The problem of identifying causative organisms that cannot be easily cultured, particularly in patients who have received antibiotics, may be overcome by the application of special laboratory techniques. One of these is counterimmunoelectrophoresis (CIE), a sensitive test that permits the detection of bacterial antigens in the CSF in a matter of 30 to 60 min. It was in the past particularly useful in patients with partially treated meningitis, in whom the CSF still contains bacterial antigens but no organisms on a smear or grown in culture but it has been replaced by more sensitive methods described in the following text.
Several other serologic methods, radioimmunoassay (RIA) and latex-particle agglutination (LPA), as well as an enzyme-linked immunosorbent assay (ELISA), may be even more sensitive than CIE. An argument has been made that these procedures are not cost-effective, as—in virtually all instances in which the bacterial antigen can be detected—Gram stain also shows the organism. Gene amplification by the polymerase chain reaction (PCR) is the most recently developed and most sensitive technique. As it has become more widely available in clinical laboratories, rapid diagnosis has been facilitated but the use of carefully Gram-stained preparations still needs to be encouraged.
In the past, much was made of the interesting finding that chloride concentrations in the CSF are usually low in meningitis, possibly reflecting dehydration and low serum chloride levels. In contrast, CSF lactate dehydrogenase (LDH), although also infrequently measured, can be of diagnostic and prognostic value. A rise in total LDH activity is consistently observed in patients with bacterial meningitis; most of this is because of fractions 4 and 5, which are derived from granulocytes. Fractions 1 and 2 of LDH, which are presumably derived from brain tissue, are only slightly elevated in bacterial meningitis but rise sharply in patients who develop neurologic sequelae or later die. Various enzymes in the CSF, derived from leukocytes, meningeal cells, or plasma, may also be increased in meningitis, but the clinical significance is unknown. Levels of lactic acid in the CSF (determined by either gas chromatography or enzymatic analysis) are also elevated in both bacterial and fungal meningitides (greater than 35 mg/dL) and may be helpful in distinguishing these disorders from viral meningitides, in which lactic acid levels remain normal; however, these ancillary tests are infrequently performed.
In addition to CSF cultures, blood cultures should be obtained if possible because they are positive in 40 to 60 percent of patients with H. influenzae, meningococcal, and pneumococcal meningitis, and may provide the only definite clue as to the causative agent. Routine cultures of the oropharynx are as often misleading as helpful, because pneumococci, H. influenzae, and meningococci are common in the throats of healthy persons. In contrast, cultures of the nasopharynx may aid in diagnosis, although often not in a timely way; the finding of encapsulated H. influenzae or groupable meningococci may provide the clue to the etiology of the meningeal infection. Conversely, the absence of such a finding prior to antibiotic treatment makes an H. influenzae and meningococcal etiology unlikely. The leukocyte count in the blood is generally elevated, and immature forms are usually present. Meningitis may be complicated after several days by severe hyponatremia, the result of inappropriate secretion of antidiuretic hormone (ADH).