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1、结核性脑膜炎英文第1页，本讲稿共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第2页，本讲稿共47页TBM(Tuberculous meningitis)u TBM is the most serious complication of tuberculosis in children and is usually fatal w
2、ithout 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第3页，本讲稿共47页Tuberculous BacilliPrimary ComplexBacteremiaRich FociSubarachnoid SpaceBrain or Spinal Cord PerenchymaTub
3、erculomasMeningitisPATHOPHYSIOLOGYTrauma/Diseases measles,pertussis Miliary TB4第4页，本讲稿共47页PATHOLOGICAL EFFECTSMeningesuDiffuse HyperemiauEdemauInflammatory Exudates uConformation of Tubercles 5第5页，本讲稿共47页PATHOLOGICAL EFFECTSSubarachnoid SpaceuA large amount of thick gelatinous exudates concentrate t
4、o 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第6页，本讲稿共47页PATHOLOGICAL EFFECTSCerebral ParenchymaTuberculous meningoencephalitisuswelling and hyperemia of the
5、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 paraplegina.7第7页，本讲稿共4
6、7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 obliterative vasculitis,wh
7、ich may facilitate the ischemia,encephalomalacia and necrosis of parenchyma.8第8页，本讲稿共47页Circulation of CSFChoroid plexusLateral ventricleInterventricular foramenthe 3rd ventricleCerebral aqueduct4th ventricle2 Lateral foramina1 Medial foramenSubarachnoid spaceArachnoid granulationsDural sinusVenous
8、drainage9第9页，本讲稿共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 ventricleNoncommunicating hydrocephal
9、us10第10页，本讲稿共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第11页，本讲稿共47页CLINICAL MANIFESTIONS A.Prodrome(1-2 week)1.Fever,fatigue,malaise,myalgia,drowsiness,headache,
10、vomiting2.Mental status changes3.Focal neurologic signs are absent4.CSF abnormity 12第12页，本讲稿共47页CLINICAL MANIFESTIONSB.Meningeal Irritation Stage (1-2 week)1.More serious TB toxic symptoms2.Intracranial hypertension:severe headache,irritation,projectile vomiting,seizures;Bulging of anterior fontanel
11、le,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,abnormal movements and speech impair
12、ment 13第13页，本讲稿共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 retention 3.progressive abnormalities of vital
13、signs,and eventual die from cerebral hernia 14第14页，本讲稿共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 fontanelle and widening of cranial sutures in i
14、nfant 15第15页，本讲稿共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 Variation of host immunityu Appropriate therape
15、utic regimenu Completion of the antituberculor agent regimen16第16页，本讲稿共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 apparent etiology.17第17页，本讲稿共47页DIAGNOSIS HistoryClinic
16、al Symptoms and SignsAuxiliary Examinations18第18页，本讲稿共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 of immunosuppression from a known disease or drug ther
17、apy19第19页，本讲稿共47页DIAGNOSIS Symptoms and signs uA gradual onset uFever,headache,alternant of irritability and drowsiness,vomiting,constipation of unknown originuAltered mental status20第20页，本讲稿共47页DIAGNOSIS Tuberculin Skin Test Purified protein derivative(PPD)1.Injected intradermally on the volar surf
18、ace 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第21页，本讲稿共47页DIAGNOSIS Spinal Tap Cerebrospinal Fluid1.Gross appearanceClear or slightly turbida fine clot rese
19、mbling 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第22页，本讲稿共47页DIAGNOSIS Spinal Tap Cerebrospinal Fluid5.Chloridate：low 6.Acid-
20、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第23页，本讲稿共47页DIAGNOSIS Spinal Tap Cerebrospinal Fluid10.Total IgG,IgA and IgM11.PCR:specific PCR to detect
21、the gene of M tuberculosis bacilli can provide a rapid and reliable diagnosis of TBM,although false-negative results potentially occur24第24页，本讲稿共47页DIAGNOSIS Chest X-ray Chest x-ray:Posteroanterior and lateral views may reveal the followinglHilar lymphadenopathylSimple pneumonialInfiltratelPleural e
22、ffusion/pleural scar25第25页，本讲稿共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 scan lack specificity,but help in monitoring complications that require neuros
23、urgery,making the differentiations,and knowing the prognosis26第26页，本讲稿共47页DIFFERENTIAL DIAGNOSISuViral Meningocephalitisu Pyogenic Meningitisu CNS Cryptococcosis27第27页，本讲稿共47页DIFFERENTIAL DIAGNOSISViral Meningocephalitis Mumps,polio,enteroviruses,Measles,Herpes viruses,EBV,and Japanese encephalitis
24、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 Chloridate:normal 28第28页，本讲稿共47页DIFFERENTIAL DIAGNOSISPyogenic MeningitisClinical man
25、ifestationAcute 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 foci located other sites of the hostlTypical rash of meningococcal infectionlExaminati
26、on of CSF 29第29页，本讲稿共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 level as 10,000 cells/mm3,predominantly neutrophils)Decreased glucose concentrationInc
27、reased protein concentration Gram stain and culture of CSF identify the etiological organism30第30页，本讲稿共47页Brain surface(Pyogenic meningitis)31第31页，本讲稿共47页TBM32第32页，本讲稿共47页DIFFERENTIAL DIAGNOSISCNS CryptococcosisuCryptococcosis is the most common fungal infection of the central nervous system uIt is
28、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 notable intracranial hypertension:severe headacheuVisual disturbances and papilledema are common33第33页
29、，本讲稿共47页DIFFERENTIAL DIAGNOSISCNS CryptococcosisCSFlAppearance can be clear or turbid.lProtein levels exceed lGlucose and ChloridatelMononuclear pleocytosis,numbers vary from 50 to 500 mononuclear cells/mm3.lIt is easy to get the positive result for C neoformans of CSFlIndia ink stain is positive CS
30、F or serum cryptococcal antigen tests are positive34第34页，本讲稿共47页Cryptococcus is a cause of meningitis,a common complication in AIDS.The organisms are usually easy to demonstrate histologically.In this slide they are the circular-to-ovoid structures with thick capsules.35第35页，本讲稿共47页TREATMENTu Suppor
31、tive treatment u Antituberculous drugsu Decreasing intracranial pressureu Corticosteriodsu Symptomatic treatmentu Follow-up visit 36第36页，本讲稿共47页TREATMENTSupportive treatmentuBed rest and close respiratory contacts uNutritional support are paramount uKeep good hygiene for the coma children to prevent
32、 of secondary infections,help them to change position frequently to prevent decubitalu Management of electrolyte abnormalities uAntipyreticsuControl of seizures:Diazepam(Valium)37第37页，本讲稿共47页TREATMENTAntituberculous drugsuisoniazid INH,rifampin RIF,pyrazinamide PZA,streptomycin SM,and sometimes etha
33、mbutol 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 found in macrephages.uenter CSF readily in the presence of meningeal inflammation.38第38页，本讲稿共47页TREATMENTAntit
34、uberculous drugsu Any regimen must contain multiple drugsu In addition,the therapy must be taken regularly and continued for a sufficient period.39第39页，本讲稿共47页TREATMENTAntituberculous drugs1.intensification chemotherapy stage:3-4 months INH(15-25mg/kg),RFP,PZA,SM2.consolidation chemotherapy stage:wi
35、th 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第40页，本讲稿共47页TREATMENT Decreasing intracranial pressureuDehydrant:Mannitol(MNT)uDiuretic agent:Acetazolamide Decreasing CSF secretion by the choroid plexus
36、 uVentricular tap or Open ventricular drainage uRepeat LPs and intrathecal injectionuShunting:to establish a communication between the CSF(ventricular or lumbar)and a drainage cavity.Performed only in cases of communicating hydrocephalus.Ventricular shunt to cisterna magna41第41页，本讲稿共47页TREATMENTCort
37、icosteriodsu 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 meningeal irritation.Improve the CSF circulation Reduce the adherence and prevent the hydrocephalus.u Dexamethasoneu pay at
38、tention to the side effects of corticosteriods42第42页，本讲稿共47页Criteria for RecoveryFollow-up visit u Disappearance of all clinical manifestationsu CSF examination is normalu No relapse within 2 years after completion of antituberculosis treatment43第43页，本讲稿共47页Which symptom should be excluded in the ea
39、rly stage of TBM?a)Drowsinessb)Low fever,night sweat,poor appetite,loss of weightc)Personality changesd)Headachee)Recurrent convulsion 44第44页，本讲稿共47页A baby who was definited 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
40、 definited as full recovery?a)11/2 yb)2 yc)21/2 yd)3 ye)4 y 45第45页，本讲稿共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第46页，本讲稿共47页THNAK YOU!47第47页，本讲稿共47页