Rationalising the use of polymerase chain reaction based tests for diagnosis of common viral infections of the central nervous system

Polymerase chain reaction (PCR) based tests have proved to be useful for establishing the aetiology of many infections of the central nervous system (CNS). As a result there has been a rise in the demand for these relatively expensive tests. A recent study has shown that the detection of herpes simplex virus (HSV) by PCR is highly unlikely if the leucocyte count and protein concentration of the cerebrospinal spinal fluid (CSF) are within the normal range. They suggest that not performing PCR tests for HSV on CSF specimens with a normal leucocyte count and protein concentration will result in considerable savings without decreasing sensitivity for the detection of common viral infections of the CNS.¹

We reviewed the leucocyte count, protein concentration, and glucose concentration of all CSF specimens that were tested for viral pathogens using PCR during a 12 month period (March 2000 to February 2001). The PCR tests were performed at the Public Health Laboratory, Addenbrookes Hospital, Cambridge, UK. All specimens were initially screened using two in house testing panels, which included HSV, varicella zoster virus, enteroviruses, and ECHO 22 virus by a method described by Read et al.² Further tests for individual viruses were performed if the screening tests were positive.

Forty five CSF specimens were tested by PCR. Thirty of 45 specimens had a raised leucocyte count (> 4/cm²) or protein concentration (> 600 mg/litre). Six of these 30 CSF specimens with a raised leucocyte count or protein concentration were positive for enteroviruses (five) or HSV (one). Only one of 15 “normal” CSF specimens (normal leucocyte count and protein concentration) was PCR positive for HSV. However, this patient had advanced AIDS with severe neutropenia.

Although the number of patients studied is relatively small, our results not only confirm the observations of Tang et al but show that the PCR tests for other common viruses are also very unlikely to be positive in CSF specimens with a normal leucocyte count and protein concentration, except in immunocompromised patients.¹

We are aware that many clinicians frequently use a negative PCR to stop empirical aciclovir treatment for patients with suspected HSV encephalitis (HSVE). We are unable to find the scientific evidence for this strategy. The question is does negative PCR exclude HSV encephalitis? There is evidence that even PCR may be negative in early HSVE.³ We entirely agree that empirical treatment should be initiated for patients with suspected HSVE, but subsequent clinical progress, CSF findings, electroencephogram results, and computed tomography scans, rather than a negative HSV PCR, should determine the need to continue treatment. Furthermore, in many hospitals such as ours, facilities for performing HSV PCR are not available in house. Dependence on negative PCR results to stop aciclovir treatment will entail referral of specimens to a reference laboratory and the continuation of treatment until the results are available.

We conclude that PCR based tests are best reserved for those patients in whom the CSF findings are compatible with viral meningitis or encephalitis; that is, raised white cell count (> 4 /cm²) and raised protein (> 600 mg/litre). Such a strategy will promote cost effective use of laboratory resources without compromising clinical care.