At a Glance

The classical symptoms and signs of meningitis are:


headache (typically severe)

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meningismus (stiff neck)

altered mental status (typically temporally follows headache)

There are many infectious causes of meningitis, including:

viral (e.g., HSV and enterovirus)

bacterial (e.g., Streptococcus pneumoniae and Haemophilis influenza)

fungal (e.g., Cryptococcus neoformans)

protozoan (e.g., Naegleria fowleri)

mycobacterial (e.g., Mycobacterium tuberculosis complex)

spirochetal (e.g., Treponema pallidum and Borrelia burgdorferi)

noninfectious (e.g., tumor, medications, and trama)

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The diagnosis of meningitis is centered on the examination and evaluation of cerebral spinal fluid (CSF), blood cultures, and radiology.

The initial approach to confirmation of meningitis first requires examination of the patient and classification of the patient either as without papilledema or focal neurological deficits or as having papilledema or focal neurological deficits. Lumbar puncture in patients with papilledema or focal neurological deficits has been associated with herniation and, thus, would not be the first step.

In patients without papilledema or focal neurological deficits:

Obtain 3-4 sets of blood cultures from at least two different sites.

Send a serum glucose.

Perform a STAT lumbar puncture to obtain CSF for analysis:

˚ Measure opening pressure.

˚ At least 3 (preferably 4) sterile tubes should be collected, numbered, and placed on wet ice:

Tube 1 for chemistries (glucose and protein levels):

Glucose levels are reduced in bacterial meningitis (<40mg/dL with CSF-to-serum glucose ratio <0.3 in 60-70% of cases).

Protein levels are typically elevated in bacterial meningitis (>100mg/dL).

CSF Glucose can be slightly low and protein slightly high in viral meningitis, but both can be normal.

Tube 2 for microbiology/cultures (gram stain and aerobic culture):

Other secondary tests can be ordered, depending on suspicion. These include cryptococcal antigen, fungal culture, mycobacterial smears and culture,viral culture, VDRL, specific polymerase chain reaction (PCR) assays for HSV, enterovirus, HIV or arboviruses, and specific antibodies to certain pathogens, such as B. burgdorferi.

Itis not possible to order all tests on every suspected case of meningitis, so it is imperative that the differential diagnosis based on patient history be a guide to prioritizing test selection.

Anaerobic culture is not routinely performed, as anaerobic bacterial meningitisis quite rare. However, this might be suspected if the gram stain is positive, but there is no growth in the aerobic cultures.

Tube 3 for cellular analysis (white blood cell [WBC] with differential, red blood cell [RBC]):

Cytology and flow cytometry can also be ordered if malignancy is suspected.

WBC count is usually 1000-5000/mm3with a neutrophil predominance in bacterial meningitis and alymphocytic predominance in viral meningitis. However, the differential can be misleading in some cases.

Tube 4 for additional add-on testing after the results from Tubes 1-3 are completed:

Strongly recommended to avoid bacterial antigen testing.

Results can be misleading and offer no advantages over gram stains.

In patients with papilledema or neurological deficits:

Obtain 3-4 sets of blood cultures from at least two different sites.

Administer dexamethasone and empiric antimicrobial therapy.

Obtain a STAT CT scan of the head:

˚ If a mass is present, the cause is not likely infectious and the risk of herniation with lumbar puncture should be considered before performing a tap.

˚ If no mass is present, proceed quickly with lumbar puncture and testing as described for patients with no neurological deficits.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

There are a number of factors that can affect CSF analysis, most preanalytical in nature.

  • Blood in CSF due to a traumatic lumbar puncture:

    ˚ Complicates interpretation of both chemistry and cellular analysis.

  • Presence of skin flora in CSF secondary to improper preparation of the skin prior to performing the lumbar puncture:

    ˚ Coagulase negative Staphylococcus is a common contaminant in CSF cultures, and, unless present in significant amounts, is not typically fully worked up in most microbiology laboratories.

    The exception to this is if the patient has a cerebral shunt or any foreign material that might be in contact with the CSF.

    Administration of antimicrobials prior to obtaining CSF:

    ˚ Administration of antimicrobials appropriate for the organism present can inhibit the growth of the organism in as little as 2-4 hours after administration.

    This is why a STAT CT and lumbar puncture are crucial in patients with neurological deficits.

    Delayed CSF testing or failure to place tubes on ice:

    ˚ Especially if blood is present, ongoing glycolysis can artificially lower glucose levels.

    ˚ Some more fastidious organisms may lose viability.

    ˚ Some contaminating organisms could overgrow, suppressing growth of a true pathogen.

What Lab Results Are Absolutely Confirmatory?

This can be a complex question for any microbiological analysis, as the presence of a microorganism (or viral nucleic acid) in a clinical sample is not 100% confirmatory, but rather the presence of that organism (or viral nucleic acid) must be determined to be the clinically relevant pathogen based on the clinical scenario.

It has been stated that the following profile predicts bacterial meningitis with up to 99% certainty:

CSF Glucose less than 34 mg/dL with a CSF-serum ratio less than 0.23

CSF Protein greater than 220 mg/dL

More than 2000/mm3 CSF WBC’s with more than 1180 of those being neutrophils

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A discussion of meningitis is not complete without a short reminder of the most common causative pathogens. The most common bacterial pathogens have changed over the years primarily because of immunization with the Haemophilus influenza B vaccine. This vaccine has dramatically reduced the incidence of H. influenza meningitis. In fact, meningitis is now considered more of a disease of adults than children. The most common pathogens identified in all patients are Streptococcus pneumoniae, Neisseria. meningitidis, H. influenza, and Literia monocytogenes.

The most common viral pathogens are enterovirus, HSV, HIV, and the arboviruses. However, the latter are more important causes of encephalitis (see module on encephalitis for more information).