Meningitis, Acute

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

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
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

Recommended Use 

May be helpful in differentiating bacterial from viral etiology

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

Recommended Use 

Useful in assessing metabolic derangement as cause of altered consciousness

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

Recommended Use 

Identify bacteria in CSF

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Recommended Use 

Useful in assessing metabolic derangement as cause of altered consciousness

Cell Count, CSF 0095018
Method: Cell Count/Differential

Recommended Use 

Aids in differentiating bacterial from viral meningitis

Glucose, CSF 0020515
Method: Enzymatic

Recommended Use 

May be helpful in differentiating bacterial from viral etiology

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

Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

Recommended Use 

May be helpful in differentiating bacterial from viral etiology

Blood Culture 0060102
Method: Continuous Monitoring Blood Culture/Identification

Recommended Use 

Identify possible source of meningitis

Limitations 

Limited to the University of Utah Health Sciences Center only

Fungal Culture 0060149
Method: Culture/Identification

Recommended Use 

May identify fungal causes or help identify organism responsible for meningitis

Limitations 

Need 5cc fluid to culture for fungus

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

Recommended Use 

Identifies enterovirus, parechovirus, or HSV as etiological agents of meningitis

Test includes enterovirus and parechovirus by RT-PCR, and HSV PCR

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

Recommended Use 

Identifies CMV, EBV, HSV, or VZV as etiological agents of meningitis

Test includes CMV, EBV, HSV, and VZV by PCR

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

Recommended Use 

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

Susceptibility will be performed on organisms isolated from a sterile source and for isolates of Mycobacterium chelonae, M. abscesses, M. fortuitum complex, M. immunogenum, M. mucogenicum; susceptibility testing will be performed by request only on M. kansaii and M. marinum; susceptibility testing of M. gordonae is inappropriate

Streptococcus pneumoniae Antigen, CSF 0061162
Method: Qualitative Immunochromatography

Recommended Use 

Identify presence of Streptococcus pneumoniae

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

Recommended Use 

Identify presence of Naegleria and Acanthamoeba in CSF specimen

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

Recommended Use 

Evaluate for presence of meningitis

Panel components include WNV, measles, mumps, VZV, HSV-1, and HSV-2

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

Recommended Use 

Evaluate for presence of meningitis

Panel components include WNV, measles, mumps, VZV, HSV-1, and HSV-2

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

Recommended Use 

Assess immunocompetence following Neisseria meningitidis vaccination

For assessment of suspected immunodeficiency, use pre- and post-vaccination serology

Limitations 

Not intended for diagnosis of infection or serotyping

Acanthamoeba and Naegleria Culture 0060245
Method: Qualitative Culture/Microscopy

Recommended Use 

Identify Acanthamoeba or Naegleria as an etiological agent of meningitis

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

Recommended Use 

Identify WNV as an etiological agent of meningitis

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

Recommended Use 

Identify Ehrlichia or Anaplasma as etiological agent of meningitis

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

Recommended Use 

Identify LCM as an etiological agent of meningitis

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

Recommended Use 

Identify Cryptococcus as an etiological agent of meningitis

CAP requires confirmation by culture for this test; when test is ordered by the University of Utah Hospital, Huntsman Cancer Hospital, or VA Hospital of SLC, CSF culture will be ordered automatically; other clients should order culture separately

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

Recommended Use 

Detect both IgG and IgM antibodies in acute and convalescent samples

Confirm coccidioidal disease as an etiological agent of meningitis

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

Recommended Use 

Identify Blastomyces as an etiological agent of meningitis

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

Recommended Use 

Diagnose and monitor response to therapy in Histoplasma-caused disease

Limitations 

Rarely positive in chronic cases

General References

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

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

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

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

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

Putz K, Hayani K, Zar FA. 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 MJ, 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 AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006; 354(1): 44-53. PubMed

Ziai WC, Lewin JJ. 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 SR, Fisher MA, Ryan ME, Khasawneh FA. Rhodococcus erythropolis encephalitis in patient receiving rituximab. Emerg Infect Dis. 2012; 18(8): 1377-9. PubMed

Durtschi JD, Erali M, Bromley K, Herrmann MG, Petti CA, Smith RE, Voelkerding KV. 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 KE, Alexander BD, 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 TB, Jaskowski TD, Tebo A, Hill HR. 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 CR, Petti CA. Assessment of the utility of viral culture of cerebrospinal fluid. Clin Infect Dis. 2006; 43(12): 1578-9. PubMed

Powers AE, Bender JM, Kumánovics A, Ampofo K, Augustine N, Pavia AT, Hill HR. 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

Couturier, Marc Roger, PhD, D(ABMM), Medical Director, Microbial Immunology, Parasitology and Fecal Testing, and Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Fisher, Mark A., PhD, D(ABMM), Medical Director, Bacteriology and Antimicrobials at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Hanson, Kimberly E., MD, MHS, Medical Director, Mycology, Mycobacteriology, and Virology at ARUP Laboratories; Associate Professor of Internal Medicine and Adjunct Assistant Professor of Pathology, University of Utah

Hillyard, David R., MD, Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Clinical Pathology, Adjunct Professor of Biology, University of Utah

Last Update: August 2016

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