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1、结核性脑膜炎英文现在学习的是第1页，共47页EPIDEMIOLOGY-TBM Tuberculous Meningitis(TBM)u The younger the children,the more readily to develop TBM.u 60%in Children aged 1-3 yearsu Death rate:15-30%2现在学习的是第2页，共47页TBM(Tuberculous meningitis)u TBM is the most serious complication of tuberculosis in children and is usually f
2、atal without treatment.u TBM always be a part of systemic disseminated tuberculosis.u TBM often occurs within 1 year of initial infection,especially in the first 2 to 6 months of infection.3现在学习的是第3页，共47页Tuberculous BacilliPrimary ComplexBacteremiaRich FociSubarachnoid SpaceBrain or Spinal Cord Pere
3、nchymaTuberculomasMeningitisPATHOPHYSIOLOGYTrauma/Diseases measles,pertussis Miliary TB4现在学习的是第4页，共47页PATHOLOGICAL EFFECTSMeningesuDiffuse HyperemiauEdemauInflammatory Exudates uConformation of Tubercles 5现在学习的是第5页，共47页PATHOLOGICAL EFFECTSSubarachnoid SpaceuA large amount of thick gelatinous exudate
4、s concentrate to the pavimentum cerebri,optic chiasma,bridge of varolius,bulbus rhachidicus and Sylvian fissure.u Basal meningitis accounts for the frequent dysfunction of cranial nerves III,VI,and VII.6现在学习的是第6页，共47页PATHOLOGICAL EFFECTSCerebral ParenchymaTuberculous meningoencephalitisuswelling and
5、 hyperemia of the parenchyma contribute to the intracranial hypertension,then ischemia of parenchyma occur,finally lead to the foci of encephalomalacia and necrosis.Hemiplegia may be present because of this change.uMeninges,spinal,and spinal nerve root also involvement.The later always leads to para
6、plegina.7现在学习的是第7页，共47页PATHOLOGICAL EFFECTSCerebral VesselsuThe bacteria invade the adventitia directly in the early stage and initiate the process of acute vasculitis.uProgressive destruction of adventitia,disruption of elastic fibers,and finally intimal destruction(endoarteritis),lead to the oblit
7、erative vasculitis,which may facilitate the ischemia,encephalomalacia and necrosis of parenchyma.8现在学习的是第8页，共47页Circulation of CSFChoroid plexusLateral ventricleInterventricular foramenthe 3rd ventricleCerebral aqueduct4th ventricle2 Lateral foramina1 Medial foramenSubarachnoid spaceArachnoid granul
8、ationsDural sinusVenous drainage9现在学习的是第9页，共47页PATHOLOGICAL EFFECTSHydrocephalusHyperemia of choroids overproduction of CSF Inflammatory adherence of Meningedefective absorption of CSF Communicating hydrocephalus CSF flow is obstructed on the route before the cerebral aqueduct and the 4th ventricleN
9、oncommunicating hydrocephalus10现在学习的是第10页，共47页In tuberculous meningitis there is a tendency for the exudate to be primarily located on the under surface of the brain,particularly over the ventral surface of the brain stem.11现在学习的是第11页，共47页CLINICAL MANIFESTIONS A.Prodrome(1-2 week)1.Fever,fatigue,mal
10、aise,myalgia,drowsiness,headache,vomiting2.Mental status changes3.Focal neurologic signs are absent4.CSF abnormity 12现在学习的是第12页，共47页CLINICAL MANIFESTIONSB.Meningeal Irritation Stage (1-2 week)1.More serious TB toxic symptoms2.Intracranial hypertension:severe headache,irritation,projectile vomiting,s
11、eizures;Bulging of anterior fontanelle,widening of cranial sutures in infant 3.Meningeal Irritation:nuchal rigidity,hypertonia Kernig sign or Brudzinski sign 4.Cranial nerve abnormalities:3,6,75.Some children have no evidence of meningeal irritation but may have signs of encephalitis:disorientation,
12、abnormal movements and speech impairment 13现在学习的是第13页，共47页CLINICAL MANIFESTIONSC.Coma Stage(1-3 week)1.Frequent convulsion,progressive altered state of consciousness:lethargy,confusion,semicoma,deep coma,decerebrate or decorticate posturing2.Depletion:extremely maransis,constipation,urinary retentio
13、n 3.progressive abnormalities of vital signs,and eventual die from cerebral hernia 14现在学习的是第14页，共47页Characteristics of TBM in infants and young children1.A rapid onset with convulsion,abruptly high fever2.Atypical miningeal irritation3.Intracranial hypertension manifests as bulging of anterior fonta
14、nelle and widening of cranial sutures in infant 15现在学习的是第15页，共47页PROGNOSISu The prognosis of tuberculous meningitis correlates most closely with the clinical stage of diagnosis and treatment.u Age:infants or younger children are generally worse than that of older childrenu Drug resistant strain u Va
15、riation of host immunityu Appropriate therapeutic regimenu Completion of the antituberculor agent regimen16现在学习的是第16页，共47页It is imperative that antituberculosis treatment be considered for any child who develops basilar meningitis and hydrocephalus,cranial nerve palsy,or stroke with no other apparen
16、t etiology.17现在学习的是第17页，共47页DIAGNOSIS HistoryClinical Symptoms and SignsAuxiliary Examinations18现在学习的是第18页，共47页DIAGNOSIS-History Elucidate the following:1.Medical and social history,including recent contact with patients with TB2.Negative history for Bacille Calmette-Guerin(BCG)vaccination3.History
17、of immunosuppression from a known disease or drug therapy19现在学习的是第19页，共47页DIAGNOSIS Symptoms and signs uA gradual onset uFever,headache,alternant of irritability and drowsiness,vomiting,constipation of unknown originuAltered mental status20现在学习的是第20页，共47页DIAGNOSIS Tuberculin Skin Test Purified prote
18、in derivative(PPD)1.Injected intradermally on the volar surface of the forearm2.Reaction peaks at 48 to 72 hours3.A nonreactive result does not exclude M.tuberculosis infection or disease,the tuberculin skin test is nonreactive in up to 50%of cases21现在学习的是第21页，共47页DIAGNOSIS Spinal Tap Cerebrospinal
19、Fluid1.Gross appearanceClear or slightly turbida fine clot resembling a pellicle or cobweb may form2.Cell counts,differential count50-500cells/mm3Lymphocytic predominancebut Polymorphonuclear cells may predominate early 3.GlucoseHypoglycorrhachia4.ProteinHigh protein level with 1-3g/L22现在学习的是第22页，共4
20、7页DIAGNOSIS Spinal Tap Cerebrospinal Fluid5.Chloridate：low 6.Acid-fast stain(+),Gram stain,India ink7.Culture for M tuberculosis(+)8.ELISA test for Specific PPD-IgM and PPD-IgG in CSF9.ELISA test for Specific TB-antigen in CSF is a sensitive and rapid method23现在学习的是第23页，共47页DIAGNOSIS Spinal Tap Cere
21、brospinal Fluid10.Total IgG,IgA and IgM11.PCR:specific PCR to detect the gene of M tuberculosis bacilli can provide a rapid and reliable diagnosis of TBM,although false-negative results potentially occur24现在学习的是第24页，共47页DIAGNOSIS Chest X-ray Chest x-ray:Posteroanterior and lateral views may reveal t
22、he followinglHilar lymphadenopathylSimple pneumonialInfiltratelPleural effusion/pleural scar25现在学习的是第25页，共47页DIAGNOSIS CT or MRIu CT scan and MRI of the brain reveal hydrocephalus,basilar meningeal thickening,infarcts,edema,and tuberculomas,all these are helpful clues,but nonspecificu MRI and CT sca
23、n lack specificity,but help in monitoring complications that require neurosurgery,making the differentiations,and knowing the prognosis26现在学习的是第26页，共47页DIFFERENTIAL DIAGNOSISuViral Meningocephalitisu Pyogenic Meningitisu CNS Cryptococcosis27现在学习的是第27页，共47页DIFFERENTIAL DIAGNOSISViral Meningocephaliti
24、s Mumps,polio,enteroviruses,Measles,Herpes viruses,EBV,and Japanese encephalitis virus,etcCSF examination is the most important test in differentiating the cause of meningitis:lClear appearancelCells:50-200 cells/mm3,Mononuclear cell predominancelProtein:slightly elevated or normal lGlucose and Chlo
25、ridate:normal 28现在学习的是第28页，共47页DIFFERENTIAL DIAGNOSISPyogenic MeningitisClinical manifestationAcute onset of intense headache,fever,nausea,vomiting,photophobia,and stiff neck Group B streptococci,Neisseria meningitidis,Streptococcus pneumoniae,Haemophilus influenzae,and Staph.aureus,etc.lPyogenic fo
26、ci located other sites of the hostlTypical rash of meningococcal infectionlExamination of CSF 29现在学习的是第29页，共47页DIFFERENTIAL DIAGNOSISPyogenic MeningitisTypical CSF abnormalities in meningitisinclude the following:Appearance is turbidPleocytosis of PMN(WBC counts always above 1000,even to a very high
27、 level as 10,000 cells/mm3,predominantly neutrophils)Decreased glucose concentrationIncreased protein concentration Gram stain and culture of CSF identify the etiological organism30现在学习的是第30页，共47页Brain surface(Pyogenic meningitis)31现在学习的是第31页，共47页TBM32现在学习的是第32页，共47页DIFFERENTIAL DIAGNOSISCNS Cryptoc
28、occosisuCryptococcosis is the most common fungal infection of the central nervous system uIt is the fourth most common cause of opportunistic infections in patients with AIDSuDisease onset is usually insidious and has a longer latent perioduFever always be absent at beginning of disease uVery notabl
29、e intracranial hypertension:severe headacheuVisual disturbances and papilledema are common33现在学习的是第33页，共47页DIFFERENTIAL DIAGNOSISCNS CryptococcosisCSFlAppearance can be clear or turbid.lProtein levels exceed lGlucose and ChloridatelMononuclear pleocytosis,numbers vary from 50 to 500 mononuclear cell
30、s/mm3.lIt is easy to get the positive result for C neoformans of CSFlIndia ink stain is positive CSF or serum cryptococcal antigen tests are positive34现在学习的是第34页，共47页Cryptococcus is a cause of meningitis,a common complication in AIDS.The organisms are usually easy to demonstrate histologically.In th
31、is slide they are the circular-to-ovoid structures with thick capsules.35现在学习的是第35页，共47页TREATMENTu Supportive treatment u Antituberculous drugsu Decreasing intracranial pressureu Corticosteriodsu Symptomatic treatmentu Follow-up visit 36现在学习的是第36页，共47页TREATMENTSupportive treatmentuBed rest and close
32、 respiratory contacts uNutritional support are paramount uKeep good hygiene for the coma children to prevent of secondary infections,help them to change position frequently to prevent decubitalu Management of electrolyte abnormalities uAntipyreticsuControl of seizures:Diazepam(Valium)37现在学习的是第37页，共4
33、7页TREATMENTAntituberculous drugsuisoniazid INH,rifampin RIF,pyrazinamide PZA,streptomycin SM,and sometimes ethambutol EMB.uINH and RIF are bactericidal for all M.tuberculosis population in any milieu.uSM is most effective against rapidly multiplying organisms.uPZA is most effective against organisms
34、 found in macrephages.uenter CSF readily in the presence of meningeal inflammation.38现在学习的是第38页，共47页TREATMENTAntituberculous drugsu Any regimen must contain multiple drugsu In addition,the therapy must be taken regularly and continued for a sufficient period.39现在学习的是第39页，共47页TREATMENTAntituberculous
35、 drugs1.intensification chemotherapy stage:3-4 months INH(15-25mg/kg),RFP,PZA,SM2.consolidation chemotherapy stage:with total course 1 year at least in order to prevent relapse,permit elimination organisms persistent exist in the host INH,RFP or EMB(ethambutol)40现在学习的是第40页，共47页TREATMENT Decreasing i
36、ntracranial pressureuDehydrant:Mannitol(MNT)uDiuretic agent:Acetazolamide Decreasing CSF secretion by the choroid plexus uVentricular tap or Open ventricular drainage uRepeat LPs and intrathecal injectionuShunting:to establish a communication between the CSF(ventricular or lumbar)and a drainage cavi
37、ty.Performed only in cases of communicating hydrocephalus.Ventricular shunt to cisterna magna41现在学习的是第41页，共47页TREATMENTCorticosteriodsu Children should be treated for 6-8 weeks u More effective in early stageu Decrease the immflamatory exudates,there fore lower the intracranial pressure.Relieve the
38、meningeal irritation.Improve the CSF circulation Reduce the adherence and prevent the hydrocephalus.u Dexamethasoneu pay attention to the side effects of corticosteriods42现在学习的是第42页，共47页Criteria for RecoveryFollow-up visit u Disappearance of all clinical manifestationsu CSF examination is normalu No
39、 relapse within 2 years after completion of antituberculosis treatment43现在学习的是第43页，共47页Which symptom should be excluded in the early stage of TBM?a)Drowsinessb)Low fever,night sweat,poor appetite,loss of weightc)Personality changesd)Headachee)Recurrent convulsion 44现在学习的是第44页，共47页A baby who was defi
40、nited as TBM when he was 1 years old and began to receive regular treatment with antituberculosis drugs.How old is he when he can be definited as full recovery?a)11/2 yb)2 yc)21/2 yd)3 ye)4 y 45现在学习的是第45页，共47页Which one is the typically cellular characteristics of CSF in TBM?a)50-500 cells/mm3,with neutrophils predominanceb)50-500 cells/mm3,with mononuclear predominancec)0-50 cells/mm3,with mononuclear predominanced)1000,sometimes can above 10,000 with neutrophil predominancee)0-50cells/mm3 with neutrophils predominance46现在学习的是第46页，共47页THNAK YOU!47现在学习的是第47页，共47页