GuillainBarre Synd格林巴利英文課件

Guillain-BarreSyndromeWilliamWoodfinMDK.F.40y.o.r/hwoman3/17Nausea,diarrhea&severemyalgiasSondxedcrotavirus1wk.Previously4/21“Creepy-crawlies”legs>arms4/25Weaknesslegsprogressing4/26Handwritinglookslike“henscratch”K.F.40y.o.woman4/28Admittedtooutsidehospital.L.P.wnlEMGpositivewavesinsomelegmusclesNCVsabsentH-reflexesFresponses&motorlatencieswnlK.F.40y.o.woman4/29TransferredtoPHDHx.:diabeticx10yrs.hypothyroid-treatedxyrs.nosphincterdisrubanceachingpainlowback&buttocksmildposturallightheadednessnoSOBorpalpatationsExamBP150/90P80Wt.250lbs.Mildweaknessneckflexors4/5biceps,grip&interossei-symmetric2/5iliopsoas&quadriceps3/5hamstrings&adductors4/5abductors4/5ankles&toes-extensors&flexorsExamSensory-intactDTRs-biceps,BR,kneesaretracecreinforcement.Triceps&anklesunobtainablePlantars-flexorFtoN-intactGait-nottestableLabH/H10.3/33.5cmicrocyticindicesA1cHgb10.1TSH0.97LDL182Serumimmunofixation-wnl.NoIgAdef.FVCs-consistently4+litersMRILSspines&ccontrast-nonerverootenhancementCourseinhospitalTreatedcIVIG0.4gms/kgmdailyx5StrengthfluctuatedonlymildlyBloodsugarsokinAM,highinafternoonsRepeatedNCVsshowmilddispersionofFwavesTransferredbacktoreferringhospital5/6TelephoneFUAmbulatingfairlywellcwalker.Strengthclearlyimproving.Stillbotheredby“creepy-crawlies”WhatistheGBS?Duetothebreadthofclinicalpresentationitisoflimitedhelptotrytodefinerigiddiagnosticcriteria.ThomasMunsat1965:“…TheGBSiseasytodiagnosebutdifficulttodefineThetypicalillnessevolvesoverweeksusuallyfollowinganinfectiousdiseaseandinvolves:1.Paresthesiaesusuallyhearldthedisease2.Fairlysymmetricweaknessinthelegs,laterthearmsand,often,respiratoryandfacialmuscles3.DimunitionandlossoftheDTRs4.Albuminocytologicdissociation5.RecoveryoverweekstomonthsHistoryWaldrop1834Olliver1837Landry1859Graves1884Ross&Bury1893Brussel’sConf.1937Haymaker&Kernohan1949Waksman&Adams1955MillerFisher1956Asbury,Aranson&Adams1969Guillain,Barre&Strohl1916-1920Notesurlaparalysieascendanteaigue1859March16-afebrileillnessMay11-mildsensorysymptomsinthefingersandtoesJune13-kneesbuckleJune16-unabletowalkSubsequentrespiratoryfailureanddeath.Autopsyunrevealing.PeripheralnervesprobablynotexaminedLate19thcentury

Westphal1876-“Landry’sAscendingParalysis”Graves1884-localizedneurologicdiseasetotheperipheralnerves,“thenervouscords”Ross&Bury1893-90cases.AdiseaseoftheperipheralnervesNumerousreportsemphasizingvariousaspectsofthediseasewithmostauthorscreditingLandryGeorgesGuillainRevueNeurologique1916Guillain,Barre&Strohl1916

RevueNeurologiqueTwosoldiersinAmiensdevelopingparalysisandlossofDTRs.Anewdiagnosticfeature:albuminocytologicdissociationintheCSFNomentionofLandryFoundationsQuincke-CSFobservations25yearsearlierSiccard&Foix-“albuminocytologicdissociation”inPott’sdiseaseLate19thcentury:examinationofthereflexeshadbecomeapartoftheneurologicexamwithappreciatedasasignofneuropathybasedonobservationsintabesdorsalisareflexia

Haymaker&Kernohan1949Landmarkinpathologicaldescriptionc50fatalcases&detailedreviewofclinicalfindingsEmphasizedprominentdamagetoproximalnervesoftenatjunctionofventral&dorsalroots.LittlestudyofmoredistalnervesUnifiedfindingsofLandry&Guillain,Barre&StrohlWaksman&Adams1955ExperimentalAllergicNeuritisFirstanimalmodelofanoninfectiousinflammatoryneuritisRabbitnerveandFreund’sadjuvantinjectedintradermallyTargetofactivatedTcellsuncertainAsbury,Aranson&Adams196919pts.AllwithwelldevelopedmononuclearinfiltratesinspinalrootsandnerveswithindaysofclinicalonsetPathologicalhallmark:perivascularmononuclearinflammatoryinfiltratestoadjacenttotheareasofdemyelinationOverviewofAdaptiveImmunityLymphocytes:“command&control,”identifyantigencomponents,respondspecifically,mobilizeotherelementsanddirecttheattackcmemoryforeachantigenicassaultAntibodies:specializedimmunoglobulinmoleculesdirectlyneutralizeandremoveantigenTlymphocytesCD8-recognizeepitopespairedcMHC-ICD4-activateandcontroltheimmuneresponseScavengercellsbreakdownantigenintosmallpeptidefragments(Tcellepitopes),MHC-IIepitopecomplexesareexpressedonthesurface&thescavengerbecomeanAPCwhichdocksonaCD4cacompatibleTCR.CD4proliferatesreleasingcytokines.AntibodiesCytokinesactivateotherlymphocytesincludingBcellsthatdifferentiateintoplasmacellsandserveasimmunoglobulinfactories.AbsareIgmoleculesthatrecognize,bind,neutralizeandopsonizeAgforphagocytosis.Theyactivatecomplement(membraneattackcomplex)&inducetargetcellstoactivatetheinflammatoryresponseCellular&HumoralImmuneMechanismsSelf-toleranceTheprocessofselfrecognitionT&BcellslearnselftoleranceduringmaturationAutoimmunityoccurswhenthemechanismsofselfprotectionaredefectiveMechanismsofAutoimmunityMolecularmimicry-microbecellsurfaceAgresemblesselfprotein.Damageresultsfrom“friendlyfire”TheincitingAgisusuallyunidentified&maynotexistasasinglestimulus.ExcessivecytokinereleaseduetoprofoundimmunestimulusmayawakenselftolerantTcellsormaycauseexpressionofMHCcomplexes.SelfAgsboundtodrugsmaylosetoleratedstatusAntecedentEvents:InfectiousViral:Influenza,Coxsackie,EBV,Herpes,HIV,Hepatitis,CMV,WNVBacterial:Campylobacterjejuni,Mycoplasma,E.coliParasitic:Malaria,ToxoplasmosisAntecedentEvents:SystemicdiseaseHodgkinsCLLHyperthyroidismSarcoidosisCollagenVasculard.Renald.OtherantecedenteventsSurgeryImmunizationPregnancyEnvenomizationBonemarrowtransplantationDrugingestionFeaturesofAIDP2/3shaveidentifiableprecedingevent50%beginwithparesthesiasfollowedbyweaknessinlegs;10%beginwitharmweakness;rarelybeginsinfaceOphthalmoplegia:partial15%,total5%Autonomicdysfunctionin65%,arrhythmias,hypotension,urinaryretentionin10-15%,pupillaryinequalityAIDPProgressesfordaysto4weeks15%withseveredisabilityMortality3-5%CSF:proteinmaybenormalearly,elevatedin90%byclinicalnadir,cells<10in95%,>50suggestsHIVEDX:prolongedF&distalmotorlatencies,conductionblock30-40%inroutinestudiesAIDPPathology:immuneattackdirectedatschwanncellplasmalemmaesp.atnerverootswithIgG&complementdepositsprecedingdemyelinationCIDPEvolvesovermonthsFluctuatesRespiratoryfailure,dysautonomia,facialweakness,ophthalmoplegia-allarerareCSFproteinoftenhighlyelevatedMarkedslowingofmotornerveconductionSteroidresponsive

FeaturesofAMSANCommonlyprecededbydiarrheaesp.c.jejuniAbruptonsetofweaknesscrapidprogressiontoquadriplegia&respiratoryinsufficiencyOtherfeaturesascAIDPLongerrecovery,moreresidual&mortality10-15%AMSANCSFasinAIDPEDX:noresponseinsomemotornerves,decreasedamplitudeoftheCMAPs,fibrillationsonneedlestudy,absentSNAPsImmuneattackdirectedataxonplasmalemmaatnodesofRanvier.WalleriandegenerationFeaturesofAMANOftenprecededbydiarrheaaffectingyoungerpopulationinChina.SporadicinUSAPrognosissimilairtoAIDPMortality<5%EDX:reducedCMAPscnormalF&distalmotorlatenciesandsensorystudies.Fibrillationsin2-3weeksAMANPathology:againaxonalplasmalemmaatnodesofRanviersometimeslimitedtophysiologicdysfunctioncnodallengthening.Maygoontoextensionthroughaxonalbasallamina.MostaxonsrecoversWalleriandegenerationMillerFisherSyndromeOphthalmoplegia,Ataxia,AreflexiaMaybeheterogonous:1.RelatedtootherpatternsofGBS2.Relatedtobrainstemencephalitis,Bickerstaff19523.CNSdemyelinationinassociationwithGBSMillerFisherSyndrome95%haveserumIgGAbtogangliosideGQ1bStudiesshowpreferentiallocationofanti-GQ1btocerebellarmolecularlayer&CranialNerves3,4&6MayactatN-MjunctiondepletingacetylcholinefromnerveterminalsAcutePanautonomicNeuropathyManifestsover1-2weeksbutmaybeofsubacuteonsetFrequentprecedinginfectionDTRslostin1/3,distalsensorychanges1/4AlbuminocytologicdissociationEDX:NCVsusuallynormalRecoveryisgradualandincompleteDifferentialDiagnosisConsiderthepossibilityofanuppermotorneuronlesionOtherconsiderationsarerare.Diphtheriticneuritis&poliomyelitisbelongmoretothehistorysectionofthispresentation.AnewpossibilityisWestNileVirus.Differential N-M:MG,LES,AntibioticsToxic:Cigutera(ciguatoxin),Pufferfish(tetrodotoxin),Shellfish(saxitioxin),Botulism,Tickparalysis(LoneStartick,GulfCoasttick),Gluesniffing,BuckthornMononeuritismultiplexassoc.cWegner’s.PAN,SLE,RA,Sjogren’s,Cryoglobulinemiaetc.DifferentialMetabolic:Periodicparalyses,Hypokalemia,Hypermagnesemia,Hypophoshatemiacparenteralhyperailimentation,Thyrotoxicosis,ICUmyoneuropathy(CIP)Heavymetal:Lead,Arsenic,Thallium,Bariumchypokalemia

Differential:MillerFisherSyn.MultiplesclerosisEncephalitisPosteriorcirculationischemiaorinfarctOther:Botulism,MG,TickTreatmentRespiratoryfailureAutonomicdysfunctionDVT&PEPainPositioning&SkincarePhysicaltherapyNutrition

RespiratoryFailureOropharyngealweaknessin~25%withimpairedswallowingofsecretions&aspirationMechanicalrespiratoryfailure-mainlyduetodiaphragmaticweakness(Phrenicnerves.)InspiratorycMIF(Max.Inspir.Force)agoodsupplementmeasuretoFVCRespiratoryFailure~33%requireintubationAvg.timetointubationis1week&thesepts.havesubstantiallylongerrecoverytimeNeedisunlikelyifpatientdoeswellfor2wks.postonsetofparesthesiaesGuidelines:FVC<15mL/kgmMIF<25cmwaterPsychologicalFearHelplessnessCommunicationPainSleepdeprivation&hallucinosisDepressionVisitsfromotherGBSpatientsPersonalExperienceBowes,Denise;Thedoctoraspatient:anencounterwithGuillain-Barresyndrome.CanMedAssocJ131:1343-1348Corticosteroids

Lancet1993242pts.

IVMethylprednisilone500mgm/dayx5.IneffectiveMaycauserelapsePlasmaExchangeRemovaloftheblood’sliquidsolublecomponentsincludingcomplement,immunoglobulin,immunecomplexes,cytokinesandinterleukinsAtypicalsessionremovesabout60%ofthebodymassofplasmaproteinswhichisreplacedcsaline,albumin&FFPDoneqodfor3-5sessionsPlasmaExchangeVariousstudiessince1985Timeonventilatorreducedby?F