DIAGNOSIS OF VIRAL-INFECTIONS OF THE CENTRAL-NERVOUS-SYSTEM - CLINICAL INTERPRETATION OF PCR RESULTS

Background Standard laboratory techniques, such as viral culture and s erology, provide only circumstantial or retrospective evidence of vira l infections of the central nervous system (CNS). We assessed the diag nostic accuracy of PCR of cerebrospinal fluid (CSF) in the diagnosis o f viral infections of the CNS. Methods We examined all the CSF samples that were received at our diagnostic virology laboratory between May, 1994, and May, 1996, by nested PCR for viruses associated with CNS in fections in the UK. We collected clinical and laboratory data for 410 patients from Oxford city hospitals (the Oxford cohort) whose CSF was examined between May, 1994, and May, 1995. These patients were classif ied according to the likelihood of a viral infection of the CNS. We us ed stratified logistic regression analysis to identify the clinical fa ctors independently associated with a positive PCR result. We calculat ed likelihood ratios to estimate the clinical usefulness of PCR amplif ication of CSF. Findings We tested 2233 consecutive CSF samples from 2 162 patients. A positive PCR result was obtained in 143 patients, incl uding 22 from the Oxford cohort. Logistic regression analysis of the O xford cohort showed that fever, a virus-specific rash, and a CSF white -cell count of 5/mu L or more were independent predictors of a positiv e PCR result. The likelihood ratio for a definite diagnosis of viral i nfection of the CNS ir? a patient with a positive PCR result, relative to a negative PCR result, was 88.2 (95% CI 20.6-378). The likelihood ratio for a possible diagnosis of viral infection of the CNS in a pati ent with a negative PCR result, relative to a positive PCR result, was 0.10 (0.03-0.39).Interpretation A patient with a positive PCR result was 88 times as likely to have a definite diagnosis of viral infection of the CNS as a patient with a negative PCR result. A negative PCR re sult can be used with moderate confidence to rule out a diagnosis of v iral infection of the CNS. We believe that PCR will become the first-l ine diagnostic test for viral meningitis and encephalitis.