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Polymerase Chain Reaction as a Diagnostic Adjunct in Herpesvirus Infections of the Nervous System

Polymerase chain reaction (PCR) is a powerful technique that allows detection of minute quantities of DNA or RNA in cerebrospinal fluid (CSF), vesicle and endoneurial fluids, blood, fresh‐frozen, and even formalin‐fixed tissues. Various infectious agents can be detected with high specificity and sensitivity, including bacteria, parasites, rickettsia and viruses. PCR analysis of CSF has revolutionized the diagnosis of nervous system viral infections, particularly those caused by human herpesviruses (HHV), and has now replaced brain biopsy as the gold standard for diagnosis of herpes simplex virus (HSV) encephalitis. PCR analysis of both CSF and nervous system tissues has also broadened our understanding of the spectrum of disease caused by HSV‐1 and ‐2, cytomegalovirus (CMV), Epstein‐Barr virus (EBV), varicella zoster virus (VZV), and HHV‐6. Nonetheless, positive tissue PCR results must be interpreted cautiously, especially in cases that lack corroborating clinical and neuropathologic evidence of infection. Moreover, positive PCR results from tissues do not distinguish latent from productive (lytic) viral infections. In several neurological diseases, negative PCR results have provided strong evidence against a role for herpesviruses as the causative agents. This review focuses on the use of PCR tests to diagnose HSV and VZV infections of the nervous system.