Meningitis, Acute

Diagnosis

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
        • Monocytes predominate in viral and fungal meningitis
        • Exception in patients who are immunocompromised
      • Immunocompromised patients and those with Listeria monocytogenes may have normal values
        • Listeria may also present with normal WBC counts and high protein CSF
      • Normal 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 meningitis and tuberculous disease; normal to minimally low in viral and fungal
    • Gram stain – useful if positive
    • Bacterial culture – gold standard for diagnosis
      • Anaerobic culture may be important for post-neurosurgical meningitis or shunt meningitis
    • CSF antigen antibody testing, when appropriate (eg, pneumococcal antigen, dimorphic fungi serology, cryptococcal antigen)
    • Fungal and AFB cultures (when clinically indicated) require HIGH VOLUME taps (at least 10cc fluid [minimum 5cc for each test])
    • Viral culture from CSF not indicated
  • Blood cultures – may be positive in up to 2/3 of patients in Western countries
    • Not as sensitive if antibiotics administered 
  • Other tests to consider
    • Malaria blood film – in areas where malaria is endemic
      • Has a negative predictive value of 98%
    • Rapid serum HIV antibody and plasma viral load testing – rule out acute HIV infection
      • Use for patients with risk factors and aseptic meningitis
    • Urinalysis – may reveal urinary tract infection as etiology of bacteremia
    • Consider serologies – mumps, EBV, if clinical situation is compatible

Imaging Studies

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

Differential Diagnosis

Monitoring

  • Serology should not be used to monitor status of disease

Clinical Background

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 – 11/100,000 in U.S.
  • 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%
    • Brudzinski sign – spontaneous flexion of hips and knees on passive flexion of the neck
  • 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
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

May be helpful in differentiating bacterial from viral etiology

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

Useful in assessing metabolic derangement as cause of altered consciousness

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

Identify organism causing meningitis

   
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Useful in assessing metabolic derangement as cause of altered consciousness

   
Cell Count, CSF 0095018
Method: Cell Count/Differential

Aids in differentiating bacterial from viral meningitis

   
Glucose, CSF 0020515
Method: Enzymatic

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

May be helpful in differentiating bacterial from viral etiology

   
Blood Culture 0060102
Method: Continuous Monitoring Blood Culture/Identification

Identify possible source of meningitis

Limited to the University of Utah Health Sciences Center only

 
Fungal Culture 0060149
Method: Culture/Identification

May identify fungal causes or help identify organism responsible for meningitis

Need 5cc fluid to culture for fungus

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

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

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

Identify M. tuberculosis as etiological agent of meningitis

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

Identify presence of Streptococcus pneumoniae 

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

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

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

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

Assess immunocompetence following Neisseria meningitidis vaccination

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

Not intended for diagnosis of infection or serotyping

 
Acanthamoeba and Naegleria Culture 0060245
Method: Qualitative Culture/Microscopy

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

Identify WNV as an etiological agent of meningitis

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

Identify Ehrlichia or Anaplasma as etiological agent of meningitis

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

Identify LCM as an etiological agent of meningitis

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

Identify Cryptococcus as an etiological agent of meningitis

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

Detect both IgG and IgM antibodies in acute and convalescent samples

Confirm coccidioidal disease as an etiological agent of meningitis

 

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

Identify Blastomyces as an etiological agent of meningitis

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

Diagnose and monitor response to therapy in Histoplasma-caused disease

Rarely positive in chronic cases

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Enterovirus Detection by PCR 0050249
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Identify enterovirus as an etiological agent of meningitis

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

Identify enterovirus and parechovirus as etiological agents of meningitis

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

Identify HSV as an etiological agent of meningitis

Cytomegalovirus by Qualitative PCR 0060040
Method: Qualitative Polymerase Chain Reaction

Rapid test to identify CMV as an etiological agent of meningitis

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

Identify EBV as an etiological agent of meningitis

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

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 EIA 2002926
Method: Quantitative Enzyme Immunoassay
Blastomyces dermatitidis Identification by DNA Probe 0062224
Method: Nucleic Acid Probe

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

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

Least sensitive in pulmonary cavitary disease

Coccidioides immitis Antibodies by Immunodiffusion 0050183
Method: Qualitative Immunodiffusion

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

Serum

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

Aids in the diagnosis of histoplasmosis

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

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