What is the recommended treatment for tuberculous meningitis complicated by arachnoiditis?

Treatment of Tuberculous Meningoencephalitis with Arachnoiditis

For tuberculous meningoencephalitis complicated by arachnoiditis, initiate immediate treatment with four-drug anti-TB therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol) for 2 months followed by isoniazid and rifampicin for 7-10 months (total 9-12 months), combined with adjunctive dexamethasone 12 mg/day IV (or prednisolone 60 mg/day) tapered over 6-8 weeks, as this reduces mortality by approximately 25%. 1, 2

Anti-Tuberculosis Chemotherapy Regimen

Initial Intensive Phase (First 2 Months)

• Daily administration of four first-line drugs is strongly preferred over intermittent dosing 1:

  • Isoniazid (INH)
  • Rifampicin (RIF)
  • Pyrazinamide (PZA)
  • Ethambutol (EMB) - preferred as the fourth drug in adults 1, 2

• For patients unable to take oral medications due to altered mental status, use parenteral formulations of isoniazid, rifampicin, aminoglycosides, capreomycin, or fluoroquinolones 1

Continuation Phase (Months 3-12)

• Continue daily isoniazid and rifampicin for an additional 7-10 months after completing the intensive phase 1, 2
• Total treatment duration must be 9-12 months (preferably 12 months) - the standard 6-month pulmonary TB regimen is inadequate for CNS tuberculosis and associated with higher failure/relapse rates 1, 2, 3

Adjunctive Corticosteroid Therapy

Adult Dosing (≥25 kg)

Dexamethasone regimen (preferred): 2, 4

• Initial dose: 12 mg IV daily (or 0.4 mg/kg/day, maximum 12 mg) for 3 weeks
• Tapering: Gradually decrease over the following 3 weeks (total 6 weeks)

Alternative prednisolone regimen: 1, 2

• 60 mg/day for 4 weeks
• 30 mg/day for 4 weeks
• 15 mg/day for 2 weeks
• 5 mg/day for week 11 (final week)

Pediatric Dosing

• Children <25 kg: Dexamethasone 8 mg/day IV with same tapering schedule 2, 4
• Children ≥25 kg: Use adult dosing (12 mg/day) 2, 4

Critical Implementation Points

• Initiate corticosteroids before or concurrently with the first dose of anti-TB medication for maximum mortality benefit 2, 4
• The mortality benefit is most pronounced in Stage II (lethargic) patients, reducing mortality from approximately 40% to 15% 2, 4
• Even in Stage III (comatose) patients, complete the full tapered corticosteroid course 2

Management of Arachnoiditis-Specific Complications

Optochiasmatic Arachnoiditis

Tuberculous arachnoiditis with basal exudates in the suprasellar and interpeduncular cisterns represents a particularly devastating complication that frequently causes profound vision loss 5. This entity:

• More frequently affects young adults, particularly females with younger age and elevated CSF protein 5
• Often develops paradoxically during treatment with anti-TB drugs 5
• Requires continuation of standard anti-TB therapy and corticosteroids despite paradoxical worsening 5

Monitoring and Surveillance

• Perform repeated lumbar punctures to monitor CSF cell count, glucose, and protein trends, especially early in therapy 1, 2, 4
• Serial neuroimaging (MRI preferred) to assess for hydrocephalus, tuberculomas, and extent of basal exudates 5

Neurosurgical Referral Criteria

Immediate neurosurgical consultation is indicated for 1, 2, 4:

• Hydrocephalus requiring shunt placement
• Tuberculous cerebral abscess
• Paraparesis or spinal cord compression
• Progressive neurological deficits despite medical therapy

Critical Pitfalls and How to Avoid Them

Never Stop Corticosteroids Abruptly

• Complete the full 6-8 week tapered course regardless of clinical response to prevent life-threatening adrenal crisis from HPA axis suppression 2, 4
• Abrupt discontinuation after prolonged high-dose therapy can cause acute adrenal insufficiency 2

Paradoxical Reactions Are Not Treatment Failure

• Development of tuberculomas or new enhancing lesions during therapy represents a paradoxical inflammatory response 1, 2, 5
• This does NOT indicate treatment failure and is NOT a reason to discontinue steroids or anti-TB drugs 2, 5
• Continue standard therapy; some patients regain vision following continued anti-TB drugs and corticosteroids 5

Distinguish Treatment Duration from Pulmonary TB

• Do not use the 6-month regimen - CNS tuberculosis requires 9-12 months total therapy 1, 2, 3
• After 2 months of four-drug therapy, discontinue pyrazinamide and ethambutol only if susceptibility to isoniazid and rifampicin is confirmed 1

Special Populations

HIV-Positive Patients

• Delay ART initiation for 8 weeks after starting anti-TB therapy, even with CD4 <50 cells/μL, due to increased risk of severe or fatal neurological complications from immune reconstitution inflammatory syndrome (IRIS) 4
• For moderate-to-severe paradoxical TB-IRIS, prednisone approximately 1.25 mg/kg/day significantly reduces need for hospitalization and surgical intervention 2, 4
• Monitor for drug interactions between rifampicin and antiretrovirals 6

Drug-Resistant TB

• If local incidence of drug resistance is >4% or unknown, ensure at least two active drugs are included 7
• Consult an expert for multidrug-resistant cases 7
• Fluoroquinolones and higher-dose IV rifampicin are being evaluated in ongoing trials 1

Salvage Therapy for Refractory Cases

For cases unresponsive to standard anti-TB drugs and corticosteroids, thalidomide has been used as salvage therapy with variable success 8, 5:

• Case reports demonstrate resolution of paradoxical tuberculomas resistant to corticosteroids 8
• Typical duration: 2 months of thalidomide added to standard anti-TB regimen 8
• Consider only after failure of standard therapy due to limited evidence 5