Meningitis & Encephalitis

Elizabeth W. Kelly MD & Michael T. Fitch, MD PhD
Wake Forest University School of Medicine
Winston-Salem, North Carolina

Edited By: Emily Senecal, MD
Harvard Medical School, Boston Massachusetts

Meningitis and Encephalitis Objectives

Upon completion of this self-study module, you should be able to:

  • List the classic triad of meningitis
  • Perform physical examination maneuvers to test for signs of meningeal irritation
  • Describe signs and symptoms concerning for encephalitis
  • Interpret laboratory studies for diagnosing meningitis and encephalitis
  • Explain the recommended treatments for meningitis and encephalitis

Bacterial meningitis and viral encephalitis are two life-threatening causes of infection and inflammation within the central nervous system (CNS). Patients with these infectious diseases may present to the Emergency Department with similar signs and symptoms, and the diagnosis can be challenging to discern in the early stages of illness. Evaluation in the acute care setting is focused on identifying patients who require urgent diagnostic testing and/or empiric treatment.

Until antibiotics became available at the beginning of the 20th century, bacterial meningitis was nearly 100% fatal. [1] Although the disease is treatable with antibiotics, throughout the world morbidity and mortality remain high even with appropriate antimicrobial therapy. Meningitis affects patients of all ages, but those who are very young, elderly, or immunosuppressed are at increased risk. [2] It is important for emergency medicine providers to accurately diagnose this life-threatening disease and administer timely antibiotics and other adjunctive therapies to those patients suspected of having bacterial meningitis. [3]

Encephalitis is an infection of the brain parenchyma causing inflammation within the CNS and is often viral in origin. It can be caused by a variety of viral pathogens including herpes simplex virus (HSV), which is the most treatable cause of encephalitis. In the acute care setting it can be difficult to distinguish encephalitis from severe cases of bacterial meningitis.

Classic Presentation

Fever

Altered Mental Status

Stiff Neck

The classic triad of meningitis includes fever, neck stiffness, and altered mental status. However, recent studies demonstrate that this triad is present in less than half of adult patients with bacterial meningitis. [2, 4] Many of the early symptoms of meningitis are nonspecific and include headache, neck pain, nausea, and vomiting. Diagnosis of this condition is therefore difficult in the initial period of illness. One prospective study found that 95% of patients with bacterial meningitis had at least 2 of the following: fever, headache, neck stiffness, and altered mental status. [4] Patients at the extremes of age, immunocompromised individuals, or patients already taking antibiotics may present with more subtle signs and symptoms. [2] Chief complaints for young infants are nonspecific and may include lethargy, irritability, poor feeding, rash, a bulging fontanel, or hypothermia.[5]

Nuchal Rigidity
severe neck stiffness

Classically described meningeal signs include nuchal rigidity (severe neck stiffness), Kernig's sign (flexing the hip and extending the knee elicits pain in the back and legs), and Brudzinski's sign (passive neck flexion elicits involuntary hip flexion.) It is important to remember, however, that these findings of meningeal irritation are only rarely present and some studies show that neck stiffness may only be present in 30% of patients. [6] Other symptoms may include confusion, seizure associated with fever, and skin findings such as petechiae or purpura.

Kernig's Sign
flexing the hip and extending the knee elicits pain in the back and legs

Brudzinski's sign
passive neck flexion elicits involuntary hip flexion.

The clinical presentation of patients with encephalitis can be similar to patients with meningitis, although encephalitis is characterized by the presence of altered mental status or focal neurologic findings. [7]

Initial Actions and Primary Survey

Patients with suspected CNS infection who are ill-appearing should be promptly evaluated and monitored appropriately. If bacterial meningitis is a likely diagnosis, antibiotics should be given immediately after a prompt lumbar puncture (LP), or soon after blood cultures are drawn if there is an anticipated delay in obtaining the LP. In the acute care setting, the pathogen is not known at the time of initial evaluation and therefore broad empiric antimicrobial coverage is recommended.

Emergency care providers should consider the diagnosis of encephalitis in cases of suspected CNS infection accompanied by altered mental status or a focal neurologic deficit. Antiviral therapy is recommended if HSV encephalitis is suspected.

Diagnostic Testing

After a history and physical, a prompt lumbar puncture (LP) is the diagnostic procedure of choice in patients with suspected bacterial meningitis or encephalitis.

A CT scan of the brain before LP should be considered under the following circumstances[3, 8]:

The purpose of the CT scan is to screen for possible contraindications to an LP, such as an occult mass from infection or brain tumor, or signs of brain shift or herniation.

When an LP is performed, four tubes of CSF, each containing about 1mL of fluid, should be obtained and sent to the laboratory for analysis. Typical CSF studies include cell count and differential, protein and glucose levels, and a Gram's stain and culture.

Additional CSF studies may be ordered in immunocompromised patients, or if a CNS infection is confirmed using these initial laboratory evaluation. These other studies may include HSV or enterovirus PCR, bacterial antigen testing, or specialized fungal testing.

Blood cultures may also be useful to obtain in suspected bacterial meningitis, as they have been shown to reveal the causative pathogen for bacterial meningitis even when CSF cultures are negative.

How do I make the diagnosis?

History and physical exam are useful to help decide the likelihood of a CNS infection and to determine if further diagnostic testing is indicated. History and physical examination alone cannot confirm the diagnosis, and therefore if a considerable amount of uncertainty remains, an LP is recommended.

Elevated numbers of white blood cells in the CSF are diagnostic for meningitis or encephalitis, although this finding alone cannot determine the cause of the CNS inflammatory response. Greater than 5 WBC/mL in CSF is abnormal and must be assessed.

CSF findings suggestive of bacterial meningitis include the following:

Table 1: Classically described CSF findings in bacterial, viral, and fungal meningitis.
CSF findings Bacterial Viral Fungal
Opening Pressure Elevated Normal Elevated
White Blood Cell count 1,000-10,000* < 300* < 500*
Neutrophiles >80% 1% - 50% 1% - 50%
Glucose Reduced Normal Reduced
Protein Elevated Normal Elevated
Gram Stain Bacteria Nothing Nothing

*There can be considerable overlap in CSF white blood cell counts between the various causes of meningitis, and cell counts should be interpreted in the context of other CSF findings and individual patients' clinical presentations.

While these general guidelines may be helpful to broadly characterize CSF findings in many cases, several studies have demonstrated that no single laboratory finding, including the CSF WBC count, can accurately categorize the cause of CSF pleocytosis in all patients.[9] For example, in a small number of cases bacterial meningitis has been described in patients with fewer than 100 cells per mm3 in the CSF. [3]

Encephalitis will lead to abnormal results with increased numbers of white blood cells in the CSF, as well. Due to neuronal cell death leading to edema, hemorrhage, and necrosis, patients can have increased CSF red blood cells and CSF white blood cells with a lymphocytic pleocytosis. [7, 10-12]

Treatment

For patients with suspect bacterial meningitis, empiric intravenous antibiotic therapy and admission to the hospital is recommended. See Table 2 for age-based antibiotic recommendations. Patients with severe disease may require ICU level care depending on the clinical circumstances.

The treatment for most cases of encephalitis is supportive care. HSV encephalitis is the only cause of this disease with a specific treatment, and intravenous acyclovir is recommended for patients suspected to have this infection.

Studies have demonstrated that adjunctive corticosteroid treatment started before or concurrently with the first dose of antibiotics has been shown to decrease mortality and neurologic sequelae related to bacterial meningitis. Therefore, intravenous dexamethasone is indicated every 6 hours for 4 days in adults and children 3 months and older when it is initiated before or at the same time antibiotics are given. See Table 2 for recommended empiric therapy for suspected bacterial meningitis.

In patients who need a CT scan of the brain prior to LP, blood cultures should be drawn and steroids and empiric antimicrobial therapy administered prior to CT to avoid additional delays to beginning treatment.

Empiric therapy for patients with suspected bacterial meningitis.
Patient age Intravenous empiric therapy*
Neonate
<1 month
  • Ampicillin and Cefotaxime
  • Alternative: Ampicillin and Gentamicin
Infants
1-3 months
  • Ampicillin
  • and Cefotaxime
Children
>3 months
  • Dexamethasone (initiate before or with first dose of antibiotics)
  • and (Cefotaxime or Ceftriaxone)
  • and Vancomycin
Adults
<50 years
  • Dexamethasone (initiate before or with first dose of antibiotics)
  • and (Ceftriaxone or cefotaxime)
  • and Vancomycin
Adults
>50 years
  • Dexamethasone (initiate before or with first dose of antibiotics)
  • and (Ceftriaxone or cefotaxime)
  • and Vancomycin
  • and Ampicillin
*Consult with your local Infectious Disease Department for local regimens
Remember to add Acyclovir in cases of possible HSV encephalitis

Disposition

Patients who are diagnosed with possible bacterial meningitis based on CSF results should be admitted to the hospital for empiric IV antibiotics and further evaluation. Patients with encephalitis will also require inpatient care. Some well-appearing patients with suspected viral meningitis may be suitable for outpatient treatment with careful return precautions and close outpatient follow-up plans in place. However, if the diagnosis is unclear after emergency evaluation and bacterial meningitis remains a likely possibility, then the patient should be admitted to the hospital for observation and possible empiric antibiotic treatment.

If the lumbar puncture results are negative for CSF infection, additional inpatient or outpatient diagnostic testing may be appropriate to identify an alternative diagnosis as appropriate for the clinical circumstances.

Pearls and Pitfalls

Selected References

  1. Quagliarello, V.J. and W.M. Scheld, Treatment of bacterial meningitis. N Engl J Med, 1997. 336(10): p. 708-16.
  2. Mace, S.E., Acute bacterial meningitis. Emerg Med Clin North Am, 2008. 26(2): p. 281-317, viii.
  3. Fitch, M.T. and D. van de Beek, Emergency diagnosis and treatment of adult meningitis. Lancet Infect Dis, 2007. 7(3): p. 191-200.
  4. van de Beek, D., et al., Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med, 2004. 351(18): p. 1849-59.
  5. Edwards, M., Postnatal bacterial infections. 8th edition ed. Fanaroff and Martin's neonatal-perinatal medicine: diseases of the fetus and infant., ed. F.A. Martin RJ, Walsh MC. Vol. 2. 2006, Philadelphia: Mosby Elsevier.
  6. Ziai, W.C. and J.J. Lewin, 3rd, Advances in the management of central nervous system infections in the ICU. Crit Care Clin, 2006. 22(4): p. 661-94; abstract viii-ix.
  7. Tyler, K.L., Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's. Herpes, 2004. 11 Suppl 2: p. 57A-64A.
  8. Straus, S.E., K.E. Thorpe, and J. Holroyd-Leduc, How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis? JAMA, 2006. 296(16): p. 2012-22.
  9. Fitch, M.T., et al., Emergency department management of meningitis and encephalitis. Infect Dis Clin North Am, 2008. 22(1): p. 33-52, v-vi.
  10. Eisenstein, L.E., A.J. Calio, and B.A. Cunha, Herpes simplex (HSV-1) aseptic meningitis. Heart Lung, 2004. 33(3): p. 196-7.
  11. Cinque, P., et al., The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis. J Neurol Neurosurg Psychiatry, 1996. 61(4): p. 339-45.
  12. Thompson, K.A., W.W. Blessing, and S.L. Wesselingh, Herpes simplex replication and dissemination is not increased by corticosteroid treatment in a rat model of focal Herpes encephalitis. J Neurovirol, 2000. 6(1): p. 25-32.