Meningitis

1. Introduction and Definition

• Definition: Meningitis is the inflammation of the leptomeninges (pia and arachnoid mater) with variable involvement of the encephalon.
• Classification:** Acute meningitis is classified by etiology into bacterial (pyogenic), viral (aseptic), fungal, or parasitic. Bacterial meningitis is a medical emergency with high mortality if untreated.

2. Epidemiology and Etiology

The etiological agents vary significantly by age and immune status.

A. Common Etiological Agents

Age Group / Context	Common Organisms	Remarks
< 2 years	Streptococcus pneumoniae	Commonest cause; serotypes 6, 1, 19, 14, 5 & 7 prevalent in India.
< 3 years	Haemophilus influenzae type b	Incidence reducing due to Hib vaccination.
Epidemics / Older Children	Neisseria meningitidis	Serogroups A, B, C, Y, W135.
Neonates / Hospital Acquired	E. coli, Klebsiella, Pseudomonas	Associated with prolonged hospital stay or sepsis.
Shunts / Head Injury	Staphylococcus (Coag negative/positive)	Associated with VP shunts, trauma, neurosurgery.

B. Predisposing Factors

• Hematogenous spread: From distant foci (lungs, skin, bones).
• Contiguous spread: Otitis media, mastoiditis, sinusitis.
• Anatomical defects: Neural tube defects, fracture base of skull (CSF rhinorrhea), pilonidal sinus.
• Immunocompromised states: HIV, asplenia (Sickle cell disease), hypogammaglobulinemia, complement deficiency.

3. Pathogenesis

The bacteria typically colonize the nasopharynx and invade the bloodstream.

Sequence of Events:

1. Colonization: Nasopharyngeal colonization by organisms.
2. Invasion: Cleavage of cell junctions and IgA protease activity allows entry into the bloodstream.
3. Bacteremia: Survival in blood (evasion of complement/phagocytosis via capsule).
4. CNS Entry: Lodging in the choroid plexus and crossing the blood-brain barrier.
5. Inflammation: Bacterial lysis releases cell wall components $\to$ production of cytokines (IL-1, IL-6, TNF).
6. Pathology:
   • Cerebral Edema: Vasogenic, cytotoxic, and interstitial.
   • Raised ICP: Due to edema and obstructed CSF flow (hydrocephalus).
   • Neuronal Damage: Cortical injury from inflammation and ischemia.

4. Clinical Features

Presentation depends on the age of the child and duration of illness.

A. Symptoms

• Constitutional: High-grade fever ($\ge$ 80%), lethargy, irritability, anorexia.
• Raised ICP: Headache (worse in mornings), vomiting (projectile), bulging fontanelle (in infants).
• Neurological: Seizures (1/3rd of patients), altered sensorium (drowsy, stupor, coma), photophobia.

B. Signs of Meningeal Irritation

These may be absent in very young infants or deeply comatose children.

1. Neck Rigidity: Resistance to passive neck flexion.
2. Kernig’s Sign: Pain/resistance on extending the knee beyond 135° when the hip is flexed to 90°.
3. Brudzinski’s Sign: Spontaneous flexion of knees/hips upon passive flexion of the neck.

C. Other Signs

• Skin: Petechiae/purpura (Meningococcemia).
• Neurological Deficits: Focal deficits (10-20%), VI nerve palsy (false localizing sign).
• Fundus: Papilledema is uncommon in acute meningitis; if present, suggests complications like abscess or venous sinus thrombosis.

5. Investigations

Lumbar Puncture (LP) is the gold standard diagnostic test

A. Lumbar Puncture

• Timing: Perform as soon as possible unless contraindicated. Do not delay antibiotics for LP if the patient is unstable.
• Contraindications: Papilledema (raised ICP), infection at LP site, bleeding diathesis, cardio-respiratory instability.
• Procedure: Lateral recumbent position, L3-L4 or L4-L5 space.

B. CSF Analysis (Comparison Table)

Parameter	Normal	Pyogenic (Bacterial)	Tubercular (TBM)	Viral (Aseptic)
Appearance	Clear	Turbid	Clear/Cobweb	Clear
Pressure	Normal	Elevated	Elevated	Normal/Mild high
Cells	<5 (lymphocytes)	100–1000s (Neutrophils)	25–500 (Lymphocytes)	10–100 (Lymphocytes)
Protein (mg/dl)	<40	High (100–500)	Very High (100–500+)	Normal/Slight high
Sugar (mg/dl)	>50 ($\ge$2/3 bld)	Low (<40)	Low (<50)	Normal
Stains	Negative	Gram Stain (+ve)	AFB/GeneXpert	Negative

C. Other Investigations

• Blood: CBC (Leukocytosis), Blood Culture (Positive in 50%), CRP, Electrolytes (SIADH).
• Latex Agglutination: For partially treated cases (detects antigens of Hib, Pneumococcus, Meningococcus).
• Neuroimaging (CT/MRI): Not routine. Indicated for focal signs, persistent fever, suspected abscess, or raised ICP.

6. Management of Acute Bacterial Meningitis

Goal: Rapid sterilization of CSF and control of intracranial pressure.

A. Empiric Antibiotic Therapy

Start immediately after samples are drawn.

Organism/Age	Antibiotic of Choice	Duration
Unknown Etiology	Ceftriaxone (100 mg/kg/day) OR Cefotaxime (200 mg/kg/day)	10 days
Pneumococcus	Penicillin G (if sens) OR Ceftriaxone + Vancomycin (60 mg/kg/d)	10–14 days
H. influenzae	Ceftriaxone OR Cefotaxime	10–14 days
Meningococcus	Penicillin G OR Ceftriaxone	7 days
Staphylococcus	Vancomycin + Rifampicin/Linezolid	28 days
Pseudomonas	Ceftazidime + Aminoglycoside	21 days

B. Steroid Therapy (Dexamethasone)

• Rationale: Reduces cytokine-mediated inflammation, hearing loss, and neurological sequelae.
• Dose: 0.15 mg/kg/dose IV every 6 hours for 4 days.
• Timing: Must be given 15 minutes before or with the first dose of antibiotics.
• Indication: Strongly recommended for H. influenzae and Pneumococcal meningitis.

C. Supportive Care

1. Fluids: Maintenance fluids recommended. Restrict to 2/3rd maintenance only if SIADH is confirmed (Na <120 mEq/L). Avoid hypotonic fluids.
2. Raised ICP: Elevate head to 30°. Mannitol (0.25-0.5 g/kg) if signs of herniation. Hyperventilation (maintain pCO2 25-30 mmHg) in ventilated patients.
3. Seizures: Treat with IV Benzodiazepines and Phenytoin.
4. Vitals: Maintain normothermia, normoglycemia, and adequate perfusion.

7. Complications

Acute (First few days)

• Seizures (early onset <4 days).
• Raised Intracranial Tension / Herniation.
• Shock / DIC (Waterhouse-Friderichsen syndrome).
• Hyponatremia (SIADH).

Subacute/Chronic

• Subdural Effusion: Suspect if persistent fever, increasing head size. Treat only if symptomatic (taps).
• Subdural Empyema: Requires surgical drainage.
• Hydrocephalus: Communicating or obstructive.
• Brain Abscess: Focal deficits, fever.

Sequelae

• Sensorineural Hearing Loss (10-25%).
• Mental Retardation / Developmental Delay.
• Epilepsy.
• Motor deficits (Hemiparesis).

8. Prevention

A. Vaccination

1. Hib Vaccine: Dramatically reduced H. flu meningitis (>95% reduction).
2. Pneumococcal Conjugate Vaccine (PCV): Prevents invasive pneumococcal disease.
3. Meningococcal Vaccine: For epidemics and high-risk groups (>2 yrs).

B. Chemoprophylaxis for Contacts

• Meningococcus: Rifampicin (20 mg/kg/day BD for 2 days) OR Ciprofloxacin (single dose).
• H. influenzae: Rifampicin (20 mg/kg/day OD for 4 days).

9. Addendum: Tuberculous Meningitis (Chronic Meningitis)

• Definition: Chronic meningitis (>4 weeks duration) caused by Mycobacterium tuberculosis.
• Clinical Stages:
  • Stage I (Prodrome): Nonspecific fever, anorexia, irritability.
  • Stage II (Meningitic): Signs of meningeal irritation, cranial nerve palsies, lethargy.
  • Stage III (Coma): Deep coma, decerebrate posturing.
• Diagnosis:
  • CSF: Cobweb coagulum, Lymphocytic pleocytosis, High protein, Low sugar .
  • Imaging: Basal exudates, Hydrocephalus, Tuberculomas, Infarcts (Triad).
• Treatment:
  • ATT: 2 HRZS + 10 HR (Total 12 months).
  • Steroids: Prednisolone/Dexamethasone for 4-6 weeks (improves survival and reduces sequelae).

10. ADDENDUM: HAEMOPHILUS INFLUENZAE MENINGITIS

1. Introduction and Etiology

• Agent: Haemophilus influenzae is a Gram-negative coccobacillus.
• Virulence: Serotype b (Hib) is the most virulent strain causing invasive disease.
• Epidemiology:
  • Classically the commonest cause of bacterial meningitis in children $\le 3$ years of age.
  • Endemic occurrence is more common than epidemics.
  • Incidence has declined significantly (>95% reduction) in regions with effective Hib vaccination programs.

2. Predisposing Factors

• Age: Infants and young children ($\le 3$ years) are most susceptible.
• Immune Status: Immunocompromised states, asplenia, and hypogammaglobulinemia increase risk.
• Environmental: Malnutrition and overcrowding are contributing factors.

3. Clinical Specifics

While general features mimic other pyogenic meningitis, certain associations are notable:

• Onset: Typically presents with fever, vomiting, and irritability.
• Subdural Effusions: More frequently associated with H. influenzae and Streptococcus pneumoniae etiologies compared to other agents.
• Sequelae:
  • Hearing Loss: Sensorineural deafness occurs in 10–25% of survivors and is more common in H. influenzae infections.
  • Neurological Deficits: Mental retardation and motor deficits are potential consequences.

4. Diagnosis

• CSF Findings:
  • Appearance: Turbid.
  • Cytology: Polymorphonuclear pleocytosis.
  • Biochemistry: Elevated protein (100–500 mg/dl) and low sugar (<40 mg/dl).
  • Gram Stain: Reveals Gram-negative coccobacilli.
• Rapid Diagnostics: Latex agglutination tests can detect Hib antigens, useful in partially treated meningitis.

5. Management

A. Antibiotic Therapy

• Resistance Pattern: Resistance to $\beta$-lactams (Ampicillin) is common; therefore, Ampicillin + Chloramphenicol is no longer the preferred empiric choice.
• Drug of Choice:
  • Ceftriaxone: $100$ mg/kg/day in 2 divided doses.
  • Cefotaxime: $200$ mg/kg/day in 3-4 divided doses.
• Duration: Therapy should continue for 10–14 days.

B. Adjuvant Corticosteroids

• Indication: Dexamethasone is specifically indicated for H. influenzae meningitis to reduce audiologic and neurologic sequelae.
• Dose: $0.15$ mg/kg/dose every 6 hours for 4 days.
• Timing: Must be administered 15 minutes before the first dose of antibiotics.

C. Complication Management

• Subdural Effusions: Usually resolve spontaneously; drainage is indicated only if they cause raised intracranial pressure (ICT) or lateralizing signs.

6. Prevention

A. Chemoprophylaxis

• Indication: Recommended for household contacts to eliminate nasopharyngeal carriage.
• Regimen: Rifampicin $20$ mg/kg/day (max 600 mg) as a single daily dose for 4 days.

B. Immunoprophylaxis

• Hib Vaccine: Highly effective in reducing the burden of severe disease in children <2 years.
• Target: Critical for immunocompromised and asplenic children.