In addition to the aforementioned bacterial infections that can cause aseptic meningitis, several other categories of disease may cause a sterile, predominantly lymphocytic or mononuclear reaction in the leptomeninges: (1) foci of bacterial infection lying adjacent to the meninges, such as spinal or cranial epidural abscess (parameningeal infection); (2) partially treated bacterial meningitis; (3) meningeal infections in which the organism is difficult or impossible to isolate—fungal and tuberculous meningitis are at times in this category and parasitic infections are in this group; (4) neoplastic invasion of the leptomeninges (lymphomatous and carcinomatous meningitis); (5) granulomatous, vasculitic, or other inflammatory diseases such as sarcoidosis, Behçet disease, and granulomatous angiitis; (6) acute or chronic recurrent inflammatory meningitides as a result of chemical irritation, including an aseptic chemical meningitis incited by rupture of a craniopharyngioma or other cystic structure containing proteinaceous fluid—these are described earlier on under the section “Chronic Persistent and Recurrent Meningitis”; (7) rarely, children with a mundane infectious disorders develop meningeal signs and slight pleocytosis, the result of a sterile inflammation that does not involve invasion of the meninges by organisms—the same may occur in bacterial endocarditis; (8) an idiosyncratic, presumably immunologic meningitis as mentioned earlier, may result from the use of nonsteroidal anti-inflammatory drugs, intravenous immune globulin (due probably to a carrier chemical in the solution), and, rarely, from other drugs, including certain antibiotics. Individuals with systemic lupus erythematosus have an increased risk of aseptic meningitic reactions to anti-inflammatory medications.
In respect to the first two categories, parameningeal and partially treated bacterial infections, smoldering paranasal sinusitis or mastoiditis may produce a CSF picture of aseptic meningitis because of epidural or subdural extension into the intracranial compartments; it is infrequent that the entire syndrome of meningitis is present. Uncomplicated sinusitis alone does not cause a meningeal reaction.
Antibiotic therapy given for a systemic or pulmonary infection may suppress a bacterial meningitis to the point where mononuclear cells predominate, glucose is near normal, and organisms cannot be cultured from the CSF although they may still be evident by Gram stain. Careful attention to the history of recent antimicrobial therapy permits recognition of these cases.
Syphilis, cryptococcosis, and tuberculosis are the important members of the third group that cause aseptic meningitis and in which the organism may be difficult to culture, as detailed in Chap. 31. Tuberculous meningitis, in its initial stages, may masquerade as innocent aseptic meningitis and the diagnosis may be delayed. Similarly, the diagnosis of cryptococcosis, other fungal infection, or nocardiosis is occasionally missed because the organisms may be present in such low numbers as to be overlooked in smears, especially in HIV patients. Brucellosis (Mediterranean fever, Malta fever) is a rare disease that may present as an acute meningitis or meningoencephalitis, with the CSF findings of aseptic meningitis. The diagnosis depends on the detection of high serum antibody titers and Brucella-specific immunoglobulins, using the ELISA or serum agglutination testing. There are also new genetic detection techniques, alluded to earlier, that may expose the cause of an otherwise obscure meningitis (see Wilson et al).