Human cytomegalovirus (HCMV) encephalitis in an immunocompetent young person and diagnostic reliability of HCMV DNA PCR using cerebrospinal fluid of nonimmunosuppressed patients

Abstract

Human cytomegalovirus (HCMV) encephalitis in adult nonimmunosuppressed patients has rarely been reported. We have diagnosed HCMV encephalitis in an anti-HCMV immunoglobulin G-negative, nonimmunosuppressed young woman by HCMV DNA PCR and virus isolation from cerebrospinal fluid (CSF). At the same time, HCMV antigen and HCMV DNA could be demonstrated in peripheral blood leukocytes, and the virus was isolated in fibroblast cultures. After 22 days of acute illness, the virus disappeared from the CSF. Remarkably, the patient did not generate detectable anti-HCMV antibodies within 5 months after the beginning of illness. To investigate the significance of HCMV DNA detection in CSF, samples of CSF, blood cells, and serum from 35 nonimmunosuppressed patients with various neurological disorders (but no herpes simplex virus central nervous system [CNS] disease) were tested for HCMV DNA, antigen, and antibodies. Eleven of these patients were found to be positive for virus DNA and/or antigen in peripheral blood leukocytes. Additionally, HCMV DNA was detected in the CSF of two patients with noninflammatory CNS diseases. A causative role of HCMV in the CNS diseases of these two patients was not evident. In summary, HCMV DNA amplification from CSF samples is a very suitable method to verify HCMV-associated encephalitis, but it should be taken into consideration that there are few cases of positive PCR with DNA from CSF without any known clinical correlative.

FIG. 1

Results of Southern hybridization of PCR products from CSF collected from the study patient on different days after hospitalization. DNA fragments were separated on a 2% agarose gel, transferred to a nylon membrane, and hybridized with the radiolabeled internal oligonucleotide CS3 according to the method of Gozlan et al. (12). (A) Lanes 1 and 7, buffer control; lane 2, 0.1 pg of AD169 control DNA; lane 3, 0.01 pg of AD169 control DNA; lane 4, positive control (CSF from an HCMV-infected child); lane 5, negative control (human placental DNA); lanes 6 and 8, DNA from 40 μl of CSF collected on day 1 after hospitalization. (B) Lane 1, 0.01 pg of AD169 control DNA; lane 2, 0.1 pg of AD169 control DNA; lane 3, negative control (human placental DNA); lane 4, buffer control; lane 5, DNA from CSF collected on day 8 after hospitalization; lane 6, DNA from CSF collected on day 17 after hospitalization; lane 7, DNA from PBL collected on day 17 after hospitalization.