Herpes simplex encephalitis. Early diagnosis and immune activation in the acute stage and during long-term follow-up

From a series of in all 93 patients with herpes simplex encephalitis (HSE), verified by biopsy and/or the demonstration of intrathecal synthesis of antibodies to the virus, cerebrospinal fluid (CSF) and serum samples were analysed and compared with samples from 80 patients with non-HSE, i.e. acute encephalitis of non-HSV origin (approximately 50% with other known aetiology, 50% of unknown origin) treated on the suspicion of HSE but in whom no signs of intrathecal HSV antibody synthesis were found, and samples from an additional 42 patients with other verified or suspected diseases of the CNS. To improve the early non-invasive diagnosis of HSE, a HSV IgG capture enzyme linked immunosorbent assay (ELISA) was developed to demonstrate intrathecal synthesis of antibodies to the virus and the results were compared to those of the indirect ELISA. The capture ELISA was found to be advantageous in detecting the early antibody response and yielded more clear-cut results. No correction for damage to the blood-CSF barrier was needed and the method was therefore less labour-intensive than the indirect ELISA. Furthermore, a polymerase chain reaction (PCR) assay, with two "nested" primers pairs selected in the glycoprotein D gene of HSV-1, was developed for the amplification of HSV DNA in CSF. The method was found to be a rapid and non-invasive means of diagnosing HSE in a very early stage of the disease; it was highly sensitive and specific. With a combination of nested PCR assays for HSV-1 and HSV-2 (primers in the glycoprotein G gene) in 10 microliters of CSF, HSV DNA was detected in CSF from 88 out of 93 patients (95%) with HSE. Evidence of HSV-2 aetiology was found in 6 of 93 consecutive cases of HSE in immunocompetent patients by type-specific assays for the demonstration of HSV-2 DNA (primers in the gG gene) and HSV-2 antibodies (to gG2 antigen) in the CSF. Five of the 6 patients with HSV-2 encephalitis exhibited a clinical picture of severe HSE indistinguishable from that of "classical" HSV-1 encephalitis. The combined use of PCR for the detection of HSV DNA in the CSF and the demonstration of intrathecal synthesis of antibodies to the virus will yield a reliable diagnosis and is now the method of choice for the diagnosis of HSE.(ABSTRACT TRUNCATED AT 400 WORDS)