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.

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

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

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

Primary Tests

May be helpful in differentiating bacterial from viral etiology

Useful in assessing metabolic derangement as cause of altered consciousness

Identify bacteria in CSF

Useful in assessing metabolic derangement as cause of altered consciousness

Aid in differentiating bacterial from viral meningitis

May be helpful in differentiating bacterial from viral etiology

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

May be helpful in differentiating bacterial from viral etiology

Detect presence of bacteria in blood

Limited to the University of Utah Health Sciences Center only

Gold standard test to diagnose fungi as agent of infection

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

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

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

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

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

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

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. fortuitumcomplex, 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

Aid in the diagnosis of pneumococcal meningitis

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

Identify presence of Naegleria and Acanthamoeba in CSF specimen

Wright Stain

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

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

Assess immunocompetence following N. meningitidis vaccination

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

Not intended for diagnosis of infection or serotyping

Detect Acanthamoeba spp and Naegleria fowleri in various specimen types

Preferred test is West Nile IgM antibody

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

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

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

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

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

Aid in the diagnosis of histoplasmosis

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

Cross-reactivity withBlastomyces dermatiditis, Coccidioides immitis, and possibly Talaromyces marneffei has been observed

Related Tests

Detect enterovirus in blood, CSF, or nasopharyngeal specimens

Detect enterovirus and parechovirus

Preferred test for detecting HSV infection in CSF, neonates, or when rapid diagnostic test for suspected HSV infection is necessary

Detect CMV but does not quantify viral load; potentially useful for specimen types other than blood

CMV by quantitative PCR on plasma is preferred for most clinical indications

Do not use for diagnosis of infectious mononucleosis

Order to detect EBV in individuals suspected of having EBV-related disease

Detect VZV in blood, CSF, ocular fluid, tissue, or vesicle fluid

Monitor respiratory specimens in previously diagnosed patients

Should NOT be ordered without culture in previously undiagnosed patients

For panel test that includes culture and stain, refer to AFB culture and AFB stain test

Panel includes PCR testing to detect M. tuberculosis complex (MTBC) isolates and determine possible resistance to rifampin treatment

Test may be ordered for client-processed specimens; refer to specimen requirements

Diagnose and monitor B. dermatitidis

For urine specimens, refer to Blastomyces antigen quantitative by EIA, urine

Diagnose and monitor B. dermatitidis

For serum specimens, refer to Blastomyces antigen quantitative by EIA

Rapid test for identifying B. dermatitidis (yeast or mold form) from a pure isolate

Not recommended as a stand-alone test; refer to the enzyme-linked immunosorbent assay with reflex to immunodiffusion

Rapid test for identifying C. immitis (yeast or mold form) from a pure isolate

Preferred serology test to detect coccidioidomycosis (Valley fever)

Panel includes Coccidioides antibody IgG and IgM, Coccidiodes immitus antibodies, and coccidiode titer

For initial establishment of diagnosis, refer to Coccidioides Antibodies Reflexive Panel

Panel includes coccidioides antibody by CF; coccidioides immitis antibodies by immunodiffusion; coccidioides antibody, IgG and IgM by ELISA

Aid in diagnosis of coccidioidal meningitis (Valley fever)

May aid in diagnosis of coccidioidomycosis (Valley fever)

Preferred test for establishment of diagnosis is Coccidioides Antibodies Reflexive Panel

Aid in diagnosis of coccidioidal meningitis (Valley fever)

Titers may aid in monitoring coccidioidomycosis (valley fever) and treatment response

Preferred test for establishment of diagnosis is Coccidioides Antibodies Reflexive Panel

Aid in diagnosis of coccidioidal meningitis (Valley fever)

Not recommended

Preferred test for establishment of diagnosis is Coccidioides Antibodies Reflexive Panel

Not recommended

Not recommended as a stand-alone test

Preferred test for establishment of diagnosis is Coccidioides Antibodies Reflexive Panel

Not recommended as a stand-alone test

Not recommended as a stand-alone test

Preferred test for establishment of diagnosis is Coccidioides Antibodies Reflexive Panel

Not recommended as a stand-alone test

Identify C. neoformans as the infectious agent of invasive cryptococcal disease

Aid in the diagnosis of histoplasmosis

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

Rapid test for identifying H. capsulatum (yeast or mold form) from a pure isolate

Aid in the diagnosis of histoplasmosis

Recommend testing in conjunction with serum antigen and urine galactomannan antigen tests

Not recommended as a stand-alone test

Refer to the combined complement fixation and immunodiffusion test

Gold standard test to diagnose fungi as agent of infection in blood

Preferred test for diagnosing West Nile encephalitis

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

Fisher

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

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®