Tuberculous meningitis

Epidemiology
1. 0.3% of untreated primary TB in children
2. Age: 6 mo to 4
3. Sex equal; more male in adult TBM
4. Asian and black population
5. Risk factors:
1. HIV co-infection
2. Malnutrition
3. Corticosteroid therapy
4. Pertusis
5. Measles
 Mode of meningeal Infection
I. Tuberculous meningitis (TBM) develops in 2 steps.
1. Mycobacterium tuberculosis bacilli enter the host by
droplet inhalation. Localized infection escalates within the
lungs, with dissemination to the regional lymph nodes
Bacilli seed to the meninges or brain parenchyma,
resulting in the formation of small subpial or
subependymal foci of metastatic caseous lesions, termed
Rich foci.
2. Tubercles rupturing into the subarachnoid space cause
meningitis.
2. It can occur as part of miliary TB
Time line
 Pathogenesis
1. The lesion increase in size and discharge bacilli into
subarachnoid space
2. Exudate is formed in subarachnoid space
3. Inflammatory changes produce vasculitis of cortical
and meningeal blood vessels
4. Vascular obstruction produce cerebral infarctions
5. Brain stem inflammation and infarctions lead to
cranial nerve III, VI, and VII lesions
6. CSF flow is obstructed at the level of basilar cistern
leading to communicating hydrocephalus
 Pathology
1. Crebral Vasculitis
2. Cerebral Infarction
3. Cerebral edema
4. Iappropriate ADH secretion
5. Cranial nerve palsies: The brainstem is often the site of
greatest involvement, associated dysfunction of cranial
nerves III, VI, and VII.
6. Hydrocephalus: The exudate also interferes with the
normal flow of cerebrospinal fluid (CSF) in and out of
the ventricular system at the level of the basilar
cisterns, leading to a communicating hydrocephalus
7. Optic atrophy
 Clinical
• Progression
– Rapid : several days
– Gradual: several weeks
 Slow progression (common)
1. Stage I:
1. Lasts for 1-2 weeks
2. Non specific symptoms:
Fever, headache, irritability, drowziness, malaise
3. Milestones stagnate or lost
4. No focal signs
2. Stage II:
1. Abrupt onset
2. Lethargy, neck stiffness, seizures
3. Hypertonia
4. Vomiting
5. Cranial nerve palsies
6. Focal neurological deficits
7. Kernig and Brudzinski signs become positive
8. Hydrocephalus
9. Cerebral edema and increased ICT
10. Encephalitis like illness with lees meningeal
signs:
1. Marked disorientation
2. Lack of movements
3. Loss of speech
 Stage III
1. Coma
2. Hemiplegia /paraplegia
3. Hypertension due to hypothalamic
involvement
4. Decerebrate posturing
5. Irregular respiration
6. Death
Data from ICH
 Ocular involvement in TBM
1. Papilledema
2. primary optic atrophy
3. chorioretinitis,
4. optic neuritis,
5. internuclear ophthalmoplegia,
6. Choroid tubercles.
 Prognosis
1. Fatal without treatment
2. Worse prognosis in younger age group
3. Treatment in stage I: may show good recovery
4. Treatment in stage III: survives with permanent
disabilities:
1. Blindness
2. Deafness
3. Paraplegia
4. Diabetes insipitus
5. Mental retardation
6. Epilepsy
7. Hydrocephalus
 Diagnosis
• H/o contact with open PT
• In 50% Mantoux is negative
• In 20-50% CXR is normal
• Lumbar CSF: (Ventricular CSF may be normal)
1. Leukocytes: 10-500 cells/dL; Neutrophils initial stage;
later predominantly lymphocytes
2. Glucose < 40 mg/dL
3. Protein: 400-500 mg/dL (web formation) partly due to
CSF block
4. AFP positive in 30%
5. Culture positive in 50-70%
6. CSF pressure is increased
 Normal CSF
• colour: Clear
• Glucose: 60% of blood level
• Protein: 20-45 mg/dl
• Chloride: 116-122
• Pressure: 100-200 mm of water
• Cells: < 5 lymp

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 CSF in meningitis
1. Bacterial
– Cells: 200-2000 WBC/uL (PMN)
– Protein: >130 mg/dl
– Glucose: <2.5 mmol/L
2. Viral
– Cells: 0-200 WBC/uL (LYM)
– Protein: <40 mg/dl
– Glucose: 2.5-3.6 mmol/L
3. TBM
– Cells: >100 lymphocytes
– Protein >> 100 mg/dl
– Glucose > 2.5 mmol/dl
– Cob web AFB
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 Investications
Mantoux skin test
• Basis: Delayed cellular
hypersensitivity

• 0.1 ml intradermal

• 5 TU of PPD Tween 80

• Read after 48-72 hrs

• Early reaction not positive

• Delayed reaction is positive

 Mantoux
False positive: False Negative:
• Non tuberculous mycobacteria
• Anergy
• BCG ( up to 5 yrs; <10 mm)
• Infant
• Malnutrition
• Suppressed immunity
• Vaccine: Measles; MMR
• Measles infection
• Miliary TB
• Technical error
 Mantoux reading
positive reaction
I. Contact history Symptoms of PC

HIV

Immuno supression > 5 mm

II. High prevalence area >10 mm

III. Low prevalence area > 15 mm

IV. Recent Mx conversion >10 mm

V. Serial Mantoux: becomes positive

 CT brain
• Normal in early phase
• Cerebral edema
• Communicating
hydrocephalus
• Focal ischemia
• Tuberculoma
 MRI
• T2-weighted magnetic
resonance image of a
biopsy-proven, right
parietal tuberculoma.
Note the low–signal-
intensity rim of the
lesion and the
surrounding
hyperintense vasogenic
edema
 Bacterial isolation and culture

• Gastric aspirate- 3 consecutive morning

samples

• Bronchoscopy

• Negative culture and smear do not rule out TB

 AFB
Ziehl-Neelsen stain
• Heat fix
• Smear with carbol fuchsin
• Steam – 5 mts
• Rinse
• Add 3% acid – alcohol - 5
minutes
• Rinse
• Methylene blue-1 mt
• Rinse
• Dry
• Bright red purple bacilli
 Auramine-rhodamine florescent stain.

• Requires a fluorescent
microscope.
• The fluorochrome dyes
used
• The fluorescing
mycobacteria are seen
as bright yellow-orange
bacilli against a dark
background.
 Culture
Lowenstein-Jensen medium

• Egg medium

• glycerol enhances the growth of

M.tuberculosis

• also used in drug susceptibility

testing

• > 3 weeks for growth

• > 4 weeks for sensitivity

• rough, tough and buff colonies

CXR
Miliary TB
Calcified hilar adenitis
 Other tests

• Interferon release by T cells towards MT

antigens
• Quantiferon TB c-gold

• T Spot- TB

• Elispot (elliza identifies T cells specific for TB)

 TB & HIV
• 30% more in HIV
• Mx – ve
• Rapid progression
• Lymphocytosis favours viral replication-vicious
cycle
• Rifampicin toxicity increased by ART
 DD
• Viral encephalitis
• Encephalopathy
• Bacterial meningitis
• Status epilepticus
• Cerebral abscess
 Treatment
• INH, Rifampicin and pyrazinamide for 2 months
• INH, Rifampicin for next 7-12 months
• MDR TB:
• Add ehtambutol and SM
• Corticosteroids: prednisolone 1 mg/kg for 6-8
weeks
• Reduce inflammation
• Reduce ICT
• Improves vision in optic atrophy
 Prevention
BCG
• Bacille Calmette-guerin
• Live Attenuated bovine TB bacilli
• .5 ml intradermal
• 50% effective in PT
• 80% protective in CNS TB
• No protection for adults as effect wanes after 5 years
• Contraindicated in symptomatic HIV
• Also used for diagnosis