A rising titer of neutralizing antibodies can be demonstrated from the acute to the convalescent stage, but this is not of diagnostic help in the acutely ill patient and may not be significant in patients with recurrent herpes infections of the oral mucosa. Tests for the detection of HSV antigen in the CSF by PCR have been developed and are useful in diagnosis while the virus is replicating in the first few days of the illness (Rowley et al). A refinement in this technique (a nested PCR assay described by Aurelius and coworkers) reportedly has a sensitivity of 95 percent and gives very few false-positive tests in the first 3 weeks of illness. In the experience of Lakeman and colleagues, the test was 98 percent positive in cases proven by cultures of brain biopsy material and gave 6 percent false positives. Antiviral treatment did not appear to affect the results. False-negative tests are most likely to occur in the first 48 h of febrile infection. When the clinical features are consistent with the disease and the PCR test is negative, it is advisable to repeat it in several days, and to obtain PCR testing for HSV-2 as well, while antiviral treatment is continued.
Alternative ways to establish the diagnosis of acute HSV encephalitis are by fluorescent antibody study or culture of cerebral tissue obtained from brain biopsy. The approach to biopsy as a diagnostic test is now infrequently employed with the availability of PCR. We have found it necessary to perform biopsy in only exceptional cases.
Until the late 1970s, there was no specific treatment for HSV encephalitis. A collaborative study sponsored by the National Institutes of Health and also a Swedish trial indicated that the antiviral agent acyclovir significantly reduces both mortality and morbidity from the disease (Whitley et al; Sköldenberg et al). For this reason, it has become general practice to initiate treatment while confirmatory testing is being carried out. Acyclovir is given intravenously in a dosage of 30 mg/kg/d and continued for 14 to 21 days in order to prevent relapse. Acyclovir carries limited risk and can be discontinued if further clinical or laboratory features point to another diagnosis. The main problems that arise from the drug are local irritation of the veins used for infusion, mild elevation of hepatic enzymes, or transient impairment of renal function. Nausea, vomiting, tremor, or an encephalopathy that is difficult to distinguish from the encephalitis itself occurs in a few patients.
When a large volume of brain tissue is involved, the hemorrhagic necrosis and surrounding edema act as an enlarging mass that requires separate attention. Coma and pupillary changes should not be attributed to the mass effect unless compression of the upper brainstem is evident on brain imaging, as the infection is capable of spreading to the mesencephalon from the contiguous deep temporal lobe, thereby causing coma by a direct destructive effect. All measures used in the management of brain edema from mass lesions are applicable here, but there are insufficient data by which to judge their effectiveness. The concern that corticosteroids may aggravate the infection has not been borne out by clinical experience, but a detrimental effect cannot be discounted and their value is uncertain. Our experience (reported by Barnett et al) and that of Schwab and colleagues have been that the presence of raised intracranial pressure early in the illness presages a poor outcome. Seizures are usually brought under control by high doses of conventional antiepileptic drugs. The value of these medications prophylactically for seizures has not been resolved.