Correlation of Cerebrospinal Fluid (CSF) Cell Counts and Elevated CSF Protein Levels with Enterovirus Reverse Transcription-PCR Results in Pediatric and Adult Patients

Abstract

We found that in the group of patients aged >2 months, the absence of pleocytosis was highly predictive of a negative RT-PCR result. Elevated CSF protein level was not a good predictor of RT-PCR positivity for enterovirus and did not add to the diagnostic sensitivity or specificity of pleocytosis.Enteroviruses (EVs) cause annual seasonal epidemics of aseptic meningitis in temperate climates and are the most common cause of this clinical syndrome in the United States. The infections are most clinically noticeable in children, but they are also clearly present in adults (9). The viruses are maintained within the human population in tropical climates year-round and at low but detectable levels in both children and adults during the cold months in temperate climates (3).Reverse transcription (RT)-PCR has become the method of choice for the rapid and efficient diagnosis of EV infections from cerebrospinal fluid (CSF). The use of commercially available (6,11,12,20) and in-house assay methods (6) is currently common in molecular diagnostic virology laboratories and often results in fewer tests being performed, less medication being used, and earlier release from the hospital than with previous diagnostic methods for patients with CSF samples with positive RT-PCR results for EV (EV RT-PCR) and negative Gram stains (4,8,10,14,15).Whether CSF pleocytosis plays an important role in defining aseptic meningitis or in prioritizing the differential diagnosis has been investigated but is still not completely clear (7,14,17). In this era of rapidly rising health care costs, it is important, if possible, to limit laboratory-based testing by encouraging syndrome-directed testing and actively discouraging testing that is not consistent with the clinical picture or with other laboratory results. Additionally, quality control within the laboratory can be enhanced by monitoring laboratory-based data to look for important correlations that will provide insight for clinicians and laboratory workers with regard to future testing requests.During the 2001, 2002, and 2003 EV seasons, we collected all available CSF cell count data and CSF protein data (available for 2001 and 2002 only) for patients for whom EV RT-PCR of CSF samples had been requested. Our suspicion that CSF with a nucleated cell count of Յ5 per mm 3 from patients more than 2 months old was not likely to be RT-PCR positive proved to be true, although a large number of CSF samples with high cell counts did not test positive for EV. MATERIALS AND METHODSCSF specimens (n ϭ 1,706) were submitted to the St. Louis Children's Hospital Virology Laboratory during the 2001, 2002, and 2003 EV seasons (roughly May to November of each year) for EV RT-PCR testing. Relevant CSF cell count data was available from the laboratory information system for 728 of the patients who were seen at Washington University Medical Center and tested by EV RT-PCR. Of the patients included in the study, 549 were pediatric (Յ18 years of age) and 179 were adults. The data analyzed included patient age, EV RT-PC...

Enteroviral Central Nervous System Infections in Children of the Region of Monastir, Tunisia: Diagnosis, Laboratory Findings of Cerebrospinal Fluid and Clinical Manifestations

“…In the current study, 60 % of EVs positive cases had elevated leukocyte counts in the CSF. In accordance with previous reports, the absence of pleocytosis was frequent in children under 2-years-old [18,20,29,36,50]. Lymphocytes were predominant in 80 % of EVs positive patients.…”

Prevalence and Management of Invalid GeneXpert Enterovirus Results Obtained with Cerebrospinal Fluid Samples: a 2-Year Study

“…The invalid GXEA results were reported for 43 (8.2%) specimens and correlated with increased visibility of red blood cells (P < 0.0001) but not with CSF xanthochromia and clotting. Invalid GXEA result rates were markedly diminished by 82.1% and 96.0% and test sensitivities were minimally decreased by 1.7% and 3.6% when these specimens were tested at a 1:5 dilution and after a freeze-thaw cycle, respectively.Enterovirus (EnV) meningitis can be difficult to distinguish from disease caused by other etiologic agents when patients present with nonspecific pathogenic symptoms and signs, such as fever, headache and stiff neck, and pleocytosis in cerebrospinal fluid (CSF) (4,8,9). Nucleic acid amplification-based procedures for the detection of EnV RNA in CSF have replaced cell culture as the test of choice (10,11,14).…”

“…Enterovirus (EnV) meningitis can be difficult to distinguish from disease caused by other etiologic agents when patients present with nonspecific pathogenic symptoms and signs, such as fever, headache and stiff neck, and pleocytosis in cerebrospinal fluid (CSF) (4,8,9). Nucleic acid amplification-based procedures for the detection of EnV RNA in CSF have replaced cell culture as the test of choice (10,11,14).…”

Enterovirus infections in Singaporean children: an assessment of neurological manifestations and clinical outcomes

“…3 ) and a negative bacterial culture of the CSF samples obtained from lumbar puncture. (16,17) Encephalitis was defined as having an acute brain infection associated with alteration in the level of consciousness. (18) Poor feeding was defined as taking less than half of the normal oral intake or requiring intravenous hydration.…”