What is the treatment for tubercular meningoencephalitis?

Treatment of Tubercular Meningoencephalitis

For tuberculous meningitis, initiate immediate four-drug antituberculous therapy (isoniazid, rifampin, pyrazinamide, and ethambutol) for 2 months followed by isoniazid and rifampin for 7-10 additional months (total 9-12 months), combined with adjunctive dexamethasone or prednisolone tapered over 6-8 weeks. 1, 2

Antituberculous Chemotherapy Regimen

Initial Intensive Phase (2 months)

• Four-drug regimen: Isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) given daily 1, 2
• Adult dosing: INH 5 mg/kg (max 300 mg), RIF per standard dosing, PZA per standard dosing, EMB as fourth drug preferred over injectable agents 1, 3
• Pediatric dosing: INH 10-15 mg/kg (max 300 mg daily), with consideration of aminoglycoside or ethionamide instead of EMB in young children whose visual acuity cannot be monitored 1, 3

Continuation Phase (7-10 months)

• Two-drug regimen: Continue INH and RIF only after completing 2 months of four-drug therapy 1, 2
• Total treatment duration: 9-12 months for tuberculous meningitis, which is longer than the 6 months used for pulmonary tuberculosis 1, 3
• Daily dosing preferred: Once-daily administration is recommended over intermittent dosing for extrapulmonary tuberculosis including meningitis 1

Adjunctive Corticosteroid Therapy

This is a strong recommendation with moderate certainty evidence and should be initiated immediately upon starting antituberculous therapy. 1, 4

Dexamethasone Regimen (Preferred)

• Adult dosing: 0.4 mg/kg/day (maximum 12 mg/day) intravenously for 3 weeks, then gradually tapered over the following 3 weeks (total 6 weeks) 2, 4
• Pediatric dosing: 8 mg/day for children <25 kg; 12 mg/day for children ≥25 kg, using the same tapering schedule as adults 4

Prednisolone Alternative

• Initial dose: 60 mg/day for adults 4
• Tapering schedule: Gradually reduced over 6-8 weeks, with one suggested protocol being 60 mg/day for 4 weeks, 30 mg/day for 4 weeks, 15 mg/day for 2 weeks, and 5 mg/day for the final week 4
• Pediatric alternative: Approximately 1 mg/kg body weight initially, tapered proportionately 4

Critical Corticosteroid Principles

• Timing: Initiate before or concurrently with the first dose of antituberculous medication for maximum mortality benefit 4
• Mortality reduction: Corticosteroids reduce mortality by approximately 25% (RR 0.75,95% CI 0.65-0.87), with greatest benefit in Stage II disease (lethargic presentation) 4
• Never stop abruptly: Complete the full 6-8 week tapered course regardless of clinical improvement to prevent life-threatening adrenal crisis from HPA axis suppression 4
• Paradoxical reactions: Development of tuberculomas during therapy does not indicate treatment failure and is not a reason to discontinue steroids 4

Monitoring and Follow-Up

• Repeated lumbar punctures: Consider serial CSF analysis to monitor cell count, glucose, and protein changes, especially early in therapy 1, 4
• Drug susceptibility testing: Must be performed on initial isolates; if resistance develops, change to susceptible agents 3
• Neuroimaging: CT or MRI to identify complications requiring intervention 5, 6

Management of Complications

Neurosurgical Referral Indications

• Hydrocephalus: Requires prompt neurosurgical evaluation for possible shunting, especially with symptoms of raised intracranial pressure 1, 2, 5
• Tuberculous cerebral abscess: Surgical intervention may be necessary 1
• Spinal cord compression from Pott's disease: Urgent neurosurgical consultation 1

HIV Co-infection Considerations

• Same chemotherapy regimen: Use the standard four-drug regimen despite HIV status 1, 6
• Drug interactions: Screen antimycobacterial drug levels in advanced HIV disease to prevent malabsorption and emergence of multidrug-resistant TB 3
• Immune reconstitution inflammatory syndrome (IRIS): Monitor carefully after initiating antiretroviral therapy 2, 7
• Corticosteroid benefit unclear: Evidence for adjunctive corticosteroids in HIV-positive patients is less robust 7

Drug-Resistant Tuberculous Meningitis

• Minimum five effective drugs: Include a fluoroquinolone and injectable agent based on drug susceptibility testing 2
• Expert consultation: Strongly recommended for all cases of multidrug-resistant tuberculous meningitis 3, 6
• Individualized therapy: Treatment must be tailored to susceptibility patterns 1, 3

Critical Pitfalls to Avoid

• Delayed treatment initiation: Start empiric therapy immediately when clinical suspicion is supported by CSF findings (lymphocytic pleocytosis, elevated protein, low glucose), as outcomes depend critically on early treatment before neurologic deterioration 2, 6, 8
• Inadequate treatment duration: Do not use the 6-month regimen appropriate for pulmonary TB; meningitis requires 9-12 months 1, 3
• Premature corticosteroid discontinuation: Complete the full tapered course even in comatose Stage III patients 4
• Omitting the fourth drug: Always include ethambutol (or alternative) in the initial phase unless community isoniazid resistance is documented <4% 3