Since acyclovir is generally a safe drug, empirical administration in cases of suspected herpes simplex encephalitis is justified on clinical grounds or when polymerase chain reaction diagnostic tests are equivocal or unavailable. The role of brain biopsy in establishing the diagnosis of herpes simplex encephalitis remains controversial. Advocates of routine biopsy for patients with suspected herpes simplex encephalitis point out the lack of pathognomonic clinical features in early herpes simplex encephalitis, which frequently create diagnostic confusion, and that acyclovir therapy is not completely without risk, particularly with regard to acute renal toxicity. However, the increasing availability of polymerase chain reaction assays for viral DNA makes these arguments less persuasive. Acyclovir therapy can be suspended if the subsequent clinical course suggests an alternative diagnosis or polymerase chain reaction analysis of cerebrospinal fluid is negative. Brain biopsy is indicated when compelling clinical or radiographic evidence suggests an alternative diagnosis, or the patient continues to deteriorate despite appropriate acyclovir therapy.
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