Meningitis, Acute

Diagnosis

Indications for Testing

  • Fever, headache, altered sensorium, and stiff neck

Laboratory Testing

  • CDC testing recommendations
  • 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, but may be used for pre and post vaccination IgG status to determine immunoglobulin defects
  • IgG level pre- and 1 month post-vaccination to determine immunoglobulin deficiency

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

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

Identify enterovirus 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

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

Identify HSV 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

    
Cytomegalovirus by PCR 0060040
Method: Qualitative Polymerase Chain Reaction

Rapid test to identify CMV as an etiological agent of meningitis

    
Acid-Fast Bacillus (<TestName>AFB) Culture and AFB Stain, Sputum<TestName> 0060152
Method: Stain/Culture

Identify M. tuberculosis as etiological agent of meningitis

Need 5cc fluid (sputum, CSF, urine, body fluid, tissue or gastric aspirate) for AFB culture

  
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

    
Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG 2001765
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Evaluate for presence of meningitis

Panel components include California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, WNV, measles, mumps, VZV, HSV types 1 and 2, and LCM antibodies

    
Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG 2001764
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Chemiluminescent Immunoassay

Evaluate for presence of meningitis

Panel components include California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, WNV, measles, mumps, VZV, HSV types 1 and 2, and LCM antibodies

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

Serotype species

Determine pre- and post-vaccination status

    
Acanthamoeba and Naegleria Culture 0060245
Method: Qualitative Culture/Microscopy

Identify Acanthamoeba or Naegleria as an etiological agent of meningitis

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

Identify WNV as an etiological agent of meningitis

    
Arbovirus Antibodies, IgM, CSF 2001595
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Identify arbovirus as an etiological agent of meningitis

    
Ehrlichia and Anaplasma Species by Real-Time PCR 2003078
Method: Real-Time Polymerase Chain Reaction/DNA Probe Hybridization

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 & 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
Acid-Fast Bacillus (AFB) Stain Only 0060151
Method: Auramine O Stain
Mycobacterium tuberculosis Amplified Detection , CSF 0060063
Method: Qualitative Transcription Mediated Amplification (Gen-Probe®)
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 Antibody by ID 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 Antibody by ID 0050183
Method: Qualitative Immunodiffusion
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 Antigen Detection EIA, Urine 2006110
Method: Qualitative Enzyme Immunoassay
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 Antibody by ID 0050174
Method: Qualitative Immunodiffusion
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy
Encephalitis Panel, CSF with Reflex to HSV Type 1 & 2 Glycoprotein G-Specific Ab, IgG 2001741
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody
Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001742
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody
Blood Culture, Fungal 0060070
Method: Continuous Monitoring Blood Culture/Identification