Acute Bacterial Meningitis (LP Contraindications, Ceftriaxone, Dexamethasone) and Viral Encephalitis (Aciclovir)

Pediatric CNS Infections: Meningitis and Encephalitis

Central nervous system infections represent some of the most critical medical emergencies in pediatrics. Acute bacterial meningitis carries a mortality rate of 5% to 10% in developed nations and inflicts permanent neurodevelopmental sequelae—including sensorineural hearing loss, motor deficits, epilepsy, and intellectual disability—in up to 20% to 30% of survivors. Rapid recognition, immediate initiation of bactericidal antimicrobials, adherence to lumbar puncture safety rules, and prompt administration of adjuvant therapy are paramount.

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Etiology Categorized Strictly by Age Group

The microbial pathogens causing acute bacterial meningitis vary dramatically by patient age, reflecting immune system maturation and maternal antibody transfer.

1. Neonates (<1 Month / <28 Days)

• Group B Streptococcus (Streptococcus agalactiae): The most common pathogen overall (causing ~50% of neonatal cases). Acquired vertically during delivery (early-onset) or postnatally (late-onset).
• Gram-Negative Enteric Bacilli: Predominantly Escherichia coli (especially strains expressing the K1 capsular antigen, which facilitates blood-brain barrier invasion), Klebsiella pneumoniae, and Enterobacter species.
• Listeria monocytogenes: Transmitted transplacentally or through maternal ingestion of unpasteurized dairy. Intrinsically resistant to all cephalosporins.

2. Infants and Children (>1 Month to 18 Years)

• Neisseria meningitidis (Meningococcus): Serogroups B, C, W-135, and Y. In Europe, serogroup B accounts for the majority of pediatric cases following widespread immunization against serogroup C. Characterized by rapid progression to septic shock, purpura fulminans, and disseminated intravascular coagulation (DIC).
• Streptococcus pneumoniae (Pneumococcus): A major cause of bacterial meningitis in vaccinated older infants and children. Associated with the highest mortality rate (~8–10%) and the highest rate of permanent sensorineural hearing loss (up to 30%).
• Haemophilus influenzae type b (Hib): Markedly reduced across Europe by routine conjugate vaccination; remains an important cause in unvaccinated, incompletely vaccinated, or immigrant populations.

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Clinical Manifestations: Neonates vs. Older Children

Recognizing meningitis requires an understanding of age-specific presentations. Young infants rarely display classic meningeal signs.

+---------------------------------------------------------------------------------------------------------+
|                               AGE-SPECIFIC PRESENTATIONS OF MENINGITIS                                  |
+---------------------------------------------------+-----------------------------------------------------+
| Neonates & Young Infants (<12-18 Months)          | Older Children & Adolescents (>18 Months)           |
+---------------------------------------------------+-----------------------------------------------------+
| - Temperature instability (fever or hypothermia)  | - Classical triad: High fever, headache, stiff neck |
| - Lethargy, stupor, poor suck, weak feeding       | - Photophobia, phonophobia, nausea, vomiting        |
| - "Paradoxical irritability" (cries when held)   | - Positive Kernig's and Brudzinski's signs          |
| - Tense, bulging, or full anterior fontanelle     | - Confusion, delirium, obtundation, coma            |
| - High-pitched cry, apnea, seizures               | - Petechial / purpuric non-blanching rash (Meningo) |
| - Neck stiffness and Kernig/Brudzinski ABSENT!    | - Focal neurological deficits or cranial palsies    |
+---------------------------------------------------+-----------------------------------------------------+

Clinical Examination Signs of Meningeal Irritation

• Nuchal Rigidity: Inability to flex the neck forward passively to touch the chin to the chest due to painful spasm of the extensor paraspinal muscles.
• Kernig's Sign: With the patient supine and the hip flexed at 90°, passive extension of the knee elicits severe pain and resistance beyond 135°.
• Brudzinski's Sign: Passive flexion of the patient's neck causes involuntary, spontaneous flexion of the hips and knees.
• "Paradoxical Irritability": While a normal irritable infant is comforted by parental rocking and cuddling, an infant with meningitis cries more violently when held because moving the spine stretches inflamed meninges.
• Non-Blanching Rash: Petechial (<2 mm) and ecchymotic/purpuric (>2 mm) lesions that do not blanch under pressure from a clear drinking glass (glass tumbler test) indicate acute meningococcal septicemia and mandate immediate emergency resuscitation.

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Emergency Resuscitation and Lumbar Puncture Safety

                         [Suspected Acute Bacterial Meningitis]
                                           |
                      [ABCDE Assessment & Blood Cultures Taken]
                                           |
                    +----------------------+----------------------+
                    |                                             |
    [ABSOLUTE CONTRAINDICATION TO LP?]               [NO CONTRAINDICATIONS TO LP]
                    |                                             |
                   YES                                            NO
                    |                                             |
- DO NOT PERFORM LP!                                - Perform LP immediately
- Give age-appropriate IV antibiotics               - Give age-appropriate IV antibiotics
- Resuscitate shock / Stabilize airway              - Send CSF for microscopy, biochemistry, PCR
- Neuroimaging when indicated, after stabilization  - Target antibiotics to gram stain/culture

Absolute Contraindications to Immediate Lumbar Puncture

Performing a lumbar puncture in an unstable patient or in the presence of an intracranial mass / significant cerebral edema creates a pressure gradient that drives brain parenchyma downward, precipitating fatal cerebellar tonsillar or transtentorial herniation (coning).

1. Signs of Significantly Raised Intracranial Pressure:
   • Papilledema on funduscopy.
   • Severely depressed or deteriorating consciousness (NICE NG240: GCS ≤9, or a progressive/sustained or rapid fall in consciousness).
   • Focal neurological deficits (e.g., hemiparesis, unilateral pupillary dilation, facial asymmetry).
   • Abnormal posturing (decorticate or decerebrate rigidity).
   • Cushing's triad (hypertension, bradycardia, irregular breathing).
2. Hemodynamic Instability or Septic Shock: Capillary refill time >3 seconds, hypotension, cool/mottled peripheries, or severe tachycardia. Forcing an infant into the hyperflexed spinal position further compromises venous return and precipitously worsens cardiovascular collapse.
3. Severe Coagulopathy or Bleeding Diathesis: Thrombocytopenia (platelets <50,000/microL), rapidly evolving purpuric rash / DIC, or ongoing therapeutic anticoagulation. Puncture can lacerate epidural venous plexuses, causing a compressive spinal epidural hematoma and irreversible paraplegia.
4. Severe Respiratory Insufficiency: Respiratory distress, apnea, or impending respiratory arrest (spinal flexion occludes upper airways in young infants).
5. Local Cutaneous Infection: Active cellulitis, furunculosis, or sepsis over the proposed lumbar puncture site (L3–L4 or L4–L5), which would seed bacteria directly into the subarachnoid space.

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Empirical Antibiotic Regimens and Adjuvant Dexamethasone

Empirical Antibiotic Regimens by Age

Adjuvant Dexamethasone Protocol

• Eligibility, Dose and Duration: For suspected bacterial meningitis beyond the neonatal period, 0.15 mg/kg IV every 6 hours; NICE advises specialist discussion at 28 days to 3 months. Continue for 4 days for Hib or pneumococcus; stop for other organisms. Not routine in neonates or meningococcal sepsis.
• Timing: Give dexamethasone before or with the first antibiotic dose when possible. Never delay antibiotics to obtain dexamethasone.
• Mechanism: Antibiotic-induced bacterial lysis releases massive quantities of cell-wall components (endotoxin, teichoic acid, peptidoglycan) into the subarachnoid space, triggering a violent inflammatory burst driven by TNF-alpha, IL-1beta, and prostaglandins. Dexamethasone suppresses cytokine transcription and limits subarachnoid inflammation.
• Evidence-Based Benefits: Randomized controlled trials in European pediatric populations demonstrate that early dexamethasone significantly reduces the incidence of severe sensorineural hearing loss in Haemophilus influenzae type b and Streptococcus pneumoniae meningitis, and reduces overall neurological sequelae.

• Warning

  A missed first dose does not establish absence of benefit. NICE NG240: give delayed dexamethasone promptly if less than 12 hours have elapsed; after 12 hours, seek infection-specialist advice.

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Cerebrospinal Fluid (CSF) Analysis Interpretation

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Chemoprophylaxis for Close Contacts of Meningococcal Disease

Close contacts of patients with confirmed or suspected invasive meningococcal disease have an estimated 500- to 1,000-fold increased risk of developing disease. Chemoprophylaxis eradicates nasopharyngeal carriage of Neisseria meningitidis.

Indications for Chemoprophylaxis

• All household members residing in the same dwelling.
• Daycare or preschool classroom contacts within the 7 days prior to disease onset.
• Anyone with direct exposure to oral secretions (e.g., kissing, mouth-to-mouth resuscitation, endotracheal intubation without face mask/eye protection).

Recommended Regimens

1. Oral Ciprofloxacin: Preferred first-line agent for adults and children due to single-dose convenience:
   • Children: Single oral dose of 20 mg/kg (maximum 500 mg).
   • Adults: Single oral dose of 500 mg.
2. Oral Rifampicin:
   • Children <1 month: 5 mg/kg orally every 12 hours for 2 days (4 doses total).
   • Children ≥1 month: 10 mg/kg orally every 12 hours for 2 days (4 doses total; max 600 mg/dose).
   • Counseling: Stains body secretions (urine, sweat, tears) a bright orange-red; permanently discolors soft contact lenses; potent inducer of hepatic CYP450 enzymes that reduces efficacy of oral contraceptive pills.
3. Intramuscular Ceftriaxone:
   • Children <12 years: Single IM injection of 125 mg.
   • Adults & Children ≥12 years: Single IM injection of 250 mg.
   • Drug of choice in pregnant women.

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Viral Encephalitis: Herpes Simplex Virus and High-Dose Aciclovir

While viral meningitis is typically a self-limiting inflammation of the leptomeninges, viral encephalitis represents direct viral invasion and inflammation of the brain parenchyma, presenting with marked cerebral dysfunction.

Clinical Distinction: Meningitis vs. Encephalitis

• Meningitis: Meningeal inflammation typically causes fever, headache, photophobia, and stiff neck. Bacterial meningitis can also cause altered consciousness, seizures, or focal deficits; these findings do not establish a viral cause.
• Encephalitis: Features of parenchymal brain involvement:
  • Altered consciousness: Confusion, delirium, disorientation, lethargy, stupor, or coma.
  • Focal neurological deficits: Hemiparesis, cranial neuropathies, aphasia/dysphasia.
  • Seizures: Frequently focal or secondarily generalized motor seizures.
  • Behavioral and psychiatric disturbances: Agitation, hallucinations, bizarre behavior, personality change.

Herpes Simplex Virus Type 1 (HSV-1) Encephalitis

• Pathophysiology: The most common cause of non-epidemic, sporadic, fatal viral encephalitis in children and adults. HSV-1 reaches the brain via retrograde axonal transport along the olfactory or trigeminal nerves, exhibiting an intense predilection for the temporal lobes, orbitofrontal cortex, and limbic system, causing severe hemorrhagic necrotizing encephalitis.
• Clinical Presentation: Acute onset of high fever, hemicranial headache, progressive confusion, focal seizures (often temporal semiology), expressive dysphasia, memory deficits, and bizarre psychiatric manifestations.
• Diagnostic Workup:
  • CSF Analysis: Lymphocytic pleocytosis (50 to 500 WBC/microL), elevated protein (0.6 to 1.5 g/L), normal glucose, and presence of erythrocytes (RBCs) or xanthochromia resulting from temporal lobe hemorrhagic necrosis.
  • Molecular Gold Standard: CSF HSV PCR (sensitivity and specificity >95%). Note: If CSF is sampled within the first 24 to 48 hours of symptoms, PCR may occasionally be false-negative. If clinical suspicion is high, continue aciclovir and repeat LP at 48 to 72 hours.
  • Neuroimaging (Contrast-Enhanced MRI Brain): Hyperintensity on T2-weighted and FLAIR sequences with restricted diffusion characteristically localized to the inferior and medial temporal lobes, insular cortex, and orbital surfaces of the frontal lobes (typically asymmetrical).
  • Electroencephalography (EEG): Periodic Lateralized Epileptiform Discharges (PLEDs) and sharp-and-slow wave complexes over the affected temporal lobe.
• Emergency Pharmacotherapy:

  • Important

  • IMMEDIATE EMPIRICAL ACICLOVIR: Initiate high-dose intravenous aciclovir immediately upon clinical suspicion. Never withhold aciclovir while awaiting PCR results or neuroimaging.

  • Pediatric Dosage: Young infants: 20 mg/kg IV every 8 hours; 3 months–12 years: 500 mg/$m^2$ IV every 8 hours; above 12 years: 10 mg/kg IV every 8 hours. Adjust for renal function; infuse over 1 hour.
  • Duration: At least 21 days in neonates and children through 12 years; older children generally 14–21 days. Repeat CSF HSV PCR before stopping; if still positive, continue treatment and repeat PCR weekly until negative.
  • Renal Protection: Aciclovir can precipitate as crystals in the renal tubules, leading to acute crystalline nephropathy. Maintain generous intravenous hydration and monitor serum creatinine regularly.

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Acute Flaccid Weakness and Peripheral Neuropathies

Guillain–Barré Syndrome (GBS)

• An immune-mediated polyradiculoneuropathy that often follows a respiratory or gastrointestinal infection, such as Campylobacter jejuni. It causes progressive, roughly symmetrical, ascending weakness with reduced or absent reflexes. Young children often present with pain, irritability or refusal to walk.
• Nadir is usually reached within 4 weeks. Danger signs are respiratory failure, bulbar weakness and autonomic instability (arrhythmias and blood pressure swings), so monitor vital capacity, swallowing, heart rate and blood pressure.
• Investigations: CSF typically shows raised protein with a normal cell count (albuminocytological dissociation), although it may be normal in the first week. Nerve conduction studies support the diagnosis.
• Treatment: for patients who cannot walk unaided, give intravenous immunoglobulin 0.4 g/kg/day for 5 days (2 g/kg in total) within 2 weeks of onset, or plasma exchange within 4 weeks. Corticosteroids are not recommended, and a second immunoglobulin course is not recommended for a poor prognosis. Most children recover well with rehabilitation.
• Miller Fisher syndrome combines ophthalmoplegia, ataxia and areflexia and is associated with anti-GQ1b antibodies.

Inherited Neuropathies

Charcot–Marie–Tooth disease is the commonest inherited neuropathy; type 1A is an autosomal dominant PMP22 duplication. It causes slowly progressive distal weakness and wasting, pes cavus, toe walking or frequent tripping and reduced reflexes, with slowed nerve conduction in demyelinating forms.

Source: EAN/PNS Guideline on diagnosis and treatment of Guillain–Barré syndrome.