The Physician's Guide to Laboratory Test Selection and InterpretationMeningitis, Acute
Clinical Background
Meningitis is defined as inflammation of the leptomeninges, the tissues surrounding the brain and spinal cord, which 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, ie, trauma as nidus for development of infection)
Classification
- Viral (aseptic) – most common cause
- Enterovirus – most common cause
- Herpes simplex virus (HSV)
- Arboviruses
- West Nile virus (WNV)
- Mumps virus
- Lymphocytic choriomeningitis (LCM)
- Other viruses – Epstein-Barr virus (EBV), cytomegalovirus (CMV), acute human immunodeficiency virus (HIV), human herpesvirus 6(HHV6), and adenoviruses
- Bacterial
- Neisseria meningitidis
- Streptococcus pneumoniae
- Haemophilus influenzae
- Listeria monocytogenes
- Escherichia coli
- Beta-hemolytic group B streptococcus
- Mycobacterial – Mycobacterium tuberculosis
- Fungal
- Blastomyces dermatitidis
- Cryptococcus neoformans
- Histoplasma capsulatum
- Coccidioides immitis
- Parasites
- Amoeba – Acanthamoeba and Naegleria
- Angiostrongylus cantonensis
- Spirochetes
- Tickborne illnesses
- Rickettsia rickettsii (Rocky Mountain spotted fever)
- Ehrlichia chaffeensis
- Anaplasma phagocytophilum
Risk Factors
- Advanced age
- Male sex
- Low socioeconomic status
- Crowded living conditions
- African American ethnicity
- Dural defects
- Intravenous drug abuse
- Immunosuppression
- Indwelling shunts
Clinical Presentation
- Headache
- Fever
- Meningismus, 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
- Rash – Varicella-zoster virus (VZV), meningococcus, Rocky Mountain spotted fever, ehrlichiosis
- Complications
- Shock
- Disseminated intravascular coagulation
- Focal permanent neurologic deficits
- Deafness, blindness, paresis
- Hydrocephalus
- Central nervous system abscess
- Seizure disorder
- Recurrent meningitis
- Congenital anatomical defects
- Neurogenic cysts
- Asplenia
- Congenital immunodeficiencies
- Acquired immunodeficiencies
- Mollaret meningitis (caused by HSV)
Treatment
- Immediate institution of antimicrobial therapy if bacterial, tuberculosis, or fungal meningitis is suspected
- For bacterial – covers Streptococcal pneumonia, N. meningitidis, H. influenzae
- For focal neurologic causes – cover for HSV until studies rule out HSV
Prevention
- Viral – mumps vaccination
- Bacterial
- H. influenzae vaccination
- S. pneumoniae vaccination
- Conjugate vaccine for infants, polysaccharide vaccine for other at-risk groups
- N. meningitidis vaccination
- Chemoprophylaxis for close contacts of patients with N. meningitidis
Diagnosis
Indications for Testing
- Fever, headache, altered sensorium and stiff neck
Laboratory Testing
- Cerebrospinal fluid (CSF) exam – necessary to determine presence of meningitis
- CSF opening pressure – limited value if normal; usually >300mm in bacterial but ≤300 in all others
- Microscopic exam – white count >1,000 cells/µL in >90% of patients with bacterial meningitis
- Neutrophils usually predominate in bacterial meningitis; monocytes predominate in viral and fungal meningitis
- 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
- CSF antigen antibody testing, when appropriate (eg, pneumococcal antigen, dimorphic fungi serology, cryptococcal antigen)
- Fungal and/or AFB culture (when clinically indicated) requires a HIGH VOLUME tap (at least 10cc fluid [minimum 5cc for each test])
- Viral culture from CSF not indicated (perform nucleic-acid amplification testing)
- PCR testing for enterovirus, EBV, HSV, VZV, CMV
- Blood cultures – may be positive in up to 2/3 of patients in Western countries
- Not as sensitive if antibiotics administered
- Malaria blood film – in areas where malaria is endemic, this has a negative predictive value of 98%
- Rapid serum HIV antibody and plasma viral load testing – rule out acute HIV infection; used 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 pneumococcus)
Differential Diagnosis
- Connective tissue CNS disease
- Vasculitic CNS disease
- Behçet disease
- Wegener granulomatosis
- Granulomatous CNS disease
- Migraine headache
- Malignant meningitis
- Carcinoma
- Lymphoma
- Leukemia
- Subarachnoid hemorrhage
- Fabry disease
- Medications (multiple drugs can cause aseptic meningitis)
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 & Automated Differential 0040003 Method: Automated Cell Count with Flow Cell Differential |
May be helpful in differentiating bacterial from viral etiology |
||
| Electrolyte Panel 0020410 Method: Ion-Selective Electrode/Enzymatic |
Useful in assessing metabolic derangement as cause of altered consciousness |
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| CSF Bacterial Culture (Includes Gram Stain 0060101) 0060106 Method: Standard reference procedures for bacterial stain, aerobic culture, and identification |
Identify organism causing meningitis |
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| Glucose, Plasma or Serum 0020024 Method: Enzymatic |
Useful in assessing metabolic derangement as cause of altered consciousness |
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| Cell Count, CSF 0095018 Method: Cell Count/Differential |
Aids in differentiating bacterial from viral meningitis |
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| Glucose, CSF 0020515 Method: Enzymatic |
May be helpful in differentiating bacterial from viral etiology Usually low (<10mg/dL) in bacterial meningitis and tuberculous disease |
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| Protein, Total, CSF 0020514 Method: Reflectance Spectrophotometry |
May be helpful in differentiating bacterial from viral etiology |
||
| Blood Culture 0060102 Method: Bactec® continuous monitoring system. Standard reference procedures for identification of aerobic and anaerobic microorganisms |
Identify possible source of meningitis |
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| Fungal Culture 0060149 Method: Standard reference procedures for fungal culture. Standard reference procedures for identification and/or ITS rDNA Sequencing. DNA probes available for Histoplasma, Coccidioides, and Blastomyces |
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: Reverse Transcription/Polymerase Chain Reaction |
Identify enterovirus as an etiological agent of meningitis |
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| Epstein-Barr Virus by PCR 0050246 Method: Polymerase Chain Reaction |
Identify EBV as an etiological agent of meningitis |
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| Herpes Simplex Virus by PCR 0060041 Method: Polymerase Chain Reaction |
Identify HSV as an etiological agent of meningitis |
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| Varicella-Zoster Virus by PCR 0060042 Method: Polymerase Chain Reaction |
Identify VZV as an etiological agent of meningitis |
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| AFB Culture (Includes AFB Stain 0060151) 0060152 Method: Standard reference procedures for stain and culture. Identification of AFB is ordered and billed separately. DNA probes are available for M. tuberculosis complex and M. avium-intracellulare complex as indicated. DNA sequencing and other molecular techniques are used for identification. For drug susceptibilities, refer to Antimicrobial Susceptibility - AFB Mycobacteria (0060217). |
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: Immunochromatographic Assay |
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 |
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| Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG 2001765 Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody |
Panel components include California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, WNV, measles, mumps, VZV, HSV type 1 and 2, and LCM antibodies |
||
| Meningoencephalitis Panel, Serum with Reflex to HSV Type 1 & Type 2 Glycoprotein G-Specific Ab, IgG 2001764 Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody/Chemiluminescent Immunoassay |
Panel components include California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, WNV, measles, mumps, VZV, HSV type 1 and 2, and LCM antibodies |
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| Acanthamoeba Culture 0060245 Method: Culture/Microscopic Identification |
Identify Acanthamoeba or Naegleria as an etiological agent of meningitis |
Stain will detect Naegleria spp and other free-living amoeba |
|
| West Nile Virus Antibodies, IgG & IgM by ELISA, CSF 0050228 Method: Enzyme-Linked Immunosorbent Assay |
Identify WNV as an etiological agent of meningitis |
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| Arbovirus Antibodies, IgM, CSF 2001595 Method: Indirect Fluorescent Antibody/Enzyme-Linked Immunosorbent Assay |
Identify arbovirus as an etiological agent of meningitis |
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| 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 |
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| Lymphocytic Choriomeningitis (LCM) Virus Antibodies, IgG & IgM, CSF 2001628 Method: Indirect Fluorescent Antibody |
Identify LCM as an etiological agent of meningitis |
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| Cryptococcus Antigen, CSF 0050195 Method: Enzyme Immunoassay |
Identify Cryptococcus as an etiological agent of meningitis |
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| Coccidioides Antibodies Panel, CSF by CF, ID, ELISA 0050710 Method: Complement Fixation/Immunodiffusion/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 |
|
| Histoplasma Antigen by EIA, Serum 0092522 Method: Enzyme Immunoassay |
Diagnose and monitor response to therapy in Histoplasma-caused disease |
Rarely positive in chronic cases |
|
| Blastomyces Antibodies by CF & ID 0050626 Method: Complement Fixation/Immunodiffusion |
Identify Blastomyces as an etiological agent of meningitis |
Click the plus sign to expand the table of additional tests.
| Test Name and Number | Comments |
|---|---|
| AFB Stain Only 0060151 Method: Auramine O Stain |
|
| Mycobacterium tuberculosis Amplified Detection , CSF 0060063 Method: Transcription Mediated Amplification (Gen-Probe®) |
|
| Blastomyces dermatitidis Antigen EIA 2002926 Method: Enzyme Immunoassay |
|
| Blastomyces dermatitidis Identification by DNA Probe 0062224 Method: Nucleic Acid Probe |
Not from patient specimen |
| Blastomyces Antibody by CF 0050130 Method: Complement Fixation |
|
| Blastomyces Antibody by ID 0050172 Method: 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: Complement Fixation/Immunodiffusion/Enzyme-Linked Immunosorbent Assay |
|
| Coccidioides Antibody by CF 0050170 Method: Complement Fixation |
Least sensitive in pulmonary cavitary disease |
| Coccidioides Antibody by ID 0050183 Method: Immunodiffusion |
|
| Coccidioides Antibody, IgG by ELISA 0050179 Method: Enzyme-Linked Immunosorbent Assay |
|
| Coccidioides Antibody, IgM by ELISA 0050178 Method: Enzyme-Linked Immunosorbent Assay |
|
| Cryptococcus Antigen, Serum 0050196 Method: Enzyme Immunoassay |
Serum |
| Histoplasma Antigen by EIA, Urine 0060730 Method: Enzyme Immunoassay |
|
| Histoplasma capsulatum Identification by DNA Probe 0062226 Method: Nucleic Acid Probe |
Not from patient specimen |
| Histoplasma Antibodies by CF & ID 0050627 Method: Complement Fixation/Immunodiffusion |
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| Histoplasma Antibody by ID 0050174 Method: Immunodiffusion |
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| Urinalysis, Complete 0020350 Method: Reflective Photometry/Microscopic by Yellow IRIS |
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| Encephalitis Panel, CSF with Reflex to HSV Type 1 & 2 Glycoprotein G-Specific Ab, IgG 2001741 Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody |
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| Encephalitis Panel, Serum with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001742 Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody |
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| Neisseria meningitidis Tetravalent Antibodies (Serogroups A, C, W-135, & Y), IgG 2001603 Method: Multi-Analyte Fluorescent Detection |
|
| Blood Culture, Fungal 0060070 Method: BD Continuous monitoring system. Standard reference procedures for identification and/or DNA Sequencing |
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