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Neurological System

Tuberculous Meningitis (TBM)

Meningitis caused by Mycobacterium tuberculosis infection spreading to the meninges, usually secondary to pulmonary or miliary TB. Typically has a subacute onset and carries high morbidity and mortality if not diagnosed and treated promptly.

Also known as: TB Meningitis

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Referral and warning signs

When to refer

ALL suspected cases of Tuberculous Meningitis MUST be referred urgently to Hospital (H) for confirmation (LP, imaging if needed), initiation of ATT and corticosteroids, and management of complications.

Red flags

  • Subacute onset of headache, fever, altered mental status (esp. in HIV+ or child)
  • Cranial nerve palsies
  • Neck stiffness
  • Seizures with subacute neurological symptoms
  • Signs of TB elsewhere (persistent cough, weight loss, night sweats)

Signs and symptoms

  • Subacute onset (weeks, can be more rapid).
  • Prodromal phase (1-2 weeks): Malaise, fatigue, low-grade fever, headache, irritability, personality changes, weight loss, anorexia, vomiting.
  • Meningitic phase: Worsening headache, persistent vomiting, neck stiffness (may be mild initially), confusion, lethargy, cranial nerve palsies (esp. VI, III, IV, VII), seizures, focal neurological deficits (hemiparesis).
  • Advanced stage: Stupor, coma, decerebrate/decorticate posturing, signs of raised ICP.
  • May have symptoms/signs of TB elsewhere (cough, night sweats, lymphadenopathy).

Risk factors

  • Active Tuberculosis (pulmonary or miliary).
  • HIV co-infection (major risk factor).
  • Immunocompromise (other causes).
  • Malnutrition.
  • Young children (<5 years).
  • Close contact with active TB case.
  • Incomplete or inadequate previous TB treatment.

Diagnosis

Clinical assessment

Suspect in patients (especially HIV+ or young children) with subacute onset of headache, fever, vomiting, altered mental status, and/or cranial nerve palsies. Look for evidence of TB elsewhere.

Investigations

  • Lumbar Puncture (LP) and CSF Analysis: Essential but challenging.
  • - Appearance: Often clear or slightly opalescent; may form a fibrin web/pellicle on standing.
  • - Opening Pressure: Often elevated.
  • - Cell Count/Differential: Moderate pleocytosis (50-500 cells/µL), typically lymphocyte predominant (neutrophils may dominate early).
  • - Glucose: Low (<50% of serum glucose, often <40 mg/dL).
  • - Protein: Markedly elevated (>100 mg/dL, often >200).
  • - Ziehl-Neelsen (ZN) Stain for Acid-Fast Bacilli (AFB): Low sensitivity (<10-20%), requires large volume, repeated LPs may increase yield.
  • - CSF Culture for M. tuberculosis: Gold standard but slow (weeks), sensitivity variable.
  • - CSF GeneXpert MTB/RIF Assay: Recommended diagnostic test. More rapid than culture, higher sensitivity than ZN stain (~50-80%), also detects rifampicin resistance.
  • - CSF Adenosine Deaminase (ADA): May be elevated, but non-specific.
  • Chest X-ray: Look for evidence of pulmonary TB (infiltrates, cavities, hilar lymphadenopathy, miliary pattern). Normal CXR does not exclude TBM.
  • Sputum AFB Smear/Culture/GeneXpert: If pulmonary symptoms present, confirms TB infection.
  • HIV Test.
  • CD4 Count (if HIV+).
  • Consider Brain Imaging (CT/MRI with contrast): May show basilar meningeal enhancement, hydrocephalus, tuberculomas (granulomas), infarcts (due to vasculitis). Useful to assess complications and exclude other diagnoses.

Diagnostic criteria

Diagnosis often presumptive/empirical based on clinical picture (subacute meningitis, esp. in high-risk patient) + characteristic CSF findings (lymphocytic pleocytosis, low glucose, high protein) +/- supportive evidence (positive GeneXpert, AFB smear, CXR findings, TB elsewhere). Awaiting culture confirmation should not delay treatment.

Management

Non-pharmacological management

  • Immediate referral to hospital (H).
  • Supportive Care: Manage airway, breathing, circulation. Nutritional support (NGT if needed). Manage seizures. Monitor neurological status.
  • Management of Raised ICP/Hydrocephalus: May require therapeutic LPs, osmotic agents (mannitol), or neurosurgical intervention (ventricular shunt) if hydrocephalus develops.

Pharmacological treatment

  • Antituberculosis Therapy (ATT): Start empirically IMMEDIATELY if TBM is suspected. Delays worsen outcome significantly.
  • - Standard Regimen (per UCG / National TB Program): Intensive Phase (2 months): Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E). Dosage based on weight bands.
  • - Continuation Phase (Prolonged - 10 months): Isoniazid (H), Rifampicin (R).
  • - Total duration = 12 months (2RHZE / 10RH).
  • - Ensure adequate dosing, especially of Isoniazid and Pyrazinamide which penetrate CSF well. Consider higher Isoniazid dose (10mg/kg) if feasible.
  • Adjunctive Corticosteroids: Recommended for all patients with TBM (unless contraindicated). Reduce inflammation, mortality, and neurological sequelae.
  • - Prednisolone: Start concurrently with ATT. Dose typically 1-2 mg/kg/day (max 60-80mg) for 2-4 weeks, then taper gradually over 4-8 weeks. OR Dexamethasone IV initially if severe/unable to take oral, then switch to Prednisolone.
  • Pyridoxine (Vitamin B6): Give 10-25 mg daily to all patients receiving Isoniazid to prevent peripheral neuropathy.
  • Management of HIV co-infection: Start ART as soon as feasible after starting ATT (usually within 2-8 weeks, balancing TBM severity vs IRIS risk - follow National HIV guidelines).
  • Treat seizures with standard AEDs (Phenobarbital, Phenytoin, Carbamazepine).

Monitoring

Monitor clinical response (fever, headache, mental status, neurological signs). Monitor for ATT side effects (hepatotoxicity - check LFTs baseline and if symptoms; peripheral neuropathy; optic neuritis with Ethambutol). Monitor for complications (hydrocephalus, seizures, stroke). Monitor adherence to ATT and steroids. Monitor for IRIS (paradoxical worsening after starting ATT/ART).

Complications

  • Hydrocephalus (communicating or obstructive)
  • Cranial nerve palsies
  • Vasculitis leading to cerebral infarcts (stroke)
  • Seizures / Epilepsy
  • Tuberculomas (brain granulomas)
  • Spinal cord involvement (TB arachnoiditis, myelopathy)
  • Permanent neurological deficits (cognitive, motor, visual, hearing)
  • Endocrine dysfunction (SIADH, hypopituitarism)
  • Death (mortality remains high, ~20-50%)

Prevention

  • BCG vaccination at birth (provides partial protection against severe childhood TB, including TBM).
  • Early diagnosis and effective treatment of pulmonary TB to prevent dissemination.
  • TB preventive therapy (TPT) for eligible individuals (e.g., HIV+, close contacts).
  • HIV prevention and treatment.
  • Infection control measures for TB.

Patient education

  • Explain the seriousness of TB infection in the brain.
  • Stress the absolute necessity of prolonged ATT (12 months) and adherence.
  • Explain the role and importance of corticosteroids and the tapering schedule.
  • Educate on potential side effects of ATT and when to report them.
  • Discuss importance of nutritional support.
  • Explain rationale for ART initiation in HIV co-infected patients.
  • Contact tracing and screening for household contacts.

Uganda-specific notes

TBM is a significant cause of meningitis, particularly in HIV-positive individuals and young children. Diagnosis relies heavily on clinical suspicion and characteristic CSF findings, as microbiological confirmation (esp. AFB smear) is often difficult/delayed. GeneXpert on CSF is the preferred rapid test. Prompt empirical ATT and steroid initiation based on strong suspicion is crucial. Follow National TB and Leprosy Program (NTLP) and HIV guidelines for treatment regimens and monitoring.

References

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 2, Section 2.1.5.3

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 5, Section 5.3 (Treatment of Extrapulmonary TB)

  • National Tuberculosis and Leprosy Program (NTLP) Guidelines, Uganda

    (Refer to latest version)

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