內(nèi)科學(xué)教學(xué)課件：Tuberculous Meningitis (TBM)

TuberculousMeningitis(TBM)1Let’sstartwithacase62-yowoman.Previouslyhealthy.3-wkfever,fatigue,nightsweats,headache,andvomiting.2-mofprogressiveweightloss.Reportedmemoryloss,poorconcentration,andinsomnia.NEJM1999,341(16):11972Onneurologicexamination,ConfusedAnsweredquestionsslowlyNostiffnessoftheneck,cranial-nervepalsies,orpyramidalsigns.CSFPleocytosis(WBC340,80%LC)Prot2.4g/lGlu38mg/dl3CXR&chestCT:Normal.MRI:EnhancementofthebasalmeningesInflammation?4PrimaryimpressionanddifferentialHighlysuggestiveoftuberculousmeningitis.DD:SarcoidosisWegener’sgranulomatosisFungalmeningitisChronicmeningitisduetonocardiaoractinomyces.5Furtherinvestigationandfollow-upCSFAcid-fastbacillineg.onZiehl–Neelsenstaining.ButM.tuberculosisgrew4wklater.TBMconfirmed,anti-TBwithEMB/PZA/INH/RIFandcorticosteroids.Asymptomatic1mlater.Meningeallesions(onMRI)disappeared3mlater.6ObjectivesUnderstandtheepidemiologyofTB.FamiliarwiththediagnosisandclinicalmanagementofTBM.AppreciatetheadjunctivetherapyofsteroidsinTBM.ExplainwhyTBisstillathreattohumanhealth.7EpidemiologyofTBNEnglJMed.2013Feb21;368(8):745-55Numberofnewcasesofactivetuberculosis8EpidemiologyofTBNEnglJMed.2013Feb21;368(8):745-559NEnglJMed.2013Feb21;368(8):745-55EpidemiologyofTB10RiskfactorsInlow-incidenceareasImmigrantgroupsfromhigh-incidenceareasAlcoholordrugsabuserImmunosuppressionfromanycauseHIVPovertyCrowdedOtherfactors?PeterR.Donald,JohanF.Schoeman.TuberculousMeningitis.NEJM351;17:1119.11TBMInsub-SaharanAfrica,TBMisnowthemostcommonformofbacterialmeningitis.TypicallyadiseaseofyoungchildrenincountrieswithahighincidenceofTB.MorecommonlyaffectsadultsincountrieswithalowincidenceofTB.PeterR.Donald,JohanF.Schoeman.TuberculousMeningitis.NEJM351;17:1119.12TBM:0.7-2.1%TB;5-7%extra-pulmonaryTB13PathogenesisofTBMReleaseofbacillifromoldfocallesionsincommunicationwiththemeninges(Richfoci).Granulomascancoalescetoformtuberculomas.TheadhesiveexudatecanobstructCSFcausinghydrocephalusandcompromiseefferentcranialnerves.Obliterativevasculitiscancauseinfarctionandstrokesyndromes.RichAR,McCordockHA.Anenquiryconcerningtheroleofallergy,immunityandotherfactorsofimportanceinthepathogenesisofhumantuberculosis.BullJohnsHopkinsHosp1929;44:273-382.Idem.Thepathogenesisoftuberculousmeningitis.BullJohnsHopkinsHosp1933;52:5-37.1415Asterisks:ventriculardilatation.Blackarrows:inflammatoryexudates.Whitearrows:sub-acute,ischemianecrosis,vasculitis-associated.PeterR.Donald,JohanF.Schoeman.TuberculousMeningitis.NEJM351;17:1119.16GuyEThwaites,TranTinhHien.Tuberculousmeningitis:manyquestions,toofewanswersLancetNeurol2005;4:160–70SymptomsonpresentationSymptoms(proportionofpatientsaffected)Headache(50-80%)Fever(60-95%)Vomiting(30-60%)Anorexia(60-80%)Photophobia(5-10%)17GuyEThwaites,TranTinhHien.Tuberculousmeningitis:manyquestions,toofewanswersLancetNeurol2005;4:160–70SymptomsonpresentationNeckstiffness(40-80%)Confusion(10-30%)Coma(30-60%)Anycranialnervepalsy(30-50%)CranialnerveIII,IV,VI,VIImorecommonHemiparesis(10-20%)Paraparesis(5-10%)Seizures(children:50%;adults:5%)18GuyEThwaites,TranTinhHien.Tuberculousmeningitis:manyquestions,toofewanswersLancetNeurol2005;4:160–70SymptomsonpresentationCSF(proportionorrange)Appearance(80-90%clear)Openingpressure(50%>25cmH2O)TotalWBC(5-1000×103/ml)Neutrophils(10-70%)Lymphocyte(30-90%)Protein(45-250mg/dL)Lactate(5-10mmol/L)19ClinicaldiagnosisFiveclinicalvariableswerepredictiveofTBMSx>6daysOpticatrophyFocalneurologicaldeficitAbnormalmovementsNeutrophils<50%inCSF.KumarR,SinghSN,KohliN.Adiagnosticrulefortuberculousmeningitis.ArchDisChild1999;81:221–24 Sensitivity specificity>=1feature 98% 44%

>=3features 55% 98% 20Bacteriologicaldiagnosis(CSF)Stain/culturepositive:80%,dependingonMeticulousmicroscopyLargevolume(>5mL)ofCSFnucleic-acid-amplificationassays(NAATs):Sensitivity56%(95%CI46–66)Specificity98%(97–99)Moreusefulafterstartinganti-TBThwaitesGE,etal.Comparisonofconventionalbacteriologywithnucleicacidamplification(amplifiedmycobacteriumdirecttest)fordiagnosisoftuberculousmeningitisbeforeandafterinceptionofantituberculosischemotherapy.JClinMicrobiol2004;42:996–1002.DonaldPR,etal.Polymerasechainreactioninthediagnosisoftuberculousmeningitis.ScandJInfectDis1993;25:613–17GuyEThwaites,TranTinhHien.Tuberculousmeningitis:manyquestions,toofewanswersLancetNeurol2005;4:160–7021LabInvestigationCSFWhitebloodcellcount(<300/mm3),predominanceoflymphocytesLowglucose(<2.2mmol/l)Elevatedprotein(>0.8g/l)Apositivetuberculintestcanprovidediagnosticsupport,buttestresultsmaybenegativeinpatientswithTBM.CXRshowschangescompatiblewithtuberculosisin50-80%ofcases.PeterR.Donald,JohanF.Schoeman.TuberculousMeningitis.NEJM351;17:1119.22RadiologicaldiagnosisKumarR,etal.ValueofCTscaninthediagnosisofmeningitis.IndianPediatr1996;33:465–68Onestudysuggests:Basalmeningealenhancement,tuberculoma,orbothwere89%sensitiveand100%specificforthedxofTBMGuyEThwaites,TranTinhHien.Tuberculousmeningitis:manyquestions,toofewanswersLancetNeurol2005;4:160–70BasalenhancementTuberculomaHydrocephalusInfarction23Treatment(1):anti-TBChemotherayFirst2months--IntensivephaseIsoniazid(IHN)Rifampicin(RIF)pyrazinamide(PZA)andethambutol(EMB)orstreptomycin(SM)Next7-10m--ContinuationphaseIHNandRIFTotalduration9-12m18mifRIFnottolerate.24Anti-TBagentsIHNpotentearlybactericidalactivitypassesfreelyintotheCSFRIF,CSFcon<10%,butmandatory.killslowornon-replicatingbacilli.PZAkillsthoseinsites,hostiletothepenetrationandactionoftheotherdrugs.EMB,poorBBBpenetration.effectiveforresistantbacilli2526Treatment(2):ManagementofhydrocephalusandelevatedICPNoncommunicating:ventriculoperitonealshunt(VPshunt)Communicating:medicaltreatmentwithfurosemide,acetazolamide,ifnotresponse,VPshunt.27Treatment(3):Steroids(controversial)DEXstronglyassociatedwithareducedriskofdeath(RR0·69,95%CI0·52–0·92,p=0·01).Butdidnotpreventseveredisabilityinthesurvivors.Associatedwithlesssevereadverseevents,inparticularhepatitis.QuagliarelloV.Adjunctivesteroidsfortuberculousmeningitis:moreevidence,morequestions.NEnglJMed2004;351:1792–94PatientswithoutHIV,givedexamethasone,regardlessofpatients'ageordiseaseseverity28Corticosteroidregimensassociatedwithsubstantialimprovementsinsurvivalincontrolledtrials29Co-infectionwithHIVNotaltertheclinicalpresentationofTBM.Increasethecomplications.Morebacilliinmeninges.Activeextra-meningealTBismorecommon.FatalityfromTBMisgreater.GuyEThwaites,TranTinhHien.Tuberculousmeningitis:manyquestions,toofewanswersLancetNeurol2005;4:160–7030PrognosticfactorsforoutcomeBeneficialeffectofdexamethasoneonsurvivalinTBM(>14yo).EarlytreatmentinitiationUninterruptedcontinuationSeverityonpresentation,Seizures,stroke,cranialnerveinvolvementCSFcellcountandlactatelevelsHyponatreamiaCoinfectionwithHIVThwaitesGE,etal.Dexamethasoneforthetreatmentoftuberculousmeningitisinadolescentsandadults.NEnglJMed2004;351:1741-51.BrancusiF,FarrarJ&HeemskerkD.FutureMicrobiol.(2012)7(9),1101–111631TBMisdifficulttodiagnoseandtreat:

manyquestions,toofewanswersClinicalSx:non-specific,Stain/culture:insensitiveNAATsvalueassessment:notcomplete.Optimumtreatment:unknown.Anti-TBdrugs:30yo.Death/disability>50%.Resistance.Adjunctivecorticosteroids?ImprovessurvivalButnotpreventsseveredisability.GuyEThwaites,TranTinhHien.Tuberculousmeningitis:manyquestions,toofewanswersLancetNeurol2005;4:160–7032Objectives(again)UnderstandtheepidemiologyofTBM.RecognizethediagnosisandclinicalmanagementofTBM.AppreciatetheadjunctivetherapyofsteroidsinTBM.ExplainwhyTBisstillathreattohumanhealth.33SummaryTBMisthemostsevereformofTB.PREVENTION,EARLYRECOGNITION,DIAGNOSIS&TREATMENTarefundamentaltoimprovingoutcomes34病例分析35病例分析男，48歲，既往糖尿病史；因發(fā)熱、頭痛1周、昏迷3天入MICU病房；LP：壓力正常，WBC257/ul，M96%，Prot9.2G/L頭顱MRI：左側(cè)頂枕部多發(fā)占位？胸部CT：右上及左上多發(fā)小結(jié)節(jié)。36如何處理診斷考慮？下一步檢查目前如何治療內(nèi)科保守治療手段？外科干預(yù)指證？禁忌證？3708-2-253808-2-27394008-3-14108-3-7424344100例結(jié)腦患者中，男性49例，女性51例。年齡31±11歲(5月～67歲)，以青壯年為主。入院前病程超過4周者70例(70%)，26例呈亞急性起病(病程>2周)，4例急性起病，病程<1