Meningitis
Description
- Inflammation of the leptomeninges - pia and arachnoid - and the CSF within the subarachnoid space
- Classic triad: fever + neck stiffness + altered mental state
- *All three present in fewer than half. But ~95% have at least two of fever, headache, neck stiffness or altered mental state*
- Meningism = headache, photophobia, neck stiffness (Kernig and Brudzinski signs are specific but insensitive)
- Meningitis vs encephalitis vs meningoencephalitis
- Meningitis - meningeal irritation, normal cerebral function
- Encephalitis - altered conscious state, personality change, seizures, focal deficit = brain parenchymal involvement
- The distinction drives empirical therapy: encephalitis mandates aciclovir
Epidemiology
- Bacterial meningitis ~1-2 per 100,000/yr in Australia - falling with conjugate vaccination
- Viral (aseptic) meningitis is much commoner, ~10-20 per 100,000/yr, and peaks in summer and autumn
- Meningococcal disease: bimodal - infants and 15-24 year olds; serogroup B predominates in Australia since MenACWY vaccination
- Higher incidence and worse outcomes in Aboriginal and Torres Strait Islander communities and in remote settings
- Cryptococcal meningitis - advanced HIV, and increasingly in other immunosuppressed groups
Aetiopathogenesis
Bacterial - by host
| Group | Organisms |
|---|---|
| Adults (16-50) | **Streptococcus pneumoniae - the commonest cause of bacterial meningitis in adults*; Neisseria meningitidis* |
| >50 yrs, pregnant, immunosuppressed, alcohol misuse | Add *Listeria monocytogenes - the reason for adding benzylpenicillin or amoxicillin* |
| Neonates | Group B Streptococcus, E. coli, Listeria |
| Post-neurosurgery, shunt, penetrating trauma | *Coagulase-negative staphylococci, S. aureus, Gram negatives incl. Pseudomonas*** |
| Basal skull fracture / CSF leak | S. pneumoniae, H. influenzae, group A strep |
| Immunosuppressed | Listeria, TB, Cryptococcus, Nocardia, Gram negatives |
Viral
- *Enteroviruses are the commonest cause of viral meningitis* (echovirus, coxsackie) - summer/autumn
- HSV-2 (meningitis, often recurrent - Mollaret), HSV-1 (encephalitis), VZV
- HIV seroconversion - always consider and test
- Mumps, arboviruses (Murray Valley encephalitis, Japanese encephalitis, West Nile/Kunjin), measles, LCMV
Other
- TB meningitis - subacute, basal meningitis, cranial nerve palsies, hydrocephalus; high mortality, and treatment is often started empirically
- Cryptococcal - HIV with CD4 <100; raised opening pressure is the key management issue
- Fungal (Candida, Coccidioides), syphilis, Lyme, leptospirosis, amoebic
- Non-infective: malignant/leptomeningeal, drug-induced (NSAIDs, trimethoprim, IVIg), sarcoid, Behcet, SLE, vasculitis
Mechanism
- Nasopharyngeal colonisation -> mucosal invasion -> bacteraemia -> crossing the blood-brain barrier (or direct spread from sinus, mastoid, skull fracture)
- Bacterial cell wall components -> cytokine release (TNF, IL-1) -> BBB breakdown, cerebral oedema, raised ICP, dec cerebral blood flow, vasculitis and thrombosis
- *Antibiotic-induced bacterial lysis amplifies the inflammatory burst - which is why dexamethasone is given with or before the first antibiotic dose*
Diagnosis
Clinical
- Fever, headache, neck stiffness, photophobia, vomiting, altered conscious state
- Non-blanching petechial or purpuric rash -> meningococcaemia; may be absent or late, and its absence proves nothing
- Seizures (~15-30% of pneumococcal), focal deficits, cranial nerve palsies (TB, Listeria, basal meningitis)
- Look for the source: otitis media, sinusitis, mastoiditis, endocarditis, pneumonia, CSF rhinorrhoea
The pathway - order matters
- *Do not delay antibiotics for a CT or an LP*
- Blood cultures + empirical antibiotics + dexamethasone immediately, then LP as soon as safe
- CT head BEFORE LP only if: dec conscious state (GCS <=12 or fluctuating), focal neurological deficit, new seizure, papilloedema, immunocompromised, or a history of CNS disease
- A normal CT does not exclude raised ICP - use clinical judgement
- Do not LP if coagulopathy, platelets <50, spinal abscess at the site, or cardiorespiratory instability
CSF interpretation - the core table
| Bacterial | Viral | TB | Cryptococcal | |
|---|---|---|---|---|
| Appearance | Turbid | Clear | Clear/fibrin web | Clear |
| Opening pressure | High | Normal/mildly up | High | Very high |
| Cells | Raised, NEUTROPHIL predominant, often >100 (may be >1000) | Raised, LYMPHOCYTE predominant, usually <1000 (neutrophils may predominate in the first 24 h) | Lymphocytic, 50-500 | Lymphocytic, may be low or normal in advanced HIV |
| Protein | Often >1.0 g/L | Mildly raised, 0.5-1.0 g/L | Very high, often >1-2 g/L | Raised |
| Glucose | Low | Normal or only slightly low | Low | Low |
| CSF:serum glucose | Very low (<0.4) | Normal or near-normal | Very low | Low |
| Other | Gram stain, culture, PCR | Enterovirus/HSV/VZV PCR | AFB smear (low yield), TB PCR, culture; take a large volume (>=6-10 mL) | India ink, cryptococcal antigen (CrAg - high sensitivity) |
- Always send: cell count and differential, protein, glucose (with a PAIRED serum glucose), Gram stain, culture, and PCR panel
- *Partially treated bacterial meningitis shifts the picture toward lymphocytes with a negative Gram stain - the glucose and protein remain the best discriminators*
- Raised lactate (>3.5 mmol/L) favours bacterial
Other tests
- Blood cultures x2 before antibiotics (positive in ~50-80% of bacterial meningitis)
- Meningococcal and pneumococcal PCR on blood - remains positive after antibiotics
- FBE, UEC, LFT, CRP, coagulation, glucose, blood gas
- HIV test in everyone; consider syphilis serology
- CXR; consider echocardiogram (endocarditis), CT sinuses/temporal bones
- Notify public health immediately for meningococcal disease - contact tracing and clearance antibiotics
Management
A. Empirical therapy - within 1 hour, before imaging or LP if there is any delay
- Dexamethasone 10 mg IV 6-hourly for 4 days - give with, or just before, the first antibiotic dose
- Proven mortality and hearing-loss benefit in pneumococcal meningitis
- Stop it if the pathogen turns out to be Listeria or if bacterial meningitis is excluded
- Ceftriaxone 2 g IV 12-hourly (or cefotaxime 2 g IV 6-hourly)
- *PLUS benzylpenicillin 2.4 g IV 4-hourly (or amoxicillin/ampicillin 2 g IV 4-hourly) for Listeria cover* if:
- Age >50, pregnant, immunocompromised, alcohol misuse, or debilitated
- PLUS vancomycin if Gram-positive diplococci are seen, pneumococcus is suspected, or there is risk of a ceftriaxone-resistant strain
- Add aciclovir 10 mg/kg IV 8-hourly if there is ANY suggestion of encephalitis - altered conscious state, seizures, personality change, focal deficit
- The cost of unnecessary aciclovir is trivial; the cost of missing HSV encephalitis is not
- In the community with suspected meningococcaemia: benzylpenicillin IM/IV before transfer
B. Then refine
| Organism | Therapy |
|---|---|
| *S. pneumoniae* | Ceftriaxone +/- vancomycin per susceptibility; 10-14 days |
| *N. meningitidis* | Ceftriaxone or benzylpenicillin; 5-7 days |
| *L. monocytogenes* | Benzylpenicillin or amoxicillin +/- gentamicin; at least 21 days. Cephalosporins have NO activity - this is the exam point |
| Gram negative bacilli | Ceftriaxone/meropenem; 21 days |
| **S. aureus / shunt infection** | Flucloxacillin or vancomycin; remove the device |
| TB | Isoniazid, rifampicin, pyrazinamide, ethambutol for 2 months then continuation to 12 months, PLUS corticosteroid |
| Cryptococcal | Induction liposomal amphotericin B + flucytosine, then fluconazole; serial therapeutic LPs for raised pressure |
| HSV encephalitis | Aciclovir 14-21 days |
C. Supportive
- Careful fluid management - euvolaemia; neither restrict nor overload; monitor for SIADH
- Manage raised ICP: head up 30 degrees, avoid hypotonic fluids, treat seizures, neurosurgical input; repeated therapeutic LP in cryptococcal disease
- ICU if dec GCS, shock, seizures or respiratory compromise; early inotropic support in meningococcal septicaemia
- Analgesia, antiemetics, VTE prophylaxis
- Formal audiology in every survivor of bacterial meningitis before discharge - sensorineural hearing loss is the commonest sequela and cochlear ossification makes late implantation harder
D. Public health and prevention
- Notify immediately - meningococcal and Haemophilus disease are urgently notifiable
- Chemoprophylaxis for close contacts of meningococcal disease: ciprofloxacin, rifampicin or ceftriaxone - household, intimate and childcare contacts, and healthcare workers with direct exposure to respiratory secretions
- Vaccination: MenACWY and MenB (funded for infants, adolescents and Aboriginal and Torres Strait Islander children under the NIP), 13/23-valent pneumococcal, Hib
- Asplenia, complement deficiency (including eculizumab/ravulizumab therapy), HIV, transplant - all need meningococcal and pneumococcal vaccination and, for eculizumab, antibiotic prophylaxis
- Investigate recurrent bacterial meningitis: CSF leak/basal skull fracture, complement deficiency (C5-C9), asplenia, hypogammaglobulinaemia, parameningeal focus
E. Viral meningitis
- Supportive - analgesia, antiemetics, fluids
- Stop antibiotics once bacterial disease is excluded; do not treat enteroviral meningitis with aciclovir
- Usually self-limiting over 7-10 days
Associations
- Asplenia/hyposplenism - encapsulated organisms (pneumococcus, meningococcus, Hib)
- Terminal complement deficiency (C5-C9) and properdin deficiency - recurrent meningococcal disease
- Eculizumab, ravulizumab and other complement inhibitors - a 1000-2000x increase in meningococcal risk; vaccinate and give prophylactic antibiotics
- HIV - cryptococcal, TB, syphilis, lymphoma; and seroconversion illness itself
- Head injury with a basal skull fracture or CSF rhinorrhoea; cochlear implant
- Otitis media, mastoiditis, sinusitis, dental infection; endocarditis
- Alcohol misuse, cirrhosis, diabetes, malignancy, corticosteroids, transplantation
- Ventriculoperitoneal shunt and neurosurgery
- Crowding - university halls, military barracks, Hajj pilgrimage (MenACWY required)
- Pregnancy - Listeria (soft cheese, deli meats)
Natural history & complications
- Bacterial meningitis mortality ~15-25% in adults even with optimal therapy
- Pneumococcal ~20-30% (the highest); meningococcal ~5-10%; Listeria ~15-30%; TB meningitis ~20-50%
- Neurological sequelae in ~20-30% of bacterial survivors
- Viral meningitis: excellent prognosis, full recovery in almost all (though headache and fatigue may persist for weeks)
- HSV encephalitis untreated: >70% mortality; treated: ~20%, with frequent memory and behavioural sequelae
Poor prognostic factors
- Low GCS on presentation, seizures, focal deficits
- Delay to antibiotics - the strongest modifiable determinant
- Pneumococcal aetiology, age >60, immunocompromise
- Shock, DIC, thrombocytopenia, high CSF protein with low CSF white cell count (overwhelming infection)
Complications
- Sensorineural hearing loss (~10-30%) - the commonest sequela
- Cognitive impairment, memory and concentration deficits, fatigue
- Seizures and epilepsy; hydrocephalus (especially TB); subdural empyema or effusion
- Cerebral infarction from vasculitis, venous sinus thrombosis, cerebral abscess
- SIADH and hyponatraemia
- Meningococcal septicaemia: DIC, purpura fulminans, peripheral gangrene and limb loss, Waterhouse-Friderichsen adrenal haemorrhage
- Cranial nerve palsies (III, VI, VII, VIII)
Monitor
- Conscious state, focal signs, seizures, fluid balance and sodium
- Audiology before discharge and again at follow-up
- Neuropsychological assessment where cognitive complaints persist
- Complement, immunoglobulins and spleen imaging after any second episode
- Vaccination status and contact prophylaxis completion
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