Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (113 page)

   CSF viral culture has a low diagnostic yield for CNS infections, especially for nonenteroviral and non-HSV CNS infections.

   West Nile virus should be carefully considered because of its frequency of occurrence.

   HSV should be ruled out by PCR in all patients with acute encephalitis of unknown cause because of its prominence in the differential diagnosis and the severity of sequelae in untreated infection.

   PCR is the diagnostic method of choice for most patients with acute encephalitis. The specific target pathogens are prioritized on the basis of pretest probability.

   Specific PCR for
M. pneumoniae
on CSF and throat specimens is recommended for children with acute encephalitis in whom another cause is not identified.

   Serologic testing is of limited value for patients with acute encephalitis but may be useful in patients in whom initial testing is not diagnostic. Serologic tests that may support specific diagnoses include detection of intrathecal antibody formation, production of serum or CSF IgM, or rise in antibody titer in acute and convalescent (typically >3 weeks after onset of symptoms) serum specimens. Demonstration of specific IgM in CSF provides a diagnosis of West Nile virus encephalitis.

   Brain biopsy, with routine and immunohistologic staining, may provide specific diagnosis for patients in whom initial testing by noninvasive testing is uninformative (see eBook Figure 4-36).

   In patients with postinfectious encephalitis, the virus responsible for the inflammatory response cannot be isolated from affected tissue.

MENINGITIS

Meningitis generally refers to infection in the subarachnoid space, the space between the middle (arachnoid) layer and the layer adjacent to the neural tissue (pia mater). Because the subarachnoid space is the major reservoir of CSF, CSF is usually the specimen of choice for tests to diagnose meningitis. The subarachnoid space is intrinsically “immunocompromised” outside of barrier defenses. There are relatively few phagocytic cells, and the concentrations of complement and antibodies are low. Bacteria that gain access to the subarachnoid space are able to proliferate efficiently. There is a high morbidity and mortality associated with acute bacterial meningitis, even when antibiotics are promptly administered. “Aseptic” meningitis refers generically to syndromes associated with signs and symptoms of meningeal irritation, but negative routine bacterial cultures.

Aseptic meningitis
is usually caused by viruses, most commonly Enterovirus. A number of these viruses are also able to cause parenchymal infection, and distinguishing between meningitis, encephalitis, and meningoencephalitis can be challenging. Encephalitis is primarily characterized by neurologic dysfunction, whereas patients with aseptic meningitis most commonly present with photophobia, stiff neck, headache, and fever. Patients with severe aseptic meningitis, however, may develop seizures and altered mental status and progress to significant neurologic dysfunction.

A wide variety of viruses have been implicated as causing aseptic meningitis; the most common viruses are as follows:

   Enteroviruses: The incidence of enteroviral meningitis peaks in late summer and early fall, but enteroviruses cause low-level, endemic disease year-round.

   HSV-2: A significant percentage of patients with primary genital herpes simplex infection also demonstrate signs and symptoms of aseptic meningitis. HSV-2 may also cause recurrent aseptic meningitis associated with flares of genital infection.

   HIV: A subset of patients with primary HIV infection will develop signs and symptoms of aseptic meningitis or meningoencephalitis, which is usually self-limited.