🧠 Meningitis - Comprehensive PBL Lecture Explained

PART 1: Clinical Approach

What is Meningitis?

Causative Organisms

History Taking

• Fever (high grade, abrupt)
• Severe "worst of my life" headache
• Photophobia & phonophobia
• Nausea/vomiting
• Altered consciousness (GCS decline - ominous)
• Seizures (in 20-40% of bacterial cases)
• Non-blanching petechial/purpuric rash = meningococcal septicaemia until proven otherwise

• Rapidly evolving purpuric rash
• GCS <13
• Focal neurological deficit
• Papilloedema
• New-onset seizures

Clinical Signs and Their Accuracy

Complications

• Cerebral oedema → raised ICP → brain herniation
• Subdural empyema
• Waterhouse-Friderichsen syndrome (bilateral adrenal haemorrhage in meningococcal)
• DIC, septic shock, SIADH

• Sensorineural hearing loss (5-35% - most common, especially in pneumococcal)
• Cognitive impairment, epilepsy
• Hemiplegia, visual impairment
• Amputations (from purpura fulminans)
• PTSD, anxiety, developmental delay in children

PART 2: Investigations

Blood Tests

• Blood glucose (BEFORE LP - needed for CSF:serum ratio)
• FBC: neutrophilia (bacterial), lymphocytosis (viral/TB), thrombocytopenia (DIC)
• CRP: >100 mg/L in bacterial; modest in viral
• Procalcitonin (PCT): >0.5 ng/mL = bacterial (best serum biomarker; Sens 87%, Spec 89%)
• Blood cultures x2: positive in 50-80% if taken before antibiotics
• Meningococcal/pneumococcal PCR: remains positive after antibiotics
• HIV test: routine in all patients

Lumbar Puncture (LP)

• GCS 15
• No focal neurological deficit
• No papilloedema
• Not immunocompromised
• No history of CNS disease
• Not post-seizure

• GCS <13 or declining
• Focal signs or papilloedema
• Immunocompromised
• Coagulopathy
• Suspected mass lesion

CSF Analysis - Key Values

CSF Microbiology

• Gram stain: Sensitivity 60-90% (drops to 40-60% with antibiotic pre-treatment)
  • Gram-positive diplococci = S. pneumoniae
  • Gram-negative diplococci = N. meningitidis
  • Gram-positive rod = Listeria
• CSF Culture: Gold standard (70-85% positive in untreated)
• PCR (meningococcal): Sensitivity 91-94%; remains positive 48-96h after antibiotics
• BioFire multiplex panel: Tests 14 pathogens in <1 hour
• Cryptococcal antigen (CrAg): Sensitivity and specificity >99%
• India ink: Rapid for Cryptococcus (sensitivity 75-85% in HIV)

Imaging

• Better for brainstem, posterior fossa
• Detects leptomeningeal enhancement (FLAIR + post-contrast T1)
• Best for TB meningitis: shows basal exudate, hydrocephalus, lacunar infarcts
• DWI detects early ischaemia

PART 3: Pathophysiology, Management & Epidemiology

Pathophysiology in Brief

1. Nasopharyngeal colonisation → mucosal invasion → bacteraemia
2. Bacteria breach the blood-brain barrier via transcytosis
3. Rapid multiplication in CSF (low antibody/complement environment)
4. Release of LPS/teichoic acid → TLR activation → massive cytokine storm (TNF-α, IL-1β, IL-6)
5. 3 types of cerebral oedema:
   • Vasogenic: BBB breakdown → protein leak
   • Cytotoxic: PMN enzymes → cell death
   • Interstitial: Hydrocephalus → CSF backup
6. Raised ICP → reduced cerebral perfusion → ischaemia → neuronal death

Emergency Management - First Hour

1. ABCDE approach: O₂ target SpO₂ >94%, intubate if GCS <8
2. IV access x2, blood cultures, glucose, FBC, CRP, PCT, coagulation
3. IV antibiotics within 1 hour (every 30 min delay increases mortality)
4. Dexamethasone 0.15 mg/kg IV 6-hourly x4 days - MUST be given WITH or BEFORE first antibiotic dose
5. Fluid resuscitation if hypotensive, strict fluid balance, analgesia, antiemetics
6. Notify public health immediately if meningococcal disease suspected

Empirical Antibiotics by Age

Dexamethasone - The Evidence

• Reduces hearing loss in pneumococcal meningitis (NNT = 11)
• Reduces neurological sequelae in adults (de Gans trial, NEJM 2002)
• Timing is everything: Given LATE (after antibiotics) loses its benefit
• Stop if: organism is not S. pneumoniae (in children), or Listeria/TB diagnosed
• Do NOT use in neonates (insufficient evidence)
• Not beneficial in low-income countries (different organisms, HIV, malnutrition)

Specific Treatments

• Enteroviruses: Supportive care (self-limiting)
• HSV meningitis: IV Aciclovir 10 mg/kg TDS x 14-21 days

• Induction (2 weeks): IV Amphotericin B + oral Flucytosine
• Consolidation (8 weeks): Fluconazole 400 mg/day
• Therapeutic LP daily for raised ICP (target opening pressure <20 cmH₂O) - this is critical

• 2 months: RIPE (Rifampicin + Isoniazid + Pyrazinamide + Ethambutol)
• 10 months: Rifampicin + Isoniazid
• Always add Dexamethasone 0.4 mg/kg/day tapered over 6 weeks

Raised ICP Management

• Head of bed at 30°
• Mannitol 20% (0.5-1 g/kg IV) or hypertonic saline 3%
• Avoid hypercapnia (CO₂ is a cerebral vasodilator)
• Avoid hyponatraemia (SIADH is common)
• EVD for obstructive hydrocephalus
• ICP monitoring if GCS <8

Prevention: Vaccines

• Ciprofloxacin 500 mg oral stat (preferred adult regimen)
• Or Rifampicin 600 mg BD x 2 days
• Report to public health within 24 hours (notifiable disease)

Follow-Up After Bacterial Meningitis

Key Golden Rules (Exam Must-Know)

✅ Classic triad present in <44% - always maintain high suspicion ✅ Non-blanching rash = meningococcal until proven otherwise - treat immediately ✅ Jolt accentuation = most sensitive clinical sign (97%) ✅ Never delay antibiotics for CT or LP in a deteriorating patient ✅ Dexamethasone before or with first antibiotic dose ✅ CSF lactate >3.5 = best test to distinguish bacterial vs viral (persists after antibiotics) ✅ PCR remains positive 48-96h after antibiotics - request even in pre-treated patients ✅ Add amoxicillin for Listeria cover in >50y, immunocompromised, neonates ✅ Audiological testing mandatory before discharge in all bacterial meningitis ✅ "When in doubt, treat" - the golden rule of meningitis