Acute Meningitis

Meningitis is the inflammation of the leptomeninges, the tissues surrounding the brain and spinal cord. Prompt identification and treatment of infectious meningitis may prevent irreversible neurological sequelae. Evaluation of the cerebrospinal fluid (CSF) for white blood cells (WBCs), red blood cells (RBCs), malignant cells, bacterial, viral or fungal elements, protein and glucose levels, as well as other markers is critical to determine correct treatment and optimal outcomes.

Diagnosis

Indications for Testing

  • Fever
  • Headache
  • Altered sensorium
  • Stiff neck

Laboratory Testing

  • CDC meningitis overview
  • Initial testing is nonspecific – CBC, electrolytes
    • Normal WBC does not rule out meningitis
  • CSF exam – necessary to determine presence of meningitis
    • CSF opening pressure – limited value if normal; usually >300 mm in bacterial but ≤300 in all others
    • Microscopic exam – white count >1,000 cells/µL in >90% of patients with bacterial meningitis
      • Neutrophils (typically >80%) usually predominate in bacterial meningitis
        • Lymphocytes/monocytes predominate in viral and fungal meningitis – early viral disease may have ≥50% neutrophils, but shift toward lymphocytes/monocytes
        • Immunocompromised patients may not demonstrate elevated WBC results in bacterial meningitis
      • Immunocompromised patients and those with Listeria monocytogenes may have normal CSF WBC results – Listeria may also present with normal WBC results and high protein CSF
      • Normal WBC result does not exclude bacterial meningitis
    • Protein – usually elevated (>200 mg/dL) in bacterial and fungal meningitis; usually <200 in viral
    • Glucose – usually low (<10mg/dL) in bacterial and tuberculous meningitis; normal to minimally low in viral and fungal meningitis
    • Gram stain – useful if positive
    • Culture
      • Bacterial culture – gold standard for diagnosis of bacterial meningitis
        • Anaerobic culture may be important for postneurosurgical meningitis or shunt meningitis
      • Fungal and acid-fast bacilli (AFB) cultures require HIGH VOLUME taps (at least 10cc fluid)
      • Viral culture from CSF not indicated
    • CSF antigen antibody testing, when appropriate (eg, pneumococcal antigen, dimorphic fungi serology, cryptococcal antigen)
  • Polymerase chain reaction (PCR) testing for enterovirus, Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), arboviruses
  • Blood cultures – may be positive in up to 2/3 of patients in Western countries in bacterial meningitis
    • Less sensitive if antibiotics have been administered
  • Other tests to consider
    • Rapid serum HIV antibody and plasma viral load testing – rule out acute HIV infection
      • Use for patients with risk factors and aseptic meningitis
    • Rapid plasma reagin (RPR) – rule out syphilis
    • Urinalysis – may reveal urinary tract infection as etiology of bacteremia
    • Malaria blood film – in areas where malaria is endemic
      • Has a negative predictive value of 98%

Imaging Studies

  • Computed tomography (CT)/magnetic resonance imaging (MRI) – consider prior to CSF tap if focal findings are present or patient is significantly immunocompromised,
  • Chest x-ray – may be useful in diagnosing pneumonia as etiology (usually Streptococcus pneumoniae)

Differential Diagnosis

Monitoring

Serology should not be used to monitor status of disease.

Background

Epidemiology

  • Incidence
    • Bacterial – 4-6/100,000
    • Viral – ~10/100,000 in U.S. (Putz, 2014)
  • Occurrence/transmission
    • Hematogenous dissemination (bacteremia, viremia)
    • Trauma – surgery, head trauma (basilar skull fracture, as nidus for development of infection)

Classification

Risk Factors

  • Advanced age
  • Male sex
  • Low socioeconomic status
  • Crowded living conditions
  • African American ethnicity
  • Dural defects
  • Intravenous drug abuse
  • Immunosuppression (eg HIV, connective tissue diseases, malignancy)
  • Indwelling shunts
  • Recent neurologic surgery

Clinical Presentation

  • Headache
  • Fever
  • Meningismus, nuchal rigidity, altered sensorium, seizures, photophobia
    • Kernig sign – resistance to passive extension of the knee when the hip is flexed at 90% (highly insensitive, very specific [Putz, 2014])
    • Brudzinski sign – spontaneous flexion of hips and knees on passive flexion of the neck (highly insensitive, very specific [Putz, 2014])
  • Nausea, emesis
  • Focal neurologic deficits, hemiparesis
  • Rash – VZV, meningococcus, Rocky Mountain spotted fever, ehrlichiosis
  • Complications
    • Shock
    • Disseminated intravascular coagulation
    • Focal permanent neurologic deficits
      • Deafness, blindness, paresis
    • Hydrocephalus
    • CNS abscess
    • Seizure disorder
    • Recurrent meningitis
      • Congenital anatomical defects
      • Neurogenic cysts
      • Asplenia
      • Congenital immunodeficiencies (eg, complement deficiency)
      • Acquired immunodeficiencies (eg, HIV)
      • Mollaret meningitis (caused by HSV)

Prevention

  • Viral – mumps vaccination
  • Bacterial
    • H. influenzae vaccination in childhood
    • S. pneumoniae vaccination in childhood
      • Conjugate vaccine for infants, polysaccharide vaccine for other at-risk groups
    • N. meningitidis vaccination in children 11-18 years (if vaccinated between 11 and 15 years, recommend booster), freshmen entering college, complement-deficient patients, asplenic patients
      • Chemoprophylaxis for close contacts of patients with N. meningitidis

ARUP Laboratory Tests

Primary Tests

Useful in assessing metabolic derangement as cause of altered consciousness

Useful in assessing metabolic derangement as cause of altered consciousness

May be helpful in differentiating bacterial from viral etiology

Usually low (<10mg/dL) in bacterial meningitis and tuberculous disease

May be helpful in differentiating bacterial from viral etiology

Gold standard test to diagnose fungi as agent of infection

Use to rapidly detect a panel of common viruses, bacteria, and fungi associated with meningitis and encephalitis

Do NOT use as a replacement for CSF bacterial and/or fungal culture and Cryptococcal antigen testing for at-risk patients

Gold standard test for diagnosing the presence of mycobacteria organisms

Specimen from any suspected site, including sputum, CSF, tissue, urine, and other body fluid or gastric aspirate, may be used

Aids in the diagnosis of pneumococcal meningitis

Use to identify the presence of Naegleria and Acanthamoeba in CSF specimen

Wright Stain

Use to detect Acanthamoeba spp and Naegleria fowleri in various specimen types

Preferred panel for diagnosing possible tickborne disease (ie, Anaplasmosis or Ehrlichiosis) during the acute phase of the disease

Aids in the diagnosis of LCM viral infection in the central nervous system

Use to identify Cryptococcus as an etiological agent of meningitis

Use to detect Blastomyces antibodies in serum

For diagnosis of blastomycosis, consider testing in conjunction with histology or culture

Use to detect Blastomyces antibodies in CSF

For diagnosis of blastomycosis, consider testing in conjunction with histology or culture

Aids in the diagnosis of histoplasmosis

Recommend in conjunction with complement fixation, immunodiffusion antibody, and urine galactomannan antigen testing

Related Tests

Use to detect enterovirus in blood, CSF, or nasopharyngeal specimens

Use to detect parechovirus in CSF, plasma, or serum specimens

Use to detect enterovirus and parechovirus

Use to genotype HSV types 1 and 2

Use to detect CMV 

Does not quantify viral load; potentially useful for specimen types other than blood

Quantitative PCR on plasma is preferred for most clinical indications

Do not use for diagnosis of infectious mononucleosis

Use to detect EBV in individuals suspected of having EBV-related disease

Use to detect VZV in blood, CSF, ocular fluid, tissue, or vesicle fluid

Use to monitor respiratory specimens in previously diagnosed patients

Should NOT be ordered without culture in previously undiagnosed patients

Use to detect M. tuberculosis complex (MTBC) isolates and determine possible resistance to rifampin treatment

Use to diagnose and monitor B. dermatitidis

For urine specimens, refer to Blastomyces Antigen Quantitative by EIA, Urine

Use to diagnose and monitor B. dermatitidis

For serum specimens, refer to Blastomyces Antigen Quantitative by EIA

Use to identify B. dermatitidis (yeast or mold form) from a pure isolate

Use to identify C. immitis (yeast or mold form) from a pure isolate

Aids in the diagnosis of coccidioidomycosis (Valley fever)

Panel includes Coccidioides antibody IgG and IgM, Coccidiodes immitus antibodies, and coccidiodes titer

Comprehensive test to aid in the diagnosis of coccidioidal meningitis (Valley fever)

Use to identify C. neoformans as the infectious agent of invasive cryptococcal disease

Aids in the diagnosis of histoplasmosis

Recommend in conjunction with complement fixation, immunodiffusion antibody, and serum antigen testing

Use to identify H. capsulatum (yeast or mold form) from a pure isolate

Aids in the diagnosis of histoplasmosis

Recommend in conjunction with serum antigen and urine galactomannan antigen testing

Gold standard test to diagnose fungi as agent of infection in blood

Preferred test to diagnose West Nile encephalitis

References

Additional Resources

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Professor of Pathology (Clinical), University of Utah
Medical Director, Emerging Public Health Crises, Parasitology/Fecal Testing, and Infectious Disease Antigen Testing, ARUP Laboratories
Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)
Associate Professor of Pathology (Clinical), University of Utah
Medical Director, Bacteriology, Special Microbiology, and Antimicrobial Susceptibility Testing, ARUP Laboratories
Contributor

Hillyard

David R. Hillyard, MD
Adjunct Associate Professor of Pathology, University of Utah
Medical Director, Molecular Infectious Diseases, ARUP Laboratories