Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella-zoster virus infection of the nervous system

Objective

To study cerebrospinal fluid (CSF) and serum samples from 34 consecutive patients suspected of having varicella‐zoster virus (VZV) infection of the central nervous system (CNS).

Population and methods

The patients were divided into three groups. The first group consisted of 27 patients with a rash in one to three dermatomes and clinical suspicion of meningitis and radiculitis; among them, three subgroups were distinguished according to the affected dermatome: ophthalmicus (n?=?9), oticus (n?=?11) and cervico‐thoraco‐lumbar zoster (n?=?7). Four cases of zoster sine herpete (ZSH) were included in the second group: these patients presented with either radiculitis (n?=?2) or meningoencephalitis (n?=?2), without cutaneous eruption. The third group consisted of three patients with a generalised rash and encephalitis. A polymerase chain reaction (PCR) for VZV DNA and antigen‐driven immunoblots for oligoclonal anti‐VZV antibodies were carried out on all CSF samples.

Results

PCR of the CSF was positive in 44% of the patients from the first group, mainly within the first 7?days after eruption. In addition, intrathecal synthesis of anti‐VZV antibodies was detected in 37% of patients, always after an interval of 7?days (p<0.0001). Among the four patients with ZSH, a positive VZV PCR was detected in three patients and CSF‐specific oligoclonal anti‐VZV antibodies in two. PCR was also positive in the CSF of two of the three patients with generalised rash and encephalitis; local production of anti‐VZV antibodies was seen in a second CSF sample in one patient, and was also present in the third patient.

Conclusion

Amplification of VZV DNA by PCR in the CSF and antigen‐driven immunoblots have important diagnostic value in suspected VZV infection, although their presence depends on the timing of the CSF sampling. VZV is thought to be a causative agent in unexplained cases of meningitis associated with radiculitis or focal CNS symptoms, even in the absence of skin manifestations. In such patients, rapid diagnosis by this combined approach permits early antiviral treatment.Varicella‐zoster virus (VZV), an exclusively human herpesvirus, causes chickenpox (varicella), becomes latent in the cranial nerve and dorsal root ganglia, and may reactivate decades later in 10–20% of the population to produce shingles (zoster).¹ Shingles is characterised by unilateral radicular pain and a vesicular rash that is generally limited to one to three contiguous dermatomes. The annualised incidence of shingles is about 1.5–3 cases per 1000 people, but increases to 11 cases per 1000 in the population >60?years of age.² VZV can also cause neurological complications, very rarely during the primary infection (most often a varicella cerebellitis) and more often during the reactivation phase. The main complication is post‐herpetic neuralgia, a neuropathic pain syndrome that persists after the dermatomal rash has healed. Acute neurological complications may, however, occur, and affect either the peripheral nervous system (cranial neuropathies, motor radiculopathies of the arm or the leg, bladder and bowel dysfunction) or the central nervous system (CNS; meningitis, myelitis and vasculitic encephalitis). The same neurological complications may be observed in zoster sine herpete (ZSH), which is defined by a dermatomal pain without antecedent rash.³Cerebrospinal fluid (CSF) analysis is a key tool in the diagnosis of CNS infection with VZV. The amplification of VZV DNA by polymerase chain reaction (PCR) and the detection of intrathecal synthesis (ITS) of anti‐VZV‐specific antibodies are the most reliable ways of establishing a definite diagnosis of VZV CNS infection.⁴ We present a retrospective study on CSF samples collected from 34 consecutive patients suspected of harbouring CNS VZV infection. Our population included four cases with ZSH and three with disseminated rash with meningoencephalitis. We discuss correlations between the CSF results, the timing of CSF samples and the clinical picture.