAntigens, CDAntigens, Differentiation, T-LymphocyteAutoantigensBlood Cell CountCD4 Lymphocyte CountCD8-Positive T-LymphocytesChildData Interpretation, StatisticalFemaleFlow CytometryHumansImmune ToleranceInterleukin-2 Receptor alpha SubunitLectins, C-TypeLymphocyte CountMaleStreptococcal InfectionsT-LymphocytesTic DisordersTourette SyndromeConceptsT reg cellsRegulatory T cellsReg cellsTourette syndromeT cellsTS patientsFluorescence-activated cell sortingHealthy age-matched control childrenHealthy age-matched control subjectsT reg cell numbersBeta-hemolytic streptococcal infectionAge-matched control subjectsHost T-cell immunityPathogenesis of TSHemolytic streptococcal infectionT cell immunitySignificant decreaseAge-matched control childrenAutoimmune inflammationCell immunityStreptococcal infectionAutoreactive lymphocytesImmune toleranceAutoimmune responsePeripheral blood
2005
Antineural antibody in patients with Tourette’s syndrome and their family members
Yeh CB, Wu CH, Tsung HC, Chen CW, Shyu JF, Leckman JF. Antineural antibody in patients with Tourette’s syndrome and their family members. Journal Of Biomedical Science 2005, 13: 101-112. PMID: 16215701, DOI: 10.1007/s11373-005-9033-y.Peer-Reviewed Original ResearchConceptsAntineural antibodiesTourette syndromeTS patientsTic disordersControl groupFirst-degree family membersAge-matched control groupFamily membersSera of controlsImmunological pathophysiologyStreptococcal infectionPrimary cell culturesPatientsInfectious agentsSyndromeNeuropsychiatric disordersWestern blottingAntibodiesRat tissuesInteraction of geneticsGenetic vulnerabilitySerumDisordersFuture studiesCell cultures
2004
Prospective Longitudinal Study of Children With Tic Disorders and/or Obsessive-Compulsive Disorder: Relationship of Symptom Exacerbations to Newly Acquired Streptococcal Infections
Luo F, Leckman JF, Katsovich L, Findley D, Grantz H, Tucker DM, Lombroso PJ, King RA, Bessen DE. Prospective Longitudinal Study of Children With Tic Disorders and/or Obsessive-Compulsive Disorder: Relationship of Symptom Exacerbations to Newly Acquired Streptococcal Infections. Pediatrics 2004, 113: e578-e585. PMID: 15173540, DOI: 10.1542/peds.113.6.e578.Peer-Reviewed Original ResearchConceptsGABHS infectionSymptom exacerbationObsessive-compulsive disorderControl subjectsTourette syndromeAcute exacerbationTime pointsHealthy control subjectsBeta-hemolytic streptococciAcute inflammatory responseAcute symptom exacerbationsProspective longitudinal studyAutoimmune mechanismsPediatric patientsStreptococcal infectionNeuropsychiatric symptomsGABHS infectionsNonspecific markerInflammatory responseTic disordersUnselected groupObsessive-compulsive symptom severityExacerbationPatientsObsessive-compulsive symptoms
2000
Preliminary Findings of Antistreptococcal Antibody Titers and Basal Ganglia Volumes in Tic, Obsessive-compulsive, and Attention-Deficit/Hyperactivity Disorders
Peterson BS, Leckman JF, Tucker D, Scahill L, Staib L, Zhang H, King R, Cohen DJ, Gore JC, Lombroso P. Preliminary Findings of Antistreptococcal Antibody Titers and Basal Ganglia Volumes in Tic, Obsessive-compulsive, and Attention-Deficit/Hyperactivity Disorders. JAMA Psychiatry 2000, 57: 364-372. PMID: 10768698, DOI: 10.1001/archpsyc.57.4.364.Peer-Reviewed Original ResearchConceptsBasal ganglia volumesAttention-deficit/hyperactivity disorderAntistreptococcal antibody titersObsessive-compulsive disorderAntibody titersGanglia volumesStreptococcal infectionAntistreptococcal antibodiesPreliminary serological evidencePrior streptococcal infectionRecurrent streptococcal infectionsHyperactivity disorderPresence of ADHDBasal ganglia nucleiHigh antibody titersGlobus pallidus nucleusDSM-IV diagnosisStreptococcal exposurePallidus nucleusAntistreptolysin OOCD comorbiditySerological evidenceSusceptible personsTic disordersDiagnostic comorbidity