What is the recommended treatment for tuberculous meningitis with arachnoiditis?

Treatment of Tuberculous Meningitis with Arachnoiditis

Treat tuberculous meningitis with arachnoiditis using a 12-month course of four-drug anti-TB therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, then isoniazid and rifampicin for 10 more months) combined with adjunctive dexamethasone 12 mg IV daily tapered over 6 weeks, starting immediately with the first anti-TB dose. 1

Anti-Tuberculosis Drug Regimen

Intensive Phase (First 2 Months):

• Administer daily isoniazid, rifampicin, pyrazinamide, and ethambutol 2, 1
• Ethambutol is the preferred fourth drug for adults over aminoglycosides or ethionamide 1
• Daily dosing is strongly preferred over intermittent regimens 1

Continuation Phase (Months 3-12):

• Continue isoniazid and rifampicin daily for an additional 7-10 months (preferably 10 months for total 12-month duration) 2, 1
• Discontinue pyrazinamide and ethambutol after 2 months only when susceptibility to isoniazid and rifampicin is confirmed 1

Critical Duration Error to Avoid:

• A 6-month regimen adequate for pulmonary TB is insufficient for CNS tuberculosis and represents the most common critical error 1
• The total treatment duration must be 9-12 months, preferably 12 months 1, 3

Adjunctive Corticosteroid Therapy

Dexamethasone Dosing (Preferred):

• Adults ≥25 kg: 12 mg IV daily (or 0.4 mg/kg/day, maximum 12 mg) 1, 4
• Children <25 kg: 8 mg IV daily 1, 4
• Children ≥25 kg: 12 mg IV daily 1, 4

Administration Schedule:

• Give the full dose intravenously for the first 3 weeks 1, 4
• Taper gradually over the next 3 weeks (total 6-week course) 1, 4
• Timing is critical: Start corticosteroids immediately before or concurrently with the first anti-TB dose—delay is not permitted 1

Alternative Oral Prednisolone Regimen:

• If IV access is unavailable, use oral prednisolone 60 mg daily 1, 4
• Taper over 6-8 weeks: 60 mg × 4 weeks → 30 mg × 4 weeks → 15 mg × 2 weeks → 5 mg × 1 week 1, 4

Evidence for Mortality Benefit:

• Corticosteroids reduce mortality by approximately 25% (relative risk 0.75) 1, 3
• The greatest benefit occurs in Stage II (lethargic) disease, reducing mortality from 40% to 15% 1, 3
• Even in comatose (Stage III) patients, complete the full tapered course 4, 3

Special Considerations for Arachnoiditis

High-Dose Corticosteroids for Spinal Arachnoiditis:

• When arachnoiditis causes cord compression, paraparesis, or sphincter dysfunction, high-dose systemic corticosteroids are essential 5, 6
• Case reports demonstrate spectacular clinical improvement within 8 days when corticosteroids are added to anti-TB therapy 6
• MRI of the spine confirms the diagnosis and monitors response 5, 6

Optochiasmatic Arachnoiditis:

• This devastating complication affects the optic chiasm and nerves, causing blindness 7, 8
• Predictors include female sex, younger age, and elevated CSF protein 8
• Standard corticosteroids often provide unsatisfactory response 8
• In refractory cases with progressive vision loss despite corticosteroids, thalidomide has shown dramatic recovery in small case series 7

Critical Implementation Pitfalls

Never Stop Steroids Abruptly:

• Complete the full 6-8 week taper regardless of clinical improvement 1, 4
• Abrupt discontinuation causes life-threatening adrenal crisis from HPA axis suppression 4
• Gradual tapering allows adrenal glands to resume normal cortisol production 4

Paradoxical Reactions Do Not Indicate Treatment Failure:

• Development of tuberculomas or worsening arachnoiditis during therapy is a paradoxical inflammatory response 4, 3, 8
• This does not mean treatment failure and is not a reason to stop steroids 4, 3
• Continue the full corticosteroid taper and anti-TB therapy 4

Monitoring Requirements

Cerebrospinal Fluid Monitoring:

• Perform repeat lumbar punctures early in therapy to monitor CSF cell count, glucose, and protein 2, 1, 3
• Serial CSF parameters assess biological response but do not dictate treatment duration 1

Neurological Monitoring:

• Conduct regular neurological examinations to detect improvement or deterioration 1
• Monitor for signs of cord compression, paraparesis, or visual changes 1, 5

Laboratory Monitoring:

• Monitor liver function for hepatotoxicity from isoniazid, rifampicin, and pyrazinamide 1
• Watch for steroid-related complications: hyperglycemia, gastrointestinal bleeding, and invasive bacterial infections 1, 3

Neurosurgical Referral Indications

Immediate neurosurgical consultation is required for: 2, 1, 3

• Hydrocephalus requiring ventriculoperitoneal shunt placement
• Tuberculous cerebral abscesses
• Paraparesis or spinal cord compression from arachnoiditis
• Decompressive laminectomy may be needed for spinal cord compression 5

HIV-Positive Patients

Antiretroviral Therapy Timing:

• Delay ART for 8 weeks after starting anti-TB treatment, even when CD4 <50 cells/µL, to reduce severe or fatal neurological IRIS 1

Paradoxical TB-IRIS Management:

• For moderate to severe paradoxical TB-IRIS, prednisone 1.25 mg/kg/day significantly lowers hospitalization need 1, 3