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Tuberculous Meningitis

CHCUMSCHCUMS

DIVISION OF INFECTIOUS DISEASE AND DIVISION OF INFECTIOUS DISEASE AND GASTROENTEROLOGYGASTROENTEROLOGY

November 24th, 2004

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EPIDEMIOLOGY - TBM

Tuberculous Meningitis (TBM) The younger the children, the more

readily to develop TBM. 60% in Children aged 1-3 years Death rate: 15-30%

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TBM (Tuberculous meningitis)

TBM is the most serious complication of tuberculosis in children and is usually fatal without treatment.

TBM always be a part of systemic disseminated tuberculosis.

TBM often occurs within 1 year of initial infection, especially in the first 2 to 6 months of infection.

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Tuberculous Bacilli

Primary Complex

Bacteremia

Rich Foci

Subarachnoid Space

Brain or Spinal Cord PerenchymaTuberculom

as

Meningitis

PATHOPHYSIOLOGY

Trauma/Diseases measles, pertussis

Miliary TB

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PATHOLOGICAL EFFECTS

Meninges Diffuse Hyperemia Edema Inflammatory Exudates Conformation of Tubercles

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PATHOLOGICAL EFFECTS

Subarachnoid SpaceA large amount of thick gelatinous

exudates concentrate to the pavimentum cerebri, optic chiasma, bridge of varolius, bulbus rhachidicus and Sylvian fissure.

Basal meningitis accounts for the frequent dysfunction of cranial nerves III, VI, and VII.

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PATHOLOGICAL EFFECTS

Cerebral ParenchymaTuberculous meningoencephalitis swelling and 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.

Meninges, spinal, and spinal nerve root also involvement. The later always leads to paraplegina.

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PATHOLOGICAL EFFECTS

Cerebral VesselsThe bacteria invade the adventitia directly in

the early stage and initiate the process of acute vasculitis.

Progressive destruction of adventitia, disruption of elastic fibers, and finally intimal destruction (endoarteritis), lead to the obliterative vasculitis, which may facilitate the ischemia, encephalomalacia and necrosis of parenchyma.

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Circulation of CSFChoroid plexus

Lateral ventricle

Interventricular foramen

the 3rd ventricle

Cerebral aqueduct

4th ventricle

2 Lateral foramina

1 Medial foramen

Subarachnoid space

Arachnoid granulations

Dural sinus

Venous drainage

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PATHOLOGICAL EFFECTSHydrocephalus

Hyperemia of choroids overproduction of CSF

Inflammatory adherence of

Meninge

defective absorption of CSF

Communicating hydrocephalus

CSF flow is obstructed on the route before the cerebral aqueduct and the

4th ventricle

Noncommunicating hydrocephalus

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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.

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CLINICAL MANIFESTIONS

A. Prodrome (1-2 week)

1. Fever, fatigue, malaise, myalgia, drowsiness, headache, vomiting

2. Mental status changes

3. Focal neurologic signs are absent

4. CSF abnormity

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CLINICAL MANIFESTIONS

B. 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 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 impairment

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CLINICAL MANIFESTIONS

C. Coma Stage (1-3 week)1. Frequent convulsion, progressive altered

state of consciousness: lethargy, confusion, semicoma, deep coma, decerebrate or decorticate posturing

2. Depletion: extremely maransis, constipation, urinary retention

3. progressive abnormalities of vital signs, and eventual die from cerebral hernia

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Characteristics of TBM in infants and young children

1. A rapid onset with convulsion, abruptly high fever

2. Atypical miningeal irritation3. Intracranial hypertension

manifests as bulging of anterior fontanelle and widening of cranial sutures in infant

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PROGNOSIS

The prognosis of tuberculous meningitis correlates most closely with the clinical stage of diagnosis and treatment.

Age: infants or younger children are generally worse than that of older children

Drug resistant strain Variation of host immunity Appropriate therapeutic regimen Completion of the antituberculor agent regimen

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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.

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DIAGNOSIS

History Clinical Symptoms and Signs Auxiliary Examinations

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DIAGNOSIS - History

Elucidate the following:1. Medical and social history, including

recent contact with patients with TB

2. Negative history for Bacille Calmette-Guerin (BCG) vaccination

3. History of immunosuppression from a known disease or drug therapy

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DIAGNOSIS – Symptoms and signs

A gradual onset Fever, headache, alternant of irritability and

drowsiness, vomiting, constipation of

unknown origin Altered mental status

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DIAGNOSIS – Tuberculin Skin Test

Purified protein derivative (PPD)1. Injected intradermally on the volar

surface of the forearm

2. Reaction peaks at 48 to 72 hours

3. A nonreactive result does not exclude M. tuberculosis infection or disease, the tuberculin skin test is nonreactive in up to 50% of cases

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DIAGNOSIS – Spinal Tap

Cerebrospinal Fluid1. Gross appearanceClear or slightly turbida fine clot resembling a pellicle or cobweb may form

2. Cell counts, differential count50-500cells/mm3

Lymphocytic predominancebut Polymorphonuclear cells may predominate early

3. GlucoseHypoglycorrhachia

4. ProteinHigh protein level with 1-3g/L

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DIAGNOSIS – Spinal Tap

Cerebrospinal Fluid5. Chloridate ： low

6. Acid-fast stain (+), Gram stain, India ink

7. Culture for M tuberculosis (+)

8. ELISA test for Specific PPD-IgM and PPD-IgG in CSF

9. ELISA test for Specific TB-antigen in CSF is a sensitive and rapid method

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DIAGNOSIS – Spinal Tap

Cerebrospinal Fluid10. Total IgG, IgA and IgM

11. 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

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DIAGNOSIS – Chest X-ray

Chest x-ray: Posteroanterior and lateral views may reveal the followingHilar lymphadenopathySimple pneumoniaInfiltratePleural effusion/pleural scar

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DIAGNOSIS – CT or MRI

CT scan and MRI of the brain reveal hydrocephalus, basilar meningeal thickening, infarcts, edema, and tuberculomas, all these are helpful clues, but nonspecific

MRI and CT scan lack specificity, but help in monitoring complications that require neurosurgery, making the differentiations, and knowing the prognosis

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DIFFERENTIAL DIAGNOSIS

Viral Meningocephalitis Pyogenic Meningitis CNS Cryptococcosis

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DIFFERENTIAL DIAGNOSIS

Viral Meningocephalitis Mumps, polio, enteroviruses, Measles, Herpes

viruses, EBV, and Japanese encephalitis virus, etc

CSF examination is the most important test in differentiating the cause of meningitis:

Clear appearance

Cells: 50 -200 cells/mm3 , Mononuclear cell predominance

Protein: slightly elevated or normal Glucose and Chloridate : normal

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DIFFERENTIAL DIAGNOSIS

Pyogenic 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.

Pyogenic foci located other sites of the hostTypical rash of meningococcal infectionExamination of CSF

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DIFFERENTIAL DIAGNOSIS

Pyogenic MeningitisTypical CSF abnormalities in meningitis

include the following:• Appearance is turbid• Pleocytosis of PMN ( WBC counts always above

1000, even 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

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Brain surface (Pyogenic meningitis )

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TBM

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DIFFERENTIAL DIAGNOSIS

CNS CryptococcosisCryptococcosis is the most common fungal

infection of the central nervous system It is the fourth most common cause of

opportunistic infections in patients with AIDSDisease onset is usually insidious and has a

longer latent periodFever always be absent at beginning of disease Very notable intracranial hypertension: severe

headacheVisual disturbances and papilledema are

common

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DIFFERENTIAL DIAGNOSIS

CNS CryptococcosisCSF

Appearance can be clear or turbid.Protein levels exceed Glucose and ChloridateMononuclear pleocytosis , numbers vary from

50 to 500 mononuclear cells/mm3.It is easy to get the positive result for C

neoformans of CSFIndia ink stain is positive CSF or serum

cryptococcal antigen tests are positive

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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.

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TREATMENT

Supportive treatment Antituberculous drugs Decreasing intracranial pressure Corticosteriods Symptomatic treatment Follow-up visit

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TREATMENT

Supportive treatmentBed rest and close respiratory contacts Nutritional support are paramount Keep good hygiene for the coma children to

prevent of secondary infections, help them to change position frequently to prevent decubital

Management of electrolyte abnormalities AntipyreticsControl of seizures: Diazepam (Valium)

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TREATMENT

Antituberculous drugs isoniazid INH, rifampin RIF, pyrazinamide

PZA, streptomycin SM, and sometimes ethambutol EMB.

INH and RIF are bactericidal for all M. tuberculosis population in any milieu.

SM is most effective against rapidly multiplying organisms.

PZA is most effective against organisms found in macrephages.

enter CSF readily in the presence of meningeal inflammation.

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TREATMENT

Antituberculous drugs Any regimen must contain multiple

drugs In addition, the therapy must be taken

regularly and continued for a sufficient period.

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TREATMENT

Antituberculous 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)

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TREATMENT

Decreasing intracranial pressure Dehydrant: Mannitol (MNT) Diuretic agent: Acetazolamide Decreasing CSF secretion by the choroid plexus Ventricular tap or Open ventricular drainage Repeat LPs and intrathecal injection Shunting: 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

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TREATMENT

Corticosteriods Children should be treated for 6-8 weeks More effective in early stage 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.

Dexamethasone pay attention to the side effects of corticosteriods

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Criteria for Recovery

Follow-up visit Disappearance of all

clinical manifestations CSF examination is

normal No relapse within 2

years after completion of antituberculosis treatment

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Which symptom should be excluded in the early stage of TBM?

a) Drowsiness

b) Low fever, night sweat, poor appetite, loss of weight

c) Personality changes

d) Headache

e) Recurrent convulsion

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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 definited as full recovery?

a) 11/2 y

b) 2 y

c) 21/2 y

d) 3 y

e) 4 y

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Which one is the typically cellular characteristics of CSF in TBM?

a) 50-500 cells/mm3, with neutrophils predominance

b) 50-500 cells/mm3, with mononuclear predominance

c) 0-50 cells/mm3,with mononuclear predominance

d) >1000, sometimes can above 10,000 with neutrophil predominance

e) 0-50cells/mm3 with neutrophils predominance

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THNAK YOU !