1、 1Tuberculous MeningitisNovember 24th,2004 2EPIDEMIOLOGY-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%3TBM(Tuberculous meningitis)u TBM is the most serious complication of tuberculosis in children and is u
2、sually fatal 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.4Tuberculous BacilliPrimary ComplexBacteremiaRich FociSubarachnoid SpaceBrain or Spinal Cord Perenchyma
3、TuberculomasMeningitisPATHOPHYSIOLOGYTrauma/Diseases measles,pertussis Miliary TB 5PATHOLOGICAL EFFECTSMeningesuDiffuse HyperemiauEdemauInflammatory Exudates uConformation of Tubercles 6PATHOLOGICAL EFFECTSSubarachnoid SpaceuA large amount of thick gelatinous exudates concentrate to the pavimentum c
4、erebri,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.7PATHOLOGICAL EFFECTSCerebral ParenchymaTuberculous meningoencephalitisuswelling and hyperemia of the parenchyma contribute to the
5、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.8PATHOLOGICAL EFFECTSCerebral VesselsuT
6、he 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,which may facilitate the ischemia,encephal
7、omalacia and necrosis of parenchyma.9Circulation of CSFChoroid plexusLateral ventricleInterventricular foramenthe 3rd ventricleCerebral aqueduct4th ventricle2 Lateral foramina1 Medial foramenSubarachnoid spaceArachnoid granulationsDural sinusVenous drainage 10PATHOLOGICAL EFFECTSHydrocephalusHyperem
8、ia 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 hydrocephalus 11In tuberculous meningitis there is a tendency for the e
9、xudate to be primarily located on the under surface of the brain,particularly over the ventral surface of the brain stem.12CLINICAL MANIFESTIONS A.Prodrome(1-2 week)1.Fever,fatigue,malaise,myalgia,drowsiness,headache,vomiting2.Mental status changes3.Focal neurologic signs are absent4.CSF abnormity 1
10、3CLINICAL MANIFESTIONSB.Meningeal Irritation Stage (1-2 week)1.More serious TB toxic symptoms2.Intracranial hypertension:severe headache,irritation,projectile vomiting,seizures;Bulging of anterior fontanelle,widening of cranial sutures in infant 3.Meningeal Irritation:nuchal rigidity,hypertonia Kern
11、ig 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 impairment 14CLINICAL MANIFESTIONSC.Coma Stage(1-3 week)1.Frequent convulsion,progressive altered sta
12、te of consciousness:lethargy,confusion,semicoma,deep coma,decerebrate or decorticate posturing2.Depletion:extremely maransis,constipation,urinary retention 3.progressive abnormalities of vital signs,and eventual die from cerebral hernia 15Characteristics of TBM in infants and young children1.A rapid
13、 onset with convulsion,abruptly high fever2.Atypical miningeal irritation3.Intracranial hypertension manifests as bulging of anterior fontanelle and widening of cranial sutures in infant 16PROGNOSISu The prognosis of tuberculous meningitis correlates most closely with the clinical stage of diagnosis
14、 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 therapeutic regimenu Completion of the antituberculor agent regimen 17It is imperative that antituberculosis treatment be considered for a
15、ny child who develops basilar meningitis and hydrocephalus,cranial nerve palsy,or stroke with no other apparent etiology.18DIAGNOSIS History Clinical Symptoms and Signs Auxiliary Examinations 19DIAGNOSIS-History Elucidate the following:1.Medical and social history,including recent contact with patie
16、nts with TB2.Negative history for Bacille Calmette-Guerin(BCG)vaccination3.History of immunosuppression from a known disease or drug therapy 20DIAGNOSIS Symptoms and signs uA gradual onset uFever,headache,alternant of irritability and drowsiness,vomiting,constipation of unknown originuAltered mental
17、 status 21DIAGNOSIS Tuberculin Skin Test Purified protein 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 ca
18、ses 22DIAGNOSIS Spinal Tap Cerebrospinal 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
19、 protein level with 1-3g/L 23DIAGNOSIS 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 method 24DIAGNOSIS Sp
20、inal Tap Cerebrospinal 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 occur 25DIAGNOSIS Chest X-ray Chest x-ray:Posteroanterior and lateral views may reveal th
21、e followinglHilar lymphadenopathylSimple pneumonialInfiltratelPleural effusion/pleural scar 26DIAGNOSIS 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 specific
22、ity,but help in monitoring complications that require neurosurgery,making the differentiations,and knowing the prognosis 27DIFFERENTIAL DIAGNOSISuViral Meningocephalitisu Pyogenic Meningitisu CNS Cryptococcosis 28DIFFERENTIAL DIAGNOSISViral Meningocephalitis Mumps,polio,enteroviruses,Measles,Herpes
23、viruses,EBV,and Japanese encephalitis virus,etcCSF examination is the most important test CSF examination is the most important test in differentiating the cause of meningitis:in differentiating the cause of meningitis:lClear appearancelCells:50-200 cells/mm3,Mononuclear cell predominancelProtein:sl
24、ightly elevated or normal lGlucose and Chloridate:normal 29DIFFERENTIAL DIAGNOSISPyogenic MeningitisClinical manifestationAcute onset of intense headache,fever,nausea,vomiting,photophobia,and stiff neck Group B streptococci,Neisseria meningitidis,Streptococcus pneumoniae,Haemophilus influenzae,and S
25、taph.aureus,etc.lPyogenic foci located other sites of the hostlTypical rash of meningococcal infectionlExamination of CSF 30DIFFERENTIAL DIAGNOSISPyogenic MeningitisTypical CSF abnormalities in meningitisinclude the following:Appearance is turbid Pleocytosis of PMN(WBC counts always above 1000,even
26、to a very high level as 10,000 cells/mm3,predominantly neutrophils)Decreased glucose concentration Increased protein concentration Gram stain and culture of CSF identify the etiological organism 31Brain surface(Pyogenic meningitis)32TBM 33DIFFERENTIAL DIAGNOSISCNS CNS CryptococcosisCryptococcosisuCr
27、yptococcosis 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 notable intracra
28、nial hypertension:severe headacheuVisual disturbances and papilledema are common 34DIFFERENTIAL DIAGNOSISCNS CNS CryptococcosisCryptococcosisCSFlAppearance can be clear or turbid.lProtein levels exceed lGlucose and ChloridatelMononuclear pleocytosis,numbers vary from 50 to 500 mononuclear cells/mm3.
29、lIt is easy to get the positive result for C neoformans of CSFlIndia ink stain is positive CSF or serum cryptococcal antigen tests are positive 35Cryptococcus is a cause of meningitis,a common complication in AIDS.The organisms are usually easy to demonstrate histologically.In this slide they are th
30、e circular-to-ovoid structures with thick capsules.36TREATMENTu Supportive treatment u Antituberculous drugsu Decreasing intracranial pressureu Corticosteriodsu Symptomatic treatmentu Follow-up visit 37TREATMENTSupportive treatmentuBed rest and close respiratory contacts uNutritional support are par
31、amount 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)38TREATMENTAntituberculous drugsuisoniazid INH,rifampin RIF,pyraz
32、inamide 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 found in macrephages.uenter CSF readily in the presence of menin
33、geal inflammation.39TREATMENTAntituberculous drugsu Any regimen must contain multiple drugsu In addition,the therapy must be taken regularly and continued for a sufficient period.40TREATMENTAntituberculous drugs1.intensification chemotherapy stage:3-4 months INH(15-25mg/kg),RFP,PZA,SM2.consolidation
34、 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)41TREATMENT Decreasing intracranial pressureuDehydrant:Mannitol(MNT)uDiuretic agent:Acetazolamide Decreasing CSF secretion by the chor
35、oid 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 cavity.Performed only in cases of communicating hydrocephalus.Ventricular shunt to cisterna magna 42TREATMENTCorti
36、costeriodsu 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 att
37、ention to the side effects of corticosteriods 43Criteria for RecoveryFollow-up visitFollow-up visit u Disappearance of all clinical manifestationsu CSF examination is normalu No relapse within 2 years after completion of antituberculosis treatment 44Which symptom should be excluded in the early stag
38、e of TBM?a)Drowsinessb)Low fever,night sweat,poor appetite,loss of weightc)Personality changesd)Headachee)Recurrent convulsion 45A 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 definited as full r
39、ecovery?a)11/2 yb)2 yc)21/2 yd)3 ye)4 y 46Which 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 predominance 47THNAK YOU!
