Diagnostic Tests

The diagnosis of bacterial meningitis rests largely on examination of the CSF, but the rapidity of the patient's course may dictate the appropriate timing of the lumbar puncture. Patients with a rapid clinical course (< 24 h) and/or focal neurological signs, seizures, altered consciousness, or evidence of intracranial hypertension (e.g., papilledema) require initial empiric antibiotic therapy prior to a lumbar puncture; the antibiotic choice may be based upon available history including age, underlying medical conditions, prior antibiotic therapy, and the status of immunity (17,18).

In patients without papilledema or focal neurologic signs on physical examination, the risk of herniation due to lumbar puncture is felt to be low; however, older adults are more commonly afflicted with space-occupying lesions such as brain abscess, tumors, or other masses that might predispose to herniation. Additionally, some epidemiologic studies have documented the frequent occurrence (39-43%) of focal neurologic findings in older adults with bacterial meningitis (3, 12). Thus, CT scan of the brain may be deemed necessary in the majority of older adults suspected of bacterial meningitis. Talan and colleagues reviewed the issue of administration of antibiotic therapy prior to performance of the lumbar puncture and concluded that empiric therapy probably did not adversely affect the diagnostic properties of examination of the CSF, particularly if the delay before the lumbar puncture was not prolonged. Similar conclusions were reached by others utilizing rabbit models of bacterial meningitis (18).

With bacterial meningitis, the CSF generally has the characteristics shown in Table 3 and, in surveys of this disease in older adults, no differences were noted in the diagnostic criteria including pleocytosis, hypoglycorrhachia, or positive cultures. Additionally, the rate at which blood cultures were positive also seemed similar to that in younger patients. The determination of hypoglycorrhachia may be more difficult in patients with peripheral blood hyperglycemia or hypoglycemia. A serum glucose drawn at approximately the same time as the lumbar puncture is mandatory; ratios of CSF glucose to serum glucose of less than 0.31 are consistent with hypoglycorrhachia and bacterial meningitis (20). A minority of patients with bacterial meningitis may demonstrate atypical CSF parameters, particularly a lymphocytic response or lower percentage of neutrophils or a Gram stain without organisms (19). This scenario is especially seen with L. monocytogenes meningitis in which the Gram stain is positive in fewer than one third of cases, and with Gram-negative bacillary meningitis where the pleocytosis may be less and the percentage of neutrophils may be somewhat lower than with typical bacterial meningitis. Usually, however, the glucose, Gram stain and other tests strongly suggest a bacterial etiology (8).

Table 3

Cerebrospinal Fluid Findings in Meningitis

CSF findings

Normal CSF

Acute bacterial

Viral

Tuberculous

Opening pressure (cm H2O)

Protein (mg/dL)

Glucose (mg/dL)

Miscellaneous

6-20

0-5, (about 85% lymphocytes)

18-45

45-80 or 0.6 X serum glucose

For traumatic taps add 1 WBC

and 1 mg/dL protein for each 1000 RBCs

Usually elevated

Usually several hundred to >60,000,

PMNs predominate

Usually 100-500, occasionally >1000

Usually 5-40 or <0.3X serum glucose

Gram-stain + in about 60-80%; Sp = Gram + diplococci; Nm = Gram neg diplococci; Lm = Gram + bacillus

Normal to moderately elevated

5 to a few hundred but may be more than 1000. Lymphocytes predominate but may be >80% PMNs in the first few days

Frequently normal or slightly elevated <100; may show greater elevation in severe cases

Usually normal, but can be low with mumps, HSV 2

Usually do not need to find specific causal virus

Usually elevated

Usually 25-100, rarely >500. Lymphocytes predominate except early stages where PMNs may account for >80% of cells

Nearly always elevated, usually 100-200 but may be much higher if dynamic block

Usually reduced; <45 in 3/4 of cases

AFB + stain in 25%, culture + in >2/3 of cases (but may take 4-8 wk for growth)

Sp, S. pneumoniae; Nm, N. meningitidis; Lm, L. monocytogenes; AFB, acid-fast bacilli; HSV 2, Herpes simplex type II; CSF, cerebrospinal fluid; PMNs, polymorphonuclear neutrophils; RBCs, red blood cells; WBCs, white blood cells; +, positive; cmH2O, centimeter of water; neg, negative.

The frequent use of antibiotics in the community generates many cases of meningitis where this prior antibiotic administration clouds the etiologic diagnosis. Several studies have concluded that prior antibiotics can alter the Gram-stain results, delay the growth of organisms on culture, and occasionally change the CSF parameters. In general, however, the CSF results are sufficiently unaltered to allow appropriate suspicion of a bacterial rather than a viral or aseptic etiology and to permit the growth of the etiologic agent (3,6,19,22). The delay in specific diagnosis, particularly due to the effect of prior antibiotics on the Gram-stain results, is of concern and may prevent the use of specific antibiotic therapy. To address this issue, bacterial antigen testing of the CSF is indicated, with tests available for S. pneumoniae, N. meningitidis, H. influenzae, group B streptococci, and E. coli. The overall sensitivities of these tests is approximately 50-75% and the specificities approach 100%; thus, a positive test is quite helpful as it is likely to be a true positive, whereas a negative test is not helpful as it may be either a true negative or a false negative (3,6,23). Improved diagnostic testing is currently being sought and polymerase chain reaction (PCR) or DNA probe technology to identify specific bacteria in the CSF may be clinically useful in the near future.

The differential diagnosis of bacterial meningitis includes conditions that can cause altered mental status and fever, with or without meningeal signs. Thus, conditions that should also be considered include encephalitis, brain abscess, subdural empyema, epi-dural abscess, cancers (either primary or metastatic malignancies of the CNS), cere-brovascular disease, or vasculitis. A clinical prediction rule has been proposed to help in the diagnosis of acute bacterial meningitis (24,25).

Encephalitis in the older adult may be secondary to viral etiologies such as herpes simplex, equine encephalitis viruses, or others. The presentation of this syndrome is usually one of more profound alteration of level of consciousness or mental function with less prominent meningeal signs; seizures occur more commonly than with bacterial meningitis. The differentiation of these entities on clinical grounds, however, may be difficult, and the clinician may need to rely on the CSF examination to exclude bacterial meningitis. The diagnosis of encephalitis is more highly suspected with demonstration of areas of inflammation of the brain on CT or MRI (especially with herpes encephalitis) scan and by serologic tests for etiologic viruses or, in the case of herpes simplex, with a PCR of the CSF.

Patients with brain abscess may present in varying fashions. Fever is found in less than 75% of cases, and even headache or alteration of mental function are not universal symptoms. The diagnosis of brain abscess is best determined by imaging studies such as CT or MRI scan of the brain.

Individuals with subdural empyema may have clinical courses indistinguishable from bacterial meningitis, and indeed, this syndrome may be a complication of bacterial meningitis. The diagnosis is suspected in individuals whose response to antibiotic therapy is incomplete or delayed, and the presence of subdural fluid may be confirmed with CT or MRI scan. The precise diagnosis and treatment is best obtained with drainage of the subdural collection and appropriate antibiotic therapy based on culture results.

Epidural abscesses are generally of hematogenous origin, and are generally best treated with aspiration or debridement and appropriate antibiotics (26).

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