- Suspect diagnosis if presentation fits: The most important aspect in making the diagnosis of meningitis in children is to first suspect the diagnosis. Several reviews have been published to establish criteria to aid in the diagnosis of bacterial meningitis (16, 71).
- Signs of elevated ICP direct evaluation: In patients with papillary or ocular mobility abnormalities, bradycardia, hypertension, or stupor suggestive of severely increased ICP and impending herniation, or in the presence of focal neurological deficits, CT or MRI scanning should be performed prior to lumbar puncture to rule out mass lesions that could cause herniation after the procedure. The absence of these findings identifies a patient likely to have a normal CT scan with a negative predictive value of 97% (32).
- Lumbar puncture desired: Once the diagnosis is suspected, lumbar puncture should be performed to obtain CSF for analysis and culture. If the ICP is mildly to moderately increased, lumbar puncture can be performed with a small needle, collecting the minimal CSF sample needed for diagnosis. In some cases, mannitol may be administered to help control ICP prior to the lumbar puncture. It is imperative to perform the lumbar puncture as atraumatically as possible. Contamination of the CSF with peripheral blood makes the analysis of the CSF very difficult. A mild pleocytosis, such as occurs in viral or early bacterial meningitis, may be missed. A traumatic tap may be distinguished from subarachnoid hemorrhage by comparing the cell counts from the first and fourth tube drawn and also the presence or absence of xanthochromia due to previous hemorrhage.
- Tuberculous meningitis signs: The diagnosis should be suspected when a causative organism is not seen on Gram stain or recovered in routine cultures or antigen screens. Six factors that favor the diagnosis of tuberculous meningitis are 1) duration of illness more than 5 days, 2) presence of headache, 3) CSF WBC count of less than 1000 cells/mm3, 4) clear CSF, 5) lymphocyte count greater than 30%, and 6) CSF protein level greater than 100 mg/dl (77). In addition, patients should undergo chest x-ray and tuberculosis antigen skin testing, and a detailed history for possible tuberculosis exposures should be taken.
The CSF obtained from lumbar puncture should be examined for total WBC count, with differential, red blood cell (RBC) count, and glucose and protein concentrations. It should be stained for microorganisms (Gram stain for bacteria, India ink or KOH prep for fungi, acid-fast stain if tuberculosis is suspected), and a rapid technique for detection of bacterial antigens such as latex agglutination should be performed. The CSF should be cultured for bacteria and for other organisms as clinically indicated, including fungi, mycobacteria, or viruses (58, 68).
Normal findings in CSF of children at various ages*
|Neonate||Infants and children|
|WBC count (cells/mm3)||<30||<10|
|Polymorphonuclear WBC (%)||<60||<10|
|CSF/blood glucose ratio||>0.6||>0.5|
|Manometric pressure (mm H20)||<60||<90|
- Appearance varies with cause: The CSF findings in patients with meningitis vary with the cause of the infection. The classic cloudy CSF with markedly elevated WBC count, polymorphonuclear leukocyte predominance, and low glucose with elevated protein are common in bacterial meningitis. Other forms of meningitis may demonstrate more subtle CSF abnormalities.
CSF cell count
- Bacterial meningitis – cell count rises as disease progresses to > 1,000 cells/mm3: In patients with acute bacterial meningitis, CSF WBC counts may be in the 1,000–10,000 cells/mm3 range. Very early in the course, however, the cell count may be normal, even with a positive culture. In such cases, repeat lumbar puncture will yield more characteristic WBC counts and polymorphonuclear leukocyte predominance. In less than 2% of cases, infants and children will have a normal CSF WBC count, compared to up to 10–15% of neonates with bacterial meningitis having normal counts. Classically, the differential WBC count in bacterial meningitis demonstrates greater than 85% polymorphonuclear leukocytes, compared to acute viral meningitis, which will have a predominance of mononuclear cells (>50%).
- Viral meningitis – cell count does not worsen to the degree in bacterial meningitis and cell types become mononuclear: Early in the course of viral meningitis, there may be a polymorphonuclear leukocyte predominance. In this case, it is very difficult to distinguish early bacterial meningitis, partially treated bacterial meningitis, and early viral meningitis. The subsequent clinical course and repeat CSF sampling may distinguish these entities. A patient with viral meningitis will have no significant neurological findings, a CSF WBC count less than 500 cells/mm3 with a predominance of mononuclear cells, and a normal CSF glucose level as the disease progresses.
- Tuberculous meningitis – cell count less than 1000 cells/ mm3 and signs of systemic disease: A moderately elevated CSF WBC count (50–500 cells/mm3) with a mononuclear predominance typifies tuberculous meningitis.
- Normal is 50% of serum glucose: The normal CSF glucose level is greater than 50% of the serum glucose level. In the absence of serum glucose levels, a value of 40 mg/dl is considered the low cut-off for normal. In newborns, values of as low as 25 mg/dl may be seen normally.
- Bacterial and tuberculous meningitis – levels 0–30 mg/dl: In most cases of bacterial and tuberculous meningitis, CSF glucose values of 0–30 mg/dl are seen. Levels below 20 mg/dl are associated with increased incidence of hearing impairment. In most cases of bacterial meningitis, CSF glucose levels return to normal within 48 hours of adequate antibiotic therapy. In cases of tuberculous meningitis, CSF glucose levels may remain low or even worsen early in the treatment course.
- Viral meningitis – levels ≥ 30 mg/dl: Levels below 30 mg/dl are rarely seen in viral meningitis.
- Normal range is 25–40 mg/dl: The normal CSF protein level is 25– 40 mg/dl, although in newborns it may be as high as 170 mg/dl. In general, CSF protein levels are the least reliable parameter in distinguishing between types of meningitis.
- Bacterial meningitis – levels 100–1000 mg/dl: In the majority of bacterial meningitis cases, CSF protein levels are markedly elevated to the 100 to 1000 mg/dl range, although they may occasionally be normal.
- Tuberculosis meningitis – levels >100 mg/dl: In cases of tuberculous meningitis, CSF protein levels may also be significantly elevated.
- Viral meningitis – levels 50–100 mg/dl: In cases of viral meningitis, CSF protein levels are commonly only mildly elevated in the 50–150 mg/dl range.
CSF microbiological inspection
- Grain stain and special stains when indicated: The CSF is stained for microorganisms. This will almost always include a Gram stain looking for bacteria. H&E for viral, India ink or KOH prep for fungi, and acid-fast stain for tuberculosis should be performed when these infections are suspected.
- Always done when CSF sampled: Cultures should be performed on all CSF specimens, even those showing normal CSF WBC counts.
- Bacterial – latex agglutination test: The latex agglutination test provides for the very rapid and accurate detection of bacterial antigens in the CSF. This method may be used for the diagnosis of S. pneumoniae, H. influenzae, and group B streptococcus. The sensitivity is greater than the Gram stain, approaching 90–100%, as fewer bacteria are required for detection. The latex agglutination test may be very helpful in the diagnosis of patients with partially treated meningitis and negative CSF cultures.
- Tuberculosis – ELISA and PCR: More than 60% of patients will have CSF antimycobacterial antibody to A60 M. tuberculosis antigen. An enzyme-linked immunologic assay (ELISA) test for this antigen is readily available through state health laboratories (63). A polymerase chain reaction (PCR) test has been developed for M. tuberculosis DNA in CSF, with a sensitivity of 60–85% and a specificity of 94–100% (10, 23).
- Viral – PCR: The addition of PCR-based tests has greatly aided the diagnosis of viral meningitis (55).
- Fungal – ELISA, lateral flow assay: Serologic testing of blood and CSF may confirm diagnosis of fungal infection. ELISA for cryptococcal antigen testing of blood or CSF is positive in virtually 100% of patients with the disease. Since ELISA testing is often not available in developing countries, a lateral flow assay (LFA) was developed for detection of Cryptococcal antigen in blood, CSF, or even urine. Results from LFA have good correlation with results of ELISA testing and can be obtained in as little as 10 minutes, thereby providing new hope for improved care in the developing world (35).
- Imaging prior to lumbar puncture: Imaging studies are often requested before lumbar puncture to rule out increased ICP and to be sure it is “safe” to perform the lumbar puncture (32, 34). A normal CT scan does not necessarily mean that the lumbar puncture is safe (56), and an abnormal CT scan is rare in children unless certain clinical or neurological signs are present.
- Tuberculous meningitis: Neuroimaging with CT or MRI scan provides valuable information for diagnosis of tuberculous meningitis and characterization of potential complications. Basal meningeal enhancement and hydrocephalus are frequently present. Infarcts, focal tuberculomas, and cerebral edema may also be seen (4).
- Fungal meningitis: Neuroimaging studies do not show the basal meningitis present in tuberculous meningitis.
- Preferred modality due to accessibility: CT scan is the diagnostic modality of choice, particularly for acute meningitis. In patients with focal neurological signs, CT scan should be performed before lumbar puncture to rule out brain abscess, subdural empyema, or other pathology.
- Leptomeningeal enhancement: Scans with contrast will show leptomeningeal enhancement and extraaxial fluid collections. A normal CT scan does not rule out elevated ICP.
- More sensitive for extraaxial collections: MRI scans are useful after the initial assessment and are more sensitive for detecting possible extraaxial collections.
- Gadolinium enhancement for empyema: Scans with gadolinium may also help to determine whether such collections are hygromas or possible subdural empyema. MRI scans will also demonstrate brain abscesses, ventriculitis, edema, and developing infarcts.
Nuclear Medicine Tests
- Evaluation of vasculitis: Brain SPECT scan may show changes in perfusion from meningitis-associated vasculitis and may provide early detection of developing infarcts.
- EEG: In patients presenting with seizures, EEG monitoring is a useful adjunct in the treatment of meningitis.
- Track recovery: Neuropsychological tests may play an important role in the recovery phase of meningitis. Patients who present acutely ill are unable to provide baseline testing results, but after treatment recovery may be monitored with neuropsychological testing to assess cognitive effects of the infection.