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Meningitis — Davidson's Principles and Practice of Medicine

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1. What Is Meningitis?

• Pyrexia (fever)
• Headache
• Meningism — headache, photophobia, and neck stiffness, sometimes with:
  • Kernig's sign: extension at the knee with the hip joint flexed causes spasm in the hamstring muscles
  • Brudzinski's sign: passive flexion of the neck causes flexion of the hips and knees

Meningitis frequently presents without meningism. Kernig's and Brudzinski's signs are specific but their sensitivity can be as low as 5%. Meningitis should therefore be considered in anyone who presents with fever and headache.

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2. Epidemiology

• Viruses are the most common cause of meningitis globally.
• Bacterial meningitis — geographical patterns of causative organisms vary and are strongly age-related.
• In the 'meningitis belt' of sub-Saharan Africa, drought and dust storms (Harmattan winds) are associated with meningococcal outbreaks.
• Most bacterial causes are normal commensals of the upper respiratory tract; new pathogenic strains are acquired by droplet spread, requiring close contact.
• Epidemics of meningococcal meningitis occur in cramped living conditions or hot, dry climates.
• Tuberculosis and cysticercosis may not be prevalent in high-income countries but are common in other regions and occur in returning travellers or immigrants.
• Fungal meningitis is uncommon and almost exclusively occurs in the immunosuppressed.
• Streptococcus suis, a rare zoonotic cause, is an important cause in parts of Asia (Vietnam, Thailand) and is associated with porcine contact — >50% of survivors develop some hearing loss.
• Antibiotic use has reduced bacterial meningitis frequency, but mortality and morbidity remain significant.

Bacterial Causes by Age Group

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3. Aetiologies

Infective

• Streptococcus pneumoniae (pneumococcus)
• Neisseria meningitidis (meningococcus — serogroups A, B, C, Y, W135)
• Mycobacterium tuberculosis
• Haemophilus influenzae
• Listeria monocytogenes
• Staphylococcus aureus (skull fracture)
• Other streptococci including Streptococcus suis

• Enteroviruses (echo, Coxsackie, polio) — most common viral cause
• Herpes simplex virus type 2 (Mollaret's meningitis)
• Varicella zoster virus
• Herpes simplex type 1
• Epstein–Barr virus
• Cytomegalovirus
• Measles, Mumps
• Lymphocytic choriomeningitis virus, West Nile virus, HIV

• Cryptococcus neoformans (most common fungal cause; strongly associated with HIV)
• Candida, Histoplasma, Blastomyces, Coccidioides, Sporothrix

Non-infective ('Sterile')

• Sarcoidosis
• Systemic lupus erythematosus (SLE)
• Behçet's disease

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4. Pathophysiology (Chronological)

Bacterial Meningitis

• Adhesions may obstruct the free flow of CSF → hydrocephalus
• They may damage cranial nerves at the base of the brain → hearing loss (a frequent complication)
• CSF pressure rises rapidly; protein content increases; a cellular reaction develops (type and severity vary with the causative organism)

Tuberculous Meningitis

• Most commonly occurs shortly after a primary TB infection in childhood or as part of miliary tuberculosis.
• The usual source is a caseous focus in the meninges or brain substance adjacent to the CSF pathway.
• The brain becomes covered by a greenish, gelatinous exudate especially around the base.
• Numerous scattered tubercles appear on the meninges.
• The slower, more insidious nature (onset over 2–8 weeks) distinguishes it from other bacterial meningitides.

Viral Meningitis

• Results in a benign, self-limiting illness.
• The acute immune response causes lymphocytic infiltration of the CSF.
• Unless associated encephalitis occurs, prognosis is excellent.

Fungal Meningitis (Cryptococcus neoformans)

• Occurs predominantly in the immunosuppressed (HIV infection).
• Leads to raised intracranial pressure (CSF opening pressure often very raised).
• CSF findings resemble tuberculous meningitis (lymphocytes, elevated protein, low glucose).

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5. Clinical Manifestations

General Features (All Meningitis)

• Fever and headache — most common presenting features
• Meningism: neck stiffness, photophobia
• Kernig's sign; Brudzinski's sign (specific but low sensitivity ~5%)
• Altered consciousness — more common in older patients

Bacterial Meningitis

• 90% of patients have any two of: headache, pyrexia, meningism, and altered consciousness

• Drowsiness, progressing to coma in severe cases
• Focal neurological signs (later in disease)
• Seizures — occur in ~25% of patients
• Rash — in meningococcal meningitis (morbilliform, petechial, or purpuric)
• Rapid onset obtundation due to cerebral oedema when accompanied by sepsis

• Pneumococcal meningitis: accompanying otitis media, pneumonia; more common in older patients, alcoholics, and those with hyposplenism; very purulent CSF; high mortality
• Meningococcal meningitis: rash (petechial/purpuric), can progress to septicaemia; complications include shock, intravascular coagulation, renal failure, peripheral gangrene, arthritis (septic or reactive), pericarditis
• Listeria monocytogenes: causes rhombencephalitis (brainstem encephalitis) in immunosuppressed, neonates, older adults, diabetics, alcoholics, and pregnant women
• Chronic meningococcaemia (rare): weeks/months of recurrent fever, sweating, joint pains, transient rash

Tuberculous Meningitis (onset over 2–8 weeks)

• Stage I (early): Non-specific symptoms/signs, no alteration of consciousness — complete recovery usual with treatment
• Stage II (intermediate): Altered consciousness without coma or delirium + minor focal neurological signs
• Stage III (advanced): Stupor or coma, severe neurological deficits, seizures, or abnormal movements — death or serious neurological deficit in up to 30% even with treatment

Viral Meningitis

• Occurs mainly in children or young adults
• Acute onset of headache, irritability and rapid development of meningism
• Headache is usually the most severe feature
• High pyrexia possible; focal neurological signs are rare

Fungal Meningitis

• Atypical presentation: subacute or chronic meningism, fever, headache
• Symptoms of raised intracranial pressure

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6. Investigations (Most to Least Important)

1. Lumbar Puncture (LP) — Most Critical

• Mandatory unless contraindicated
• CSF analysis differentiates the cause (Box 28.6 in Davidson's)
• Contraindications to immediate LP:
  • Signs of severe sepsis or rapidly evolving rash
  • Anticoagulant therapy/known thrombocytopaenia
  • Respiratory or cardiac compromise
  • Focal neurological signs
  • Papilloedema
  • Continuous or uncontrolled seizures
  • GCS ≤ 12

• Gram film and culture: may identify the organism
• Viral NAAT (nucleic acid amplification test): identifies specific viral cause
• TB: smear of centrifuged deposit (negative doesn't exclude); culture (takes up to 6 weeks); WHO recommends Xpert MT/RIF Ultra NAAT in addition to smear and culture
• Fungal: India ink test, cryptococcal PCR, cryptococcal antigen (in CSF and sometimes serum)
• Note: a bloody tap may complicate CSF findings — if WBC is above normal, treat for bacterial meningitis and disregard the red cell count

2. Blood Cultures — Immediately Essential

• Must be taken before starting antibiotics if possible
• May be positive; PCR can identify bacterial DNA on blood for several days after antibiotic treatment has started
• Meningococcal and pneumococcal PCR on blood

3. CT Brain (Before LP if Contraindicated)

• Performed to exclude a mass lesion (e.g. cerebral abscess) before LP, to prevent coning
• Should not delay empirical treatment
• Brain imaging in TB meningitis may show: hydrocephalus, basal meningeal enhancement on contrast CT/MRI, or intracranial tuberculoma

4. PCR (Blood and CSF)

• PCR techniques can identify bacterial DNA from blood and CSF for several days after antibiotic treatment has started
• Meningococcal PCR, pneumococcal PCR
• Throat swab for enterovirus PCR if viral meningitis is likely
• Xpert MT/RIF Ultra for TB

5. Full Blood Count, CRP/Procalcitonin, Biochemistry

• Full blood count, creatinine, electrolytes, glucose, liver function tests, clotting screen
• Procalcitonin or CRP — useful inflammatory markers
• Serology sample

6. MRI Brain

• More sensitive than CT in detecting early abnormalities in encephalitis
• For TB meningitis: shows basal meningeal enhancement, hydrocephalus, tuberculoma

7. EEG (Viral Encephalitis)

• Usually abnormal in early viral encephalitis
• Shows characteristic periodic slow-wave activity in the temporal lobes in herpes simplex encephalitis

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7. Expected Outcome (Prognosis)

Adverse Prognostic Factors (Bacterial Meningitis):

• Hypotensive shock
• Rapidly developing rash
• Haemorrhagic diathesis
• Multisystem failure
• Age over 60 years
• Presentation with sepsis rather than meningitis (doubles mortality in meningococcal disease)

Common Sequelae:

• Hearing loss — frequent complication (>50% of S. suis survivors; common in bacterial meningitis)
• Cranial nerve palsies
• Hydrocephalus
• Cognitive impairment
• Focal neurological deficits
• Epilepsy

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8. Management (Most to Least Important)

Immediate Priorities

1. Resuscitate and Stabilise the Patient

• Assess GCS within the first hour after arrival
• Assess need for intensive care (cardiac, respiratory, or renal involvement; CNS depression)
• Early endotracheal intubation and mechanical ventilation protect the airway and may prevent ARDS in severe cases

2. Blood Cultures + Empirical Antibiotics — Start Within 1 Hour

• If LP cannot be performed immediately, start empirical antibiotic treatment after blood cultures and within the first hour
• If predominantly sepsis or rapidly evolving rash: give antibiotics immediately after blood cultures, follow sepsis guidelines, and defer LP

3. Lumbar Puncture (if no contraindication)

• Perform LP if no contraindication
• If contraindicated, obtain CT first
• Note: once stable, LP may still be diagnostically useful even after several days

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Empirical Antibiotic Therapy (British Infection Association Guideline 2016)

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Targeted Antibiotic Therapy (when organism is known — Box 28.63)

Duration guide: pneumococcal 10–14 days; meningococcal ~7 days; Listeria 21 days. Local guidance should always be sought.

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4. Adjunctive Dexamethasone

• Dexamethasone 10 mg IV 4× daily for 2–4 days
• Useful in reducing hearing loss and neurological sequelae in both children and adults in high-income countries
• Evidence does not support its use in lower-income countries or where there are high rates of untreated HIV

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5. Management of Tuberculous Meningitis

• Start anti-TB chemotherapy (including pyrazinamide) as soon as diagnosis is made or strongly suspected — do not wait for culture confirmation (results may take up to 6 weeks)
• Add glucocorticoids early — improves mortality (though not focal neurological damage), regardless of HIV status
• Surgical ventricular drainage may be needed if obstructive hydrocephalus develops
• Skilled nursing, adequate hydration, and nutrition essential during acute phase

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6. Management of Fungal Meningitis

• Antifungal therapy (treatment discussed in specialist chapter p. 363)
• Treatment of raised CSF pressure may be complex and frequent — sometimes daily lumbar punctures are required

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7. Prevention of Meningococcal Infection (Chemoprophylaxis)

• Single dose of ciprofloxacin (preferred)
• Rifampicin for 2 days (alternative if unable to take ciprofloxacin)

• Household contacts (ate/slept in same dwelling within 7 days)
• Child-care and nursery-school contacts
• Persons having contact with patient's oral secretions within 7 days (kissing, shared toothbrush/utensils, mouth-to-mouth resuscitation, unprotected endotracheal intubation)
• Aircraft contacts seated next to patient for >8 hours

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8. Management of Viral Meningitis

• No specific treatment; condition is usually benign and self-limiting
• Treat symptomatically in a quiet environment
• Recovery usually occurs within days

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