Acute Meningitis

Meningitis is the inflammation of the leptomeninges, the tissues surrounding the brain and spinal cord. Prompt identification and treatment of infectious meningitis may prevent irreversible neurological sequelae. Evaluation of the cerebrospinal fluid (CSF) for white blood cells (WBCs), red blood cells (RBCs), malignant cells, bacterial, viral or fungal elements, protein and glucose levels, as well as other markers is critical to determine correct treatment and optimal outcomes.

Tabs Content

Clinical Overview

Diagnosis

Indications for Testing

Fever
Headache
Altered sensorium
Stiff neck

Laboratory Testing

CDC meningitis overview
Initial testing is nonspecific – CBC, electrolytes
- Normal WBC does not rule out meningitis
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 postneurosurgical meningitis or shunt meningitis
  - Fungal and acid-fast bacilli (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)
Polymerase chain reaction (PCR) testing for enterovirus, Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), 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
- Rapid plasma reagin (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

Computed tomography (CT)/magnetic resonance imaging (MRI) – consider prior to CSF tap if focal findings are present or patient is significantly immunocompromised,
Chest x-ray – may be useful in diagnosing pneumonia as etiology (usually Streptococcus pneumoniae)

Differential Diagnosis

Encephalitis
Connective tissue central nervous system (CNS) disease
- Sjögren syndrome
- Systemic lupus erythematosus
Vasculitic CNS disease
- Behçet disease
- Granulomatosis with polyangiitis
Granulomatous CNS disease
- Sarcoidosis
Migraine headache
Malignant meningitis
- Carcinoma
- Lymphoma
  - B cell
  - T cell
- Leukemia
  - Acute lymphoblastic leukemia
  - Acute myeloid leukemia
Subarachnoid hemorrhage
Stroke
Seizure disorder
Febrile seizures in children
Fabry disease
Medications – numerous drugs can cause aseptic meningitis

Monitoring

Serology should not be used to monitor status of disease.

Background

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

Viral (aseptic) – most common cause
- Enterovirus – most common cause
- HSV
- Arboviruses (eg, West Nile virus)
- Mumps virus
- Lymphocytic choriomeningitis
- Other viruses – EBV, CMV, acute HIV, human herpesvirus 6, VZV, and adenoviruses
Bacterial
- Neisseria meningitidis
- S. pneumoniae
- Haemophilus influenzae
- L. 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
- Treponema pallidum
- Borrelia burgdorferi
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 (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
- Shock
- Disseminated intravascular coagulation
- Focal permanent neurologic deficits
  - Deafness, blindness, paresis
- Hydrocephalus
- CNS abscess
- Seizure disorder
- Recurrent meningitis
  - Congenital anatomical defects
  - Neurogenic cysts
  - Asplenia
  - Congenital immunodeficiencies (eg, complement deficiency)
  - Acquired immunodeficiencies (eg, HIV)
  - Mollaret meningitis (caused by 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

ARUP Lab Tests

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

Aid 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

Detect presence of bacteria in blood

Limitations

Limited to the University of Utah Health Sciences Center only

Fungal Culture 0060149
Method: Culture/Identification

Recommended Use

Gold standard test to diagnose fungi as agent of infection

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

Recommended Use

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

Panel 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

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

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

Meningitis/Encephalitis Panel by PCR 2013305
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Rapidly detect a panel of common viruses, bacteria, and fungi associated with meningitis and encephalitis

Do NOT use as a replacement for CSF bacterial and/or fungal culture and Cryptococcal antigen testing for at-risk patients

Limitations

A negative result does not exclude a diagnosis of meningitis or encephalitis due to infection

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

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

Aid in the diagnosis of pneumococcal meningitis

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

Molecular testing is preferred for patients presenting with meningitis/encephalitis

Refer to meningitis/encephalitis panel by PCR

Panel components include West Nile virus (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

Not a preferred test

Refer to relevant test for the specific pathogen suspected

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 N. meningitidis vaccination

For assessment of suspected immunodeficiency, use pre- and postvaccination serology

Limitations

Not intended for diagnosis of infection or serotyping

Acanthamoeba and Naegleria Culture 0060245
Method: Qualitative Culture/Microscopy

Recommended Use

Detect Acanthamoeba spp and Naegleria fowleri in various specimen types

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

Recommended Use

Preferred test is West Nile IgM antibody

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

Recommended Use

Preferred panel for diagnosing possible tickborne disease (ie, Anaplasmosis or Ehrlichiosis) during the acute phase of the disease

Detect and speciate A. phagocytophilum, E. chaffeensis, E. ewingii/E. canis, E. muris-like

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

Recommended Use

Aid in the diagnosis of LCM viral infection in the central nervous system

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; order with CSF culture and Gram stain

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

Blastomyces dermatitidis Antibodies by EIA with Reflex to Immunodiffusion, Serum 3000236
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunodiffusion

Recommended Use

Recommended test if serology is used to aid in the diagnosis of blastomycosis

Blastomyces dermatitidis Antibodies by EIA with Reflex to Immunodiffusion, CSF 3000231
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Immunodiffusion

Recommended Use

Recommended test if serology is used to aid in the diagnosis of cerebral blastomycosis

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

Recommended Use

Aid in the diagnosis of histoplasmosis

Recommend testing in conjunction with the combined complement fixation and immunodiffusion antibody and urine galactomannan antigen tests

Medical Experts

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

Fisher, Mark A., PhD, D(ABMM), Medical Director, Bacteriology, and Special Microbiology, Antimicrobial Susceptibility Testing, at ARUP Laboratories; Associate Professor of Clinical 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

References

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

Mount HR, Boyle SD. Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention. Am Fam Physician. 2017; 96(5): 314-322. 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

Resources 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

Prasidthrathsint K, Lewis J, Couturier MR. Closing the Brief Case: Angiostrongylus cantonensis Eosinophilic Meningitis in a Returned Traveler. J Clin Microbiol. 2017; 55(10): 3147-3148. PubMed

Last Update: June 2019

Acute Meningitis

Diagnosis

Indications for Testing

Laboratory Testing

Imaging Studies

Differential Diagnosis

Monitoring

Background

Epidemiology

Classification

Risk Factors

Clinical Presentation

Prevention

ARUP Lab Tests

Medical Experts

References

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

ARUP Websites

ARUP Consult


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Acute Meningitis

Diagnosis

Indications for Testing

Laboratory Testing

Imaging Studies

Differential Diagnosis

Monitoring

Background

Epidemiology

Classification

Risk Factors

Clinical Presentation

Prevention

ARUP Lab Tests

Medical Experts

References

General References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

ARUP Laboratories

ARUP Websites

ARUP Consult