Tubercular Meningitis

1. Introduction and Epidemiology

Tubercular meningitis (TBM) is the most severe form of tuberculosis in children and a leading cause of neurological morbidity and mortality. It typically occurs as a serious complication of primary infection, usually developing within a year of the initial exposure.

• Age Distribution: TBM most commonly affects children between 6 months and 4 years of age, though it can occur at any age.
• Predisposing Factors:
  • Age: Young infants are most vulnerable.
  • Immune Status: Malnutrition (Protein Energy Malnutrition), recent measles infection, and HIV coinfection significantly increase risk.
  • Contact History: A history of household contact with an infectious adult pulmonary TB case is a strong risk factor.

2. Pathogenesis and Pathology

TBM is not a direct result of primary bacillaemia but rather a two-step process:

1. Hematogenous Dissemination: During the initial primary infection, bacilli spread through the blood and seed the meninges or brain parenchyma, forming small subpial or subependymal foci known as "Rich foci".
2. Rupture: Triggered by stress or lowered immunity, a Rich focus ruptures into the subarachnoid space, releasing mycobacterial antigens.

Pathological Triad: The resulting hypersensitivity reaction induces a thick, gelatinous exudate, primarily in the basal cisterns. This leads to three cardinal pathological features:

1. Basal Meningitis: Thick exudates encase cranial nerves (leading to palsies) and obstruct cerebrospinal fluid (CSF) pathways.
2. Vasculitis (Endarteritis): Inflammation of cerebral vessels, particularly the middle cerebral artery and perforating vessels, causes infarction, commonly in the basal ganglia, thalamus, and internal capsule.
3. Hydrocephalus: Obstruction of CSF flow (communicating or obstructive) occurs due to the thick basal exudates blocking the cisterns or arachnoid granulations.

3. Clinical Features and Staging

The onset is usually insidious (subacute), progressing over 2–3 weeks, unlike the acute onset of purulent meningitis.

A. Clinical Presentation

• Prodromal Phase (1–2 weeks): Characterized by nonspecific symptoms such as low-grade irregular fever, anorexia, weight loss, malaise, apathy (loss of playfulness), and irritability.
• Meningitic Phase: Signs of meningeal irritation develop, including headache, vomiting (often without nausea), photophobia, and nuchal rigidity. Cranial nerve palsies and seizures may occur.
• Advanced Phase: Deterioration of consciousness, coma, decerebrate posturing, and dense neurological deficits.

B. Clinical Staging

Prognosis is strictly determined by the stage of disease at the time treatment is initiated. The Medical Research Council (MRC) staging is widely used:

4. Diagnosis

Diagnosis relies on a combination of clinical features, CSF analysis, and neuroimaging. The 2022 Pediatric TB Guidelines emphasize a composite reference standard due to the paucibacillary nature of the disease.

A. Cerebrospinal Fluid (CSF) Analysis This is the critical diagnostic test. Typical findings include:

• Appearance: Clear or "ground glass"; a cobweb coagulum may form on standing.
• Cells: Pleocytosis (10–500 cells/mm³). Predominantly lymphocytic (>50%), though neutrophils may be present in the very early stage.
• Biochemistry:
  • Protein: Significantly elevated (100–500 mg/dL), often very high (>1 g/dL) if spinal block is present.
  • Glucose: Low (hypoglycorrhachia), typically <40 mg/dL or <50% of concomitant blood glucose.

B. Microbiological Confirmation

• Smear/Culture: Acid-fast bacilli (AFB) are rarely seen on smear. Culture (Liquid MGIT) is more sensitive but takes weeks.
• NAAT (GeneXpert/Truenat): Upfront molecular testing is recommended. While specificity is high, sensitivity in CSF is only about 30–40%; a negative result does not rule out TBM.

C. Neuroimaging (CECT or MRI)

Contrast-Enhanced CT (CECT) is the initial modality, but MRI is more sensitive. The diagnostic triad on imaging includes:

1. Basal Meningeal Enhancement: Intense enhancement of basal cisterns.
2. Hydrocephalus: Present in almost all cases.
3. Infarcts: Typically in the basal ganglia or thalamus.

• Tuberculomas: May present as ring-enhancing lesions with perilesional edema.

D. Diagnostic Algorithm (NTEP 2022)

TBM should be suspected in a child with insidious fever (>5 days) and neurological signs. Diagnosis is supported if 2 or more of the following criteria are met:

1. Clinical/Lab Criteria: CSF >10 cells, Lymphocytes >50%, Protein >100 mg/dL, Glucose <40 mg/dL.
2. Risk Factors: Contact with active TB, HIV, or SAM.
3. Imaging: Basal enhancement, hydrocephalus, or tuberculoma.
4. Evidence of TB elsewhere: Chest X-ray abnormalities or Mantoux positivity.

5. Differential Diagnosis

• Partially Treated Pyogenic Meningitis: Chief differential. CSF shows neutrophils, but glucose may be normal or slightly low. Culture is usually sterile.
• Viral Meningoencephalitis: Acute onset, normal CSF glucose, and lack of basal enhancement on imaging.
• Fungal Meningitis (Cryptococcal): Common in HIV/immunocompromised children. CSF India ink or antigen test is positive.
• Neurocysticercosis (NCC): Lesions are usually smaller (<20mm), cystic with a scolex, and show less perilesional edema compared to tuberculomas. Basal meningitis is absent.

6. Management

A. Antitubercular Therapy (ATT)

Treatment follows the National Tuberculosis Elimination Programme (NTEP) guidelines for extrapulmonary TB with CNS involvement. The total duration is 12 months.

• Intensive Phase (IP): 2 months of HRZE (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol).
• Continuation Phase (CP): 10 months of HRE (Isoniazid, Rifampicin, Ethambutol). Note: CP is extended to 10 months specifically for CNS and spinal TB.
• Dosages (Daily Regimen):
  • Isoniazid (H): 10 mg/kg (Range 7–15).
  • Rifampicin (R): 15 mg/kg (Range 10–20).
  • Pyrazinamide (Z): 35 mg/kg (Range 30–40).
  • Ethambutol (E): 20 mg/kg (Range 15–25).

B. Adjunctive Therapy

1. Corticosteroids:
   • Indication: Mandatory for TBM to reduce cerebral edema, basal exudates, and vasculitis. Improves survival and intellectual outcome.
   • Regimen: Prednisolone (1–2 mg/kg/day) or Dexamethasone (0.6 mg/kg/day) for 4 weeks, followed by tapering over the next 4 weeks.
2. Pyridoxine (Vitamin B6):
   • Supplementation (10 mg/day) is recommended to prevent Isoniazid-induced peripheral neuropathy, especially in malnourished children.

C. Management of Complications

1. Raised Intracranial Pressure (ICP):
   • General measures: Head elevation to 30 degrees, midline positioning.
   • Osmotherapy: Mannitol (0.25–1 g/kg) or Hypertonic Saline (3%) for acute spikes.
2. Hydrocephalus:
   • Medical: Acetazolamide and furosemide may be used temporarily for communicating hydrocephalus but have limited long-term efficacy.
   • Surgical: Ventriculoperitoneal (VP) shunt is the standard for obstructive hydrocephalus or failed medical management. Endoscopic Third Ventriculostomy (ETV) is an alternative.
3. Hyponatremia: Often due to SIADH (fluid restriction) or Cerebral Salt Wasting (fluid and salt replacement).
4. Seizures: Aggressive management with anticonvulsants is required. Prophylactic treatment is generally not recommended unless seizures occur.

7. Prognosis and Sequelae

The outcome is strictly correlated with the stage of disease at diagnosis and treatment initiation:

• Stage I: Excellent prognosis; near 100% cure with early treatment.
• Stage II: ~80% survival; roughly 50% may suffer sequelae.
• Stage III: High mortality (50%); survivors have a very high rate (80%) of severe neurological disability.

Long-term Sequelae:

• Neurological: Hemiplegia, intellectual disability, epilepsy, cranial nerve palsies.
• Sensory: Optic atrophy leading to blindness, deafness (due to disease or streptomycin toxicity).
• Endocrine: Hypothalamic/pituitary dysfunction (e.g., precocious puberty, obesity).

8. Prevention

• BCG Vaccination: Provides protection (up to 85%) against severe forms of TB, including meningitis and miliary TB, in infants.
• TB Preventive Therapy (TPT): Isoniazid preventive therapy (10 mg/kg/day) for 6 months is indicated for all children <5 years who are household contacts of a pulmonary TB patient, after ruling out active disease.