How to proceed with treatment in a patient with suspected tubercular meningitis (TBM) and altered sensorium?

Management of Suspected Tuberculous Meningitis with Altered Sensorium

In a patient with suspected tuberculous meningitis (TBM) and altered sensorium, immediate initiation of empiric anti-tuberculosis therapy with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol) along with adjunctive dexamethasone is essential and should not be delayed waiting for confirmatory test results.

Initial Assessment and Diagnosis

1. Cerebrospinal Fluid (CSF) Analysis:

   • Perform lumbar puncture with measurement of opening pressure (typically elevated >20 cm CSF)
   • Collect adequate volume (at least 22 mL) of CSF for comprehensive testing 1
   • Analyze for:
     • Cell count and differential (typically 40-400/mm³ with lymphocyte predominance in TBM)
     • Protein (elevated in TBM)
     • Glucose (low in TBM, CSF:blood glucose ratio <0.5)
     • AFB smear, culture, and PCR for M. tuberculosis
     • CSF lactate (to differentiate bacterial from aseptic meningitis)

2. Additional Testing:

   • Blood cultures before antibiotics
   • Chest X-ray to look for pulmonary TB
   • Neuroimaging (CT or MRI) to identify hydrocephalus, tuberculomas, or infarcts
   • HIV testing (recommended for all patients with suspected TB) 2

Treatment Protocol

Anti-TB Medication

1. Initial Phase (First 2 months):

   • Isoniazid: 5 mg/kg (up to 300 mg) daily 3
   • Rifampin: 10 mg/kg daily 4
   • Pyrazinamide: 15-30 mg/kg daily
   • Ethambutol: 15 mg/kg daily 5

2. Continuation Phase (7-10 months):

   • Isoniazid and rifampin for at least 7-10 months 2
   • Total treatment duration for TBM should be 9-12 months 2, 6

Adjunctive Corticosteroid Therapy

• Dexamethasone: 10 mg IV every 6 hours for 4 weeks, followed by tapering over 4 weeks 1

  • Week 1-4: 10 mg IV every 6 hours
  • Week 5-6: 6 mg IV/oral every 6 hours
  • Week 7: 3 mg IV/oral every 6 hours
  • Week 8: 2 mg IV/oral every 6 hours, then stop

• Alternatively, prednisolone 60 mg/day for 4 weeks, followed by 30 mg/day for 4 weeks, 15 mg/day for 2 weeks, and 5 mg/day for the final week 2

Management of Altered Sensorium

1. Airway Management:

   • Consider intubation for patients with Glasgow Coma Scale (GCS) <12 1
   • Maintain adequate oxygenation

2. Hemodynamic Support:

   • Maintain mean arterial pressure ≥65 mmHg
   • Target euvolemia and avoid fluid restriction 1

3. Neurological Monitoring:

   • Monitor for signs of increased intracranial pressure
   • Serial neurological examinations
   • Consider ICU admission for patients with GCS <12 1

4. Management of Complications:

   • Hydrocephalus: May require neurosurgical consultation for CSF diversion
   • Seizures: Appropriate anticonvulsant therapy
   • Electrolyte imbalances: Monitor and correct, particularly hyponatremia

Monitoring Response to Treatment

1. Clinical Monitoring:

   • Daily assessment of neurological status
   • Monitor for improvement in sensorium
   • Assess for adverse drug reactions

2. Laboratory Monitoring:

   • Monthly liver function tests
   • Visual acuity and color discrimination testing for patients on ethambutol 2
   • Consider repeat CSF analysis if clinical improvement is not observed

Special Considerations

1. HIV Co-infection:

   • All patients with suspected TB should be tested for HIV 2
   • In HIV-positive patients, consider drug interactions with antiretroviral therapy
   • Management should involve specialists in both HIV and TB 6

2. Drug-Resistant TB:

   • Consider drug-resistant TB if there is a history of prior TB treatment or exposure to drug-resistant TB
   • In areas with high isoniazid resistance (>4%), four-drug initial therapy is essential 2
   • If drug resistance is suspected, add additional agents based on local resistance patterns 2

Pitfalls and Caveats

1. Delayed Treatment:

   • TBM is a medical emergency; treatment delay is strongly associated with mortality 6
   • Do not wait for microbiological confirmation before starting treatment

2. Inadequate Steroid Regimen:

   • Failure to administer appropriate adjunctive steroids increases mortality 7
   • Ensure proper dosing and duration of steroid therapy

3. Missed Drug Resistance:

   • Never add a single drug to a failing regimen as this leads to acquired resistance 2
   • If treatment failure occurs, add at least two new drugs to which susceptibility can be inferred 2

4. Inadequate Duration:

   • TBM requires longer treatment (9-12 months) compared to pulmonary TB (6 months) 2, 6
   • Premature discontinuation of therapy increases risk of relapse and mortality

By following this comprehensive approach, you can optimize outcomes for patients with suspected TBM and altered sensorium, focusing on early diagnosis, prompt treatment initiation, and careful monitoring for complications.