HHV-6 in CSF Samples

Sir,

In a recent report by Stödberg et al, a patient with diffuse leptomeningeal oligodendrogliomatosis had repeated CSF examinations which were positive for HHV-6 A by PCR [[3]]. As the authors suggest, the patient's clinical response to antiviral treatment supports the role of the virus in the neurological symptoms, although the low titers of antibodies and the absence of viral antigen suggest non-productive infection.

An association of HHV-6 A with the neoplasm is possible and may have been facilitated by increased density of receptors in the tumor. However the finding of HHV-6 A can also be a coincidence: according to our experience, HHV-6 DNA in the CSF is not rare. While Stödberg et al found only two positive samples out of 108 tested, our rate of positivity was 5/46 in a hospital series: as part of our study on viral coinfection in subacute sclerosing panencephalitis (SSPE), we examined CSF samples of 43 SSPE patients and 46 control cases [[1]]. After isolating DNA, we performed PCR for HHV-6 using a combined, PCR-specific, biotinylated probe hybridisation kit (Hybriwell Consensus Hybridowell, Argene, France). PCR was positive for HHV-6 in five patients with SSPE and five with other disorders: epilepsy, febrile convulsion, idiopathic intracranial hypertension, leukemia, and lymphoma, one each. The latter two patients were in remisssion and receiving intrathecal chemotherapy. False-positivity is unlikely because the method used in the detection of herpes viruses is based on probe hybridisation. The tropism of herpes viruses for lymphoid and neural cells, and their predisposition for latency may lead to the presence of viral DNA in tissue containing these cells in abundance. Accordingly, HHV-6 in brain tissue was found in 42.9 % of various specimens [[2]]. We therefore suggest caution in interpreting positive PCR findings for herpes viruses.

References

• 1 Anlar B, Pinar A, Anlar F Y. et al . Viral studies in the cerebrospinal fluid in subacute sclerosing panencephalitis.  J Infect. 2002;  44 176-180
• 2 Chan P K, Ng H K, Hui M, Ip M, Cheung J L, Cheng A F. Presence of human herpesviruses 6, 7, and 8 DNA sequences in normal brain tissue.  J Med Virol. 1999;  59 491-495
• 3 Stödberg T, Deniz Y, Esteitie N. et al . A case of diffuse leptomeningeal oligodendrogliomatosis associated with HHV-6 variant A.  Neuropediatrics. 2002;  33 266-270