• Clinical science

Meningitis

Abstract

Meningitis is a serious infection of the meninges in the brain or spinal cord that is most commonly viral or bacterial in origin. Enteroviruses and herpes simplex virus are the leading causes of viral meningitis, while Neisseria meningitidis and Streptococcus pneumoniae are most commonly responsible for bacterial meningitis. Rarer forms of meningitis include tuberculous meningitis and Lyme-associated meningitis. The classic triad of meningitis is fever, headache, and neck stiffness. In infants and young children, the presentation is often nonspecific. Patients may also present with neurological deficits, altered mental status, and seizures, indicating increased intracranial pressure (ICP). The course of viral meningitis is generally much milder. Diagnostics include physical examination followed by blood cultures and lumbar puncture. If increased ICP is suspected, a cranial CT should be performed first. Bacterial meningitis requires rapid initiation of empiric treatment. A life-threatening complication of bacterial meningitis (particularly meningococcal meningitis) is Waterhouse-Friderichsen syndrome, which is characterized by disseminated intravascular coagulation and acute adrenal gland insufficiency. Bacterial meningitis is fatal if left untreated, whereas viral meningitis usually resolves on its own.

Etiology

Common causes and risk factors

Common pathogens by patient group

Newborns
Infants (1 month – 2 years)
Children and teens
Adults (18–60 years)
Elderly (> 60 years)
Immunocompromised patients
Pregnant women
Hospitalized patients

Less common pathogens

References:[1][2][3][4][5][6]

Pathophysiology

Pathways of infection

Most pathogens that cause meningitis colonize the nasopharynx or the upper airways → entry into the CNS via:

  • Hematogenous dissemination
  • Contiguous spread of infections in nose, eyes, and ears
  • Retrograde transport along or inside peripheral or cranial nerves
  • Direct infection (e.g., due to trauma or head surgery)

Incubation times

  • Bacterial meningitis: usually 3–7 days
  • Viral meningitis: depends on the type of virus; usually 2–14 days

References:[2][7][4]

Clinical features

Clinical features of bacterial and viral meningitis are similar, although viral meningitis is less acute and usually self-limiting within 7–10 days.

Children and adults

Neonatal meningitis

  • Often nonspecific and without the classic triad of meningitis
  • Early-onset: lethargy, vomiting, irritability, poor appetite, dyspnea, abnormal breathing patterns
  • Late-onset: fontanelle bulging, high-pitched crying, seizures

The classical features of acute bacterial meningitis are fever, neck stiffness, and headache, but they can only be observed in approximately half of those patients.

Subarachnoid hemorrhage can present with the classic triad of meningitis but has a more sudden onset and patients often lose consciousness.

References:[1][8][9][10]

Diagnostics

Physical examination

Laboratory tests

Lumbar puncture

Post-dural puncture headache is the most probable diagnosis in patients complaining of headache, dizziness, hearing loss/tinnitus, and nausea after lumbar puncture!

Cerebrospinal fluid analysis in meningitis

Appearance Cell type Cell count/μL Opening pressure Lactate Protein Glucose
Normal Clear fluid No granulocytes < 5 50–180 mm H2O 1.2–2.1 mmol/L 15–45 mg/100 mL 40–75 mg/100 mL (∼ ⅔ of blood glucose level)
Bacterial meningitis Cloudy, purulent fluid Significant granulocytosis > 1000 ↑↑ ↑↑
Viral meningitis1) Clear fluid Lymphocytosis 10–500 Variable Normal or ↑ Normal

Tuberculous meningitis2)

Clear fluid with spiderweb coagulum Pleocytosis (predominantly lymphocytes, but also granulocytes and mononuclear cells) 30–300 ↑↑

Lyme meningitis

Clear fluid Pleocytosis (lymphocytes, mononuclear cells) 10–1000 ↑↑ Variable Normal or ↑ Normal or ↓

Cryptococcal meningitis

Cloudy Pleocytosis (lymphocytes) 20–200 ↑↑


References:[2][8][11][12][13][14][15]

Subtypes and variants

Tuberculous meningitis

  • Pathogen: Mycobacterium tuberculosis
  • Incubation period: approximately 2–8 weeks
  • Clinical course
    • Subacute course over several weeks or months
    • Gradual manifestation with intermittent fever
  • Clinical features
    • Focal neurological deficits due to hematogenous dissemination of cranial arteritis
    • Cranial nerve deficits (basal meningitis, affecting the base of the brain, is the most common)
  • Diagnostics:
    • Acid fast stain; and culture of 3 CSF samples
  • Complications
  • Treatment: antituberculosis treatment

Cryptococcal meningitis

  • Pathogen: Cryptococcus neoformans (a type of yeast)
  • Etiology:
    • AIDS
    • Exposure to pigeon droppings
  • Clinical course: subacute onset with (low) fever, fatigue, and headaches
  • Clinical features: see “Clinical features” above; meningeal signs are often absent
  • Diagnostics: CSF and blood: detection of pathogens (encapsulated fungus, visible via India ink staining) and cryptococcal antigens
  • Treatment:

If left untreated, cryptococcal meningitis may lead to rapid death within weeks!

Lyme meningitis

Tick-borne meningoencephalitis

  • Pathogen: tick-borne encephalitis virus (TBEV)
  • Route of infection: tick-borne
    • Ixodid tick acts as a vector → transmission predominantly in June/July and September/October
    • Occasional transmission via unpasteurized dairy products from infected livestock
  • Incubation period: usually 7–14 days
  • Clinical features:
    • Nearly 90% of cases are asymptomatic.
    • Biphasic course: initial flu-like symptoms and fever; , followed (after ∼ 8 days) by a fever-free interval and subsequent increase in temperature, which is associated with the onset of meningoencephalitis
  • Treatment: symptomatic
  • Prognosis:
    • Full recovery is common (particularly in children and adolescents).
    • In symptomatic disease, residual symptoms may occur.
  • A vaccine is not available in the US.
    • Active immunization with an inactivated TBEV (inactivated vaccination): Large-scale implementation of this vaccination is not generally recommended.
    • The CDC's Advisory Committee on Immunization Practices (ACIP) recommends the vaccination only for individuals living, traveling, or working in high-risk areas (laboratory staff exposed to TBEV, foresters, etc.).

References:[2][12][16][17][18][19][20][14]

Treatment

Acute bacterial meningitis

Management algorithm

  1. Blood cultures
  2. Lumbar puncture for CSF Gram stain and culture
  3. Immediate empirical treatment

Empiric treatment

Acute viral meningitis

  • Symptomatic therapy only
  • For severe cases of HSV, EBV, and VZV meningitis, consider antiviral therapy with acyclovir (IV or PO).

References:[1][8][21][22]

Complications

Neurologic

Waterhouse-Friderichsen syndrome

Other

References:[1][8][21][23][24][25][26][27]

We list the most important complications. The selection is not exhaustive.

Prognosis

  • Bacterial meningitis
    • Fatal if left untreated
    • Prognosis in treated patients depends on age, overall condition, immune status and the pathogen(s) involved
  • Viral meningitis

References:[21]

Prevention

For meningococcal vaccination (a polysaccharide conjugate vaccine) see the immunization schedule.

Postexposure measures in bacterial meningitis

Post-exposure prophylaxis Drugs of choice (monotherapy)
Adults
Infants, children, and adolescents
Pregnancy

References:[8][11][26]

Miscellaneous

Notifiable disease: Any probable or confirmed cases of meningococcal meningitis or meningitis due to Haemophilus must be reported to the CDC.

References:[28][29]