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  • Physician

Meningitis

Summary

Meningitis is a serious infection of the meninges in the brain or spinal cord that is most commonly viral or bacterial in origin, although fungal, parasitic, and noninfectious causes are also possible. Enteroviruses and herpes simplex virus are the leading causes of viral meningitis, while Neisseria meningitidis and Streptococcus pneumoniae are the pathogens most commonly responsible for bacterial meningitis. Rarer forms of bacterial 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). Diagnostics include physical examination followed by blood cultures and lumbar puncture. If increased ICP is suspected, a CT of the head should be performed first. Bacterial meningitis requires rapid initiation of empiric treatment. A life-threatening complication of bacterial meningitis (especially meningococcal meningitis) is Waterhouse-Friderichsen syndrome, which is characterized by disseminated intravascular coagulation and acute adrenal gland insufficiency. Viral meningitis typically resolves on its own and has a far less severe course than bacterial meningitis, which is generally fatal if left untreated.

Etiology

Common causes

Risk factors

Common pathogens by patient group

Population Pathogens
Newborns

Infants

Children and teenagers
Adults 20–60 years
Adults ≥ 60 years
Immunocompromised individuals
Pregnant women
Hospitalized patients

Less common pathogens

References:[2][3][4][5][6][7]

Pathophysiology

Pathways of infection

  • Most pathogens that cause meningitis colonize the nasopharynx or the upper airways before entering the CNS via:
    • Hematogenous dissemination . [8]
    • Contiguous spread of infections in nose, eyes, and ears
    • Retrograde transport along or within peripheral or cranial nerves
  • Direct infection (e.g., due to trauma or head surgery) [1]

Incubation periods

  • Bacterial meningitis: usually 3–7 days [9]
  • Viral meningitis: usually 2–14 day, depending on the type of virus

References:[3][9][5]

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.

Neonates (neonatal meningitis)

Often nonspecific and without the classic triad of meningitis

Children and adults

Physical examination [3][11]

The classical features of acute bacterial meningitis are fever, neck stiffness, and headache. However, this triad of symptoms actually manifests in only about 50% of cases.

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

References:[2][11][14][15]

Diagnostics

Blood studies

Lumbar puncture (LP)

Normal Bacterial meningitis Viral meningitisa Tuberculous meningitisb[17] Lyme meningitis [18] Cryptococcal meningitis [19]
Appearance
  • Clear fluid
  • Clear fluid
  • Clear fluid with spiderweb coagulum
  • Clear fluid
  • Cloudy
Cell type
  • Significant granulocytosis
Cell count
  • < 5/μL
  • > 1000/μl
  • 10–500/μl
  • 30–300/μl
  • 10–1000/μl
  • 20–200/μl
Opening pressure [20]
  • 50–180 mm H2O
  • ↑↑
  • Normal or
  • ↑↑
  • ↑↑
  • ↑↑
Lactate
  • 1.2–2.1 mmol/L
  • ↑↑
  • Variable
  • Variable
Protein
  • 15–45 mg/100 mL
  • Normal or ↑
  • Normal or ↑
Glucose
  • 40–75 mg/100 mL (∼ ⅔ of blood glucose level)
  • Normal
  • Normal or ↓

a) Distinguishing tuberculous meningitis from viral meningitis based on the CSF analysis is often challenging because cell type and count in both forms of meningitis are very similar. However, lactate and glucose levels usually differ, as well as protein levels in some cases.

b) Additional diagnostics in tuberculous meningitis: PCR

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

Other tests

  • Cerebral imaging
    • CT: possible signs of ↑ ICP (e.g., effacement of the ventricles, herniation)
    • MRT: gelatinous pseudocysts in cryptococcal meningitis (soap bubble appearance)
  • Fundoscopic examination: papilledema if ↑ ICP

References:[3][11][20][18][12][17][19]

Subtypes and variants

Tuberculous meningitis

Cryptococcal meningitis

  • Pathogen: Cryptococcus neoformans (a type of encapsulated yeast)
  • Risk factors
    • AIDS
    • Exposure to pigeon droppings
  • Clinical course: subacute onset with (low) fever, fatigue, and headaches
  • Clinical features
    • See section on “Clinical features” above
    • Meningeal symptoms are often absent
  • Diagnostics
  • Treatment
    • Intrathecally amphotericin B with or without flucytosine (induction therapy lasting 10–14 days)
    • Followed by fluconazole (consolidation therapy lasting 8–10 weeks and maintenance therapy lasting at least 12 months)
    • cART therapy should be delayed for at least 2 weeks after initiation of antifungal therapy.


Lyme meningitis

Tick-borne meningoencephalitis (primarily in Eurasia)

  • Pathogen: tick-borne encephalitis virus (TBEV)
    • TBEVs are part of the Flaviviridae family and occur predominantly in parts of Europe, Russia, and Asia.
    • TBEV is very closely related to the Powassan virus in the US and Russia, which is a rare cause of encephalitis.
  • 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.
  • Prevention: A vaccine is not available in the US.

Primary amoebic meningoencephalitis [21]

  • Pathogen: Naegleria fowleri, an amoeba found in warm, still standing freshwater (e.g., ponds, hot springs)
  • Route of infection: via contaminated water entering the nose (e.g., while swimming) → invades the CNS directly via the cribriform plate
  • Clinical features: causes fulminant meningoencephalitis with rapid onset (brain-eating amoeba)
  • Diagnosis: microscopy of CSF shows amoebas
  • Treatment: amphotericin B
  • Prognosis: nearly always fatal

References:[3][18][22][23][24][25][26][17][27]

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:[2][11][28][16]

Acute management checklist

Complications

Neurologic

Waterhouse-Friderichsen syndrome

References:[2][11][28][31][33][34][35][32]

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
  • Fungal meningitis
    • Associated with neurological sequelae and a high mortality rate
    • Treatment adherence is very important to avoid relapse.

References:[28]

Prevention

Postexposure prophylaxis Drugs of choice (monotherapy)
Adults
Infants, children, and adolescents
Pregnancy

References:[11][20][35]

Miscellaneous

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

References:[36][37]