Tuberculous Meningitis - CTEC

C - Clinical Features

Presentation

• Lethargy, confusion, malaise (early)
• Cranial nerve palsies in ~20% - most commonly III, IV, VI (ocular palsies); less often VII (facial), VIII (deafness)
• Papilledema - due to raised ICP
• Seizures - especially in children; may be the presenting feature in infants
• Focal neurologic deficits - from vasculitis causing hemorrhagic infarction (Circle of Willis or primary branches)
• Hypothermia and hyponatremia - documented additional features

CSF Findings

Diagnosis

• AFB smear: sensitivity 10-50%; multiple large-volume LPs improve yield
• Culture: gold standard but slow (weeks); rapid culture techniques available (< 1 week)
• PCR (NAAT): sensitivity ~80%, 10% false-positive rate; multiplex PCR is significantly more sensitive
• Adenosine deaminase (ADA): significantly elevated in TBM vs. other types
• Dot-ELISA (antigen/antibody in CSF): positive in ~86% of suspected TBM cases
• Imaging (CT/MRI):
  • Basal meningeal enhancement (gadolinium)
  • Hydrocephalus
  • Cerebral infarcts (deep, from Circle of Willis involvement)
  • Tuberculomas (2-12 mm, ring-enhancing)
  • CT may be normal in 30% of mild disease

CT normal in 30% of mild cases - do not rely on imaging to exclude TBM

MRI in TB meningitis: axial gadolinium-enhanced MRI showing intense basal meningeal enhancement with multiple ring-enhancing foci (tuberculomas/abscesses) and hydrocephalus - Adams & Victor's Principles of Neurology

T - Treatment

Antituberculosis Drugs (4-drug intensive phase)

• Total duration: 9-12 months (if first-line drugs used; not all 4 drugs needed for the entire period)
• An alternative regimen: INH + PZA + high-dose RMP + moxifloxacin

Drug-Resistant TBM

• In multi-drug resistance (MDR-TB), add ethionamide (ETA) as a 5th drug (15-25 mg/kg/day in divided doses; causes gastric irritation)
• High-dose rifampicin + levofloxacin in INH-resistant isolates

Adjunctive Corticosteroids (MANDATORY)

• Dexamethasone IV: 0.4 mg/kg/day for 1 week, then taper over 3-6 weeks
• Or initial dose: 0.15 mg/kg IV (Rosen's recommendation)
• Evidence: RCT in Vietnam showed IV dexamethasone reduced mortality from 41% to 32%
• Indicated for: raised ICP, subarachnoid block, severe disease
• Given only in conjunction with antituberculosis drugs - never alone

Empiric Treatment

• If TBM is clinically suspected and cryptococcal/other fungal infections + meningeal neoplasia are reasonably excluded - start treatment without waiting for culture results

Neurosurgical Intervention

• Ventriculoperitoneal shunting required in 25% of patients for hydrocephalus
• Consider in obstructive hydrocephalus or mass lesions

E - Etiology / Epidemiology

Etiology

• Primary organism: Mycobacterium tuberculosis (acid-fast bacillus)
• Rarely: M. bovis, M. avium, M. kansasii, M. fortuitum (post-neurosurgery or cranial trauma)
• HIV leads to increased cases from both typical AND atypical mycobacteria

Pathogenesis (Rich's concept)

1. Hematogenous seeding of meninges/subpial brain regions → formation of tubercles (subependymal or meningeal)
2. Rupture of one or more tubercles → discharge of bacteria into subarachnoid space → intense meningeal inflammation

Epidemiology

• More common in developing countries (sub-Saharan Africa: ~25x higher than the US)
• In the US: historically declining, but increased ~16%/year from ~1985 due to HIV epidemic
• With HIV under control, incidence trend reversed in many regions
• Risk populations: HIV/AIDS (incidence ~500x general population), alcoholics, immigrants from high-burden regions (Asia, Africa, India, former Soviet Union), malnourished, immunocompromised
• In 2/3 of patients: evidence of active TB elsewhere (usually lungs; also small bowel, bone, kidney, ear)

Pathology

• Brunt of disease at base of brain (basal meninges): thick gelatinous exudate in pontine and interpeduncular cisterns, optic chiasm, undersurfaces of temporal lobes
• Microscopically: central caseation + epithelioid/giant cells + lymphocytes + plasma cells
• Not confined to subarachnoid space - penetrates pia and ependyma → true meningoencephalitis
• Ependymia and choroid plexus studded with minute glistening tubercles
• Cranial nerves frequently involved (far more so than bacterial meningitis)

C - Complications

Prognosis

• Overall mortality: ~10%
• Late diagnosis (coma): mortality approaches 50%
• HIV co-infection: mortality ~21% (delays in diagnosis + drug resistance)
• Residual deficits: 20-30% of survivors
• Early diagnosis and treatment = best outcome determinant

Recent Evidence Update