Is there more to a normal cerebrospinal fluid cell count?

Enteroviruses (EV) and parechoviruses (HPeV) both cause meningoencephalitis of varying severity in children <6 months of age.1 Investigation of an unwell infant usually includes a lumbar puncture which can be difficult to interpret, particularly with prior administration of antibiotics, traumatic taps and the wide range of age-dependent normal cerebrospinal fluid (CSF) values. Outbreaks of HPeV infections in the last few years2 have heightened physician awareness and increased requests for testing. We reviewed all CSF results in infants <6 months of age from June 2015 to July 2016 in our laboratory. EV polymerase chain reaction (PCR) is routinely performed by the GeneXpert enterovirus assay (Cepheid, Sunnyvale, CA, USA), however, in low volume or heavily blood stained specimens testing is performed by an in-house real-time PCR.3 A total of 385 CSF samples underwent analysis of which 52 (13.5%) were EV positive. Of the 333 samples, which were EV negative, HPeV was detected in 26 (7.8%). No dual viral infections or bacterial infections were identified. Of the HPeV positive samples, 25 of 26 were in children <3 months of age and 13 (50%) were ≤28 days of age. Ninety-two percent of these neonatal CSF were considered to have a normal total white cell count (<25 × 106/L). Of the HPeV positive children age 1–6 months, 8 of 13 (62%) had normal total white cell counts (≤5 × 106/L) and 12 of 13 (92%) had counts of <8 × 106/L. Most HPeV positive samples were collected from mid-October to early December with only isolated cases outside of this time. Of the EV positive samples, 22 of 52 (42%) were from children ≤28 days while 51 (98%) were from children <3 months of age. Six of 22 (27%) neonates and 8 of 30 (27%) of children aged 1–6 months, respectively, had normal CSF values. EV positive samples were detected throughout the year but there were also increased numbers during December. Viral meningitis is common in infants with 78 (20.3%) samples positive in this study. Most HPeV and EV infections were clustered during the spring-summer period. Our results suggest that EV and HPeV infection predominantly affects children <3 months of age. While lumbar puncture is recommended to exclude bacterial meningitis in neonates presenting with undifferentiated sepsis, HPeV testing should still be performed in CSF with normal cell counts as pleocytosis is uncommon and the diagnosis of viral infection will influence patient management.