Clinical Investigation: The Presence of Viral Meningitis without Pleocytosis among Pediatric Patients


Background: Viral meningitis (VM) is mostly common among infants. Its induction by enteroviruses (EVM) is associated with morbidity and is primarily diagnosed by lumbar puncture, which may yield false negatives. We evaluated the frequency of VM by polymerase chain reaction (PCR) among infants with no detected pleocytosis. Furthermore, as literature suggests EVM essentially occurs during summer and fall, we characterized the monthly distribution of EVM cases. Methods: Infants diagnosed with VM from June 2009 to May 2010 were enrolled in the current prospective study. Following each lumbar puncture, CSF was tested for enteroviruses by PCR. Outcome measures were i) the percentage of EVM cases revealed solely by PCR; and ii) the monthly distribution of EVM cases. Results:Enrolled were 173 VM-diagnosed infants, of whom 75 (43.4%) tested positive in CSF-PCR. Of these, no pleocytosis was indicated in 43 (57%), specifically in 70% and 42% of infants younger than 90 days and older than 1 year, respectively. Furthermore, 119 (69%) infants were admitted during June-November while 54 (31%) during December-May. Conclusions:Current findings stress the high frequency of infants who were tested negative for pleocytosis, yet were diagnosed with VM by PCR. This was especially noticeable among infants younger than 3 months, possibly reflecting their decreased ability to mount a robust inflammatory response to EV infection. CSF-PCR may be warranted in pediatric patients who test negative for pleocytosis. While most EVM cases occurred during the summer and fall, EVM-infants were admitted to the hospital all through the year.

Share and Cite:

Klein-Kremer, A. , Nir, V. , Eias, K. , Nir, R. , Yakubov, R. and Gershon, K. (2014) Clinical Investigation: The Presence of Viral Meningitis without Pleocytosis among Pediatric Patients. Open Journal of Pediatrics, 4, 276-282. doi: 10.4236/ojped.2014.44038.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] United States Department of Health and Human Services Centers for Disease Control and Prevention. Aseptic Meningitis 1990 Case Definition.
[2] Rantakallio, P., Leskinen, M. and Von Wendt, L. (1986) Incidence and Prognosis of Central Nervous System Infections in a Birth Cohort of 12,000 Children. Scandinavian Journal of Infectious Diseases, 18, 287-294.
[3] Kupila, L., Vuorinen, T., Vainionpaa, R., Hukkanen, V., Marttila, R.J. and Kotilainen, P. (2006) Etiology of Aseptic Meningitis and Encephalitis in an Adult Population. Neurology, 66, 75-80.
[4] Davison, K.L. and Ramsay, M.E. (2003) The Epidemiology of Acute Meningitis in Children in England and Wales. Archives of Disease in Childhood, 88, 662-664.
[5] Health Protection Agency. Diseases Notifiable (to Local Authority Proper Officers) under the Public Health (Infectious Diseases) Regulations 1988.
[6] Sawyer, M.H. and Rotbart, H. (2004) Viral Meningitis and Aseptic Meningitis Syndrome. In: Scheld, W.M., Whitley, R.J. and Marra, C.M., Eds., Infections of the Central Nervous System, 3rd Edition, Lippincott Williams & Wilkins, Philadelphia, 75-93.
[7] Logan, S.A.E. and MacMahon, E. (2008) Viral Meningitis. BMJ, 336, 36-40.
[8] Pallansch, M.A. and Roos, R.P. (2001) Enteroviruses: Polioviruses, Coxsackieviruses, Echoviruses, and Newer Enteroviruses. In: Knipe, D.M., Howley, P.M., Griffin, D.E., Lamb, R.A., Martin, M.A., Roizman, B., et al., Eds., Fields Virology, 4th Edition, Lippincott Williams & Wilkins, Philadelphia, 723-775.
[9] Rotbart, H.A., Brennan, P.J., Fife, K.H., et al. (1998) Enterovirus Meningitis in Adults. Clinical Infectious Diseases, 27, 896-898.
[10] Read, S.J. and Kurtz, J.B. (1999) Laboratory Diagnosis of Common Viral Infections of the Central Nervous System by Using a Single Multiplex PCR Screening Assay. Journal of Clinical Microbiology, 37, 1352-1355.
[11] Thomas, J.E., Falls, E., Velasco, M.E. and Zaher, A. (2000) Diagnostic Value of Immunocytochemistry in Leptomeningeal Tumor Dissemination. Archives of Pathology & Laboratory Medicine, 124, 759-761.
[12] Amarilyo, G., Alper, A., Ben-Tov, A. and Grisaru-Soen, G. (2011) Diagnostic Accuracy of Clinical Symptoms and Signs in Children with Meningitis. Pediatric Emergency Care, 27, 196-199.
[13] van de Pol, A.C., Wolfs, T.F., Jansen, N.J., van Loon, A.M. and Rossen, J.W. (2006) Diagnostic Value of Real-Time Polymerase Chain Reaction to Detect Viruses in Young Children Admitted to the Paediatric Intensive Care Unit with Lower Respiratory Tract Infection. Critical Care, 10, R61.
[14] van Doornum, G.J., Guldemeester, J., Osterhaus, A.D. and Niesters, H.G. (2003) Diagnosing Herpesvirus Infections by Real-Time Amplification and Rapid Culture. Journal of Clinical Microbiology, 41, 576-580.
[15] Nijhuis, M., van Maarseveen, N., Schuurman, R., et al. (2002) Rapid and Sensitive Routine Detection of All Members of the Genus Enterovirus in Different Clinical Specimens by Real-Time PCR. Journal of Clinical Microbiology, 40, 3666-3670.
[16] de Crom, S.C., Obihara, C.C., van Loon, A.M., et al. (2012) Detection of Enterovirus RNA in Cerebrospinal Fluid: Comparison of Two Molecular Assays. Journal of Virological Methods, 179, 104-107.
[17] Mulford, W.S., Buller, R.S., Arens, M.Q. and Storch, G.A. (2004) Correlation of Cerebrospinal Fluid (CSF) Cell Counts and Elevated CSF Protein Levels with Enterovirus Reverse Transcription-PCR Results in Pediatric and Adult Patients. Journal of Clinical Microbiology, 42, 4199-4203.
[18] Seiden, J.A., Zorc, J.J., Hodinka, R.L. and Shah, S.S. (2010) Lack of Cerebrospinal Fluid Pleocytosis in Young Infants with Enterovirus Infections of the Central Nervous System. Pediatric Emergency Care, 26, 77-81.
[19] Gomez, B., Mintegi, S., Rubio, M.C., Garcia, D., Garcia, S. and Benito, J. (2012) Clinical and Analytical Characteristics and Short-Term Evolution of Enteroviral Meningitis in Young Infants Presenting with Fever without Source. Pediatric Emergency Care, 28, 518-523.
[20] Ramers, C., Billman, G., Hartin, M., Ho, S. and Sawyer, M.H. (2000) Impact of a Diagnostic Cerebrospinal Fluid Enterovirus Polymerase Chain Reaction Test on Patient Management. JAMA, 283, 2680-2685.
[21] King, R.L., Lorch, S.A., Cohen, D.M., Hodinka, R.L., Cohn, K.A. and Shah, S.S. (2007) Routine Cerebrospinal Fluid Enterovirus Polymerase Chain Reaction Testing Reduces Hospitalization and Antibiotic Use for Infants 90 Days of Age or Younger. Pediatrics, 120, 489-496.
[22] Dewan, M., Zorc, J.J., Hodinka, R.L. and Shah, S.S. (2010) Cerebrospinal Fluid Enterovirus Testing in Infants 56 Days or Younger. Archives of Pediatrics and Adolescent Medicine, 164, 824-830.
[23] Graham, A.K. and Murdoch, D.R. (2005) Association between Cerebrospinal Fluid Pleocytosis and Enteroviral Meningitis. Journal of Clinical Microbiology, 43, 1491.
[24] Archimbaud, C., Chambon, M., Bailly, J.L., et al. (2009) Impact of Rapid Enterovirus Molecular Diagnosis on the Management of Infants, Children, and Adults with Aseptic Meningitis. Journal of Medical Virology, 81, 42-48.
[25] Meehan 3rd, W.P. and Bachur, R.G. (2008) Predictors of Cerebrospinal Fluid Pleocytosis in Febrile Infants Aged 0 to 90 Days. Pediatric Emergency Care, 24, 287-293.

Copyright © 2021 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.