The diagnosis of herpes encephalitis

Since the first description of herpes simplex virus (HSV) as a cause of encephalitis 50 years ago, herpes encephalitis has been transformed from being a disease diagnosed at autopsy to one which can be diagnosed in life. The first method to enable this, brain biopsy with direct immunofluorescent staining for detection of viral antigen, has not been surpassed in terms of speed and technical simplicity. However, use of this procedure has been the subject of controversy and the introduction of the effective, relatively non-toxic, antiviral agent acyclovir has led to a dramatic reduction in brain biopsy. The clinical diagnosis of herpes encephalitis is difficult and precise diagnostic methods are still required. Detection of intrathecal HSV-specific antibody synthesis may allow diagnosis at an early stage in many patients but cannot be considered reliable until 10-12 days after onset of neurological illness. Detection of viral antigen in lumbar cerebrospinal fluid (CSF) may allow earlier diagnosis but no reliable assays are currently available. Polymerase chain amplification allows the detection of viral DNA in lumbar CSF at a very early stage of infection and this method, together with demonstration of intrathecal HSV antibody synthesis, provide the current methods of choice. Further techniques for diagnosis are under development and neuroradiological imaging to detect the CNS accumulation of virus-selective compounds holds promise as a future, truly non-invasive technique, for diagnosis.