Meningitis, Acute

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Fever, headache, altered sensorium, and stiff neck

Laboratory Testing

  • CDC meningitis overview
  • Initial testing is nonspecific – CBC, electrolytes
    • Normal WBC does not rule out meningitis
  • Cerebrospinal fluid (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 post-neurosurgical meningitis or shunt meningitis
      • Fungal and 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)
  • PCR testing for enterovirus, Epstein-Barr virus, herpes simplex virus, varicella-zoster virus, cytomegalovirus, 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
    • 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

  • If focal findings are present or patient is significantly immunocompromised, consider CT/MRI prior to CSF tap
  • Chest x-ray – may be useful in diagnosing pneumonia as etiology (usually S. pneumoniae)

Differential Diagnosis

  • Serology should not be used to monitor status of disease

Meningitis is defined as inflammation of the leptomeninges, the tissues surrounding the brain and spinal cord. It is marked by an abnormal number of white blood cells in the cerebrospinal fluid (CSF). The focus of this review is on the infectious causes of acute meningitis.

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

Treatment

  • Immediate institution of antimicrobial therapy if bacterial, tuberculosis, or fungal meningitis is suspected
  • For bacterial – cover S. pneumonia, N. meningitidis, H. influenzae
  • For focal neurologic causes – cover HSV until studies rule out 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

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Electrolyte Panel 0020410
Method: Quantitative Ion-Selective Electrode/Enzymatic

Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
Method: Stain/Culture/Identification

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Cell Count, CSF 0095018
Method: Cell Count/Differential

Glucose, CSF 0020515
Method: Enzymatic

Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

Blood Culture 0060102
Method: Continuous Monitoring Blood Culture/Identification

Limitations

Limited to the University of Utah Health Sciences Center only

Fungal Culture 0060149
Method: Culture/Identification

Limitations

Need 5cc fluid to culture for fungus

Viral Meningitis Panel by PCR, Cerebrospinal Fluid 2007063
Method: Qualitative Polymerase Chain Reaction

Viral Meningoencephalitis Panel by PCR, Cerebrospinal Fluid 2007062
Method: Qualitative Polymerase Chain Reaction

Acid-Fast Bacillus (AFB) Culture and AFB Stain 0060152
Method: Stain/Culture/Identification/Susceptiblity

Streptococcus pneumoniae Antigen, CSF 0061162
Method: Qualitative Immunochromatography

Limitations

False positives may occur because of cross-reactivity with other members of S. mitis group; clinical correlation recommended

Patients who have received the S. pneumoniae vaccines may test positive in the 48 hours following vaccination; avoid testing within 5 days of receiving vaccination 

Samples from patients taking antibiotics >24 hours may show a false-negative result.

Wright Stain

Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, CSF 2008916
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay

Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, Serum 2008915
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay

Neisseria meningitidis Tetravalent Antibodies (Serogroups A, C, W-135 and Y), IgG 2001603
Method: Quantitative Multiplex Bead Assay

Limitations

Not intended for diagnosis of infection or serotyping

Acanthamoeba and Naegleria Culture 0060245
Method: Qualitative Culture/Microscopy

West Nile Virus Antibodies, IgG and IgM by ELISA, CSF 0050228
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Ehrlichia and Anaplasma Species by Real-Time PCR 2007862
Method: Qualitative Polymerase Chain Reaction

Lymphocytic Choriomeningitis (LCM) Virus Antibodies, IgG & IgM, CSF 2001628
Method: Semi-Quantitative Indirect Fluorescent Antibody

Cryptococcus Antigen, CSF 0050195
Method: Semi-Quantitative Enzyme Immunoassay

Coccidioides Antibodies Panel, CSF by CF, ID, ELISA 0050710
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Follow Up

For equivocal results, repeat of testing in 10-14 days may be helpful

Blastomyces Antibodies by CF and ID 0050626
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion

Histoplasma Antigen by EIA, Serum 0092522
Method: Semi-quantitative Enzyme Immunoassay

Limitations

Rarely positive in chronic cases

Additional Tests Available

Enterovirus by PCR 0050249
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Comments

Identify enterovirus as an etiological agent of meningitis

Enterovirus and Parechovirus by PCR 2005730
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Comments

Identify enterovirus and parechovirus as etiological agents of meningitis

Herpes Simplex Virus by PCR 0060041
Method: Qualitative Polymerase Chain Reaction

Comments

Identify HSV as an etiological agent of meningitis

Cytomegalovirus by Qualitative PCR 0060040
Method: Qualitative Polymerase Chain Reaction

Comments

Rapid test to identify CMV as an etiological agent of meningitis

Epstein-Barr Virus by PCR 0050246
Method: Qualitative Polymerase Chain Reaction

Comments

Identify EBV as an etiological agent of meningitis

Varicella-Zoster Virus by PCR 0060042
Method: Qualitative Polymerase Chain Reaction

Comments

Identify VZV as an etiological agent of meningitis

Acid-Fast Bacillus (AFB) Stain Only 0060151
Method: Auramine O Stain

Mycobacterium tuberculosis Complex Detection and Rifampin Resistance by PCR 2010775
Method: Qualitative Polymerase Chain Reaction

Blastomyces dermatitidis Antigen Quantitative by EIA 2002926
Method: Quantitative Enzyme Immunoassay

Blastomyces dermatitidis Identification by DNA Probe 0062224
Method: Nucleic Acid Probe

Comments

Not from patient specimen

Blastomyces Antibody by CF 0050130
Method: Semi-Quantitative Complement Fixation

Blastomyces dermatitidis Antibodies by Immunodiffusion 0050172
Method: Qualitative Immunodiffusion

Coccidioides immitis Identification by DNA Probe 0062225
Method: Nucleic Acid Probe

Comments

Not from patient specimen

Coccidioides Antibodies Panel, Serum by CF, ID, ELISA 0050588
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Coccidioides Antibody by CF 0050170
Method: Semi-Quantitative Complement Fixation

Comments

Least sensitive in pulmonary cavitary disease

Coccidioides immitis Antibodies by Immunodiffusion 0050183
Method: Qualitative Immunodiffusion

Comments

Detect current or past infection

Coccidioides Antibody, IgG by ELISA 0050179
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Coccidioides Antibody, IgM by ELISA 0050178
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Cryptococcus Antigen, Serum 0050196
Method: Semi-quantitative Enzyme Immunoassay

Comments

Serum

Histoplasma Galactomannan Antigen Quantitative by EIA, Urine 2009418
Method: Quantitative Enzyme Immunoassay

Comments

Aids in the diagnosis of histoplasmosis

Histoplasma capsulatum Identification by DNA Probe 0062226
Method: Nucleic Acid Probe

Comments

Not from patient specimen

Histoplasma Antibodies by CF & ID 0050627
Method: Semi-Quantitative Complement Fixation/Qualitative Immunodiffusion

Histoplasma spp. Antibodies by Immunodiffusion 0050174
Method: Qualitative Immunodiffusion

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Blood Culture, Fungal 0060070
Method: Continuous Monitoring Blood Culture/Identification

West Nile Virus Antibody, IgM by ELISA, CSF 0050239
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

General References

Bamberger D. Diagnosis, initial management, and prevention of meningitis. Am Fam Physician. 2010; 82(12): 1491-8. PubMed

Brouwer M, Tunkel A, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010; 23(3): 467-92. PubMed

Kim K. Acute bacterial meningitis in infants and children. Lancet Infect Dis. 2010; 10(1): 32-42. PubMed

Logan S, MacMahon E. Viral meningitis. BMJ. 2008; 336(7634): 36-40. PubMed

Mace S. Acute bacterial meningitis. Emerg Med Clin North Am. 2008; 26(2): 281-317, viii. PubMed

Putz K, Hayani K, Zar F. Meningitis. Prim Care. 2013; 40(3): 707-26. PubMed

Somand D, Meurer W. Central nervous system infections. Emerg Med Clin North Am. 2009; 27(1): 89-100, ix. PubMed

Srivastava R, Murphy M, Jeffery J. Cerebrospinal fluid: the role of biochemical analysis. Br J Hosp Med (Lond). 2008; 69(4): 218-21. PubMed

van de Beek D, de Gans J, Tunkel A, Wijdicks E. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354(1): 44-53. PubMed

Ziai W, Lewin J. Update in the diagnosis and management of central nervous system infections. Neurol Clin. 2008; 26(2): 427-68, viii. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Bagdure S, Fisher M, Ryan M, Khasawneh F. Rhodococcus erythropolis encephalitis in patient receiving rituximab. Emerg Infect Dis. 2012; 18(8): 1377-9. PubMed

Durtschi J, Erali M, Bromley K, Herrmann M, Petti C, Smith R, Voelkerding K. Increased sensitivity of bacterial detection in cerebrospinal fluid by fluorescent staining on low-fluorescence membrane filters. J Med Microbiol. 2005; 54(Pt 9): 843-50. PubMed

Hanson K, Alexander B, Woods C, Petti C, Reller B. Validation of laboratory screening criteria for herpes simplex virus testing of cerebrospinal fluid. J Clin Microbiol. 2007; 45(3): 721-4. PubMed

Martins T, Jaskowski T, Tebo A, Hill H. Development of a multiplexed fluorescent immunoassay for the quantitation of antibody responses to four Neisseria meningitidis serogroups. J Immunol Methods. 2009; 342(1-2): 98-105. PubMed

Polage C, Petti C. Assessment of the utility of viral culture of cerebrospinal fluid. Clin Infect Dis. 2006; 43(12): 1578-9. PubMed

Powers A, Bender J, Kumánovics A, Ampofo K, Augustine N, Pavia A, Hill H. Coccidioides immitis meningitis in a patient with hyperimmunoglobulin E syndrome due to a novel mutation in signal transducer and activator of transcription. Pediatr Infect Dis J. 2009; 28(7): 664-6. PubMed

Medical Reviewers

Last Update: January 2016